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WO2025046239A1 - Device for trapping tissues and/or multi-cellular objects - Google Patents

Device for trapping tissues and/or multi-cellular objects Download PDF

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Publication number
WO2025046239A1
WO2025046239A1 PCT/GB2024/052265 GB2024052265W WO2025046239A1 WO 2025046239 A1 WO2025046239 A1 WO 2025046239A1 GB 2024052265 W GB2024052265 W GB 2024052265W WO 2025046239 A1 WO2025046239 A1 WO 2025046239A1
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WIPO (PCT)
Prior art keywords
objects
channel
restrictions
fluid
electrode
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Application number
PCT/GB2024/052265
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French (fr)
Inventor
Shareen FORBES
Euan R BROWN
John Campbell
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University of Edinburgh
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University of Edinburgh
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Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502761Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502746Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means for controlling flow resistance, e.g. flow controllers, baffles
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06Fluid handling related problems
    • B01L2200/0647Handling flowable solids, e.g. microscopic beads, cells, particles
    • B01L2200/0668Trapping microscopic beads
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/06Auxiliary integrated devices, integrated components
    • B01L2300/0627Sensor or part of a sensor is integrated
    • B01L2300/0645Electrodes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0809Geometry, shape and general structure rectangular shaped
    • B01L2300/0816Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0864Configuration of multiple channels and/or chambers in a single devices comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0475Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/08Regulating or influencing the flow resistance
    • B01L2400/084Passive control of flow resistance
    • B01L2400/086Passive control of flow resistance using baffles or other fixed flow obstructions

Definitions

  • the present disclosure relates to a microfluidic device, in particular, a device for trapping and testing a plurality of objects, for example, one or more tissue and/or multicellular objects.
  • a method of using said device for example, to determine cell, tissue or object quality and/or function.
  • BACKGROUND Type 1 diabetes mellitus (T1D) is an autoimmune disease that affects 400,000 people in the UK (JDRF Editors, 2022).
  • the condition is characterised by the loss of functional beta cells that are the majority of cells located within cellular clusters known as pancreatic islets situated in the pancreas.
  • One islet contains around 1500 cells with 74% comprising beta cells.
  • beta cells normally secrete insulin on glucose stimulation but this function is lost in T1D resulting in uncontrolled and/or high blood glucose concentrations.
  • treatment with synthetic insulin injection can help control blood glucose levels, and is the mainstay of treatment, feedback control is absent and a common side-effect of insulin therapy is hypoglycaemia.
  • Repeated episodes of hypoglycaemia can lead to impaired awareness of hypoglycaemia, such that the individual has an inability to recognise when the blood glucose levels are low which can result in significant morbidity and mortality.
  • Islet transplantation by cadaveric donor for the treatment of T1D has been shown to be effective at improving glucose control. Transplantation can reduce the number of severe hypoglycaemic events and is an effective treatment in restoring hypoglycaemic awareness.
  • Islet numbers, sample purity, and islet viability are all vital parameters to meet clinical release criteria before transplantation is performed (Brooks et al., 2013; Benomar et al., 2018). In the United Kingdom, islet viability must be greater than 70% in order for a preparation to be transplanted. Overestimating viability of islet preparations can lead to relatively large numbers of non-viable and inadequate numbers of islets being transplanted while underestimation can result in otherwise viable islets being discarded. These standards protect the recipient, ensuring only pancreases that have a large number of healthy islets are transplanted. However, this results in low clinical conversion rates, which, in 2019, stood at 28% (Bunnett J & Counter C, 2019).
  • GSIS glucose-stimulated insulin secretion pathway
  • Determining electrical activity of ⁇ - cells has usually involved traditional electrophysiological methods such as single and/or whole- cell voltage clamp techniques or intracellular electrodes (Pfeiffer et al., 2011; Düfer, 2012). Such techniques are very time-consuming and require expert single cell manipulation and interpretation.
  • extracellular recordings using suction electrodes and microelectrode arrays (MEA) can detect islet electrical activity with minimal tissue micromanipulation.
  • a microfluidic device comprising: a microfluidic module comprising: a plurality of fluidic paths between an input and an output; and a plurality of restrictions, wherein each restriction is provided on a respective fluidic path of the plurality of fluidic paths, wherein each restriction is configured to trap or at least restrict movement of one or more objects, for example, one or more tissue and/or multicellular objects, in a fluid introduced along its respective fluidic path at a respective sensing region; and at least one further fluidic path between the input and a further output, wherein the at least one further fluidic path is in fluid communication with the plurality of restrictions and wherein the further fluidic path comprises a delivery portion between the input and the plurality of restrictions to allow delivery of a further fluid to the trapped and/or restricted one or more objects and an output portion to allow removal of the further fluid from the further output.
  • the sensing module may form part of a sensing and stimulating module configured to provide a stimulus and measure a response to said stimulus at the sensing region.
  • the sensing module may comprise one or more stimulating elements configured to produce an electronic stimulus and one or more sensing elements for measuring a sensed signal, optionally a potential.
  • the stimulating elements may be configured to generate an electronic stimulus and the sensing element may be configured to sense a response to the stimulus.
  • the objects may comprise at least one of: an organoid; a cell spheroid; a tissue spheroid and/or a pancreatic Islet.
  • the objects may comprise cell objects and/or tissue objects.
  • the signal may comprise an extracellular signal.
  • the device may comprise a plurality of the microfluidic modules.
  • the device may comprise a plurality of microfluidic modules and a corresponding plurality of electronic sensing modules.
  • the objects may comprise tissue spheroids derived from the pancreas.
  • the tissue and/or multicellular objects may comprise a group of objects, for example, cells having at least one functional, structural or biological property of an organ.
  • the further fluidic path may at least partially overlap with the plurality of fluidic paths at the delivery portion and wherein the output portion is spatially separate from the plurality of fluidic paths.
  • the output portion of the further fluidic path may be downstream from the delivery portion and the plurality of restrictions.
  • the further fluidic path may provide a path for flushing and/or removal of at least fluid and objects from the device via the further output.
  • the first channel may comprise a fluid and/or object delivery portion.
  • the first channel may comprise a fluidic and/or object flush portion.
  • the plurality of restrictions may be provided at or on the fluid and/or object delivery portion.
  • the plurality of restrictions may be provided adjacent to and in fluidic communication with the at least one further fluidic path.
  • the at least one further fluidic path may be arranged to expose the trapped and/or restricted objects to the further fluid.
  • the delivery portion may be a shared delivery portion and may form part of the first channel.
  • the output may comprise a common output.
  • the device may comprise a plurality of channels comprising: a first channel between the input and the further output defining the further fluidic path between the input and the further output; a second channel coupled to the plurality of restrictions and the output, wherein the second channel is coupled to the first channel via the plurality of restrictions so that at least part of the first channel and at least part of the second channel define the plurality of fluidic paths between the input and the output.
  • the first and second channels may be sized to permit fluid flow of the objects.
  • the restrictions may comprise an opening between the first channel to the second channel that is sized to prevent the object from passing through.
  • the input may comprise an inlet.
  • the output may comprise an outlet.
  • the further output may comprise a further outlet.
  • c) perform a diagnostic and/or viability indication based on sensed electrical activity at the plurality of restrictions and/or sensing regions, for example, wherein the diagnostic and/or viability indication may be based on electrical activity in response to exposing said object to a further substance, optionally comprising a chemical and/or a drug, for example, glucose and/or electrical stimulation.
  • a chemical and/or a drug may comprise a chemical and/or drug to be tested.
  • the response may be in response to a metabolic stimulus such as glucose and/or electrical stimulation.
  • the processing resource may be configured to receive sensor signals from said at least one sensing element and/or data representing said sensor signals; process said data and/or signals to determine at least one of electrical activity, viability, function and/or response to a stimulus.
  • the data and/or signals may be processed to determine a percentage of viable tissue and/or cell and/or objects in a sample.
  • the determining of at least one of electrical activity, viability, function and/or response to a stimulus may comprise generating data representing electrical activity, function and/or response to a stimulus and storing said data.
  • the processor may be configured to determine at least one of: a) a measure of electrical activity in response to a further fluid, optionally wherein the further fluid comprises a chemical and/or a drug, for example, a glucose solution; b) a number of viable and/or functional tissue and/or multicellular objects in a sample c) perform a diagnostic and/or viability indication based on sensed electrical activity at the plurality of restrictions and/or sensing regions, for example, wherein the diagnostic and/or viability indication may be based on electrical activity in response to exposing said object to a further substance, optionally comprising a chemical and/or a drug, for example, glucose and/or direct electrical stimulation of the object.
  • the apparatus may further comprise a display and a user input.
  • a microfluidic/microelectronic/multichannel device wherein at least one of said microfluidic modules comprises: (a) a first channel for receiving fluid and comprising an input and an output, and at least ten traps, disposed between the input and the output, for trapping multiple tissue(s)/organoid samples introduced into the first channel through the input, wherein the trap comprises a restriction sized to permit fluid flow therethrough, but not permit said one or more tissue(s)/organoid to pass through the restriction, the trap further comprising at least ten electrodes for detecting an electrophysiological signal of said one or more tissue(s) trapped in the traps; and (b) a second channel for receiving fluid from the first channel after the/each restriction has become occluded by said one or more tissue(s)/organoid, thereby preventing further fluid flow through the/each restriction.
  • pancreatic islets are provided as exemplary cells and/or objects herein, the present disclosure is not intended to be limited to such cells and/or objects as excitable changes in the membrane potential may be used to assess the viability and/or function of various types of excitable tissues.
  • the membrane potential refers to the voltage or potential difference across the cell membrane. The potential difference is caused by the hydrophobic membrane separating charges, acting as both a capacitor and resistor to the movement of charged ions across it.
  • the plasma membrane ensures the structural integrity of a cell, and physically separates intracellular compartments from the extracellular surroundings.
  • An electric potential gradient is present across the cell membrane due to substantial differences in ionic composition between the intracellular and extracellular compartments, a selective permeability for certain ion species, as well as due to the insulating physical properties of the phospholipid bilayers comprising the cell membrane.
  • the intracellular compartment of cells is more negatively charged with respect to the extracellular environment (with respect to potassium ions), resulting in a resting membrane potential in the range from -10 to -80 mV depending on the type of cell.
  • the electrophysiological state and/or response of cells refers to the electrical property or activity of cells, which is typically reflected in the above changes in the membrane potential.
  • the charge underlying the electrical state or activity of cells is dependent ions, such as sodium (Na + ), chloride (Cl-), potassium (K + ) and calcium (Ca 2+ ) ions, for example.
  • the dimensions of the first channel, the second channel, the trap and/or the restriction may be adapted accordingly, depending on the size of the tissue, the cluster of cells or the group of cells being provided to the microfluidic device for testing.
  • at least the first channel and the/said trap(s) should be of a size that at least one tissue object is able to fit within the dimensions of the first channel and the/said trap(s).
  • the input serves as an entry route through which fluid may be provided to the microfluidic module.
  • a fluid such as a liquid (e.g. cell culture medium, saline, buffer solution etc.) comprising one or more tissue objects provided to the microfluidic module through the input.
  • the input may comprise an input chamber through which the fluid, such as a reservoir of fluid is provided to the channels of the microfluidic module.
  • the fluid provided to the input desirably flows through the channels through gravity and capillary driven flow.
  • the use of gravity or capillary flow ensures that the tissue objects are manipulated in as gentle a fashion as possible and is distinguished from prior art systems which may employ pumps and the like to drive or draw fluid and objects through a microfluidic device.
  • the microfluidic module also comprises an output (such as an output channel and/or well/reservoir) where the fluid that has flown through the channels may be collected.
  • the microfluidic modules of the microfluidic device are connected to the same input.
  • the microfluidic modules of the microfluidic device are connected to the same output.
  • the flow of fluid through the device delivers the one or more objects to the trap(s), which occludes fluid flow through the/each restriction.
  • the trap comprises a cross-sectional area that is at least 50%, 60%, 70%, 80%, 90% or 95% larger than the cross-sectional area of the one or more objects to be tested.
  • the trap area comprises a cross-sectional area that is at least 50% larger than the cross-sectional area of the one or more objects leading to a restriction.
  • the maximum diameter of the cross-sectional area of the trap and/or the restriction may be between 10 to 60 ⁇ m.
  • the trap adjoins a restriction which is sized such that the tissue cluster or object or objects is unable to pass through the restriction(s).
  • the restriction preferably comprises a cross-sectional area that prevents the one or more objects from passing through the restriction and traps the said objects, such that the restriction becomes occluded and prevents or minimises fluid flow through the restriction following trapping of an object.
  • the size of mammalian objects tissues, clusters such as islets and cardiospheroids typically comprises 100 to 300 ⁇ m in diameter.
  • the maximum diameter of the cross- sectional area of the restriction may be 5%, 10%, 20%, 30%, 40%, 50%, or 60% of the diameter of the object being provided to the microfluidic device.
  • the maximum diameter of the cross-sectional area of the restriction may be 40 ⁇ 10 ⁇ m.
  • the dimensions of the channel(s) may comprise 450 ⁇ 50 ⁇ m in width and/or 450 ⁇ 50 ⁇ m in height.
  • the cross-sectional area of the second channel may be at least 50%, 60%, 70%, 80%, 90% or 95% larger than the cross-sectional area of the one or more tissues. In some embodiments, the cross-sectional area of the second channel may comprise a cross-sectional area that is at least 50% larger than the diameter of the object.
  • the microfluidic device may comprise a single microfluidic module. In such an example, upon occlusion of the restriction, the fluid flows through the second channel and towards the output. In other embodiments, the microfluidic device may comprise more than one microfluidic modules and thereby comprise more than one trap and restriction within each device.
  • the second channel of each of the modules may be connected to form a continuous second channel which leads to the same output.
  • the direction of fluid flow through the second channel in relation to the object trap is such that the direction of fluid flow towards the second channel may only occur once the/each restriction is occluded and the fluid overflows from the object trap to the second channel.
  • the multi-modular configuration of the microfluidic device with its microelectronic substrate provides a high throughput means through which the electrophysiological activity from multiple tissues may be measured simultaneously to determine the percentage of functional tissues therein. This feature offers a significant advantage, such as when the quality of a large number of islets need to be assessed rapidly prior to transplantation.
  • the device of the present disclosure overcomes limitations of existing techniques, which often require a complex instrumental setup, have low throughput and/or cause damage to objects during manipulation.
  • the dimensions of the first channel, the object or spheroid trap, the restriction and/or second channel may be varied to accommodate different tissue types and/or sizes by adding an adaptor or stopper capable of restricting and/or increasing the cross-sectional area.
  • the microfluidic module comprises an adaptor or a stopper for altering the cross-sectional area at defined points of the first channel and/or the second channel within a specified range.
  • the channel dimensions may comprise a diameter, height or width within the range of 200 ⁇ m and 500 ⁇ m.
  • the object trap and/or the restriction may comprise an adaptor or a stopper to alter the diameter height or width of the channel(s) depending on the object type being provided to the microfluidic device.
  • Each microfluidic module of the present disclosure may comprise at least one electrode to assess the electrophysiological state and/or response of objects to a stimulus.
  • the microfluidic device of the present disclosure comprises at least ten electrodes, which are preferably located at each object trap such that electrical activity of the objects can be detected.
  • a reference electrode is typically required to obtain a background or reference signal of the electric field.
  • the microfluidic module comprises a unified ground reference electrode. An end of each electrode reaches into the microchannel to enable measurement(s) to be obtained from within the channel.
  • each module of the microfluidic device comprises at least 10 recording electrodes.
  • the electrode of the present disclosure comprises a microelectrode.
  • the one or more electrode may form a microelectrode array.
  • a microelectrode array is commonly used in the art to measure object electrical activity.
  • the electrode(s) comprise gold and/or titanium electrode(s). In comprising a multi-module configuration, however, it is not required that all modules comprise electrode(s). In some embodiments, one or more modules of the microfluidic device do not comprise electrodes.
  • One or more modules that lack electrodes may be used as controls where the tissues used in the assay can be microscopically visualised, or used for biochemical assays, such as gene expression, compound detection, or viability assays that use optical detection (for example, absorbance or fluorescence.
  • the one or more modules may comprise an access point through which tissues may be isolated for analysis and solutions bathing the tissues may be collected without disturbing the tissue (e.g. for secretory assays).
  • the one or more modules may comprise a polymer coverslip or a glass coverslip bottom through which objects may be visualised directly through the device. If electrical information is required transparent electrodes can be printed on these coverslips.
  • the microfluidic device may be fabricated in, for example, plastics, glass, silicone or other material.
  • the channels of the microfluidic device comprise transparent polydimethylsiloxane (PDMS). While the examples disclosed herein use transparent PDMS for the channels and borosilica glass as the substrate for titanium (Ti) electrodes (which are insulated with a silicon dioxide deposition), any transparent substrates or moulded plastic known in the art to be appropriate for fabricating microfluidic devices may be used.
  • the one or more electrodes of the device may be prepared in numerous ways known in the art.
  • the microfluidic device according to the present disclosure may be prepared by printing methods wherein the one or more electrodes is printed within the first channel by plasma bonding or a pressure fixation method, for example.
  • the device of the present disclosure may further comprise a chip holder and/or an amplifier connected to a computer reading software.
  • a commercially available amplifier may be used, such as, but not limited to a Model 3600 amplifier, which may function as a multi-channel extracellular differential AC amplifier.
  • the amplifier may typically comprise at least 16-channel capability, at least 10 gain settings, at least 5 low-pass filters ranging from 50 Hz to 50kHz, at least 5 low-pass filters ranging from 0.1 Hz to 600 Hz and a notch filter (e.g. 50 or 60 Hz) per channel.
  • signals may be pre-amplified by a headstage, which is typically located proximal to the electrode(s), and recordings are collected by the amplifier.
  • a headstage typically located proximal to the electrode(s)
  • recordings are collected by the amplifier.
  • the skilled person would appreciate that the microfluidic device of the present disclosure may have various applications.
  • the microfluidic device may be used for the assessment of object electrical activity, viability, function and/or response to a stimulus.
  • the stimulus may comprise any substance that triggers a change in population cellular activity, such as glucose, ions, hormone(s), ligand(s), electrical stimulation, or drug(s).
  • the stimulus provided to the microfluidic device comprises glucose.
  • a method of adding one or more tissues to the microfluidic device as disclosed herein for measuring the electrical activity of the one or more tissues comprises providing one or more tissues in a fluid to the input of the device, wherein the fluid initially flows through the device until one or more tissues reach the trap and occlude fluid flow through the restriction. The occlusion of fluid flow through the restriction promotes fluid flow through the second channel(s) and to the output of the microfluidic device.
  • the microfluidic device and/or the method described herein may be used as a drug discovery platform or for safety screening of compounds.
  • the culture solution and/or the test solution may comprise one or more drugs in order to assess alterations in electrophysiological responses of tissue(s).
  • the one or more drugs may be a drug that increases cell viability, for therapy and/or a drug that alters the electrophysiological response of tissues.
  • the one or more drugs may include agonists of ion channels or antagonists of ion channels.
  • the one or more drugs may comprise tolbutamide, chlorpropamide or gliclazide, for example.
  • electrophysiological activity of objects may be manipulated by altering the ionic concentration of the extracellular medium.
  • Figure 1 is a top-down view of a multi-channel device microfluidic channel having a plurality of traps, in accordance with an embodiment
  • Figure 2 is a close-up view of the device of Figure 1
  • Figure 3 is a further close-up view of the device of Figure 2 showing flow direction and an indication of where objects would be trapped
  • Figure 4 depicts a top-down view and a cross-section of a further, single-trap device as a background example
  • Figure 5(a) is a top-down view of a single-trap device
  • Figure 5(b) is a view of a multi- trap device in accordance with embodiments
  • Figure 5(c) is a photograph of a microfluidic module of the device bonded to a glass micro-electrode array
  • Figure 5(d) is an example of a multichannel microfluidic chip and electrode array mounted in holding module and Figure 5(e
  • the first channel 102 has the input channel portion 102 and intermediate potion 115 between fluidic input 110 and second coupling 112.
  • the input may be an inlet port and/or the output may be an outlet port.
  • the plurality of traps 108 are disposed between the input and the output of the first channel 102, in particular, along the intermediate portion 105. As depicted in Figure 1, each of the plurality of traps 108 is in fluid communication with the first channel portion 102, the by-pass channel portion 104 and the exit channel 106.
  • the plurality of traps are provided in a serial arrangement such that, in use, a fluid flowing through the input channel 102 is provided to each of the cell spheroids is trapped in turn and such that the plurality of traps have a common input channel.
  • a fluid flow direction may be defined starting from the input 110.
  • the output portion of the further fluidic path is downstream from the delivery portion and the plurality of restrictions.
  • the input 111 correspond to an inlet port and the outputs correspond to outlets of the device. It will be understood that, in some embodiments, fluidic paths may be defined between inputs and outputs that do not correspond to the inlets/outlets.
  • the plurality of fluidic paths may be defined between an input defined at a point along the input channel 102 (for example, at a point substantially at coupling 113) and/or a shared output defined along output channel 106.
  • the further fluidic path may be defined between the same input along the input channel 102 and a further output defined along the by-pass channel portion 104.
  • more than one inlet may be coupled to the defined input and/or more than one outlet may be coupled to the shared output and/or the further output.
  • the further fluidic path has a delivery portion that overlaps with the plurality of fluidic paths and an output portion that is spatially separate from the plurality of fluidic paths.
  • FIG. 3 depicts the first trap 108a in a closed configuration and the second trap 108b in the open configuration.
  • Figure 1 depicts a multi-channel microfluidic module
  • more than one of these modules may be provided, for example, as an array, to provide additional channels.
  • Such a combination of modules can be accompanied by a corresponding array or suitably larger microelectrode array, as described below.
  • Figure 4 depicts a fluidic device having a first channel 12 and a second channel 20.
  • Figure 4 is described to illustrate the operation of a single trap, for background information.
  • the first channel 12 has a fluidic input 14 and a fluidic output 16 and between the input 14 and the output 16 a trap is provided.
  • the trap has a restriction 18 provided in the first channel 12 between the input 14 and the output 16.
  • the trap also has at least one indifferent reference or ground electrode and a measuring electrode (c’) for detecting an electrophysiological signal, for example, of one or more cell spheroids trapped in the trap.
  • the detection of electrophysiological signals using the traps is described elsewhere.
  • the channels define fluidic paths through the device. In particular, for there is a first fluidic path from the input 14 to the output 16 and the restriction 18 is a restriction on this fluidic path. In addition, a further fluidic path is defined between the input 14 and the second (or by-pass) channel 20. The first fluidic path delivers the cell spheroid to the restriction of the trap using fluid flow. The cell spheroid is thus prevented from flowing along the first fluidic path by the restriction.
  • the further fluidic path is in fluid communication with the restriction and can be used to deliver a further fluid to the trapped cell spheroid to allow for fluid exchange and/or further fluid delivery to the trapped cell spheroid.
  • the first fluidic path at least partially overlaps with the further fluidic path.
  • the trap may be in one of two configurations: an open configuration and a closed configuration.
  • the feeder channel portion 12a In the open configuration, the feeder channel portion 12a is in fluid communication with the exit channel portion 12b via the restriction 18.
  • the open configuration fluid is permitted to flow along the first channel from the feeder channel portion 14 to the exit channel portion 16 via the restriction 18.
  • the closed configuration the feeder channel portion 12a is not in fluid communication with the exit channel portion 12b due to an occlusion and/or blockage at the restriction.
  • such an occlusion is formed by a cell spheroid held in the feeder channel portion 12a at the restriction 18.
  • the cell spheroid has a size (a diameter or width) greater than the opening of the restriction, the cell spheroid, together with the members 19a, 19b in the channel 12 form a barrier to fluid flow such that substantially all of the fluid in the first channel is prevented from flowing from the feeder channel portion 12a to the exit channel portion 12b.
  • the fluid thus flows to the by-pass channel 14 at a faster rate when the restriction is occluded.
  • the trap may be moved from the first configuration to the second configuration by performing a cell spheroid seeding process using the device.
  • the device is a combination of a transparent microfluidic channel design with a ‘trap’ which is provided together with a printed microelectrode array (Figure 4 gives a single channel example).
  • the channel dimensions in the feeder and exit channels are 450 ⁇ m width and 250 ⁇ m depth ( Figure 4) while the restriction in the main channel of the trap and bypass channel are 20-50 ⁇ m (a value selected depending on the required flow rate).
  • the width of the restriction i.e. the narrower channel
  • the range of widths comprises 20-50 ⁇ m. Waste leaves the system via the output channels which can also be sampled to assess secretion of insulin or other substances (Figure 5).
  • Figure 4 provides addition detail of arrangement and dimensions of channel microfluidics and electrode array (showing a single electrode as part of a single channel example).
  • a Input channel dimensions 450 ⁇ m.
  • b width of restriction 40 ⁇ m c, reference electrode c’, measuring electrode.
  • d profile at cross section, e, PDMS channel cross section.
  • f silicon oxide insulation (100 nm thickness- not to scale), g gold electrode track and electrode pad.
  • h glass substrate.
  • I height of channel (250 ⁇ m).
  • j width of channel (450 ⁇ m as in a).
  • Figure 5(c) is an image of the device in use, in accordance with an embodiment.
  • the device has a microfluidic module 52 and an electronic module 54. Means for providing fluid to the microfluidic module, in this embodiment, a pipette 56, are also shown.
  • the microfluidic module has a plurality of restrictions, substantially as described with reference above, for example, with reference to Figures 1 to 3.
  • Figure 5(c) is a first photograph of the device and Figure 5(e) is a second photograph of the device, including electronic and microfluidic modules 52, 54.
  • the microfluidic module 52 optionally together with the electronic module may be referred to as a microfluidic chip.
  • a holder 56 is also depicted in Figure 5(d).
  • the input port 60 (also referred to as an inlet) is 1 mm in diameter and the output port 62 (also referred to as the flush outlet) is 1mm diameter.
  • the second output port 64 also referred to as the waste outlet is 6.0mm in diameter.
  • the inlet and outlets are formed by creating a void or cut-out in the PDMS layer.
  • Figures 7(a) and 7(b) depict a schematic diagram of an electrode configuration of the electronic module.
  • the sensing module is provided on a glass substrate layer 702 sized 5 x 5 cm.
  • the glass substrate layer has a thickness of 1.5mm.
  • An electrode configuration 704 is patterned on the glass substrate layer.
  • Figure 7(b) depicts a closer view of the electrode configuration 704.
  • a plurality of electrodes (in this embodiment, labelled 1 to 15) are provided such that their respective end points are in a linear arrangement and define a straight line.
  • the end of the first electrode 708 is indicated in Figure 7(b).
  • a single reference electrode 706 spans the width of the plurality of electrodes.
  • the electrode configuration is operable to sense a signal for each electrode with reference to the reference electrode.
  • each electrode is aligned at or adjacent to a respective restriction to allow a signal for a trapped object to be sensed.
  • Figure 6(e) shows trapped Islets together with the electrodes. It will be understood that, that the device may have different numbers of channels and restrictions.
  • Figure 8(a) depicts an electrode configuration for a 60-channel device.
  • Figure 8(a) depicts an electrode configuration with four reference electrodes. Each reference electrode is grouped with a set of fifteen sensing electrodes, as described with reference to Figures 7(c) and (d). It will be understood that in the embodiment of Figure 8(a), four fifteen channel microfluidic modules are combined for use with the electrode configuration.
  • the sensing module of Figure 8 is provided on a glass substrate of 10 cm x 5 cm.
  • Figure 8(b) depicts two fifteen electrode modules together to form part of a 30 channel device. In both Figure 8(a) and Figure 8(b) the modules are arranged such that the reference electrodes in each module are parallel.
  • the modules are arranged such that linear arrangement of electrode ends are in a parallel arrangement.
  • sensor signals may be sensed between the reference electrode and each trap electrode.
  • a sensor signal for each trap is sensed during the sensing process.
  • the signals from each trap/channel are isolated from each other.
  • the reference electrode may be a ground reference electrode. The positioning of the ground electrode may be such that the ground reference electrode overlaps with at least part of the further fluidic path and/or the plurality of fluidic paths.
  • a hybrid microfluidic and electronic device is described. At least part of the device may be provided as a cartridge for use with a further apparatus.
  • Figure 9 depicts an apparatus 900 in accordance with an embodiment.
  • the processing resource is provided as part of a larger apparatus configured to receive a removable chip.
  • the removable cartridge or chip may correspond to the device, as described above. In some embodiments, it is a removable cartridge.
  • the apparatus 900 has one or more displays 902, a chip holder 904 having a housing 904 and a processing resource provided, in this embodiment as part of a data processing PC 908.
  • the apparatus is configured to receive a disposable chip 906 via a first cartridge opening 908 in a first surface, an upper surface of the housing 904.
  • One of more fluidic openings may be are provided in an upper surface of the housing. In the present embodiment, the fluidic opening is sized to receive a pipette.
  • the microfluidic module of the cartridge includes 60 channels (in four separate groups each group having a separate fluidic inlet).
  • a manifold is therefore provided, either as part of the apparatus or as a removable part to be used with the pipette, to channel the received fluid to each separate fluidic inlet.
  • the fluidic inlet and cartridge openings are aligned such that, when inserted into the cartridge opening, the inlet of the microfluidic module is aligned with the fluidic opening to allow delivery of fluid to the inserted cartridge.
  • the processing resource may be configured to run software for an automated or at least partially automated data analysis of sensed signals from the cartridge.
  • the further apparatus may also comprise a user input device (not shown) to allow a user to interact and control the apparatus.
  • the user input device may allow a user to control a sensing process and/or to a data analysis and/or to select different results to be viewed).
  • the apparatus may be operable to allow a user to select the number of channels to be used (for example, up to 60) via the user input device.
  • the apparatus may further include a camera or other suitable imaging means to allow image capture of the cartridge in use.
  • the apparatus may be operable to allow selection of different captured images, for example, during data acquisition. The selection may be made using the user input device.
  • the apparatus may be further operable to allow the user to run tests on a subset of the available traps.
  • a user may determine that only a subset of the traps have a islet present and may therefore select to run tests only on those channels.
  • the display may also be configured to display results. In this embodiment, the display displays the percentage of viable islets.
  • the apparatus may be operable so that a user can select the results to be displayed using the user input device.
  • the user input device may be any suitable user input device, such as a mouse, keyboard.
  • the display forms part of the user input device.
  • at least part of the cartridge is disposable.
  • the microfluidic part may be disposable.
  • the removable cartridge includes only the microfluidic part of the device and the electronic module is provided separately (for example, as part of the apparatus or as a further component to be combined with the cartridge).
  • the additional computing and/or storage resources that are provided inside the housing.
  • the apparatus has memory storage to store data and/or may be connected to a network to allow transfer of data from the apparatus to a further computing apparatus.
  • the apparatus may have a removable storage medium.
  • An amplifier may also be provided for amplifier one or more signals sensed by the electrodes.
  • the processing resource is configured to process signals from the electrodes or data derived from the signals.
  • the processor may be configured to determine a number of viable and/or functional tissue and/or multicellular objects in a sample or to perform a diagnostic and/or viability indication based on sensed electrical activity at the plurality of restrictions and/or sensing regions, for example, wherein the diagnostic and/or viability indication may be based on electrical activity in response to exposing said object to a further substance, optionally comprising a, chemical and/or a drug, for example, glucose. While the example of glucose is described, it will be understood that other types of further fluid can be used.
  • a wash solution may be introduced for removing any solution from the device.
  • molecules for labelling trapped objects may be introduced or one or more drugs and/or cell activity stimulators or inhibitors may be introduced.
  • Figure 10 depicts results of electrical measurements from human islets.
  • a islets exposed to 3 mM then15 mM glucose; glucose stimulated insulin secretion (GSIS) measurement showing electrical response in upper trace with 15mM glucose and RMS (root mean squared) derivation of electrical noise in the lower trace with 15mM glucose.
  • GSIS glucose stimulated insulin secretion
  • RMS root mean squared
  • Figure 12 depicts, first electrode 1102 on glass substrate layer 1206, having an elongate portion 1102a and an electrode end 1102b, as described with reference to Figure 11(a).
  • the electrode is aligned beneath the chamber such that the electrode end is provided in a central portion.
  • the non-insulated portion of the electrode, the electrode ends, are exposed to the channel above.
  • the non-insulated portion of the electrode is in contact with a trapped object in the trap.
  • the non-insulated portion of the electrode is adjacent to the trapped object and in contact with the fluid containing the trapped object.
  • the microchannel module for example, the module described with reference to Figure 1 is formed in a PDMS layer.
  • Figure 13 depicts a module in accordance with an embodiment.
  • the module of Figure 13 also has an entry port 1308, a first output port 1302 and a second output port 1304.
  • the entry port is an inlet provided at the fluidic input, as described with reference to Figure 1.
  • the first output port is an outlet provided at the shared output, as described with reference to Figure 1, and may be referred to a waste output.
  • the second output port is an outlet provided at the first output, as described with reference to Figure 1, and may be referred as a flush output.
  • Each of the inlet and outlet ports is circular, in the present embodiment.
  • the channels and ports of Figure 13 are formed in a PDMS layer 1310 having a width and length of 3 cm and a height of 0.5cm.
  • Figures 14(a) and 14(b) depict an electrode array and an associated microfluidic module, in accordance with a further embodiment.
  • the device of Figure 14 has the addition of a stimulating electrode, which when in circuit with the ground electrode, is operable to provide a pulse of electrical stimulation across trapped objects.
  • the electrode array is substantially as described with reference to Figure 7 with the following differences.
  • a plurality of electrodes 1702 are provided such that their respective end points are in a linear arrangement. The end points may form part of their sensing elements.
  • the central electrode of the plurality of electrodes (labelled 1404) is a reference electrode.
  • the reference electrode is a ground electrode.
  • the single electrode 1406 spans the width of the plurality of electrode and is a stimulating electrode.
  • the central electrode 1404 is larger in width compared to the other electrodes of the plurality of electrodes.
  • the reference electrode and stimulating electrode form a stimulating electrode pair and the sensing electrodes are configured to sense a response from a stimulating signal produced by the stimulating electrode pair.
  • the electrode array is aligned with a microfluidic apparatus 1408 that is substantially as described with reference to, for example, Figure 1, but with the following difference.
  • the second channel of the microfluidic device of Figure 14 has a first portion 1416a and a second portion 1416b.
  • the second portion 1416b is provided centrally in the first portion.
  • the by-pass portion and delivery portion remain in the same configuration.
  • the central, reference electrode is aligned to have its length parallel to the centrally provided second portion 1416b of the microfluidic device.
  • a plurality of fluidic paths is defined between the input (1422) and the output (1424) via the restrictions, where the fluidic paths comprise part of the first portion 1416a and second portion 1416b.
  • the restrictions are aligned along an axis and the stimulating electrode is arranged parallel to that axis. The stimulating electrode overlaps with the plurality of fluidic paths.
  • the electrode configuration is operable to sense a signal for each electrode with reference to the reference electrode.
  • each electrode is aligned at or adjacent to a respective restriction to allow a signal for a trapped object to be sensed passively
  • the embodiment of Figure 14 specifically the single electrode 1406 is configured to produce a stimulating electrical signal.
  • the single electrode 1406 may be referred to stimulating electrode.
  • the plurality of electrodes 1402 may in turn be referred to as sensing or recording electrodes.
  • the electrical stimulation may directly evoke a simultaneous action potential discharge in the objects which may be measured and processed by the recording electrodes.
  • direct stimulation may be used in the ‘pacing’ of cardiospheroids and other excitable tissues.
  • Glucose induced electrical activity Having validated the ability of the RMS function to reflect changes in electrical activity associated with increased glucose concentration, it was used to determine if electrically active islets were responsive to glucose, and if they were viable, or nonresponsive.
  • sixteen of the twenty-four islets tested had increased RMS values using the 5.5-to-15.5 mM protocol.
  • the mean ( ⁇ SEM) RMS of islets in the 7.3 mM glucose concentration was 3.95 ⁇ 0.72 ⁇ V, which had increased significantly to 10.13 ⁇ 1.82 ⁇ V when the concentration of glucose was increased to 17.3 mM.
  • the RMS values of electrical responses ranged across 8.87 and 21.9 ⁇ V for 7.3 and 17.3 mM glucose, respectively.
  • Islet batch viability The percentage viability for each batch was calculated by identifying islets that met the criteria of being electrically active and displaying increases in their RMS values after glucose- challenge with either a 3-to-15, 5.5-to- 15.5, and 7.3-to-17.3 mM glucose protocol. As the increases in RMS values of islets responding to glucose in a 7.3-to-17.3, 3-to-15, and 5.5-to- 15.5 mM protocol were significant, the islets were characterised as being viable.
  • the design in Figure 6A features a total of 11 recording electrodes and a unified ground reference electrode (detail on Figure 6b).
  • the recording electrodes were 30 ⁇ m in diameter and the distance between the recording electrodes and the ground electrode was 50 ⁇ m.
  • AutoCAD designs were sent to Micro Lithography Services Limited (Chelmsford, UK) to be made into film or glass photomasks.
  • the MEAs were fabricated at the Heriot-Watt University nanofabrication facility.
  • Borosilicate was used as a substrate (‘h’ in Figure 6). The borosilicate was cut to measure 49 x 49 mm using a DAD3220 Wafer Dicing Saw (DISCO Corporation, Tokyo, Japan).
  • Electrodes and electrode tracks were Ti (‘g’ in Figure 6) depositions while the insulation of the tracks excluding the electrode tips and pads were SiO 2 deposition (‘f’ in Figure 6).
  • III. Spin Coating of photoresist Prior to deposition the borosilicate substrate was washed using acetone and diluted Decon 90 (Decon Laboratories Ltd, East Canal, UK). It was then rinsed with de-ionised (DI) water and blow dried using a filtered air gun. This was done in order to make sure the borosilicate surface was dust free and completely clean before starting the process.
  • DI de-ionised
  • the borosilicate blank was then placed onto the spin coater SPIN 150 (SPS Europe, Putten, Netherlands) and was held in place by a vacuum seal.
  • Negative photoresist, AZ nLOF 2070 (MicroChemicals, Ulm, Germany) was carefully placed over the whole surface of the borosilicate taking care to avoid air bubbles. It was then spun at 3500 rpm for 40 seconds.
  • the negative photoresist which normally would form a 7 thick ⁇ m layer, was previously diluted to form a 1 ⁇ m layer once spun. After this process, the substrate was hard baked at 95°C for 3 minutes. IV. Alignment and UV Exposure The next step involved aligning one of the multielectrode design film photomask with the prepared substrate.
  • PDMS was then poured over the wafer and before curing, air bubbles were removed by placing it in a vacuum chamber.
  • the PDMS was cured in an hour at 60°C.
  • PDMS modules microchannels
  • Access holes were then cut out using a 1 and 6 mm biopsy punches on either side to form wells. This was also carefully done in order to avoid damaging the microchannels.
  • PDMS /electrode array device Bonding The PDMS modules fabricated were then bonded onto custom MEAs. This was achieved by placing the PDMS modules and the electrode surfaces they would bond into a Zepto plasma system (Diener Electronic, Ebhausen, Germany).
  • the MEA/microfluidic device was connected and placed under the inverted microscope, with recordings running for five and ten minutes prior to addition of 17.3 mM glucose culture media and 15 mM glucose islet solution, respectively. Additions were made by withdrawing remaining starting solution from the inlet pipette tip (via micropipette) and adding increased glucose solution via a syringe. Positioning was reconfirmed on the inverted microscope and recordings were continued for fifteen or twenty minutes. Islets from batch 3 were assessed using a 5.5- to-15.5 mM culture media protocol, with recordings running for five minutes before and after glucose addition. A total of seven recordings were taken from batch 1, eleven for batch 2, and nineteen from batch 3.
  • the RMS was calculated at one-minute increments across the recordings and graphed with the recording to determine if changes in RMS are synchronous with changes in electrical activity.
  • RMS measurements were obtained using the power spectrum function of Clampfit (version 10.7), with the window set to no signal alteration (rectangular), output at average spectral segments, length at maximum, spectral resolution (spectral bin width) of 0.038147 Hz and RMS measurement and plot set to exclude the first spectral bin (default setting). All RMS measurements of electrical responses were in microvolts ( ⁇ V) ( Figure 7).
  • the combination of microfluidic channel design and trap or restriction is incorporated with a printed microelectrode array and input and output chambers.
  • transplant outcomes may be highly associated with islet numbers and their viability.
  • the process of transplantation is a multi-step procedure involving pancreas procurement, tissue dissociation, islet purification, cell culture and islet transplantation via the hepatic portal vein and into the liver of the recipient.
  • islets are lost (mainly due to ischemia).
  • Less than 50% of islets from a single pancreas are isolated ( ⁇ 500,000 islets) and of these it is estimated that ⁇ 50% engraft into the liver, with recipients requiring islets from two to three donor pancreases.
  • the device provides the core technology to achieve a rapid estimate (%) of functional islets in a sample.

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Abstract

A microfluidic device comprising: a microfluidic module comprising: a plurality of fluidic paths between an input and an output; and a plurality of restrictions, wherein each restriction is provided on a respective fluidic path of the plurality of fluidic paths, wherein each restriction is configured to trap or at least restrict movement of one or more objects, for example, one or more tissue and/or multicellular objects, in a fluid introduced along its respective fluidic path at a respective sensing region; and at least one further fluidic path between the input and a further output, wherein the at least one further fluidic path is in fluid communication with the plurality of restrictions and wherein the further fluidic path comprises a delivery portion between the input and the plurality of restrictions to allow delivery of a further fluid to the trapped and/or restricted one or more objects and an output portion to allow removal of the further fluid from the further output; wherein the device further comprises: an electronic sensing module comprising: at least one sensing element arranged to sense one or more signals from the respective sensing regions of the plurality of restrictions.

Description

Device for Trapping Tissues and/or Multi-Cellular Objects FIELD The present disclosure relates to a microfluidic device, in particular, a device for trapping and testing a plurality of objects, for example, one or more tissue and/or multicellular objects. There is provided a method of using said device, for example, to determine cell, tissue or object quality and/or function. BACKGROUND Type 1 diabetes mellitus (T1D) is an autoimmune disease that affects 400,000 people in the UK (JDRF Editors, 2022). The condition is characterised by the loss of functional beta cells that are the majority of cells located within cellular clusters known as pancreatic islets situated in the pancreas. One islet contains around 1500 cells with 74% comprising beta cells. These beta cells normally secrete insulin on glucose stimulation but this function is lost in T1D resulting in uncontrolled and/or high blood glucose concentrations. While treatment with synthetic insulin injection can help control blood glucose levels, and is the mainstay of treatment, feedback control is absent and a common side-effect of insulin therapy is hypoglycaemia. Repeated episodes of hypoglycaemia can lead to impaired awareness of hypoglycaemia, such that the individual has an inability to recognise when the blood glucose levels are low which can result in significant morbidity and mortality. Islet transplantation by cadaveric donor for the treatment of T1D has been shown to be effective at improving glucose control. Transplantation can reduce the number of severe hypoglycaemic events and is an effective treatment in restoring hypoglycaemic awareness. Indeed, in a minority of cases, the procedure may restore glycaemic control by achieving insulin-independence (Forbes et al., 2015). However, patient outcomes are dependent on several factors, including the quality and quantity of transplanted islets. Currently, availability of donor pancreases for islets is a major limiting factor, with around 100 available in 2019 in the UK, with many unsuitable, or yielding a poor quality and quantity of islets (Cornateanu et al., 2021). The situation is compounded by the fact that each recipient requires islets usually from 2 to 3 donors in order to significantly impact on their glycaemic control. Islet numbers, sample purity, and islet viability are all vital parameters to meet clinical release criteria before transplantation is performed (Brooks et al., 2013; Benomar et al., 2018). In the United Kingdom, islet viability must be greater than 70% in order for a preparation to be transplanted. Overestimating viability of islet preparations can lead to relatively large numbers of non-viable and inadequate numbers of islets being transplanted while underestimation can result in otherwise viable islets being discarded. These standards protect the recipient, ensuring only pancreases that have a large number of healthy islets are transplanted. However, this results in low clinical conversion rates, which, in 2019, stood at 28% (Bunnett J & Counter C, 2019). Even so, approximately 70% of islet transplant recipients in the Collaborative Islet Transplant Registry were insulin-independent at one year post-transplant and this declined to approximately 40% at five- years post-transplant (CITR Coordinating Centre, 2015). Thus, while insulin- independence in T1D is achievable, the trend of declining rates in the years post-transplant demonstrate the importance of quality and quantity of islets for long-term positive outcomes. Together, declining clinical outcomes post-transplant and the low percentage of donor pancreases that meet release criteria point toward an urgent need for objective islet assessment, with the aim of improving the number and quality of islets for transplantation purposes. Currently, membrane integrity staining with fluorescein diacetate and propidium iodide (Barnett et al., 2004) is the preferred method for assessment of viability. While this approach is quick and easy to apply there are problems as interpretation of results are subjective, resulting in frequent overestimation of viability (Boyd et al., 2008). There is now evidence accumulating that dying inflamed islets may adversely affect the whole islet graft – compromising the function of those islets that were originally healthy. Thus, the development of a robust, real-time, and more objective method of assessment of islet viability prior to transplant is an urgent priority. Measuring the electrophysiological responses β-cells in islets in response to glucose is an attractive alternative assessment as electrical responses generated by β-cells are a necessary step in a healthy glucose-stimulated insulin secretion (GSIS) pathway and as such represents an objective non-labelled method to determine viability. Determining electrical activity of β- cells has usually involved traditional electrophysiological methods such as single and/or whole- cell voltage clamp techniques or intracellular electrodes (Pfeiffer et al., 2011; Düfer, 2012). Such techniques are very time-consuming and require expert single cell manipulation and interpretation. On the other hand, extracellular recordings using suction electrodes and microelectrode arrays (MEA) can detect islet electrical activity with minimal tissue micromanipulation. Indeed, intact murine and human islet electrical activity has been demonstrated in single and multiple islets and indicate that this approach could be a feasible methodology for islet viability assessments (Pfeiffer et al., 2011; Schönecker et al., 2014, 2015) as a lack of, or abnormal, electrical activity is an indication of a loss of GSIS function. Thus, while previous studies have shown electrophysiological responses of isolated islets, the approaches involve specialised equipment, knowledge and a capacity to manually manipulate individual islets and interpret the results. It is amongst the objects of the present disclosure to obviate and/or mitigate at least one of the aforementioned disadvantages. SUMMARY In a first aspect there is provided a microfluidic device comprising: a microfluidic module comprising: a plurality of fluidic paths between an input and an output; and a plurality of restrictions, wherein each restriction is provided on a respective fluidic path of the plurality of fluidic paths, wherein each restriction is configured to trap or at least restrict movement of one or more objects, for example, one or more tissue and/or multicellular objects, in a fluid introduced along its respective fluidic path at a respective sensing region; and at least one further fluidic path between the input and a further output, wherein the at least one further fluidic path is in fluid communication with the plurality of restrictions and wherein the further fluidic path comprises a delivery portion between the input and the plurality of restrictions to allow delivery of a further fluid to the trapped and/or restricted one or more objects and an output portion to allow removal of the further fluid from the further output. The device may further comprise an electronic sensing module comprising: at least one sensing element arranged to sense one or more signals from the respective sensing regions of the plurality of restrictions. The sensing module may comprise one or more passive electrodes to measure potentials. The sensing module may include one or more stimulating electrodes configured to produce an electronic stimulus to generate a response in the object that may be measured by the passive electrodes. The sensing module may comprise one or more stimulating elements and one or more sensing elements. The stimulating elements(s) and sensing element(s) may be positioned to stimulate and sense electrical activity in the sensing region. The sensing module may comprise one or more stimulating electrodes and one or more sensing electrodes. The sensing module may form part of a sensing and stimulating module configured to provide a stimulus and measure a response to said stimulus at the sensing region. The sensing module may comprise one or more stimulating elements configured to produce an electronic stimulus and one or more sensing elements for measuring a sensed signal, optionally a potential. The stimulating elements may be configured to generate an electronic stimulus and the sensing element may be configured to sense a response to the stimulus. The objects may comprise at least one of: an organoid; a cell spheroid; a tissue spheroid and/or a pancreatic Islet. The objects may comprise cell objects and/or tissue objects. The signal may comprise an extracellular signal. The device may comprise a plurality of the microfluidic modules. The device may comprise a plurality of microfluidic modules and a corresponding plurality of electronic sensing modules. The objects may comprise tissue spheroids derived from the pancreas. The tissue and/or multicellular objects may comprise a group of objects, for example, cells having at least one functional, structural or biological property of an organ. The further fluidic path may at least partially overlap with the plurality of fluidic paths at the delivery portion and wherein the output portion is spatially separate from the plurality of fluidic paths. The output portion of the further fluidic path may be downstream from the delivery portion and the plurality of restrictions. The further fluidic path may provide a path for flushing and/or removal of at least fluid and objects from the device via the further output. The first channel may comprise a fluid and/or object delivery portion. The first channel may comprise a fluidic and/or object flush portion. The plurality of restrictions may be provided at or on the fluid and/or object delivery portion. The plurality of restrictions may be provided adjacent to and in fluidic communication with the at least one further fluidic path. The at least one further fluidic path may be arranged to expose the trapped and/or restricted objects to the further fluid. The delivery portion may be a shared delivery portion and may form part of the first channel. The output may comprise a common output. The device may comprise a plurality of channels comprising: a first channel between the input and the further output defining the further fluidic path between the input and the further output; a second channel coupled to the plurality of restrictions and the output, wherein the second channel is coupled to the first channel via the plurality of restrictions so that at least part of the first channel and at least part of the second channel define the plurality of fluidic paths between the input and the output. The first and second channels may be sized to permit fluid flow of the objects. The restrictions may comprise an opening between the first channel to the second channel that is sized to prevent the object from passing through. The input may comprise an inlet. The output may comprise an outlet. The further output may comprise a further outlet. Fluid may flow from the input to the further output via the further fluidic channel at a higher flow rate when the restrictions are substantially occluded relative to when the restrictions are substantially not occluded. The at least one restriction may form part of a trap for trapping one or more objects, for example, one or more tissue and/or objects. The objects may be cellular and/or tissue objects. The restriction may be sized to permit fluid flow therethrough and to prevent objects to pass through the restriction. The at least one sensing element may comprise an electrode. The at least one sensing element may comprise a passive high impedance electrode to measure field potentials against a passive or ground low impedance reference electrode. The at least one sensing element may be provided at a sensing region. The device may comprise a hybrid microfluidic and microelectronic device. The microelectrode array may comprise one or more stimulating electrodes for providing a stimulus to one or more sensing regions and/or a trapped object and/or one or more objects in the sensing regions. The one or more stimulating electrodes may comprise paired stimulating electrodes to provide a stimulus to the sensing region, optionally an object in the sensing region. The one or more stimulating electrodes may comprise an electrode pair utilizing the low impedance reference electrode. The sensing module may comprise at least one passive sensing electrode element, and for example, at least one stimulating electrode and reference electrode. The stimulating electrode and reference electrode may form a stimulating electrode pair. The device may comprise more than one stimulating electrode pair. The at least one stimulating and reference electrode pair may be arranged at a first side of the sensing region and the at least one sensing electrode may be arranged at a second side of the sensing region such that sensing region is provided between the at least one stimulating electrode pair and the at least one sensing electrode. One of the stimulating electrode pair may be provided at a first side of the one or more sensing regions, and the other of the stimulating electrode pair may be provided at another side of the sensing region such that the one or more sensing regions are provided between the stimulating electrode pair. The device may comprise a stimulating electrode that is shared between one or more sensing regions. The at least one stimulating electrode may be provided at a first side of the and reference electrode pair may be arranged at a first side of the sensing region and the at least one sensing electrode may be arranged at a second side of the sensing region such that sensing region is provided between the at least one stimulating electrode pair and the at least one sensing electrode. The at least one sensing electrode may be configured to sense a response in the object to electrical stimulation delivered from the stimulating electrode pair. One or more electrodes or sensing elements may be provided above or below a microfluidic device layer. The sensing module may comprise at least one passive sensing electrode element, and for example, at least one stimulating electrode and reference electrode. The stimulating electrode and reference electrode may form one or more electrode pairs. The electrode pairs may be arranged at either side of a sensing region such that sensing region is provided between a stimulating electrode and a sensing electrode. The at least one sensing electrode may be configured to sense a response in the object to electrical stimulation delivered from the stimulating electrode. The plurality of restrictions may comprise five or more, optionally at least ten, optionally, at least 15, optionally at least 60, optionally, at least 100 restrictions. The plurality of restrictions may be arranged at an overlapping portion of the plurality of fluidic paths and the further fluidic path to allow sequential delivery of objects to the restrictions, such that, when a restriction is occluded by an object, a further object in the fluid proceeds to the subsequent restriction and/or towards the further output. The plurality of fluidic paths and further fluidic path may be formed by channels sized to allow the one or more objects to flow. The at least one sensing element may be provided on a layer below the plurality of restrictions, optionally, such that the at least partially restricted and/or trapped objects contact the at least one sensing element. The at least one sensing element may comprise a plurality of sensing elements comprising one or more sensing elements for each restriction and at least one reference electrode The sensing element may be configured to sense an electrophysiological signal and/or or a signal and/or a biological signal in response to electrophysiological activity of the object. The electrophysiological or other activity of the object may be in response to a chemical and/or a chemical stimulus provided at the input. The electrophysiological or other activity of the object may be in response to a chemical and/or a chemical stimulus provided at the input and flushed through the system. The electrophysiological or other activity of the object may be in response to an electrical stimulus provided, for example, from one or more stimulating elements or electrodes to the object. The at least one sensing element may be provided as part of an electrode array aligned with and/or provided proximal to the at least one restriction. The electrode array may be aligned to contact the one or more objects. The electrode array may be aligned to optimally contact the one or more objects. The at least one sensing element may comprise one or more sensing or recording electrodes. The sensing electrodes may be passive electrodes. The sensing electrodes may comprise an exposed portion in contact with the object. The exposed portion may have a diameter in the range of 10 to 100 microns, further optionally 20 to 60 microns. The diameter of the exposed portion may depend on the material used. The sensing module may comprise a plurality of conductive tracks. The conductive tracks, for example coupled to a corresponding part, for example, a pad of an electrode, or forming part of a plurality of electrodes. The tracks may lead to a pad of a corresponding electrode. The tracks may be conductive. The tracks may be electrically insulated from the fluidic paths and/or channels of the microfluidic device. The tracks may be electrically insulated from fluidic contents of the microfluidic device, in use. The pad and/or track may comprise a conductive material, for example, a titanium or gold deposition. The track may be insulated by an insulating material, for example, Silicon Oxide. At least one pair of stimulating electrodes may be provided as part of the electrode array aligned with and/or provided proximal to at least one restriction and the passive recording electrodes. The electrode array may be substantially planar. The device may further comprise a reference sensing element. The device may further comprise a reference sensing electrode, for example, a passive electrode. The reference sensing element may be provided at or across at least part of the plurality of fluidic paths and/or at least part of the further fluidic path. The reference sensing element may form part of a pair of stimulating electrodes. The reference sensing element may be provided together with a stimulating electrode. The sensing module may comprise one or more active elements and one or more passive elements. The reference sensing element may act as a reference sensing element to at least one, optionally a plurality of sensing elements. At least part of the reference sensing element may be provided at or may be overlapping with the plurality of fluidic paths and/or the further fluidic path. The plurality of sensing electrode may be aligned with the plurality of restrictions. The plurality of sensing electrodes may be provided in a substantially linear arrangement. The spacing between subsequent sensing electrodes may correspond to the spacing between the plurality of restrictions. The sensing elements may be arranged such that each restriction is provided substantially between a corresponding sensing element and the reference element. The exposed portion of the reference electrode may be, at least part, optionally all or the entirety of an electrode pad providing a passive low impedance voltage reference. The exposed portion of the reference electrode may comprise a passive low impedance component. Each of the restrictions may comprise an opening having a cross-sectional area that is at least 50%, 60%, 70%, 80%, 90% or 95% smaller than the diameter of the one or more objects of interest. The plurality of fluidic paths and the at least one further fluidic path may be formed by channels having a cross-sectional area that is at least 50%, 60%, 70%, 80%, 90% or 95% larger than the diameter of the one or more object of interest. The object may have dimensions, for example, a width and/or a height in the range between 150 to 300 microns. The plurality of restrictions may comprise a width smaller than the width of the object of interest. The restriction may comprise a width at least 10% or 20% or 30% or 40% or 50% 60% or 70% or 80% or 90% of the width of the object of interest. The plurality of restrictions may have a width between 10 and 75 microns, optionally in the range 20 to 40 microns. The width of the channels may be in the range 300 and 1000 microns, optionally, in the range of 400 to 500 microns, further optionally 450 microns. The height of the channels may be in the range 200 and 1000 microns, optionally, in the range of 200 to 300 microns, further optionally 250 microns. The plurality of fluidic paths and the at least one further fluidic path may be formed by channels having a width that is at least 50%, 60%, 70%, 80%, 90% or 95% larger than the width of the one or more objects. The plurality of fluidic paths and the at least one further fluidic path may be formed by channels having a height that is at least 50%, 60%, 70%, 80%, 90% or 95% larger than the height of the one or more objects. The width and/or dimension of the object of interest may comprise an average or typical width and/or dimension of such an object. The plurality of fluidic paths and the further fluidic path may be formed by a plurality of channels. At least one of a width and/or height of at least one channel may be selected from a range thereby to increase or decrease the fluid flow rate. The microfluidic device may further comprise a chip holder and/or an amplifier connected to a computer reading software. The microfluidic device may be for use in assessing cell or tissue object electrical activity, viability, function and/or response to a chemical and/or a physical stimulus. The device may further comprise a processing resource configured to: receive sensor signals from said at least one sensing element and/or data representing said sensor signals; process said data and/or signals to determine at least one of electrical activity, viability, function and/or response to a stimulus. The data and/or signals may be processed to determine a percentage of viable tissue and/or objects in a sample. The determining of at least one of electrical activity, viability, function and/or response to a stimulus may comprise generating data representing electrical activity, function and/or response to a stimulus and storing said data. The processor may be configured to determine at least one of: a) a measure of electrical activity in response to a further fluid and/or direct electrical stimulation, optionally wherein the further fluid comprises a chemical and/or a drug, for example, a glucose solution, further optionally wherein the electrical stimulation is provided by one or more stimulating elements or electrodes to; b) a number of viable and/or functional tissue and/or multicellular objects in a sample. c) perform a diagnostic and/or viability indication based on sensed electrical activity at the plurality of restrictions and/or sensing regions, for example, wherein the diagnostic and/or viability indication may be based on electrical activity in response to exposing said object to a further substance, optionally comprising a chemical and/or a drug, for example, glucose and/or electrical stimulation. The chemical and/or a drug may comprise a chemical and/or drug to be tested. The response may be in response to a metabolic stimulus such as glucose and/or electrical stimulation. In accordance with a second aspect there is provided a method of providing one or more objects of interest to the device according to the first aspect, comprising providing one or more objects in a fluid to the input of the device, wherein the fluid initially flows through the device until the one or more objects reach the plurality of restrictions and are trapped and/or at least restricted at the plurality of restrictions. In accordance with a third aspect, there is provided a method for analysing a plurality of objects, for example, a plurality of tissue and/or multicellular objects, using the device according to the first aspect, said method comprising: providing a plurality of objects in a fluid to the input of the microfluidic device, wherein the fluid initially flows through the device along said plurality of fluidic paths until the plurality of objects reach the plurality of restrictions and are trapped and/or at least restricted by said restrictions; sensing at least one sensor signal for the plurality of objects using the at least one sensing element. The method may further comprise delivering a further fluid through the input to the plurality of objects trapped or at least restricted in the plurality of restrictions via the at least one further fluidic path. The method may further comprise applying electrical stimulation, optionally via one or more electrode pairs. The at least one sensor signal may be representative or indicative of biological activity of the plurality of objects. The at least one sensor signal may comprise one or more first sensor signals sensed prior to delivery of the further solution and/or electrical stimulation and one or more further sensor signals sensed after delivery of the further solution and/or electrical stimulation. The one or more first sensor signals may be representative or indicative of a baseline electrophysiological activity for the plurality of objects. The further signal may be representative or indicative of an electrophysiological activity of the plurality of objects. The at least one sensor signal may be sensed for each restriction, optionally, by a sensing element provided at said restriction, further optionally between the sensing element at each restriction and a reference electrode. At least one sensor signal may be sensed for each restriction, with respect to a reference electrode. The one or more objects may be derived from the pancreas, for example, pancreatic islets also termed islets of Langerhans. The one or more objects may be derived from other commonly available spheroidal objects such as cardio-spheroids, neural organoids, and other excitable object organoids. The one or more objects may move to the at least one restriction and/or beyond by gravity, bulk-flow and/or capillary action. The further fluid may comprise a wash solution for removing any solution and/or objects via the further output. The further fluid may comprise a glucose solution. The further fluid may comprise one or more drugs and/or object or cell activity inhibitors. The further fluid may comprise one or more molecules for labelling the objects. The further fluid may comprise a higher concentration than the fluid comprising the plurality of objects. The method may further comprise isolating the output electrical signal from trapped objects for the plurality of restrictions of the microfluidic device. The method may comprise isolating electrical signals for at least 15, optionally 30, optionally 60, traps. The method may further comprise processing the sensor signals and/or data representing the sensor signals to assess at least one of cell or object electrical activity, viability, function and/or response to a stimulus. In accordance with a fourth aspect there is provided an apparatus comprising the device of the first aspect and a processing resource. The processing resource may correspond to the processor of the first aspect. The processing resource may be configured to receive sensor signals from said at least one sensing element and/or data representing said sensor signals; process said data and/or signals to determine at least one of electrical activity, viability, function and/or response to a stimulus. The data and/or signals may be processed to determine a percentage of viable tissue and/or cell and/or objects in a sample. The determining of at least one of electrical activity, viability, function and/or response to a stimulus may comprise generating data representing electrical activity, function and/or response to a stimulus and storing said data. The processor may be configured to determine at least one of: a) a measure of electrical activity in response to a further fluid, optionally wherein the further fluid comprises a chemical and/or a drug, for example, a glucose solution; b) a number of viable and/or functional tissue and/or multicellular objects in a sample c) perform a diagnostic and/or viability indication based on sensed electrical activity at the plurality of restrictions and/or sensing regions, for example, wherein the diagnostic and/or viability indication may be based on electrical activity in response to exposing said object to a further substance, optionally comprising a chemical and/or a drug, for example, glucose and/or direct electrical stimulation of the object. The apparatus may further comprise a display and a user input. In a fifth aspect, there is provided a microfluidic/microelectronic/multichannel device, wherein at least one of said microfluidic modules comprises: (a) a first channel for receiving fluid and comprising an input and an output, and at least ten traps, disposed between the input and the output, for trapping multiple tissue(s)/organoid samples introduced into the first channel through the input, wherein the trap comprises a restriction sized to permit fluid flow therethrough, but not permit said one or more tissue(s)/organoid to pass through the restriction, the trap further comprising at least ten electrodes for detecting an electrophysiological signal of said one or more tissue(s) trapped in the traps; and (b) a second channel for receiving fluid from the first channel after the/each restriction has become occluded by said one or more tissue(s)/organoid, thereby preventing further fluid flow through the/each restriction. The second channel may also be used to remove fluid and/or object(s) after analysis. Although the present disclosure is generally described in the context of pancreatic islets, this is not to be construed as limiting. The device of the present disclosure may be provided with any type of tissue wherein the electrical responses generated by multiple active cells and/or objects therein allow for the assessment of its viability and/or the function is of interest (e.g. cardiac or neuronal tissues). In one embodiment, the one or more tissues may be derived from the pancreas. In a preferred embodiment, the one or more tissues derived from pancreatic islets comprise several thousand β-cells, for example. Whilst pancreatic islets are provided as exemplary cells and/or objects herein, the present disclosure is not intended to be limited to such cells and/or objects as excitable changes in the membrane potential may be used to assess the viability and/or function of various types of excitable tissues. The membrane potential refers to the voltage or potential difference across the cell membrane. The potential difference is caused by the hydrophobic membrane separating charges, acting as both a capacitor and resistor to the movement of charged ions across it. The plasma membrane ensures the structural integrity of a cell, and physically separates intracellular compartments from the extracellular surroundings. An electric potential gradient is present across the cell membrane due to substantial differences in ionic composition between the intracellular and extracellular compartments, a selective permeability for certain ion species, as well as due to the insulating physical properties of the phospholipid bilayers comprising the cell membrane. At steady state, the intracellular compartment of cells is more negatively charged with respect to the extracellular environment (with respect to potassium ions), resulting in a resting membrane potential in the range from -10 to -80 mV depending on the type of cell. In excitable tissues such as pancreatic islets, muscle and neurons including of stem cell origin, rapid changes in the membrane potential (for example, action potentials), can be triggered by electrical and/or chemical signals which changes the permeability of ions through ion channels Action potentials are a few milliseconds in duration and of over 100 mV in amplitude. The electrophysiological state and/or response of cells refers to the electrical property or activity of cells, which is typically reflected in the above changes in the membrane potential. The charge underlying the electrical state or activity of cells is dependent ions, such as sodium (Na+), chloride (Cl-), potassium (K+) and calcium (Ca2+) ions, for example. The flow of the ions in and out of cells are regulated by ion channels, and the movement of charged ions across the cell membrane can generate action potential scale voltage differences (around 100 mV). Electrodes, microelectrodes or microelectrode arrays, for example, externally may be used to detect synchronous cellular electrical activity of single or a multitude of cells by measuring and/or detecting the extracellular local field potentials which are a fraction of the actual potential change (5-100 ^V). Such an approach is used clinically to measure brain potentials (EEG; electroencephalogram), heart field potentials (ECG; electrocardiogram), and muscle potentials (EMG; electromyogram) where many cells are synchronously active. Thus, in an alternative embodiment, the present disclosure may relate to objects, organoids or tissue(s) derived from other organs, wherein the assessment of the whole object function and/or response through changes in extracellular local field potential is of interest. Without being limited to the examples provided herein, alternative organs from which the objects tissue(s) of the present method may be derived may include heart, brain, intestines, liver, kidney, gall bladder, stomach, or skin and endothelial tissues as well as stem-cell derived objects from a number of organs, for instance. As well as objects (or cells) derived from organs, and tissue(s) for use in accordance with the present disclosure may include cultured cell objects, especially cultured mammalian material, in order to test object viability and/or function of such cultured objects. In some embodiments, the tissue of the present disclosure may comprise a group of cells or a cluster of cells, which may be provided to the microfluidic device. For instance, such tissue(s) may comprise organoid(s) (e.g. brain organoids, cardiospheroids) or Embryonic Stem cell or induced pluripotent stem cell (iPSC) derived objects. In some embodiments, the tissue may comprise one or more clusters of cells or objects or spheroids of cells or objects. Accordingly, the skilled person in the art would also recognise that the dimensions of the first channel, the second channel, the trap and/or the restriction may be adapted accordingly, depending on the size of the tissue, the cluster of cells or the group of cells being provided to the microfluidic device for testing. In particular, at least the first channel and the/said trap(s) should be of a size that at least one tissue object is able to fit within the dimensions of the first channel and the/said trap(s). The input serves as an entry route through which fluid may be provided to the microfluidic module. In a preferred embodiment, a fluid, such as a liquid (e.g. cell culture medium, saline, buffer solution etc.) comprising one or more tissue objects provided to the microfluidic module through the input. The input may comprise an input chamber through which the fluid, such as a reservoir of fluid is provided to the channels of the microfluidic module. The fluid provided to the input desirably flows through the channels through gravity and capillary driven flow. The use of gravity or capillary flow ensures that the tissue objects are manipulated in as gentle a fashion as possible and is distinguished from prior art systems which may employ pumps and the like to drive or draw fluid and objects through a microfluidic device. The microfluidic module also comprises an output (such as an output channel and/or well/reservoir) where the fluid that has flown through the channels may be collected. In some embodiments, the microfluidic modules of the microfluidic device are connected to the same input. In some embodiments, the microfluidic modules of the microfluidic device are connected to the same output. The flow of fluid through the device delivers the one or more objects to the trap(s), which occludes fluid flow through the/each restriction. In one embodiment, the trap comprises a cross-sectional area that is at least 50%, 60%, 70%, 80%, 90% or 95% larger than the cross-sectional area of the one or more objects to be tested. In one embodiment, the trap area comprises a cross-sectional area that is at least 50% larger than the cross-sectional area of the one or more objects leading to a restriction. In a preferred embodiment, the maximum diameter of the cross-sectional area of the trap and/or the restriction may be between 10 to 60 µm. The trap adjoins a restriction which is sized such that the tissue cluster or object or objects is unable to pass through the restriction(s). The restriction preferably comprises a cross-sectional area that prevents the one or more objects from passing through the restriction and traps the said objects, such that the restriction becomes occluded and prevents or minimises fluid flow through the restriction following trapping of an object. For example, it is known in the art that the size of mammalian objects tissues, clusters such as islets and cardiospheroids, typically comprises 100 to 300 µm in diameter. Accordingly, in one embodiment, the maximum diameter of the cross- sectional area of the restriction may be 5%, 10%, 20%, 30%, 40%, 50%, or 60% of the diameter of the object being provided to the microfluidic device. In one embodiment, the maximum diameter of the cross-sectional area of the restriction may be 40 ± 10 µm. In a further embodiment, the dimensions of the channel(s) may comprise 450 ± 50 µm in width and/or 450 ± 50 µm in height. Following occlusion of fluid flow through the restriction by the one or more objects provided to the microfluidic device, any fluid flowing through the device is primarily directed towards and through the second channel. It should be noted that the fluid may flow through the second channel prior to and after the occlusion of the/each restriction by the one or more of the tissue objects. The second channel is also referred to as the bypass or bypass channel throughout this disclosure. In one embodiment, the cross-sectional area of the second channel may be at least 50%, 60%, 70%, 80%, 90% or 95% larger than the cross-sectional area of the one or more tissues. In some embodiments, the cross-sectional area of the second channel may comprise a cross-sectional area that is at least 50% larger than the diameter of the object. In one embodiment, the microfluidic device may comprise a single microfluidic module. In such an example, upon occlusion of the restriction, the fluid flows through the second channel and towards the output. In other embodiments, the microfluidic device may comprise more than one microfluidic modules and thereby comprise more than one trap and restriction within each device. In the multi-modular configuration, the second channel of each of the modules may be connected to form a continuous second channel which leads to the same output. In some embodiments, the direction of fluid flow through the second channel in relation to the object trap is such that the direction of fluid flow towards the second channel may only occur once the/each restriction is occluded and the fluid overflows from the object trap to the second channel. The multi-modular configuration of the microfluidic device with its microelectronic substrate provides a high throughput means through which the electrophysiological activity from multiple tissues may be measured simultaneously to determine the percentage of functional tissues therein. This feature offers a significant advantage, such as when the quality of a large number of islets need to be assessed rapidly prior to transplantation. Importantly, the device of the present disclosure overcomes limitations of existing techniques, which often require a complex instrumental setup, have low throughput and/or cause damage to objects during manipulation. In a further embodiment, it could be envisaged that the dimensions of the first channel, the object or spheroid trap, the restriction and/or second channel may be varied to accommodate different tissue types and/or sizes by adding an adaptor or stopper capable of restricting and/or increasing the cross-sectional area. In one embodiment, the microfluidic module comprises an adaptor or a stopper for altering the cross-sectional area at defined points of the first channel and/or the second channel within a specified range. In a specific embodiment, the channel dimensions may comprise a diameter, height or width within the range of 200 µm and 500 µm. In an alternative embodiment, the object trap and/or the restriction may comprise an adaptor or a stopper to alter the diameter height or width of the channel(s) depending on the object type being provided to the microfluidic device. Each microfluidic module of the present disclosure may comprise at least one electrode to assess the electrophysiological state and/or response of objects to a stimulus. The microfluidic device of the present disclosure comprises at least ten electrodes, which are preferably located at each object trap such that electrical activity of the objects can be detected. A reference electrode is typically required to obtain a background or reference signal of the electric field. In a preferred embodiment, the microfluidic module comprises a unified ground reference electrode. An end of each electrode reaches into the microchannel to enable measurement(s) to be obtained from within the channel. In one embodiment, each module of the microfluidic device comprises at least 10 recording electrodes. In a preferred embodiment, the electrode of the present disclosure comprises a microelectrode. In some embodiments, the one or more electrode may form a microelectrode array. A microelectrode array is commonly used in the art to measure object electrical activity. In a preferred embodiment, the electrode(s) comprise gold and/or titanium electrode(s). In comprising a multi-module configuration, however, it is not required that all modules comprise electrode(s). In some embodiments, one or more modules of the microfluidic device do not comprise electrodes. One or more modules that lack electrodes may be used as controls where the tissues used in the assay can be microscopically visualised, or used for biochemical assays, such as gene expression, compound detection, or viability assays that use optical detection (for example, absorbance or fluorescence. In such applications, the one or more modules may comprise an access point through which tissues may be isolated for analysis and solutions bathing the tissues may be collected without disturbing the tissue (e.g. for secretory assays). To enable visualisation of the one or more tissues through the microfluidic device, in some embodiments, the one or more modules may comprise a polymer coverslip or a glass coverslip bottom through which objects may be visualised directly through the device. If electrical information is required transparent electrodes can be printed on these coverslips. The microfluidic device may be fabricated in, for example, plastics, glass, silicone or other material. In a preferred embodiment, the channels of the microfluidic device comprise transparent polydimethylsiloxane (PDMS). While the examples disclosed herein use transparent PDMS for the channels and borosilica glass as the substrate for titanium (Ti) electrodes (which are insulated with a silicon dioxide deposition), any transparent substrates or moulded plastic known in the art to be appropriate for fabricating microfluidic devices may be used. The one or more electrodes of the device may be prepared in numerous ways known in the art. In one embodiment, the microfluidic device according to the present disclosure may be prepared by printing methods wherein the one or more electrodes is printed within the first channel by plasma bonding or a pressure fixation method, for example. The device of the present disclosure may further comprise a chip holder and/or an amplifier connected to a computer reading software. A commercially available amplifier may be used, such as, but not limited to a Model 3600 amplifier, which may function as a multi-channel extracellular differential AC amplifier. For instance, the amplifier may typically comprise at least 16-channel capability, at least 10 gain settings, at least 5 low-pass filters ranging from 50 Hz to 50kHz, at least 5 low-pass filters ranging from 0.1 Hz to 600 Hz and a notch filter (e.g. 50 or 60 Hz) per channel. In some instances, signals may be pre-amplified by a headstage, which is typically located proximal to the electrode(s), and recordings are collected by the amplifier. The skilled person would appreciate that the microfluidic device of the present disclosure may have various applications. In one embodiment, the microfluidic device may be used for the assessment of object electrical activity, viability, function and/or response to a stimulus. The stimulus may comprise any substance that triggers a change in population cellular activity, such as glucose, ions, hormone(s), ligand(s), electrical stimulation, or drug(s). In a preferred embodiment, the stimulus provided to the microfluidic device comprises glucose. In a sixth aspect, there is provided a method of adding one or more tissues to the microfluidic device as disclosed herein for measuring the electrical activity of the one or more tissues, wherein said method comprises providing one or more tissues in a fluid to the input of the device, wherein the fluid initially flows through the device until one or more tissues reach the trap and occlude fluid flow through the restriction. The occlusion of fluid flow through the restriction promotes fluid flow through the second channel(s) and to the output of the microfluidic device. In a seventh aspect, there is provided a method for analysing objects using the microfluidic device of the present disclosure comprising: (i) providing one or more tissues in a fluid to the input of the microfluidic device, wherein the fluid initially flows through the device until the one or more objects reach the trap and occlude fluid flow through the restriction; (ii) measuring a baseline electrophysiological activity of the one or more tissues through the one or more electrodes; (iii) delivering a test solution through the input to the one or more tissues that will cause the objects to become more or less electrically active – the substrates would be those that specifically stimulated electrical activity from specific cells or block it e.g. high glucose concentration for islets ; and (iv) measuring the electrophysiological activity of the one or more tissues through the one or more electrodes in response to the test solution. In one embodiment, the method may comprise more than one test solution, wherein steps (iii) and (iv) are repeated, with an optional step (v) comprising providing a wash solution through the input after each solution to measure electrophysiological activity of the one or more tissues in response to each test solution. In some embodiments, subsequent to the delivery of the tissues to the trap and occlusion of the restriction, the fluid of step (i) may be removed by suction of the fluid from the output prior to adding the test solution of step (iii). In an alternative embodiment, the output may initially be occluded by a stopper, which is released for removal of the solution of step (i) by gravity and capillary driven force prior to the addition of the test solution of step (iii). In one embodiment, the one or more tissues (islets of Langerhans) are derived from the pancreas. For optimal object viability, the one or more tissues of the method as disclosed herein are provided in a solution to the microfluidic device and/or maintained in a solution within the microfluidic device. In a preferred embodiment, the one or more tissues are provided to the microfluidic device in solution, such as a commercially available cell culture solution appropriate for the tissue type. Once the one or more tissues are provided to the microfluidic device, the tissue(s) objects travel along the first channel and towards the trap in order to occlude fluid flow through the restriction and enable measurement of the electrophysiological activity of the objects through the electrodes. In one embodiment, the one or more tissues move through the first channel by gravity and capillary driven fluid flow. In one embodiment, the culture solution and/or the test solution may comprise glucose. In one embodiment, the concentration of glucose in the solution may be 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 15, 16, 17, 18 or 20 mM. In an alternative embodiment, the concentration of glucose in the solution may comprise any concentration that is physiologically relevant to the condition or tissue type of interest. In one application, the microfluidic device and/or the method described herein may be used as a drug discovery platform or for safety screening of compounds. In addition, or alternatively, the culture solution and/or the test solution may comprise one or more drugs in order to assess alterations in electrophysiological responses of tissue(s). The one or more drugs may be a drug that increases cell viability, for therapy and/or a drug that alters the electrophysiological response of tissues. The one or more drugs may include agonists of ion channels or antagonists of ion channels. For instance, the one or more drugs may comprise tolbutamide, chlorpropamide or gliclazide, for example. Alternatively, electrophysiological activity of objects may be manipulated by altering the ionic concentration of the extracellular medium. In one embodiment, the test solution comprises a higher concentration of the components (e.g. ions, glucose, other nutrients) comprising the culture solution. Optionally, in some instances, the one or more drugs may comprise a hormones that stop electrical activity in the objects e.g. insulin in the case of islets. The method according to the present disclosure enables rapid, accurate and label-free assessment of viability and/or function of tissues. Alternatively, the method may comprise an additional step of isolating the one or more tissues from the first channel and/or fluid from the microfluidic device for further analysis. The one or more tissues may be isolated for further analysis of the one or more tissues, such as assessing object electrical activity, viability, function and/or response to a stimulus. The further analysis may include various techniques known in the art, such as transcriptomic analysis or fluorescence microscopy. In some embodiments, the test solution may comprise one or more molecules for labelling objects, wherein the labelled tissues are isolated for further analysis. For instance, the one or more molecules for labelling objects may comprise any commercially available fluorescent probes or dyes for staining cellular components. Features in one aspect may be provided as features in another aspect. For example, method features may be provided as device or apparatus features and vice versa. BRIEF DESCRIPTION Various aspects of the invention will now be described by way of example only, and with reference to the accompanying drawings, of which: Figure 1 is a top-down view of a multi-channel device microfluidic channel having a plurality of traps, in accordance with an embodiment; Figure 2 is a close-up view of the device of Figure 1; Figure 3 is a further close-up view of the device of Figure 2 showing flow direction and an indication of where objects would be trapped; Figure 4 depicts a top-down view and a cross-section of a further, single-trap device as a background example; Figure 5(a) is a top-down view of a single-trap device, Figure 5(b) is a view of a multi- trap device in accordance with embodiments, Figure 5(c) is a photograph of a microfluidic module of the device bonded to a glass micro-electrode array and Figure 5(d) is an example of a multichannel microfluidic chip and electrode array mounted in holding module and Figure 5(e) is a further photograph of a microfluidic module of the device bonded to a glass micro- electrode array; Figures 6(a) to (d) are further drawings and photomicrographs of the multi-channel device, and Figure 6(e) is a composite micrograph showing pancreatic islets trapped in the device; Figures 7(a) and (b) depict a sensing element module of the device, in accordance with an embodiment; Figures 8(a) and (b) depict sensing element modules of the device, in accordance with further embodiments; Figure 9 depicts an apparatus in accordance with an embodiment; Figures 10(a) to 10(d) are plots of results derived using the device; Figure 11(a) and 11(b) are further views of the device of Figure 1; Figure 12 is a further view of the device of Figure 1, and Figure 13 is top-down view of a device in accordance with an embodiment. Figure 14 is a top-down view of a device having a stimulating electrode, in accordance with an embodiment. DETAILED DESCRIPTION The present disclosure relates to a device. In accordance with embodiment, the device may be used for determining Islet of Langerhans tissue quality, maturity or developmental status through an electrical activity measurement. The device may also be deployed in similar way to measure the electrical activity of any other organoid such as but not limited to neural cells or organoids and neural stem cells, cardiospheroids etc. of similar dimensions (100-300 µm in diameter). An electrode based approach to assess viability of freshly isolated Islets has generally been perceived as not feasible. For example, in “Microelectrode Array based Functional Testing of Pancreatic Islet Cells” (Alassaf et al, 2020) It was indicated that extracellular recordings of islets using a planar MEA (Micro Electrode Array) platform (Figure 1A) (Alassaf et al, 2020) using classical MEA chips was not feasible and that recording of electrical activity requires proper contact and adhesion between islet and electrodes. Given that islets are large multicellular spheroids, limited contact area with the recording electrodes of planar MEA precludes MEA recording for functional evaluation of islets. In contrast to the device described herein, the Islets in the Alassaf et al., were then disassociated into single cells on the array and cultured for several days. Known approaches using imaging label Islets which render the Islets unusable for transplant purposes. Alternative known approaches may damage Islets which again renders the Islets unusable for transplant purposes. In the following the terms organoid, spheroid, islet and object are used as examples of tissues or tissue cultures. Organoid in this sense may refer to a cluster of cells derived from embryonic stem cells, induced pluripotent stems cells, or organ specific adult stems cells that have been developed in culture to form an identifiable structure with some or all of the anatomical and physiological/functional properties of the normally developed organ. They usually consist of several thousand cells. They include, but are not limited to, stem cell derived pancreatic islets, neural stem cell derived brain organoids, cardiospheroids, kidney, ovary gut and spleen etc. These tissues or objects are around 100-300 microns in diameter. Primary organoids on the other hand may refer to tissues derived from donor material that are the same scale such as donor pancreatic islets and muscle and brain biopsies. The devices described in the following may measure the excitation in excitable tissues the methodology for determining functionality may be best applied to excitable endocrine tissues such as pancreatic islets, brain and muscle. There is an unmet need in the art for the development of new devices and methods which can efficiently identify viable and functional clusters of cells including islets for transplantation without chemical labelling or biochemical manipulation. Rapid identification of viable islets is critical as transplant outcomes are often highly associated with islet numbers and their viability. In the context of islet transplantation as an example, the process of transplantation is a multi- step procedure which involves pancreas procurement, tissue dissociation, islet purification, islet culture and islet transplantation via the hepatic portal vein and into the liver of the recipient. At each step, islets are lost (mainly due to ischemia). Moreover, less than 50% of islets from a single pancreas are isolated (~500,000 islets) and of these it is estimated that<50% engraft into the liver. Thus, there is an urgent need for new devices and methods that can rapidly assess quality without negatively affecting the viability and function of the islets. The present disclosure is based on an approach, which obviates the need for complex manipulation of the islets (or other objects mentioned including organoids and clusters of cells) does not require a chemical manipulation or label, and gives the possibility of testing multiple islet responses (or other objects mentioned) sufficiently rapidly to give a projected estimate of batch viability. It will be understood that all living cells possess bioelectrical activity and in general many cells can respond to a chemical or physical stimuli that can augment or decrease their bioelectrical activity. For example cardiomyocytes/cardio myocyte organoids/ stem cell derived cardiomyocytes may be stimulated by isoprenaline and their electrical activity measured. Those clusters of cells which are viable would produce an extracellular coordinated electrical signal at rest and in response to such a pharmacological stimulus or electrical stimulation (pacing) but those clusters that are not viable would not produce a coherent electrical signal, or any electrical signal at all, therefore discriminating viable from non-viable clusters of cells. This device therefore may also be applied to stem cell derived neural objects and other neural cell clusters and other organoids. Figure 1 is a view from above of a device having a plurality of traps, in accordance with an embodiment. It will be understood that device 100 has a microfluidic module and an electronic sensing module and Figure 1 depicts the microfluidic module only. The electronic sensing module is descried in further detail with reference to, for example, Figure 7 onwards. The device 100 is configured to trap a plurality of objects, in particular, biological objects such as tissue and/or multicellular objects. The objects may comprise cell objects or tissue objects. In this embodiment, each trap comprises a restriction for restricting or trapping tissue or organoids in cell culture. In the following description the device is described as trapping cell spheroids however, it will be understood that the device may be used to trap objects derived from cultures or tissue cultures, for example, organoids, spheroids, for example, object spheroids, tissue spheroids, and Islets. Such objects are suspended in a fluid and conveyed through the channels of the device via fluid flow. The device may be for trapping and testing excitable tissues and/or multicellular objects to test for bioelectrical activity as a proxy for tissue viability. The microfluidic module has an input 110, also referred to as a common or shared input, and an output 111, also referred to as a common or shared output. The microfluidic module also has a further output 113. The further output 113 is separate to the shared output 111. The microfluidic arrangement has a plurality of fluidic paths between input 110 and shared output 111. In the embodiment of Figure 1, there are 11 fluidic paths defined between the input 110 and the shared output 111 with a fluidic path passing through each restriction. As described above, each restriction is configured to trap one or more tissue and/or multicellular objects in a fluid introduced to the device, via input 110, and conveyed along the respective fluidic path of the restriction. In addition to the plurality of fluidic paths defined between input 110 and shared output 111 via the restrictions, a further fluidic path is defined between the input 110 and the further fluidic output 113. The further fluidic path is in fluid communication with the plurality of restrictions but does not pass through the restrictions. The further fluidic path has a delivery portion between the input 110 and a plurality of restrictions 108 that allow delivery of a fluid to the restrictions. The further fluidic path has an output portion that allows removal of fluid from the device, via the further output 113. The microfluidic arrangement is such that the plurality of restrictions are provided adjacent to and in fluidic communication with the further fluidic path. The further fluidic path is thus arranged to expose trapped and/or restricted objects to a further fluid. The further fluidic path may be referred to as a fluid delivery and/or flush path. The plurality of fluidic paths may be referred to as object delivery paths. In the embodiment of Figure 1, the device has a first channel 101 defined between input 110 and further output 113. The first channel incorporates an input portion 102 (also referred to as an input channel portion), an intermediate portion 115 and a by-pass portion 104 (also referred to as a by-pass channel portion). The input portion 102 is coupled to the intermediate portion 115 at a first coupling 113 and the intermediate portion 115 is coupled to the by-pass portion 104 at second coupling 112 such that the intermediate portion 115 is provided between the first cooping 113 and the second coupling 112. The device has a second channel 106 (also referred to as an exit channel) coupled to the first channel 101 via the restrictions. The second channel has a first portion 106a and a second portion 106b. The second channel 106 is coupled to the first channel along the first portion 106a via the plurality of restrictions 108. In particular, the plurality of restrictions 108 provided along intermediate portion 115 of the first channel couple the intermediate portion 115 to the first portion 106a of the second channel 106. The input portion 102 and intermediate portion 115 may together form a fluid and/or object delivery portion. The by-pass portion 104 may be form a fluidic and/or object flush portion. The plurality of restrictions may therefore be provided at or on the fluid and/or object delivery portion. It will be understood that the first and second channels of the device of Figure 1 are sized to permit fluid flow of the objects. Therefore, in the present embodiment, the first channel is sized to allow flow of the objects of interest and the restrictions are sized to prevent flow of the objects of interest. In the present embodiment, the object of interest is a cell spheroid. In general, the objects of interest may be sized to be in the range 150 to 300 microns. In the present embodiments, the first and second channels have widths of 450 microns and heights of 250 microns and the restrictions are 40 microns. It will be understood that alternative dimensions may be used, in other embodiments. In particular, these design parameters may be selected depending on the object of interest. The channels are formed in a PDMS layer that is sized 3cm x 3cm x 0.5 cm. In the embodiment of Figure 1, the further fluidic path is defined by the first channel 101 between the input 110 and the further output 113. At least part of the first channel 101 and at least part of the second channel 102 define the plurality of fluidic paths between the input 110 and the output 111. In particular, in the embodiment of Figure 1, the plurality of fluidic paths are defined between the input 110 and the output 111 via the input channel portion 102, the intermediate portion 115 of the first channel, the first portion 106a of the second channel and the second portion 106b of the second channel. In the embodiment of Figure 1, the delivery portion of the further fluidic path is between input 110 and the coupling point 112, between the intermediate portion 115 of the first channel output and the by-pass portion 104 of the first channel. The further fluidic path at least partially overlaps with the plurality of fluidic paths between input 110 and point 112. It will be understood that the by-pass portion 104 of the further fluidic path is spatially separate from the plurality of fluidic paths. The further fluidic path therefore provides a path for flushing and/or removal of fluid and/or objects and/or debris from the device via the further output 113. It will be understood that in the embodiment of Figure 1, the input channel portion 102 is a common or shared input channel portion for delivering fluid to each of the plurality of traps. It is also clear from the Figure 1, that the by-pass channel portion 104 is a common output channel portion for the plurality of traps and that the exit-channel provides a common output channel for the plurality of traps. In the embodiment of Figure 1, the device 100 has 11 traps, however, it will be understood that, in other embodiments, a different number of traps may be provided. The first channel 102 has the input channel portion 102 and intermediate potion 115 between fluidic input 110 and second coupling 112. The input may be an inlet port and/or the output may be an outlet port. The plurality of traps 108 are disposed between the input and the output of the first channel 102, in particular, along the intermediate portion 105. As depicted in Figure 1, each of the plurality of traps 108 is in fluid communication with the first channel portion 102, the by-pass channel portion 104 and the exit channel 106. In the embodiment of Figure 1, the plurality of traps are provided in a serial arrangement such that, in use, a fluid flowing through the input channel 102 is provided to each of the cell spheroids is trapped in turn and such that the plurality of traps have a common input channel. A fluid flow direction may be defined starting from the input 110. In a fluid flow direction between the input and the further output 113, it will be understood that the output portion of the further fluidic path is downstream from the delivery portion and the plurality of restrictions. In the above-described embodiment of Figure 1, the input 111 correspond to an inlet port and the outputs correspond to outlets of the device. It will be understood that, in some embodiments, fluidic paths may be defined between inputs and outputs that do not correspond to the inlets/outlets. For example, the plurality of fluidic paths may be defined between an input defined at a point along the input channel 102 (for example, at a point substantially at coupling 113) and/or a shared output defined along output channel 106. Likewise, the further fluidic path may be defined between the same input along the input channel 102 and a further output defined along the by-pass channel portion 104. In such embodiments, more than one inlet may be coupled to the defined input and/or more than one outlet may be coupled to the shared output and/or the further output. In such embodiments, the further fluidic path has a delivery portion that overlaps with the plurality of fluidic paths and an output portion that is spatially separate from the plurality of fluidic paths. As described above, in the embodiment of Figure 1, the channels define fluidic paths through the device. In particular, for each trap, there is a corresponding fluidic path from the fluidic input 110 to the shared output 111 and the restriction is a restriction of that corresponding fluidic path. A plurality of fluidic paths are therefore defined between fluidic input 110 and shared output 111 via the plurality of restrictions. In addition, in the embodiment of Figure 1, as described above, the first channel 101 defines a further fluidic path through the device that by-passes the restrictions. The fluidic path for each trap delivers the object to the restriction of the trap. The object is thus prevented from flowing along that fluidic path by the restriction. The further fluidic path is in fluid communication with each of the restrictions and can be used to deliver a further fluid to the trapped object to allow for fluid exchange and/or further fluid delivery. Each of the fluidic paths is defined between the input 110 and shared output 111 via its respective trap. Each of the fluidic paths therefore at least partially overlaps with the further fluidic path between the input 110 and the by-pass channel portion 104; in particular, the overlapping part corresponds to input portion 102 and at least part of the intermediate portion 115. Figure 2 depicts, in further detail, two of the plurality of traps of Figure 1. Figure 2 depicts a first trap 108a and a second trap 108b. As shown in Figure 2, the first trap 108a has a restriction 114a. Second trap 108b also has a restriction 114b. It will be understood that each of the plurality of traps of device 100 has a respective restriction. As described in the following, the restriction of each trap operates substantially as described with reference to Figure 4. In further detail, the first channel 101, in particular, the input portion 102 of the first channel 101, delivers fluid to each trap. For each trap the first channel 101 has an input portion, an output (or by-pass) portion and a feeder channel portion. Figure 2 depicts the input portion 120a, the output or by-pass portion 122a and the feeder channel portion 116a of the first trap 108a and the input portion 120b, the output or by-pass portion 122b and the feeder channel portion 116b of the second trap 108b. The plurality of traps are provided in a serial arrangement such that the by-pass portion of a trap is coupled to the input portion of the subsequent trap in the series of traps. In this embodiment, the by-pass portion 122a of the first trap is coupled to the input portion 120a of the second trap. In the embodiment of Figures 1, 2 and 3, for each trap the input portion (120a, 20b) is substantially perpendicular to the corresponding by-pass portion (122a, 122b). In other embodiments, the input portion is provided at an alternative angle to the by-pass portion. The feeder channel portions (116a, 116b) are sized to received and hold an object and may act as an object containing chamber. Each trap is arranged such that the exit channel 106 is in fluid communication with the feeder channel portions (116a, 116b) via their respective restrictions (114a, 144b). Each trap can be considered to have an exit channel portion forming part of the exit channel 106 such that the restriction is provide between the feeder channel portion and the exit channel portion. It will be understood that each restriction is formed in a fluidic channel defined by the feeder channel portion 116a and part of the exit channel 106. As described with reference to Figure 4, each trap can be in a first configuration (referred to as an open configuration) and a second configuration (referred to as a closed configuration). In the open configuration, the first channel 101 is in fluid communication with the exit channel 106 via the restriction. For the first trap, in the open configuration, a fluidic path is defined between the input channel 101 and the exit channel 106 via the restriction 114a. In such a configuration, fluid is thus permitted to flow from the feeder channel portion 116a to exit channel 106 via the restriction 116a. In the closed configuration, the first channel 101 is effectively not in fluid communication with the exit channel 106 due to an occlusion and/or blockage at the restriction 114a. In the present embodiment, the occlusion is formed by a tissue spheroid held in the feeder channel portion 116a. The tissue spheroid is embedded or otherwise seeded in the chamber. In particular, in the present embodiment, the tissue spheroid is substantially immobilised in the chamber. It will be understood that the tissue spheroid is immobilised permanently or at least for a sufficient time period to allow a signal to be sensed by the electrode. Figure 3 depicts the immobilised or trapped cell spheroid 120 in the first trap 108a. It will be understood that the cell spheroid described with reference to Figure 3 is an example only and in other embodiments, the object being trapped may be at least one of an organoid; a tissue spheroid; and/or a pancreatic Islet; a cell or tissue object. In some embodiments, the object may be an islet derived from the pancreas. As the cell spheroid has a size (a diameter or width) greater than the opening of the opening of the restriction 114a, the cell spheroid forms a barrier to fluid flow such that substantially all of the fluid in the first channel is prevented from flowing from the first channel 101 to the exit channel 106. As described with reference to Figure 4, the trap may be moved from the first configuration to the second configuration by performing a cell spheroid seeding process using the device. When a trap is in the closed configuration, fluid bypasses the trap and flows to the subsequent trap in the series (via the by-pass portion of the closed trap and the input portion of the subsequent trap). The plurality of traps are such that one or more of the traps may be occluded by a cell spheroid. When one of the traps is occluded, fluid substantially flows via the fluidic paths defined between the input channel 101 and the exit channel 106 via any of the traps that are not occluded. If all of the traps are occluded, then fluid bypasses all of the traps and substantially flows via the further fluidic path defined between along the input channel 101, between input channel portion 102 and the by-pass channel portion 104. Figure 3 depicts the first trap 108a in a closed configuration and the second trap 108b in the open configuration. As depicted in Figure 3, the first trap 108a has a cell spheroid 120 in cell spheroid chamber forming a barrier to fluid flow from a first side of the restriction, the cell spheroid chamber side, to a second side of the restriction, the second channel 106 side. In such a closed configuration, fluid flows along the input channel 106 bypassing the first trap 108a and is then incident on the second trap 108b. In further detail, the fluid bypasses the restriction and exits the first trap 108a via by-pass portion 122a and enters the second trap 108b via the input portion 120b. In some embodiments, fluid flow across the trap in the closed configuration is closed or at least reduced relative to the open configuration. As depicted in Figure 3, the second trap 108b is in the open configuration permitting fluid flow from a first side of the restriction, the spheroid chamber side, to a second side of the restriction, the second channel 106 side. In such an open configuration, fluid flows along the input channel 101 and at least some of the fluid passes through restriction 114b to exit channel 106. In the above-described embodiment, a restriction is described. The restriction together with the chamber co-operate to trap the tissue and therefore can be considered to operate together as a trapping element configured to trap the cell spheroid. It will be understood that alternative restrictions and/or trapping elements may be provided in alternative embodiments. For example, a mesh or grating structure may be provided for restricting a cell and/or other object or tissue culture while allowing fluid to flow. A further example of a trapping element is provided with reference to Figure 4. In use, a plurality of objects in a fluid are introduced into the device via the input 110 of the microfluidic device. The fluid initially flows through the device along the plurality of fluidic paths via the input portion 102 and the restrictions 108. The plurality of objects of the fluid then reach the plurality of restrictions and are trapped and/or at least restricted by said restrictions, as described above. Once trapped at respective restrictions, a sensing process is performed to obtain sensor signals for the plurality of trapped objects using the plurality of electrodes. In some embodiments, fluid flow is by gravity and/or capillary action. The sensing process may be performed before or after delivery of a further fluid to the trapped objects. The further fluid is introduced to the device via the input 110 and is provided to the trapped objects via the further fluidic path. The fluid then flows to the further output 113. The sensing process includes sensing a sensor signal from the electrodes provided at each trap. In the present embodiment, the sensor signals are representative or at least indicative of biological activity of the plurality of trapped objects, in this embodiment objects. A first sensor signal representative or indicative of a baseline electrophysiological activity for the plurality of objects may be sensed before delivery of the further fluid and a further signal is representative or indicative of an electrophysiological activity of the plurality of objects in response to the fluid is sensed. It will be understood that while Figure 1 depicts a multi-channel microfluidic module, more than one of these modules may be provided, for example, as an array, to provide additional channels. Such a combination of modules can be accompanied by a corresponding array or suitably larger microelectrode array, as described below. Figure 4 (upper Figure) depicts a fluidic device having a first channel 12 and a second channel 20. Figure 4 is described to illustrate the operation of a single trap, for background information. The first channel 12 has a fluidic input 14 and a fluidic output 16 and between the input 14 and the output 16 a trap is provided. The trap has a restriction 18 provided in the first channel 12 between the input 14 and the output 16. The restriction 18 can be considered to define a feeder channel portion 12a and an output channel portion 12b of the first channel. The feeder channel portion 12a may also be referred to as the feeder channel and the exit channel portion 12b may also be referred to the exit channel. The restriction 18 is sized to permit fluid flow between the feeder channel portion 12a and the output channel portion 12b and is sized to prevent one or more cell spheroids to pass through the restriction. The restriction can be considered to be an opening formed by two members 19a, 19b that are provided in the first channel. The second channel 20 is in fluidic communication with the feeder channel portion 12a and may also be referred to a by-pass channel. The trap also has at least one indifferent reference or ground electrode and a measuring electrode (c’) for detecting an electrophysiological signal, for example, of one or more cell spheroids trapped in the trap. The detection of electrophysiological signals using the traps is described elsewhere. It will be understood that the channels define fluidic paths through the device. In particular, for there is a first fluidic path from the input 14 to the output 16 and the restriction 18 is a restriction on this fluidic path. In addition, a further fluidic path is defined between the input 14 and the second (or by-pass) channel 20. The first fluidic path delivers the cell spheroid to the restriction of the trap using fluid flow. The cell spheroid is thus prevented from flowing along the first fluidic path by the restriction. The further fluidic path is in fluid communication with the restriction and can be used to deliver a further fluid to the trapped cell spheroid to allow for fluid exchange and/or further fluid delivery to the trapped cell spheroid. The first fluidic path at least partially overlaps with the further fluidic path. In use, the trap may be in one of two configurations: an open configuration and a closed configuration. In the open configuration, the feeder channel portion 12a is in fluid communication with the exit channel portion 12b via the restriction 18. In the open configuration, fluid is permitted to flow along the first channel from the feeder channel portion 14 to the exit channel portion 16 via the restriction 18. In the closed configuration, the feeder channel portion 12a is not in fluid communication with the exit channel portion 12b due to an occlusion and/or blockage at the restriction. In use, such an occlusion is formed by a cell spheroid held in the feeder channel portion 12a at the restriction 18. As the cell spheroid has a size (a diameter or width) greater than the opening of the restriction, the cell spheroid, together with the members 19a, 19b in the channel 12 form a barrier to fluid flow such that substantially all of the fluid in the first channel is prevented from flowing from the feeder channel portion 12a to the exit channel portion 12b. The fluid thus flows to the by-pass channel 14 at a faster rate when the restriction is occluded. The trap may be moved from the first configuration to the second configuration by performing a cell spheroid seeding process using the device. When in the closed configuration it will be understood that fluid flows to the by-pass channel at a faster flow rate than when in the open configuration. As described above, the device is a combination of a transparent microfluidic channel design with a ‘trap’ which is provided together with a printed microelectrode array (Figure 4 gives a single channel example). In the embodiment of Figure 4, the channel dimensions in the feeder and exit channels are 450 µm width and 250 µm depth (Figure 4) while the restriction in the main channel of the trap and bypass channel are 20-50 µm (a value selected depending on the required flow rate). The width of the restriction (i.e. the narrower channel) may be selected from a suitable range of widths to ensure even flow in multiple and single channel systems. In some embodiments, the range of widths comprises 20-50 µm. Waste leaves the system via the output channels which can also be sampled to assess secretion of insulin or other substances (Figure 5). Figure 4 provides addition detail of arrangement and dimensions of channel microfluidics and electrode array (showing a single electrode as part of a single channel example). a, Input channel dimensions 450 µm. b, width of restriction 40 µm c, reference electrode c’, measuring electrode. d, profile at cross section, e, PDMS channel cross section. f, silicon oxide insulation (100 nm thickness- not to scale), g gold electrode track and electrode pad. h, glass substrate. I, height of channel (250 µm). j, width of channel (450 µm as in a). Figure 5 provides further detail of channel arrangements as a simplified examples a, Arrangement of input and output channels of single microfluidic trap shown in Figure 4 with bypass arrows show direction of flow. b, Drawings of multi-channel microfluidic device channel bypass. Arrows show direction of flow (dimensions of channels are the same as single channel device). c. Photograph of assembled multichannel electronic chip with microfluidics module attached. d, Multichannel microfluidic chip and electrode array mounted in holding module. e. A further photograph of microfluidic chip and electrode array. Figure 6 provides detailed drawings of the glass base with printed electrode arrays and demonstration of examples of functionality of multichannel devices. a, overview of alignment of drawings of electrode and microfluidic circuits. b, detail of electrode and microfluidic traps e’ electrode track, f’ reference electrode, g’ microfluidic channel. c, channel as in a, showing trapping of 150 µm glass spheres (h’). d, linear channel arrangement showing microfluidic trapping on 150 µm glass spheres on electrodes. e. A Composite photomicrograph showing an example of islets trapped on an assembled microfluidic module and microelectrode array. In some embodiments, the single or multiple microfluidic channels deliver islets to the ‘trap’ using capillary action without the need for negative or positive pressure application (for example, see Figures 4, 5 and 6 e). Once the islets are trapped, the main channel is effectively blocked and the microfluidic bypass allows flow-through of test solutions (see for example, Figure 4 and 6e). The flow -through allows the rapid exchange of the normal extracellular solution (again by capillary action and/or gravity) with a solution containing higher concentrations of glucose (e.g. 15.5 mM glucose), washing, drugs or dye labels for object counting or assessment. An increase in glucose concentration induces an increase in the electrical activity of the pancreatic beta cells in the object due to glucose sensing (Figure 10 a and b)). As beta cells are the majority of glucose sensing cells in the islet, a measurable electrical change in activity can be detected by the 30 µm electrode pad which the islet is immobilised on top of with reference to a larger ‘ground’ electrode (Figure 4). This electrical response is only observed in healthy fully functional islets. The chip electrical output is ‘read’ by connecting the array via electrical contact with the large printed metal contact pads that are connected via insulated tracts to the electrode pads located under each islet. Processing of the electrical signal yields and indication of whether the islet is responding or not. The device is proposed as one that can assess viability of batches of islets in a timely manner. A prototype has been built and has been used in an assessment of islet quality (Figure 9 D and 10 a and b). It is anticipated that one batch of islets will take around 30 minutes to assess with respect to challenges with low glucose then high glucose. In turn these results will be compared with other viability assays. It is envisaged that an islet sample from a donor pancreas may be pipetted into such a device and using the microfluidics channels and trap, separated and immobilised on the electrodes. Addition of glucose and monitoring of electrode activity will be used to give a % viability using the RMS (root mean squared noise) measurements. This process would take at most 2-3 hours. Currently in the human islets laboratories, islets are cultured for up to 48 hours and therefore the timelines would be well within this margin. It will be understood that the device is a hybrid electronic and microfluidic device. Figure 5(c) is an image of the device in use, in accordance with an embodiment. The device has a microfluidic module 52 and an electronic module 54. Means for providing fluid to the microfluidic module, in this embodiment, a pipette 56, are also shown. The microfluidic module has a plurality of restrictions, substantially as described with reference above, for example, with reference to Figures 1 to 3. Figure 5(c) is a first photograph of the device and Figure 5(e) is a second photograph of the device, including electronic and microfluidic modules 52, 54. The microfluidic module 52, optionally together with the electronic module may be referred to as a microfluidic chip. A holder 56 is also depicted in Figure 5(d). The holder, also referred to as a chip holder, is dimensioned and shaped to provide a seating for the chip. In particular, the holder is substantially U-shaped. The void allows inspection of the chip when held in the holder. The void has a rim to provide a seating for the device, in particular, for the microelectronic module. When held by the holder, the microelectronic module sits on the rim of the holder and the microfluidic module is on the microelectronic module. Figure 5(e) additional depicts an input port 58, a first output port 60, a second output port 62 corresponding to input port 1308, first output port 1302 and second output port 1304 described with reference to Figure 13. In this embodiment, the input port 60 (also referred to as an inlet) is 1 mm in diameter and the output port 62 (also referred to as the flush outlet) is 1mm diameter. The second output port 64, also referred to as the waste outlet is 6.0mm in diameter. The inlet and outlets are formed by creating a void or cut-out in the PDMS layer. Figures 7(a) and 7(b) depict a schematic diagram of an electrode configuration of the electronic module. A glass electrode array for a 15-channel device, in accordance with an embodiment. The sensing module is provided on a glass substrate layer 702 sized 5 x 5 cm. The glass substrate layer has a thickness of 1.5mm. An electrode configuration 704 is patterned on the glass substrate layer. Figure 7(b) depicts a closer view of the electrode configuration 704. A plurality of electrodes (in this embodiment, labelled 1 to 15) are provided such that their respective end points are in a linear arrangement and define a straight line. The end of the first electrode 708 is indicated in Figure 7(b). A single reference electrode 706 spans the width of the plurality of electrodes. The electrode configuration is operable to sense a signal for each electrode with reference to the reference electrode. In use with the microfluidic module, each electrode is aligned at or adjacent to a respective restriction to allow a signal for a trapped object to be sensed. Figure 6(e), described above, shows trapped Islets together with the electrodes. It will be understood that, that the device may have different numbers of channels and restrictions. Figure 8(a) depicts an electrode configuration for a 60-channel device. Figure 8(a) depicts an electrode configuration with four reference electrodes. Each reference electrode is grouped with a set of fifteen sensing electrodes, as described with reference to Figures 7(c) and (d). It will be understood that in the embodiment of Figure 8(a), four fifteen channel microfluidic modules are combined for use with the electrode configuration. The sensing module of Figure 8 is provided on a glass substrate of 10 cm x 5 cm. Figure 8(b) depicts two fifteen electrode modules together to form part of a 30 channel device. In both Figure 8(a) and Figure 8(b) the modules are arranged such that the reference electrodes in each module are parallel. In both Figure 8(a) and Figure 8(b) the modules are arranged such that linear arrangement of electrode ends are in a parallel arrangement. It will be understood that sensor signals may be sensed between the reference electrode and each trap electrode. In some embodiments, a sensor signal for each trap is sensed during the sensing process. In some embodiments, the signals from each trap/channel are isolated from each other. The reference electrode may be a ground reference electrode. The positioning of the ground electrode may be such that the ground reference electrode overlaps with at least part of the further fluidic path and/or the plurality of fluidic paths. In the above described embodiments, a hybrid microfluidic and electronic device is described. At least part of the device may be provided as a cartridge for use with a further apparatus. Figure 9 depicts an apparatus 900 in accordance with an embodiment. In Figure 9, the processing resource is provided as part of a larger apparatus configured to receive a removable chip. The removable cartridge or chip may correspond to the device, as described above. In some embodiments, it is a removable cartridge. The apparatus 900 has one or more displays 902, a chip holder 904 having a housing 904 and a processing resource provided, in this embodiment as part of a data processing PC 908. The apparatus is configured to receive a disposable chip 906 via a first cartridge opening 908 in a first surface, an upper surface of the housing 904. One of more fluidic openings may be are provided in an upper surface of the housing. In the present embodiment, the fluidic opening is sized to receive a pipette. In the present embodiment, the microfluidic module of the cartridge includes 60 channels (in four separate groups each group having a separate fluidic inlet). A manifold is therefore provided, either as part of the apparatus or as a removable part to be used with the pipette, to channel the received fluid to each separate fluidic inlet. In some embodiments, the fluidic inlet and cartridge openings are aligned such that, when inserted into the cartridge opening, the inlet of the microfluidic module is aligned with the fluidic opening to allow delivery of fluid to the inserted cartridge. The processing resource may be configured to run software for an automated or at least partially automated data analysis of sensed signals from the cartridge. The further apparatus may also comprise a user input device (not shown) to allow a user to interact and control the apparatus. The user input device may allow a user to control a sensing process and/or to a data analysis and/or to select different results to be viewed). As a non- limiting example, in some embodiments, the apparatus may be operable to allow a user to select the number of channels to be used (for example, up to 60) via the user input device. The apparatus may further include a camera or other suitable imaging means to allow image capture of the cartridge in use. The apparatus may be operable to allow selection of different captured images, for example, during data acquisition. The selection may be made using the user input device. The apparatus may be further operable to allow the user to run tests on a subset of the available traps. For example, a user may determine that only a subset of the traps have a islet present and may therefore select to run tests only on those channels. The display may also be configured to display results. In this embodiment, the display displays the percentage of viable islets. In some embodiments, the apparatus may be operable so that a user can select the results to be displayed using the user input device. The user input device may be any suitable user input device, such as a mouse, keyboard. In some embodiments, the display forms part of the user input device. In some embodiments, at least part of the cartridge is disposable. For example, the microfluidic part may be disposable. In some embodiments, the removable cartridge includes only the microfluidic part of the device and the electronic module is provided separately (for example, as part of the apparatus or as a further component to be combined with the cartridge). Not shown in Figure 9 are the additional computing and/or storage resources that are provided inside the housing. For example, it will be understood that, in some embodiments, the apparatus has memory storage to store data and/or may be connected to a network to allow transfer of data from the apparatus to a further computing apparatus. In some embodiments, the apparatus may have a removable storage medium. An amplifier may also be provided for amplifier one or more signals sensed by the electrodes. The processing resource is configured to process signals from the electrodes or data derived from the signals. The processing of the signals and/or data may be to determine a percentage of viable objects, for example, tissue and/or cellular in a sample. Alternatively, or in addition, the processing of the data may be to determine at least one of electrical activity, viability, function and/or response to a stimulus may comprise generating data representing electrical activity, function and/or response to a stimulus and storing said data. In some embodiments, the processor is configured to determine a measure of electrical activity of a trapped object in response to a further fluid being introduced through the further fluidic path. The processor may be configured to determine a number of viable and/or functional tissue and/or multicellular objects in a sample or to perform a diagnostic and/or viability indication based on sensed electrical activity at the plurality of restrictions and/or sensing regions, for example, wherein the diagnostic and/or viability indication may be based on electrical activity in response to exposing said object to a further substance, optionally comprising a, chemical and/or a drug, for example, glucose. While the example of glucose is described, it will be understood that other types of further fluid can be used. In particular, a wash solution may be introduced for removing any solution from the device. Alternatively, molecules for labelling trapped objects may be introduced or one or more drugs and/or cell activity stimulators or inhibitors may be introduced. Figure 10 depicts results of electrical measurements from human islets. a, islets exposed to 3 mM then15 mM glucose; glucose stimulated insulin secretion (GSIS) measurement showing electrical response in upper trace with 15mM glucose and RMS (root mean squared) derivation of electrical noise in the lower trace with 15mM glucose. Note there is no insulin secretion with 3mM glucose and no corresponding bioelectrical activity b, GSIS stimulation from 5.5 to 15.5 mM glucose showing results and in c, results of RMS measurements to show sensitivity of GSIS response at 7.3 then 17.3 mM glucose (results significantly different between two glucose concentrations with P˂0.0001 level student’s paired T test, N=11). d, % viability of tested islets – here 3 batches of islets were examined in response to 3mM then 15mM glucose; the numbers of islets per batch that showed electrical activity in response to 15mM glucose were calculated and expressed as a percentage for three separate batches of islets (N of islets tested per batch =16, 13, and 16 respectively). Note the 3mM glucose solution acts as a control condition where insulin secretion or electrical activity of the islets is not expected. Figure 11(a) depicts the device including the microfluidic module described with reference to Figures 1 to 3 together with a sensing element module. Figure 11(c) depicts the device of Figure 2 together with trapped object, in this case, a spheroid. Figure 12 depicts a cross- section of the device along line X-X’ marked in Figure 11(a). It will be understood that the device of Figure 11 has the same features as described with reference to Figure 1, however, a number of reference numerals are omitted for clarity. Figure 11(a) depicts a first electrode 1102, a second electrode 1104 and a reference electrode 1106. It will be understood that the first electrode 1102 is aligned with a first trap 108a and the second electrode 1104 is aligned with a second trap 108b. In particular, the first electrode 1102 is aligned along the opening of the first restriction of the first trap 108a and the second electrode is aligned along the opening of the second restriction of the second trap 108b. The first electrode has a first elongate portion 1102a and an electrode end portion 1102b. It will understood, that at least part of the elongate portion corresponds to an electrode track or trace and that only part of the elongate portion 1102a is depicted in Figure 11(a). The elongate portion is parallel with the opening of the restriction, in particular, when viewed from above, the elongate portion appears to pass through the opening of the restriction. Thus if the restriction opening is centred on a restriction axis and the elongate portion is aligned with an electrode axis, the restriction and electrode axes are in a parallel arrangement. It will be understood that the second electrode is aligned with corresponding second restriction of the second trap, however, it will be understood that one or more of the electrodes may not be aligned with the restriction, for example, the 1st and 15th electrodes of Figure 7(b). In some embodiments, the elongate portion may be an electrode track and the end part may be referred to an electrode pad. In some embodiment, the elongate portion corresponds to an electrode trace and the electrode end is the electrode itself or at least comprise the sensing portion of the electrode. It will be understood, as described with reference to Figure 12, that the elongate portion is insulated by an insulation layer and the electrode end is in contact with the fluid and/or the trapped object itself, in use. The electrodes are arranged such that each electrode end portion is provided substantially in an area corresponding to the chamber of the trap. The ground electrode 1106 is provided substantially along the delivery portion of the further fluidic path and the plurality of fluidic paths. A distance is therefore provided between each electrode end and the reference electrode. Figure 11(b) depicts the device of Figure 11(a) with two trapped objects 1110a, 1110b in a trapped position. Figure 12 depicts a cross-sectional view of the electrode arrangement in the trap at cross sections X—X’ of Figure 11a. As can be observed in Figure 12, the device has a PDMS layer 1202, an insulation layer 1204 (in this embodiment, a silicon oxide insulation layer) and a glass substrate layer 1206. In the present embodiment, the insulation layer 1204 is between the PDMS layer and the glass substrate layer 1206. As described above, a number of channels are formed in the PDMS layer to form the microfluidic module. Figure 12 also depicts a chamber 1208 of a trap defined in the PDMS layer by said channels. The chamber has a height and a width. The channel forming the chamber has a height of 250 µm and a width of 450 µm. Figure 11b also depicts the position of the electrode relative to the traps and relative to trapped organoids 1110b. The electrodes are disposed on the glass substrate and part of the electrode is insulated by insulation layer. Figure 12 depicts, first electrode 1102 on glass substrate layer 1206, having an elongate portion 1102a and an electrode end 1102b, as described with reference to Figure 11(a). The electrode is aligned beneath the chamber such that the electrode end is provided in a central portion. In the present embodiment, the non-insulated portion of the electrode, the electrode ends, are exposed to the channel above. In use, in the present embodiment, the non-insulated portion of the electrode is in contact with a trapped object in the trap. In some embodiment, the non-insulated portion of the electrode is adjacent to the trapped object and in contact with the fluid containing the trapped object. It will be understood that the microchannel module, for example, the module described with reference to Figure 1 is formed in a PDMS layer. Figure 13 depicts a module in accordance with an embodiment. In addition to the features described with reference to Figure 1, the module of Figure 13 also has an entry port 1308, a first output port 1302 and a second output port 1304. The entry port is an inlet provided at the fluidic input, as described with reference to Figure 1. The first output port is an outlet provided at the shared output, as described with reference to Figure 1, and may be referred to a waste output. The second output port is an outlet provided at the first output, as described with reference to Figure 1, and may be referred as a flush output. Each of the inlet and outlet ports is circular, in the present embodiment. The channels and ports of Figure 13 are formed in a PDMS layer 1310 having a width and length of 3 cm and a height of 0.5cm. Figures 14(a) and 14(b) depict an electrode array and an associated microfluidic module, in accordance with a further embodiment. The device of Figure 14 has the addition of a stimulating electrode, which when in circuit with the ground electrode, is operable to provide a pulse of electrical stimulation across trapped objects. As can be seen from Figure 14(a), the electrode array is substantially as described with reference to Figure 7 with the following differences. As described with reference to Figure 7, a plurality of electrodes 1702 are provided such that their respective end points are in a linear arrangement. The end points may form part of their sensing elements. In this embodiment, the central electrode of the plurality of electrodes (labelled 1404) is a reference electrode. The reference electrode is a ground electrode. In this embodiment, the single electrode 1406 spans the width of the plurality of electrode and is a stimulating electrode. As can be seen in Figure 14, the central electrode 1404 is larger in width compared to the other electrodes of the plurality of electrodes. In the embodiment of Figure 14, the reference electrode and stimulating electrode form a stimulating electrode pair and the sensing electrodes are configured to sense a response from a stimulating signal produced by the stimulating electrode pair. As described with reference to the embodiments above, the electrode array is aligned with a microfluidic apparatus 1408 that is substantially as described with reference to, for example, Figure 1, but with the following difference. Similar to the microfluidic devices described above, the second channel of the microfluidic device of Figure 14 has a first portion 1416a and a second portion 1416b. In this embodiment, while the second channel 106 remains coupled to the first channel along the first portion 1416a via the plurality of restrictions, the second portion 1416b is provided centrally in the first portion. The by-pass portion and delivery portion remain in the same configuration. The central, reference electrode is aligned to have its length parallel to the centrally provided second portion 1416b of the microfluidic device. In this embodiment, a plurality of fluidic paths is defined between the input (1422) and the output (1424) via the restrictions, where the fluidic paths comprise part of the first portion 1416a and second portion 1416b. The restrictions are aligned along an axis and the stimulating electrode is arranged parallel to that axis. The stimulating electrode overlaps with the plurality of fluidic paths. The electrode configuration is operable to sense a signal for each electrode with reference to the reference electrode. In contrast to embodiment described above, in which each electrode is aligned at or adjacent to a respective restriction to allow a signal for a trapped object to be sensed passively, the embodiment of Figure 14, specifically the single electrode 1406 is configured to produce a stimulating electrical signal. As such, the single electrode 1406 may be referred to stimulating electrode. The plurality of electrodes 1402 may in turn be referred to as sensing or recording electrodes. The electrical stimulation may directly evoke a simultaneous action potential discharge in the objects which may be measured and processed by the recording electrodes. As an example, direct stimulation may be used in the ‘pacing’ of cardiospheroids and other excitable tissues. By aligning the electrode array with the restrictions of the microfluidic apparatus, the restriction enables a high current density to be provided to the objects. Figure 14(b) depicts a close up view of the array and microfluidic device of Figure 14(a). It can be seen that the electrodes are arranged to form a distance between the stimulating electrode 1402 and each of the plurality of sensing electrodes at each chamber/sensing region/restriction. In this embodiment, a distance 1410 is depicted between the end point of a sensing electrode (for example, 1402i) and the closest portion of the stimulating electrode 1406. Due to the arrangement of electrodes, this distance is the same for each stimulating electrode. In use, for each chamber, the stimulating electrode stimulates electrical activity across this distance, in the chamber, and the corresponding sensing electrode senses an electrical response across this distance, due to contents of the chamber. The electrical response may be a measured voltage. The central reference electrode measures a reference voltage that can be used as reference for each measurement. In this embodiment, a single stimulating electrode arranged perpendicular to the plurality of sensing elements is described. In other embodiments, different electrode arrangements may be used. For example, more than one stimulating electrode may be provided and/or stimulating electrode and sensing electrode pairs may be provided. A non-limiting method of using the device of Figure 14 is described as follows. Firstly, one or more objects are trapped as described above. A trapped objects in each chamber may rest on a passive electrode (or in a sensing region of the chamber about the passive region). The passive electrode is configured to detect electrical activity in the sensing region, for example, after a time delay. An electrical stimulation is delivered to the chambers, in this embodiment, via the stimulating electrode pair which causes a response in the object. The response is measured by the passive electrode. It will be understood that the addition of the pair of stimulating electrodes (in this embodiment, the reference electrode and stimulating electrode) the device can be used for testing a number of excitable cells/objects and experimental scenarios, for example, drug testing and screening. The following non-limiting examples and experimental results are described: I. Qualitative islet responses Visual assessments were used to identify response and no response to glucose challenge from each protocol used across the three islet batches tested. Differences in glucose-induced electrical bursting activity and inactivity periods between protocols (3-to-15, 5.5-to-15.5, and 7.3-to-17.3 mM) were also visually assessed. We identified either an electrical response or no response by the islets to increased glucose concentration for all protocols (3-to-15, 5.5-to- 15.5, and 7.3-to-17.3 mM) used across the three batches. In electrophysiology experiments of the 3-to-15 mM protocol, islets were initially inactive, and later responded to glucose addition (10a) or displayed a baseline response to 5.5 mM glucose and an enhanced response to 15 mM glucose (10b). In continuous islet electrical activity seen when treated with tolbutamide and afterwards no response was observed from any glucose increase protocol. Gaps in recordings – at different times – reflects artefact of glucose addition ‘blanked’ from different recording lengths. II. Islet responses Islets were first analysed for electrical activity before being assessed for increases in electrical activity after glucose addition. The RMS output (as described above) was used to quantify electrical responses (μV) by assessing a two- (for ten minute recordings), three (for twenty minute recordings) or five- (for thirty minute recordings) minute sample before and after the addition glucose for all islet batches (1, 2, and 3). Only data from islets confirmed to be present on electrodes were included in the dataset. III. Background electrical activity Before quantifying islet electrical responses, they were first characterised as electrically active or inactive. Presence of electrical activity was taken as an islet being active. The presence of MEA channels with no activity provided a comparison between activity and no activity on the recordings. An intermediate category of dying but active – indicated by continuous activity uncoupled to glucose (non -glucose responders) was not observed. Islets (n = 16) tested in batch 1 using the 7.3-to-17.3 mM glucose protocol all displayed electrical activity (100%). In batch 2, of the islets tested in the 7.3-to-17.3 mM (n = 8) and the 3-to-15 mM (n = 16) glucose protocols, all were electrically active (100%). All islets tested using the 5.5-to-15.5 mM protocol from batch 3 (n = 24) displayed electrical activity (100%). These results indicate that even in low or control glucose some electrical activity can be detected in islets. IV. Glucose induced electrical activity Having validated the ability of the RMS function to reflect changes in electrical activity associated with increased glucose concentration, it was used to determine if electrically active islets were responsive to glucose, and if they were viable, or nonresponsive. Of the islets (n= 16) tested in the 7.3-to-17.3 mM protocol of batch 1, nine displayed an increase in RMS. In batch 2, islets tested using the 7.3-to-17.3 mM protocol (n = 8) and the 3-to-15 mM protocol (n = 16), two and eleven had displayed an increased RMS value after glucose challenge, respectively. In batch 3, sixteen of the twenty-four islets tested had increased RMS values using the 5.5-to-15.5 mM protocol. This gave protocol totals of islets with increased RMS values of 68.75%, 45.83%, and 66.66% for the 3-to-15, 7.3-to- 17.3, and 5.5-to-15.5 mM protocols, respectively (Figure 7d). There was one islet tested using the 3-to-15 mM protocol from batch 2 that displayed a marginal, 3% increase in RMS value and was not categorised as responsive to glucose. Those categorised as unresponsive to glucose displayed an unchanged or decreased RMS value when the glucose concentration was increased. It was then determined if the increases in RMS values when islets were challenged with increased glucose concentration were statistically significant. Only the RMS values of islets that displayed an increase were included. When present in the culture media, the mean RMS value of islets (n = 11) tested using the 7.3-to-17.3 mM protocol displayed a significant (Paired t- test, t = 4.625, df = 10, p = 0.0009) increase between the 7.3 mM and 17.3 mM glucose concentrations. The mean (±SEM) RMS of islets in the 7.3 mM glucose concentration was 3.95 ± 0.72 μV, which had increased significantly to 10.13 ± 1.82 μV when the concentration of glucose was increased to 17.3 mM. The RMS values of electrical responses ranged across 8.87 and 21.9 μV for 7.3 and 17.3 mM glucose, respectively. Thus, the majority of islets tested responded with measurable electrical responses to glucose increases and this was detectable by measuring RMS noise. V. Islet batch viability The percentage viability for each batch was calculated by identifying islets that met the criteria of being electrically active and displaying increases in their RMS values after glucose- challenge with either a 3-to-15, 5.5-to- 15.5, and 7.3-to-17.3 mM glucose protocol. As the increases in RMS values of islets responding to glucose in a 7.3-to-17.3, 3-to-15, and 5.5-to- 15.5 mM protocol were significant, the islets were characterised as being viable. This resulted in a batch viability being calculated at 56.25% (nine of sixteen islets tested) for batch 154.16% (thirteen of twenty-four islets tested) for batch 2 and 66.66% for batch 3 (sixteen of twenty- four islets tested). There were differences in the percentage of viable depending on the day they were tested. In batch 1, fifteen islets were tested after three days of incubation, with nine (60%) viable (displaying an increase in RMS). The one islet tested after four days of incubation was not viable (displaying a decrease in RMS). In batch 2, fifteen islets were tested after one day in incubation, with four viable (26.66%). The six islets tested after two days incubation were all viable (100%). An additional three islets were tested after six days incubation, with three viable (100%). From batch 3, five islets were tested after one day in incubation, with three viable (60%). This increased to 80% viability (four of five islets) after an additional two days incubation. After five days incubation, this decreased to 61.5% (eight of thirteen islets). Thus the rapid measurement of electrical activity using the combined chip discriminates between islet batches and islet viability. The present disclosure demonstrate that islet electrical activity varies from batch to batch per islet isolate and that impairing islet function with prolonged anoxia results in a lack of responsiveness to glucose challenge i.e. reflecting non-viable islets. These two observations indicate that electrical activity in response to glucose challenge is a good proxy for determining rapidly the health and functionality of an islet batch. This novel device successfully traps islets in a way that facilitates multichannel recording and interrogating multiple islets simultaneously. It is envisaged that it will form the core technology for a new benchtop device to determine islet quality before transplantation. Such a device could be used in each islet transplant laboratory worldwide. This would also offer standardisation of islet assessment and enable comparisons from different laboratories to be made. As well as a means to improve isolation and handling techniques leading eventually to efficient techniques to sort functional from non- functional islets. With the development also of human embryonic stem cell derived islets with early phase 1 clinical trials in man there is also an objective need to assess viability of such stem cells and there may well be scope for the use of such an instrument in this field as well. Furthermore, such a device may be used for clusters of cells from other tissue origins to test viability. The following comments on details of materials and methods of manufacture in accordance with embodiments are provided. Methods of fabrication and use I. Design of Microelectrode arrays (MEAs) The designs of the custom MEAs were carried out using AutoCAD (Autodesk, Inc, California, USA). Several different electrode configurations were found to be suitable (e.g. Figure 6A). The design in Figure 6A features a total of 11 recording electrodes and a unified ground reference electrode (detail on Figure 6b). The recording electrodes were 30 μm in diameter and the distance between the recording electrodes and the ground electrode was 50 μm. AutoCAD designs were sent to Micro Lithography Services Limited (Chelmsford, UK) to be made into film or glass photomasks. II. Fabrication of Microelectrode Arrays (MEAs). The MEAs were fabricated at the Heriot-Watt University nanofabrication facility. Borosilicate was used as a substrate (‘h’ in Figure 6). The borosilicate was cut to measure 49 x 49 mm using a DAD3220 Wafer Dicing Saw (DISCO Corporation, Tokyo, Japan). The electrode designs and the insulating patterns were transferred onto the borosilicate using photolithography. Electrodes and electrode tracks were Ti (‘g’ in Figure 6) depositions while the insulation of the tracks excluding the electrode tips and pads were SiO2 deposition (‘f’ in Figure 6). III. Spin Coating of photoresist Prior to deposition the borosilicate substrate was washed using acetone and diluted Decon 90 (Decon Laboratories Ltd, East Sussex, UK). It was then rinsed with de-ionised (DI) water and blow dried using a filtered air gun. This was done in order to make sure the borosilicate surface was dust free and completely clean before starting the process. The borosilicate blank was then placed onto the spin coater SPIN 150 (SPS Europe, Putten, Netherlands) and was held in place by a vacuum seal. Negative photoresist, AZ nLOF 2070 (MicroChemicals, Ulm, Germany) was carefully placed over the whole surface of the borosilicate taking care to avoid air bubbles. It was then spun at 3500 rpm for 40 seconds. The negative photoresist which normally would form a 7 thick μm layer, was previously diluted to form a 1 μm layer once spun. After this process, the substrate was hard baked at 95°C for 3 minutes. IV. Alignment and UV Exposure The next step involved aligning one of the multielectrode design film photomask with the prepared substrate. This was done using an MJB3 Mask Aligner (S.SS MicroTec, Garching, Germany). The film photomask was placed onto the mask holder and was then loaded and secured onto the aligner. The substrate was positioned on the substrate holder that held it in placing using vacuum suction and was then slid under the photomask. The substrate was brought into contact with the film photomask and then the separation lever manipulated in order to be able to align the design with the substrate. The alignment was done by adjusting the x and y axis in micrometres. Once the alignment was achieved, the separation lever was pushed back so that the substrate was back into contact with the film photomask. The substrate was then UV exposed for 40 seconds and once done, the substrate was carefully removed from the mask aligner. A post exposure bake was then carried out at 115°C for 90 seconds. V. Development The substrate was then developed using AZ 726 MIF (metal ion free) developer (Microchemicals). It was initially placed in the developer for 60 seconds and was closely monitored for another 15 to 30 seconds until the design features became visible. The substrate was washed in diluted Decon 90 for about 30 seconds, then rinsed with deionised double distilled water and blow dried with a filtered air gun. VI. Electrode Deposition Once substrate was deposited Ti was deposited by a technique called physical vapour deposition (PVD) using a Minilab 080 (Moorfield Nanotechnology, Knutsford, UK)). This involved directing an electron beam onto the metal that then evaporates and deposits onto the substrate. The borosilicate substrate was placed into an external chamber with the side to be coated facing downwards. The external chamber had to be degassed, in order to reach the same vacuum levels as the main chamber containing the Ti filled crucible, before sliding the substrate into the main chamber. During this manoeuvre, the parameters required were inputted into the SQM-160 rate/thickness film deposition monitor (Inficon, Bad Ragaz, Switzerland). These included the thickness of the metal layer to be deposited, the density and the ZRatio of the metal to be deposited. The thickness was set to 10 k. (1000 nm), the density of Ti at 4.500 and the Z-Ratio of Ti at 0.628. Once the substrate was secured and the main chamber door locked, the electron beam was directed onto the Ti using the controller knobs. The power was slowly increased up to 100 mA before opening the shutter to allow for the Ti to evaporate onto the borosilicate substrate. The rate was monitored and was kept between 2 to 3/s. The shutter automatically closed, and the electron beam turned off when the Ti layer reached 1000 nm. The substrate was then carefully removed from the main chamber into the external chamber, which was then pressurized to room temperature before opening to collect the substrate. The electrode deposition formed a layer of Ti across the whole surface of the borosilicate. Therefore, the next step involved removing the excess Ti to leave behind only the array design. This was carried out by dissolving the negative photoresist previously applied using TechniStrip NI555 at 80°C (MicroChemicals) until all the unwanted layer of Ti was removed. Dissolving the negative resist meant that the Ti layer that was deposited on top of it was also removed leaving behind just the Ti array design. VII. 2nd Spin Coating The next step was to prepare the surface for the deposition of the silicon dioxide (SiO2) insulating layer. The photolithography process was similar to that was described in the above section. However, this time the insulating design photomask was used instead and an AZ 1505 positive photoresist (MicroChemicals) was used. The settings for the spin coater were 2000 rpm for 30 seconds. Also, the substrate was developed in an AZ 351B Developer MIC (metal ion containing-MicroChemicals) which was used in a 1:4 dilution (1 part developer and 4 parts DI water). The substrate was then washed as previously and taken for SiO2 deposition. VIII. Insulator Deposition The SiO2 was deposited using the same process as the Ti, however the density and ZRatio parameters were changed to 2.648 and 1.000 respectively. The thickness of SiO2 was 500 nm. Following the deposition, the next step was to remove the SiO2 from the electrodes and contact pads as those were the areas that needed to be exposed. In this case, the positive photoresist was removed using acetone which only left behind SiO2 on the tracks connecting the electrodes to the contact pads. IX. Alternative Laser Lithography After testing these custom MEAs it was found that the tracks were not always fully insulated, or the electrodes not exposed. These issues were resolved by using a DWL 66+ (Heidelberg Instruments Mikrotechnik, Heidelberg, Germany) 2.5D) laser lithography system. This machine is able to laser etch structures down to 300 nm and able to do direct photoresist patterning. Therefore, it meant that the step of aligning the film photomask and exposing with UV was no longer necessary. The array designs were adjusted in KLayout (Matthias K.fferlein, Germany) in order to be read by the laser writer software. The borosilicate substrate, that was previously spin coated with a layer of negative photoresist, was placed onto the stage and then the rest was done through the software package provided by Heidelberg Instruments. The write-head automatically aligned itself with the substrate before it began etching the array design onto the photoresist. Once this was done, the same steps previously described for the Ti deposition were carried out, however this time the Ti thickness was set to 150 nm. The insulating design was also laser etched instead of using a film photomask. This meant that the electrodes and contact pads were precisely cut out and therefore exposed following the deposition (100 nm) and removal of SiO2. Design and Fabrication of Microfluidic Microchannels I. Microchannel Fabrication using Soft Lithography The microchannels were designed using Adobe Illustrator (Autodesk) and were then sent to Micro Lithography Services to be produced into a film photomask. The features of the design are shown in Figures 1,2,3,4 & 5. A soft lithography protocol (MicroChem, 2015) to prepare PDMS devices was similar to the photolithography protocol used when fabricating custom MEAs, however, had different parameters. A test grade silicon wafer (SILI-0005, PI-KEM Limited) with a diameter of 7.62 cm and thickness 380 μm +/- 50 μm) was used instead of a borosilicate substrate. II. Spin Coating and UV Exposure The silicon wafer was placed onto the spin coater (WS-650MZ-32NPP, Laurell Technologies Corporation) and held in place by a vacuum. The negative photoresist SU-82025 (Microchem) was spun onto the wafer in two stages. In the first stage the spin was 500 rpm for 10 seconds with an acceleration of 100 rpm/s and in the second stage at 3000 rpm for 39 seconds with an acceleration of 300 rpm/s. These settings gave a film thickness of 100 μm. The process was repeated a further three times to obtain a thickness of around 250-300 μm. The wafer was soft baked at 65°C for a 1 minute, then at 95°C for 5 minutes and back down to 65°C for another minute. Film photomasks with the designs were then carefully placed on top of the wafer making sure to not move them once in contact with it. The wafer was then exposed to UV for 41 seconds before carrying a post- exposure bake at the same temperatures and times as the soft bake. The clear parts of the photomask (the two compartments and microchannels) became cross-linked and the dark parts of the photomask did not. III. Development The wafer was submerged in SU-8 developer and sonicated for 60 seconds. It was then washed with isopropanol and blow dried with an air gun. The wafer was placed back into the developer for a further 60 seconds but not sonicated. The same washing steps were done until the wafer was clean. If any streaks were still visible, the wafer was placed back into the developer for a further 60 seconds and repeated the process until they were no longer present. Finally, the wafer can be used as a mould to produce the microchannels for as long as it can be kept intact. The surface of the wafer is hydrophilic which meant that it would be difficult to peel off the PDMS from it without leaving any residues or breaking the wafer. A drop of trichloro (1H,1H,2H,2H-perfluorooctyl) silane (448931, Sigma-Aldrich, Missouri, USA) was added onto the wafer and left to evaporate at room temperature in a fume hood, making sure to close the top of the petri dish. The purpose of this was to make the surface hydrophobic and therefore avoid the issues mentioned earlier. The wafer was kept in a glass petri dish to which it was glued with araldite. IV. PDMS Preparation PDMS was prepared by mixing Sylgard 184 silicone elastomer base with the curing agent at a 10:1 ratio. PDMS was then poured over the wafer and before curing, air bubbles were removed by placing it in a vacuum chamber. The PDMS was cured in an hour at 60°C. Once cured, PDMS modules (microchannels) were carefully cut out using a scalpel trying to avoid damaging any of the features on the wafer. Access holes were then cut out using a 1 and 6 mm biopsy punches on either side to form wells. This was also carefully done in order to avoid damaging the microchannels. PDMS /electrode array device Bonding The PDMS modules fabricated were then bonded onto custom MEAs. This was achieved by placing the PDMS modules and the electrode surfaces they would bond into a Zepto plasma system (Diener Electronic, Ebhausen, Germany). Surfaces were exposed to 20% O2 plasma for five minutes under vacuum. The PDMS microchannels were carefully aligned with the ground and recording electrodes before bonding onto the MEAs. This was done by hand with the aid of an inverted microscope. (Figure 6D). The following non-limiting comments regarding use of and validation of the devices are provided: I. Islets Islets were isolated from donated pancreases using enzymatic and mechanical methods the final step of which was a purification of isolated islets from exocrine tissues (Matsumoto et al., 2007). II. Electrophysiology solutions Culture media, with 7.3 mM glucose, was used as the starting condition for electrophysiology experiments. Culture media supplemented with an additional 10 mM of glucose (for a total of 17.3 mM) was used as a high-glucose solution. Solutions were also optimised to provide ‘cleaner’ electrophysiology recordings by using an islet solution (Kindmark et al., 1994) containing: NaCl 138 mM, KCl 5.6 mM, MgCl2 1.2 mM, CaCl2, HEPES 5 mM, pH 7.4. Islet solution was supplemented with 3 mM and 15 mM glucose for low (control) and high glucose conditions, respectively. III. Electrophysiology settings Field -potential recordings were acquired with the Axon CNS Digidata 1440A digitiser (Molecular Devices, California, USA), a 16-channel microelectrode amplifier, model 3600 (A- M Systems, Inc., Washington, USA), and Clampex 10.7 software (Molecular Devices, California, USA). Initially, a twenty-minute protocol was used to record islet electrical activity. This protocol was extended to thirty minutes. Electrical activity signals were pre-amplified using x10 headstage (Omnetics, Minnesota, USA). Recording settings for high and low-pass filters were 3 Hz and 5 kHz, respectively. The gain was set at x2000, GND setting selected, and notch filter on to reject line-related noise at 50/60 Hz. IV. Electrophysiology protocols Islets were used for experiments between one and six days of incubation in culture media. A 200 μl sample from a 5 mL aliquot was transferred to the inlet channel of the microfluidic channel and examined for islet positioning relative to the electrodes in the microfluidic channel. The 7.3 mM culture media was used for initial loading. This prevented islet attachment to the walls of the microfluidic channels. For 3-to-15 mM glucose experiments, after adding to the MEA device, the remainder of the culture media was withdrawn and replaced with 200 μl of 3 mM glucose islet solution. Once positioning had been confirmed (via an inverted light microscope), the islets were incubated in solution at room temp for ten minutes prior to recording. The MEA/microfluidic device was connected and placed under the inverted microscope, with recordings running for five and ten minutes prior to addition of 17.3 mM glucose culture media and 15 mM glucose islet solution, respectively. Additions were made by withdrawing remaining starting solution from the inlet pipette tip (via micropipette) and adding increased glucose solution via a syringe. Positioning was reconfirmed on the inverted microscope and recordings were continued for fifteen or twenty minutes. Islets from batch 3 were assessed using a 5.5- to-15.5 mM culture media protocol, with recordings running for five minutes before and after glucose addition. A total of seven recordings were taken from batch 1, eleven for batch 2, and nineteen from batch 3. Of these recordings, eleven were taken using a 7.3-to-17.3 mM glucose protocol, eight using the 3-to-15 mM protocol, fourteen using a 5.5-to-15.5 mM protocol, and five treated with tolbutamide (50 μM). The 3, 5.5 and 7.3 mM glucose concentrations and tolbutamide were used as a controls. The 15, 15.5, and 17.3 mM glucose were treated as elevated concentrations. After each experiment, the MEA/microfluidic device was washed with deionised water before commencing replicate experiments. All experiments were conducted at room temperature (20 °C). V. Signal Amplification A model 3600 amplifier was purchased from A-M Systems (Washington, USA) at a fraction of the cost of commercial array amplifiers. It had a 16-channel capability and eleven gain settings ranging from x2 to x20000, eight low-pass filters ranging from 100 Hz to 20 kHz, eight high- pass filters ranging from 0.3 Hz to 500 Hz and a notch filter (50 or 60 Hz) per channel. Signals were pre-amplified by a x10 headstage (Omnetics, Minnesota, USA) which was located next to the array and then passed data to the Model 3600 amplifier. A device to flexibly hold and interface the MEAs to the pre-amplifier headstage was fabricated in the electronics workshop. It consisted of a holding plate and a top plate which contained spring pins (PD8JS-2.2, Coda- Systems, Essex, UK) that had a tip diameter of 1 mm and a working travel of 0.45 mm which were used to interface with the electrode contact pads of the MEAs. In total three recording devices (RD1, RD2 and RD3) were fabricated with the help of the electronics workshop each at different arrangements of spring pins and device to amplifier connections in order to enable recording from all 59 electrodes of commercial MEAs and allow recording and stimulation when using custom MEAs. The pins were connected to the pre-amplifier headstage through a nano strip connector (NPD-18-WD-18.0-C-GS, Omnetics). Each cable was soldered to one pin with the exception of the ground and x10 Ref cables that were both soldered onto the single ground pin. VI. Signal Digitisation Analogue signals from the amplifier were digitised through a digital data acquisition system (PCle-6343, National Instruments, Texas, USA). The digital signal was viewed in real-time in Clampex (Molecular Devices, California, USA). All 16 channels could be viewed simultaneously in Clampex. VII. RMS quantification method The sensitivity of the root mean squared variance of the signal (RMS) to detect changes in electrical responses was validated by calculating the RMS of three separate recordings of islets in 7.3-to-17.3, 3-to-15 and 5.5-to-15.5 mM glucose protocols from batches 1, 2, and 3, respectively. The RMS was calculated at one-minute increments across the recordings and graphed with the recording to determine if changes in RMS are synchronous with changes in electrical activity. RMS measurements were obtained using the power spectrum function of Clampfit (version 10.7), with the window set to no signal alteration (rectangular), output at average spectral segments, length at maximum, spectral resolution (spectral bin width) of 0.038147 Hz and RMS measurement and plot set to exclude the first spectral bin (default setting). All RMS measurements of electrical responses were in microvolts (μV) (Figure 7). In accordance with an embodiment, the combination of microfluidic channel design and trap or restriction is incorporated with a printed microelectrode array and input and output chambers. The channel contains a microfluidic bypass that allows flow through of solution once the islet has become engaged in the trap. This flow through system allows the rapid exchange of the normal storage solution (5.5 mM glucose) with a solution containing high (15.5 mM glucose). The change in glucose concentration induces a measurable electrical change in the islets that is detected by the reader. This activity pattern is only seen in fully functional islets. Multiple channels (1,8 and 16 in our current devices but potentially up to 64 in a future development) enable the percentage of functional islets in a sample to be rapidly determined. The device may allow rapid, accurate and label free assessment of islet health. It will be deployed to objectively assess islet viability and enable the use of pancreases with marginal numbers of isolated islets to be utilised in surgery despite more prolonged ischaemic times. This will enable the utilisation of more material for clinical transplantation and more patients to receive a life-saving transplant leading to decreased waiting list numbers and times. In addition, as improved methods of islet maintenance, sorting and quality control are urgently needed, such device/s will also inform greater efficiency at all levels. In accordance with embodiments, islet transplantation is carried out in recipients with Type 1 diabetes using islets isolated from donated pancreases, and the area of stem cell derived human islets is a focus of intense research. It is a life-saving treatment, stabilising blood glucose control and even leading to insulin independence. However, transplant outcomes may be highly associated with islet numbers and their viability. The process of transplantation is a multi-step procedure involving pancreas procurement, tissue dissociation, islet purification, cell culture and islet transplantation via the hepatic portal vein and into the liver of the recipient. At each step, islets are lost (mainly due to ischemia). Less than 50% of islets from a single pancreas are isolated (~500,000 islets) and of these it is estimated that <50% engraft into the liver, with recipients requiring islets from two to three donor pancreases. There is no rapid methodology to establish the quality of islets in a sample prior to transplantation. The device provides the core technology to achieve a rapid estimate (%) of functional islets in a sample. It will meet the need by measuring the electrical activity of islets as a proxy for islet health. The design of the microfluidic delivery system and the electrical interface (electrode array) together may provide a ‘hands free’ module to measure islet electrical function. Uniquely, the islet samples are pipetted into 200 uL holders, the islet enters the system, and is trapped over the electrode by capillary and gravity driven flow. The unique design of the channel means that a further 200 uL of solution containing raised glucose can be pipetted into the delivery system to generate an electrical response in the live islets. The unique combination of flow by-pass system coupled with the electrode in the microfluidic module means that after measurements have been made, the sample can be flushed and the measurements repeated with another sample. The above description of specific embodiments is made by way of example only. A skilled person will appreciate that variations of the described embodiments may be made without departing from the scope of the invention. REFERENCES 1. Alassaf, A.; Ishahak, M.; Bowles, A.; Agarwal, A. (2020) Microelectrode Array based Functional Testing of Pancreatic Islet Cells. Micromachines 2020, 11, 507. https://doi.org/10.3390/mi11050507 2. Barnett MJ, McGhee-Wilson D, Shapiro AMJ & Lakey JRT (2004). Variation in human islet viability based on different membrane integrity stains. Object Transplant 13, 481– 488. 3. Benomar K, Chetboun M, Espiard S, Jannin A, Le Mapihan K, Gmyr V, Caiazzo R, Torres F, Raverdy V, Bonner C, D’Herbomez M, Pigny P, Noel C, Kerr-Conte J, Pattou F & Vantyghem MC (2018). Purity of islet preparations and 5-year metabolic outcome of allogenic islet transplantation. Am J Transplant 18, 945–951. 4. Boyd V, Cholewa O & Papas K (2008). Limitations in the Use of Fluorescein Diacetate/Propidium Iodide (FDA/PI) and Object Permeable Nucleic Acid Stains for Viability Measurements of Isolated Islets of Langerhans. Curr Trends Biotechnol Pharm 2, 66–84. 5. Brooks AM et al. (2013). Attainment of metabolic goals in the integrated UK islet transplant program with locally isolated and transported preparations. Am J Transplant 13, 3236–3243. 6. Bunnett J & Counter C (2019). Isolation Statistics. NHS BLOOD Transpl ORGAN DONATION Transplant Dir PANCREAS Advis Gr 1–7. Available at: moz- extension://92fcdea0-1508-254e-b5f0-5bbad9269de7/enhanced- reader.html?openApp&pdf=https%3A%2F%2Fnhsbtdbe.blob.core.windows.net%2Fum braco-assets-corp%2F17532%2Fisolation-statistics.pdf [Accessed May 24, 2022]. 7. CITR Coordinating Centre (2015). Scientific Summary of the Collaborative Islet Transplant Registry (CITR) 2015 (Tenth) Annual Report BACKGROUND AND PURPOSE. CITR Coordinating Center The Emmes Corporation, Rockville, MD. Available at: https://citregistry.org/system/files/10AR_Scientific_Summary.pdf[Accessed May 24, 2022]. Cornateanu SM, O’Neill S, Dholakia S, Counter CJ, Sherif AE, Casey JJ, Friend P & Oniscu GC (2021). Pancreas utilization rates in the UK – an 11-year analysis. Transpl Int 34, 1306–1318. Düfer M (2012). Determination of Beta-Object Function: Ion Channel Function in Beta Objects. In Animal Models in Diabetes Research, pp.203–217. Humana Press. Available at:
Figure imgf000052_0001
[Accessed May 23, 2022]. Forbes S, McGowan NWA, Duncan K, Anderson D, Barclay J, Mitchell D, Docherty K, Turner D, Campbell JDM & Casey JJ (2015). Islet transplantation from a nationally funded UK centre reaches socially deprived groups and improves metabolic outcomes. Diabetologia 58, 1300–1308. JDRF Editors (2022). Facts and figures about type 1 diabetes - JDRF, the type 1 diabetes charity. JDRF. Available at: https://jdrf.org.uk/information-support/about-type- 1-diabetes/facts-and-figures/ [Accessed May 23, 2022]. Kindmark H, Köhler M, Arkhammar P, Efendic S, Larsson O, Linder S, Nilsson T & Berggren PO (1994). Oscillations in cytoplasmic free calcium concentration in human pancreatic islets from subjects with normal and impaired glucose tolerance. Diabetologia 37, 1121–1131. Matsumoto S, Noguchi H, Naziruddin B, Onaca N, Jackson A, Hatanaka N, Okitsu T, Kobayashi N, Klintmalm G & Levy M (2007). Improvement of Pancreatic Islet Object Isolation for Transplantation. Baylor Univ Med Cent Proc 20, 357–362. Pfeiffer T, Kraushaar U, Düfer M, Schönecker S, Haspel D, Günther E, Drews G & Krippeit-Drews P (2011). Rapid functional evaluation of beta-objects by extraobjectular recording of membrane potential oscillations with microelectrode arrays. Pflugers Arch Eur J Physiol 462, 835–840. Schönecker S, Kraushaar U, Düfer M, Sahr A, Härdtner C, Guenther E, Walther R, Lendeckel U, Barthlen W, Krippeit-Drews P & Drews G (2014). Long-term culture and functionality of pancreatic islets monitored using microelectrode arrays. Integr Biol (United Kingdom) 6, 540–544. Schönecker S, Kraushaar U, Guenther E, Gerst F, Ullrich S, Häring HU, Königsrainer A, Barthlen W, Drews G & Krippeit-Drews P (2015). Human islets exhibit electrical activity on microelectrode arrays (MEA). Exp Clin Endocrinol Diabetes 123, 296–298.

Claims

CLAIMS 1. A microfluidic device comprising: a microfluidic module comprising: a plurality of fluidic paths between an input and an output; and a plurality of restrictions, wherein each restriction is provided on a respective fluidic path of the plurality of fluidic paths, wherein each restriction is configured to trap or at least restrict movement of one or more objects, for example, one or more tissue and/or multicellular objects, in a fluid introduced along its respective fluidic path at a respective sensing region; and at least one further fluidic path between the input and a further output, wherein the at least one further fluidic path is in fluid communication with the plurality of restrictions and wherein the further fluidic path comprises a delivery portion between the input and the plurality of restrictions to allow delivery of a further fluid to the trapped and/or restricted one or more objects and an output portion to allow removal of the further fluid from the further output; wherein the device further comprises: an electronic sensing module comprising: at least one sensing element arranged to sense one or more signals from the respective sensing regions of the plurality of restrictions.
2. The device of claim 1, wherein the objects comprise at least one of: an organoid; a spheroid; a tissue spheroid; a pancreatic Islet; a cell or tissue object.
3. The device of any preceding claim, wherein the objects comprise tissue spheroids, optionally, islets derived from the pancreas.
4. The device of any preceding claim wherein the further fluidic path at least partially overlaps with the plurality of fluidic paths at the delivery portion and wherein the output portion is spatially separate from the plurality of fluidic paths.
5. The device of any preceding claim, wherein the output portion of the further fluidic path is downstream from the delivery portion and the plurality of restrictions.
6. The device of any preceding claim, wherein the further fluidic path provides a path for flushing and/or removal of at least fluid from the device via the further output.
7. The device as claimed in any preceding claim, comprising a plurality of channels comprising: a first channel between the input and the further output defining the further fluidic path between the input and the further output; a second channel coupled to the plurality of restrictions and the output, wherein the second channel is coupled to the first channel via the plurality of restrictions so that at least part of the first channel and at least part of the second channel define the plurality of fluidic paths between the input and the output.
8. The device as claimed in any preceding claim, wherein the first and second channels are sized to permit fluid flow of the objects and wherein the restrictions comprise an opening between the first channel to the second channel that is sized to prevent the object from passing through.
9. The device of any preceding claim, wherein the plurality of restrictions comprises five or more, optionally at least ten, optionally, at least 15, optionally at least 60, optionally, at least 100 restrictions.
10. The device of any preceding claim, wherein the plurality of restrictions are arranged at an overlapping portion of the plurality of fluidic paths and the further fluidic path to allow sequential delivery of objects to the restrictions, such that, when a restriction is occluded by an object, a further object in the fluid proceeds to the subsequent restriction and/or towards the further output.
11. The device as claimed in any preceding claim, wherein said at least one sensing element is provided on a layer below the plurality of restrictions, optionally, such that the at least partially restricted and/or trapped objects contact the at least one sensing element.
12. The device as claimed in any preceding claim, wherein the at least one sensing element comprises a plurality of sensing elements comprising one or more sensing elements for each restriction and at least one reference electrode, and/or wherein the at least one sensing element is configured to sense an electrophysiological signal and/or or a signal in response to electrophysiological activity of the object.
13. The device as claimed in any preceding claim, wherein the sensing module comprises one or more stimulating elements, for example, stimulating electrodes, configured to produce an electronic stimulus, for example, a stimulus signal and one or more sensing elements, for example, sensing electrodes, configured to sense a response to the electronic stimulus, optionally wherein the one or more stimulating elements and/or sensing elements are positioned to stimulate and/or sense activity in the sensing region.
14. The device as claimed in any preceding claim, wherein the at least one sensing element is provided as part of an electrode array aligned with and/or provided proximal with the at least one restriction.
15. The microfluidic device according to any preceding claim, wherein the device further comprises a reference sensing element, optionally wherein the reference sensing element is provided at or across at least part of the plurality of fluidic paths and/or at least part of the further fluidic path.
16. The device according to any preceding claim, wherein each of the restrictions comprises an opening having a cross-sectional area that is at least 50%, 60%, 70%, 80%, 90% or 95% smaller than the diameter of the one or more objects of interest.
17. The device according to any preceding claim, wherein the plurality of fluidic paths and the at least one further fluidic path is formed by channels having a cross-sectional area that is at least 50%, 60%, 70%, 80%, 90% or 95% larger than the diameter of the one or more object of interest.
18. The microfluidic device according to any preceding claim, wherein the plurality of fluidic paths and the further fluidic path are formed by a plurality of channels, wherein at least one of a width and/or height of at least one channel is selected from a range thereby to increase or decrease the fluid flow rate.
19. An apparatus comprising the device of any of claims 1 to 18 and further comprising a processing resource configured to: receive sensor signals from said at least one sensing element and/or data representing said sensor signals; process said data and/or signals to determine at least one of electrical activity, viability, function and/or response to a stimulus, optionally provide electrical stimulation via one or more stimulating electrodes.
20. The apparatus of claim 19, wherein the processing resource is configured to determine at least one of: a) a measure of electrical activity in response to electrical stimulation and/or a further fluid, optionally wherein the further fluid comprises a chemical and/or a drug, for example, a glucose solution; b) a number of viable and/or functional tissue and/or multicellular objects in a sample. c) perform a diagnostic and/or viability indication based on sensed electrical activity at the plurality of restrictions and/or sensing regions, for example, wherein the diagnostic and/or viability indication may be based on electrical activity in response to exposing said object to a further substance or electrical stimulation, optionally comprising a chemical and/or a drug, for example, glucose.
21. A method for analysing a plurality of objects, for example, a plurality of tissue and/or multicellular objects, using the device according to claims 1 to 19, said method comprising: providing a plurality of objects in a fluid to the input of the microfluidic device, wherein the fluid initially flows through the device along said plurality of fluidic paths until the plurality of objects reach the plurality of restrictions and are trapped and/or at least restricted by said restrictions; sensing at least one sensor signal for the plurality of objects using the at least one sensing element.
22. The method of claim 21, further comprising delivering a further fluid through the input to the plurality of objects trapped or at least restricted in the plurality of restrictions via the at least one further fluidic path.
23. The method of claim 21 or 22, further comprising delivering an electrical stimulation to the plurality of objects trapped or at least restricted in the plurality of restrictions.
24. The method according to claims 21 to 23 wherein the one or more objects are derived from the pancreas, for example, pancreatic islets or islets of Langehans and/or wherein the one or more objects move to the at least one restriction and/or beyond by gravity and/or capillary action.
25. The method according to claims 21 to 24, wherein the further fluid comprises at least one of: a) a wash solution for removing any solution via the further output; b) a glucose solution; c) one or more drugs and/or cell and/or object activity inhibitors; d) one or more molecules for labelling the objects; e) a higher concentration than the fluid comprising the plurality of objects.
26. The method according to any of claims 21 to 25, wherein the method further comprises isolating the output electrical signal from trapped objects for the plurality of restrictions of the microfluidic device.
27. The method according to any of claims 21 to 26, further comprising processing the sensor signals and/or data representing the sensor signals to assess at least one of cell electrical activity, an extracellular cellularly generated electrical potential, a field potential, viability, function and/or response to a stimulus.
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