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WO2021122511A1 - Cartouche ayant un système microfluidique pour la réalisation d'une analyse d'un échantillon - Google Patents

Cartouche ayant un système microfluidique pour la réalisation d'une analyse d'un échantillon Download PDF

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Publication number
WO2021122511A1
WO2021122511A1 PCT/EP2020/086091 EP2020086091W WO2021122511A1 WO 2021122511 A1 WO2021122511 A1 WO 2021122511A1 EP 2020086091 W EP2020086091 W EP 2020086091W WO 2021122511 A1 WO2021122511 A1 WO 2021122511A1
Authority
WO
WIPO (PCT)
Prior art keywords
flow
cartridge
sample
analysis
analysis section
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/EP2020/086091
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German (de)
English (en)
Inventor
Julian Kassel
Daniel Czurratis
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Robert Bosch GmbH
Original Assignee
Robert Bosch GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Robert Bosch GmbH filed Critical Robert Bosch GmbH
Publication of WO2021122511A1 publication Critical patent/WO2021122511A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers 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
    • B01L3/502769—Containers 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 multiphase flow arrangements
    • B01L3/502776—Containers 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 multiphase flow arrangements specially adapted for focusing or laminating flows
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers 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
    • B01L3/50273—Containers 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 or forces applied to move the fluids
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B19/00—Machines or pumps having pertinent characteristics not provided for in, or of interest apart from, groups F04B1/00 - F04B17/00
    • F04B19/006—Micropumps
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B43/00—Machines, pumps, or pumping installations having flexible working members
    • F04B43/02—Machines, pumps, or pumping installations having flexible working members having plate-like flexible members, e.g. diaphragms
    • F04B43/06—Pumps having fluid drive
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/14—Optical investigation techniques, e.g. flow cytometry
    • G01N15/1456—Optical investigation techniques, e.g. flow cytometry without spatial resolution of the texture or inner structure of the particle, e.g. processing of pulse signals
    • G01N15/1459—Optical investigation techniques, e.g. flow cytometry without spatial resolution of the texture or inner structure of the particle, e.g. processing of pulse signals the analysis being performed on a sample stream
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0636—Focussing flows, e.g. to laminate flows
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0647—Handling flowable solids, e.g. microscopic beads, cells, particles
    • B01L2200/0652—Sorting or classification of particles or molecules
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0883—Serpentine channels
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0887—Laminated structure
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0481—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure squeezing of channels or chambers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0633—Valves, specific forms thereof with moving parts
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0633—Valves, specific forms thereof with moving parts
    • B01L2400/0655—Valves, specific forms thereof with moving parts pinch valves
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/08—Regulating or influencing the flow resistance
    • B01L2400/084—Passive control of flow resistance
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/14—Optical investigation techniques, e.g. flow cytometry
    • G01N15/149—Optical investigation techniques, e.g. flow cytometry specially adapted for sorting particles, e.g. by their size or optical properties
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/14—Optical investigation techniques, e.g. flow cytometry
    • G01N2015/1493—Particle size

Definitions

  • a first type of fluid transport is carried out by a drive with the aid of centrifugal force.
  • a centrifugal drive With a centrifugal drive, only one specific flow direction can be actively specified, because a rotation generates the centrifugal force, which acts in the same direction (outwards) regardless of the direction of rotation.
  • a second type of fluid transport is carried out by a drive with the aid of compressed air (also called a pneumatic drive).
  • compressed air also called a pneumatic drive
  • hydrodynamic focusing is an important area of application for lab-on-chip systems.
  • Cells are counted or sorted in different approaches.
  • Devices for hydrodynamic focusing or for counting and sorting cells are often also called "DurchDusscytometers". Individual cell types can be detected, counted and sorted in such devices.
  • the sample can then (after counting and Sort) can be discarded. If further tests are to be carried out with the sample, the sample (or components of the sample separated from one another during sorting) can be transferred to further devices.
  • Lab-on-chip systems are usually used in conjunction with processing units.
  • Lab-on-chip systems are usually designed as single-use components in the form of cartridges that can be inserted into the processing unit in order to carry out the respective analysis steps provided in or on the lab-on-chip system.
  • lab-on-chip systems offer the advantages of short analysis times, small sample and reagent volumes and easier installation in small laboratories or medical practices.
  • a cartridge with a microfluidic system for the automated implementation of an analysis of an at least partially liquid sample, having an analysis section with at least one flow area in which an analysis of components of the sample can take place and at least one flow laminarizer that operates in a flow direction upstream Arranged analysis section and set up to generate a laminar flow which flows through the flow area of the analysis section.
  • the cartridge is in particular a lab-on-chip.
  • the cartridge can preferably be inserted into a processing unit in which the cartridge is used (or controlled) in such a way that the analysis steps for its Carrying out the cartridge is intended to be carried out with the cartridge.
  • LOC cartridge plastic substrate
  • a credit card for example, where complex biological, diagnostic, chemical or physical processes can take place in miniaturized form.
  • microfluidic system refers to the entirety of all microfluidic devices (channels, chambers, valves, pumps, etc.) that are located on the cartridge.
  • the cartridge is preferably built up in layers from different substrates, which can be produced, for example, with the aid of 3D printing processes, injection molding processes and / or photolithography processes.
  • Channels and / or chambers of the microfluidic system are preferably formed as cavities in at least one substrate. Another substrate closes these chambers and channels.
  • the cartridge particularly preferably consists of a multilayer structure of at least two substrates, between which a flexible membrane can be arranged.
  • the substrates can preferably consist of thermoplastics (polycarbonate, polyamide, polystyrene, polypropylene, polyethylene, PMMA, COP, COC).
  • the flexible membrane can preferably be composed of elastomers, thermoplastic elastomers (TPU: thermoplastic elastomer based on polyurethane, TPS: thermoplastic elastomer based on styrene) or thin thermoplastics.
  • the multilayer structure can, for example, have a thickness of 0.5 to 5 mm [millimeters].
  • the flexible membrane can, for example, have a thickness of 5 to 300 ⁇ m [micrometers].
  • the membrane can e.g. have a thickness of 50 pm [micrometers] to 2 mm [millimeters].
  • the analysis section describes an area in which the actual analysis of the sample takes place.
  • the analysis path can, for example, in the manner of a Arrays be designed in which a large number of analysis steps can be carried out in parallel.
  • Flow areas denote regions within the analysis path through which the sample can flow.
  • the sample is referred to here as “at least partially liquid”. This means in particular that the sample contains liquid components.
  • the sample can also have other constituents, which can also be solid (or at least partially solid), for example.
  • Such components can be biological cells, for example.
  • the sample can be a blood sample, for example.
  • Typical types of samples are, for example, samples from the following substances and / or substances:
  • flow laminarizer here means a device with which a laminar (that is, non-turbulent) flow can be produced in the analysis section in a targeted manner.
  • a flow laminarization with the flow laminarizer is usually achieved by implementing a flow guide with a lower Reynolds number.
  • a flow laminarizer can be set up, for example, by changing the cross section of a channel through which the flow passes, whereby the flow is slowed down.
  • a flow laminarizer can also have built-in components in the channel through which the flow passes, or the flow laminarizer can be implemented by a local division or branching of the channel, by means of which a channel cross section that is decisive for the Reynolds number is reduced. Behind the Flow laminarizers can be brought together again divided and / or branched channel sections, wherein a laminarity of the flow brought about by the flow laminarizer is preferably maintained.
  • the length of the channel in the area of the flow laminarizer can be between 0.3 and 20 mm [millimeters], with the cross section being less than 1.0 mm 2 .
  • the maximum speed of the flow is usually dependent on the individual dimensioning of the channel as well as on the properties of the fluid such as viscosity.
  • the microfluidic system is preferably designed in such a way that the flow through it is not completely laminar. Turbulent flows also preferably occur, namely in particular upstream (that is to say in a flow direction in front of) the flow laminarizer.
  • the flow direction here describes in particular a preferred flow direction with which the cartridge or the microfluidic system is mainly flowed through when an analysis is carried out. If necessary, other, in particular reversed, flow directions can also occur (at least briefly), for example when the sample is sucked back into the microfluidic system with a pump.
  • the flow laminarizer is set up to generate laminar partial flows, one partial flow flowing through a flow area of the analysis section in each case.
  • the flow laminarizer comprises a compensating capacitance that adjoins a pump chamber in the direction of flow.
  • the pump chamber is preferably part of a pump, which can be part of the cartridge, but which can be located in a component external to the cartridge (for example in a processing unit in which the cartridge can be used to carry out examinations).
  • the pump or the pump chamber preferably works in a pulsed manner.
  • Usual processing units are usually constructed in such a way that only two different pressure levels are available, with an intended overpressure level and an intended negative pressure level being available.
  • the fact that a pump works in a pulsed manner means that there are regular discharge phases during which sample liquid emerges from the pump chamber and suction phases in between, in which there is no discharge of sample liquid but the pump chamber draws in sample liquid.
  • a fluctuation in the flow leaving the pump chamber can be compensated for by a compensating capacity connected to the pump chamber.
  • These fluctuations in the liquid output usually always favor turbulence.
  • the flow laminarization helps to avoid such fluctuations with a compensating capacity.
  • the compensating capacity is preferably a liquid reservoir in which the sample liquid is at least slowed down and possibly also stored. In particular, it serves to bridge suction phases and to effect an approximately equal discharge of liquid at an outlet of the compensating capacity.
  • the compensating capacity can for example comprise a chamber which is connected to a channel into which the liquid is guided or through which such a channel runs.
  • the compensating capacity enables additional To provide volume for liquid when the pressure in the channel increases - for example by means of a sliding wall of the chamber.
  • the displaceable wall of the chamber can be implemented, for example, by a flexible membrane which can perform a compensating movement when a pressure in the channel or chamber rises.
  • the minimum volume of the compensation chamber is 0.1 ml [milliliters].
  • the maximum volume of the compensation chamber is 5 ml [milliliters].
  • the increase in volume when the pressure rises, which leads to the compensatory movement of the flexible membrane, is, for example, between 5 and 50%.
  • the maximum permissible pressure is preferably 5 bar.
  • a first valve is arranged upstream of the compensating capacity in the direction of flow.
  • Such a valve is used to prevent a backflow of liquid from the compensating capacity back into the pump chamber. This supports the flow laminarization.
  • the compensating capacitance comprises a flexible membrane which can be deformed by a pressure present in the compensating capacitance.
  • the flexible membrane preferably at least partially limits the compensating capacitance.
  • the compensating capacitance is particularly preferably arranged between two substrates from which the cartridge is constructed.
  • the flexible membrane can be inserted between the two substrates.
  • the compensating capacitance is preferably arranged between a substrate and the flexible membrane.
  • a further volume is preferably arranged between a further substrate and a side of the flexible membrane opposite the compensating capacitance, in which there is, for example, a gas bubble which provides a pressure which presses the compensating capacitance.
  • the gas bubble or the volume of the gas bubble can also be referred to as the “pneumatic level”.
  • the degree of damping can be determined by the choice of the dexible membrane (modulus of elasticity,
  • Thickness of the membrane can be influenced in the compensating capacitance. It is particularly preferred if a second valve is arranged downstream of the compensating capacity in the direction of flow.
  • the cartridge is set up to work together with a pump with which a flow rate and a pressure level can be set by adjusting the switching frequency.
  • the pump can be part of the cartridge or a processing unit into which the cartridge is used to carry out analyzes.
  • the setting of the flow rate enables cost advantages to be achieved in the design of the periphery or the analysis device (or the process control unit).
  • the cartridge is also preferred if the flow laminarizer comprises a meandering channel structure arranged in the flow direction upstream of the analysis section.
  • the effect of the damping of pump strokes within the pump chamber with the flow laminarizer can in particular be defined by different geometrical designs of the compensating capacitance or the meandering channel structure.
  • the flow laminarizer preferably has at least one flow expander which expands a cross section through which the flow passes.
  • a flow expander preferably comprises a (continuous) widening of the cross section of a channel through which the flow passes.
  • the flow expander is preferably designed in such a way that (no) turbulence in the flow is caused by the expansion. This can be achieved in particular in that the channel has no protrusions, undercuts or the like in the area of the flow expander.
  • the channel preferably has in the area of the flow expander smooth wall surfaces.
  • a flow is slowed down by a flow expander.
  • the length of the extension channel can be between 0.5 and 20 mm [millimeters].
  • the length of the analysis section can (also) be between 0.5 and 20 mm [millimeters].
  • the cross section in the channel when entering the expander is preferably less than 0.1 mm 2 .
  • the cross-section of the channel when it emerges from the expander is preferably less than 0.5 mm 2 .
  • the cartridge has a sensor window in which a sensor can analyze a laminar flow of the sample and / or components (of the sample) transported by the laminar flow in the at least one flow area.
  • the senor is set up to recognize cell types.
  • the senor is connected to a control device for counting cells.
  • At least one sorting means is provided on the analysis section with which components of the sample transported by the laminar flow can be conveyed from one flow area into a further flow area.
  • a separator is arranged downstream of the analysis section in the direction of flow, with which components of the sample transported by the laminar flow can be conveyed into individual subsystems of the microfluidic system.
  • the arrangement of the sensor and sorting means on an analysis line behind a flow laminator offers the potential to separate several cell types in one step.
  • a sorting means can for example be designed with liquid nozzles with which a lateral displacement of liquid sections or transported components or cells transported in the liquid can be achieved.
  • the laser (which is to carry out the sorting) is usually individually adapted in terms of its wavelength and pulse strength to the cells or the fluorescence markers, which can dock onto cells.
  • the fluidic path of the sorter can preferably be at least greater than 1 mm. Depending on the complexity of the degree of sorting, there are preferably at least two parallel flows. A longer fluidic path of the sorter (and for example, but not exclusively a plurality of lasers) allows sorting into (up to) four or more destinations in an advantageous manner.
  • a sensor window denotes an area on the analysis path in which a sensor can act on the sample or on components of the sample.
  • the sensor itself can be part of the cartridge or part of the higher-level analysis device (the processing unit) and interact with the analysis section through the sensor window.
  • the sensor on the analysis section in combination with the flow laminarizer located in front of the analysis section offers the potential with suitable optical readout to photograph, detect and measure individual cells
  • the cartridge of a lab-on-chip system described here can be expanded.
  • hydrodynamic focusing is used to count or sort cells.
  • the cells are lined up one behind the other by means of a de-adjusted flow of the fluid and the release of the cells.
  • the correct Duidian parameters result in several (mostly three), parallel, laminar flows.
  • Biological cells in the sample can be counted using a suitable sensor (detection technology), such as optical, chemical or resistive.
  • a mixture of different cell types can be provided with a fluorescent marker to the desired ones. In the laminar flow you can stimulate every single cell and only those that have the marker will give an optical response. The number of relevant cells can also be determined from the mixture.
  • the different laminar currents can also be separated from one another and further investigated separately.
  • FIG. 2a a further embodiment of a cartridge
  • FIG. 2b the embodiment variant from FIG. 2a with a cross-sectional view from above
  • Fig. 3 a further embodiment of a cartridge
  • FIG. 1 shows an exemplary multi-layer structure of a microfluidic system 16 with the flow laminator 19 described here in a cartridge 15.
  • a direction of flow 20 through the microfluidic system 16 is indicated by an arrow.
  • the cartridge 15 or the microfluidic system 16 are constructed here with a first substrate 1 and with a second substrate 2 by way of example.
  • the microfluidic system 16 has a pump 7, which is shown with a dexible membrane 3 and which can be operated pneumatically via a pneumatic connection 29.
  • the pump 7 provides the basic functions for the microDuidic control.
  • the dexible membrane 3 of the pump 7 is integrated between the first substrate 1 and the second substrate 2 and is freely movable.
  • liquid can be drawn into a pump chamber 5 with the aid of the pump 7 or its dexible membrane 3 and transferred to an adjacent compensating capacity 9 via a valve 8.
  • the Duidic plane in which the microDuidic channels 6 and the compensating capacitance 9 are located, there is usually atmospheric pressure.
  • turbulent flows 11 initially arise in the compensating capacity 9.
  • the dexible membrane 3 can dampen or completely intercept the temporary pressure increases resulting from the pumping strokes.
  • the compensating capacitance 9 is preferably adjacent to an enclosed gas volume 13, which can be compressed and is thus suitable for compensating for pressure fluctuations in the compensating capacitance 9. This results in an almost laminar flow at the outlet 10 of the compensating capacity 9.
  • microDuidic path between pumping chamber 5 and compensating capacity 9 can be opened or closed. In this way, it can be prevented that liquid from the compensating capacitance 9 gets back into the pump chamber 5 during the pumping process.
  • the analysis section 17 adjoins the outlet 10, through which the liquid sample can flow in flow areas 18.
  • FIGS. 2a, 2b and 3 show further design variants of such microfluidic systems 16, with components that correspond to the design variant in FIG. 1 not being explained again here.
  • an additional meandering channel structure 12 can be coupled between the outlet 10 and the compensating capacitance 9 of the micro-duidic system 16.
  • This meandering channel structure 12 can lead to a further damping of the temporary pressure surges and thus to the formation of a laminar flow.
  • FIG. 2a in a representation corresponding to FIG.
  • a possible construction of the meandering channel structure 12 is shown in FIG. 2b, where a section is selected in a perpendicular orientation to the illustration in FIG. 2a.
  • a second valve 14 is also arranged between the compensating capacity 9 and the meandering channel structure 12, which valve can be opened or closed.
  • This second valve 14 can be used to prevent liquid from flowing back from the channel structure 12 into the compensating capacity 9. By means of this second valve 14, the flow can be made even more even.
  • FIG. 4 shows a diagram of the flow over time through a microfluidic system 16 of a cartridge.
  • the time axis t is shown horizontally.
  • the volume flow Q is shown vertically.
  • the course without the integration of a flow laminarizer 19, as described here, is shown on the left-hand side.
  • the infeed of the flow laminarizer 19 can be seen.
  • 5 shows an example of an analysis section 17 with flow areas 18. Subsequently, a flow expander 21 or a separator 28 for separating sample components in the flow areas 18 for different subsystems 4 is shown.
  • An analysis of the sample takes place in a sensor window 23 with at least one sensor 24, which can work optically with or without excitation of fluorescence or chemiluminescence.
  • An excitation of cells in the sample and also a possible determination of the size of cells could be realized, for example, with a laser as the sensor 24.
  • a sensor 24 for a resistive measurement in the flow itself would also be conceivable. Further detection methods can also be integrated.
  • a sorting means 27 with which sample parts and in particular transported components 25 of the samples (particularly preferably cells) can be moved back and forth between flow regions 18 in a targeted manner in order to achieve sorting.
  • a sorting means can be designed, for example, with liquid nozzles with which a lateral displacement of liquid sections or transported components / cells can be achieved.
  • the sorting means 27 can also comprise a laser in order to shift certain cells from their original laminar flow into one of the other flows (flow-through area 18). A cell mixture can thus be sorted into different cell types. As a further sorting means 27 can electric or magnetic fields are used. Other sorting mechanisms are conceivable.
  • the sorting means 17 can optionally also overlap with the sensor window 23, be identical or completely separate from it. After the detection and a possible sorting, the individual laminar
  • Streams are divided up again and the sorted cells are taken for different processing.
  • a control device 26 is also arranged here purely schematically, which, for example, counting functions determined with the aid of the sensor 24
  • a flow expander 21 which expands a cross-section 22 through which the flow passes and which is used for
  • Distribution of the flow in subsystems 4 is used.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Dispersion Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Clinical Laboratory Science (AREA)
  • Hematology (AREA)
  • General Engineering & Computer Science (AREA)
  • Mechanical Engineering (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pathology (AREA)
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  • General Physics & Mathematics (AREA)
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Abstract

L'invention concerne une cartouche (15) ayant un système microfluidique (16) pour la réalisation automatisée d'une analyse d'un échantillon au moins partiellement liquide, comprenant une ligne d'analyse (17) présentant au moins une zone d'écoulement (18) où une analyse des constituants de l'échantillon peut avoir lieu, et au moins un dispositif de production d'écoulement laminaire (19) qui est disposé avant la ligne d'analyse (17) dans une direction d'écoulement (20) et qui est configuré pour générer un écoulement laminaire qui s'écoule à travers la zone d'écoulement (18) de la ligne d'analyse (17).
PCT/EP2020/086091 2019-12-16 2020-12-15 Cartouche ayant un système microfluidique pour la réalisation d'une analyse d'un échantillon Ceased WO2021122511A1 (fr)

Applications Claiming Priority (2)

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DE102019219659.4A DE102019219659A1 (de) 2019-12-16 2019-12-16 Kartusche mit einem mikrofluidischen System für die Durchführung einer Analyse einer Probe
DE102019219659.4 2019-12-16

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WO2021122511A1 true WO2021122511A1 (fr) 2021-06-24

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DE102023126576A1 (de) * 2023-09-28 2025-04-03 Bürkert Werke GmbH & Co. KG Mikrofluidische Vorrichtung, Proteindefektdiagnosevorrichtung mit mikrofluidischer Vorrichtung, Verfahren für Proteindefektdiagnose sowie Verfahren zur Analyse von Proteindefekten
DE102023126568A1 (de) * 2023-09-28 2025-04-03 Bürkert Werke GmbH & Co. KG Mikrofluidische Vorrichtung, Proteindefektdiagnosevorrichtung mit mikrofluidischer Vorrichtung, Verfahren zum Blutprobenauftrag auf ein Sensorelement sowie Verfahren zur Analyse von Proteindefekten

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994018218A1 (fr) * 1993-02-01 1994-08-18 Seq, Ltd. Procedes et appareil de sequençage de l'adn
WO2007093939A1 (fr) * 2006-02-13 2007-08-23 Koninklijke Philips Electronics N.V. Dispositif micro-fluidique pour applications de diagnostic moleculaire
WO2011094577A2 (fr) * 2010-01-29 2011-08-04 Micronics, Inc. Cartouche microfluidique « de l'échantillon au résultat »
WO2017169647A1 (fr) * 2016-03-30 2017-10-05 Sony Corporation Trousse d'isolement d'échantillons, dispositif pour l'isolement d'échantillons

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2142279A2 (fr) 2007-04-16 2010-01-13 The General Hospital Corporation d/b/a Massachusetts General Hospital Systèmes et procédés de focalisation de particules dans des micro-canaux
US20110003330A1 (en) 2009-07-06 2011-01-06 Durack Gary P Microfluidic device
GB201509640D0 (en) 2015-06-03 2015-07-15 Sphere Fluidics Ltd Systems and methods

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994018218A1 (fr) * 1993-02-01 1994-08-18 Seq, Ltd. Procedes et appareil de sequençage de l'adn
WO2007093939A1 (fr) * 2006-02-13 2007-08-23 Koninklijke Philips Electronics N.V. Dispositif micro-fluidique pour applications de diagnostic moleculaire
WO2011094577A2 (fr) * 2010-01-29 2011-08-04 Micronics, Inc. Cartouche microfluidique « de l'échantillon au résultat »
WO2017169647A1 (fr) * 2016-03-30 2017-10-05 Sony Corporation Trousse d'isolement d'échantillons, dispositif pour l'isolement d'échantillons

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