[go: up one dir, main page]

WO2024175560A1 - Dispositif microfluidique - Google Patents

Dispositif microfluidique Download PDF

Info

Publication number
WO2024175560A1
WO2024175560A1 PCT/EP2024/054220 EP2024054220W WO2024175560A1 WO 2024175560 A1 WO2024175560 A1 WO 2024175560A1 EP 2024054220 W EP2024054220 W EP 2024054220W WO 2024175560 A1 WO2024175560 A1 WO 2024175560A1
Authority
WO
WIPO (PCT)
Prior art keywords
conduit
microfluidic device
flexible
acceleration
side wall
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/EP2024/054220
Other languages
English (en)
Inventor
Pedro Reis
Eduardo GUTIERREZ PRIETO
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.)
Ecole Polytechnique Federale de Lausanne EPFL
Original Assignee
Ecole Polytechnique Federale de Lausanne EPFL
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 Ecole Polytechnique Federale de Lausanne EPFL filed Critical Ecole Polytechnique Federale de Lausanne EPFL
Publication of WO2024175560A1 publication Critical patent/WO2024175560A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

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
    • B01L3/502746—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 for controlling flow resistance, e.g. flow controllers, baffles
    • 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
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00—Subject matter not provided for in other groups of this subclass
    • F16K99/0001—Microvalves
    • F16K99/0034—Operating means specially adapted for microvalves
    • F16K99/0063—Operating means specially adapted for microvalves using centrifugal forces
    • 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
    • B01L2400/0622—Valves, specific forms thereof distribution valves, valves having multiple inlets and/or outlets, e.g. metering valves, multi-way 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
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0633—Valves, specific forms thereof with moving parts
    • B01L2400/0638—Valves, specific forms thereof with moving parts membrane valves, flap 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
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0633—Valves, specific forms thereof with moving parts
    • B01L2400/0655—Valves, specific forms thereof with moving parts pinch valves
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00—Subject matter not provided for in other groups of this subclass
    • F16K2099/0082—Microvalves adapted for a particular use
    • F16K2099/0084—Chemistry or biology, e.g. "lab-on-a-chip" technology

Definitions

  • the present invention relates to the field of microfluidic devices. More particularly, it relates to a microfluidic device comprising at least one acceleration-actionable flexible element.
  • microfluidic devices have become widely used in research and industry, particularly in many fields related to sample testing, whether relating to chemistry or life sciences.
  • performing fluidic operations at the micro-scale i.e. with volumes at the sub-milliliter level, often down to 500 pl or even below
  • microfluidics increasingly popular, strengthening efforts to enhance the functionality of these devices and leading to the development of varied fluid handling strategies in such microfluidic devices.
  • Such devices can be broadly classified into five classes: (i) passively driven, (ii) pressure-driven, (iii) surface driven, (iv) electro-magnetically driven and (v) centrifugally driven.
  • Pressure-driven microfluidic devices utilize a pressure gradient across the device in order to drive the fluid from higher to lower pressure regions.
  • This pressure can be driven e.g. by a pipette, by gravity (due to a fluid height difference between an inlet and an outlet cistern or by tilting the entire device), by a pump or similar.
  • These devices are suitable for having pneumatic or electromagnetic sensors or actuators integrated therein, giving great flexibility of use.
  • Such devices have predictable velocity profiles, diffusive mixing can be controlled, and stable multi-phase arrangements can be operated. They can also be used continuously, and to carry out sequenced operations within a single device (a so-called “Lab-On-Chip”).
  • microvalves can be integrated, based on flexible membranes that can deform through pneumatic or mechanical deformation, and furthermore pumps, distribution valves, and all manner of fluid handling components can also be integrated.
  • Such devices while incredibly versatile and flexible, are relatively expensive, and can require complex controllers to operate properly.
  • centrifugally-driven microfluidic devices the device is placed in a centrifuge, and centrifugal forces are used to drive the fluid outwards, thereby ensuring accurate and pulse-free flow control.
  • Centrifugal actuation was first implemented in the 1960s when it was employed to separate a sample into micro-aliquots, and then in the 1990s, the company Abaxis developed a portable clinical chemistry analyzer consisting of a plastic disposable rotating cartridge for processing the sample of interest.
  • Microfabrication techniques enabled the fabrication of structures as large as a few hundred micrometers, and the implementation of hundreds or thousands of these structures allows parallel processing of up to hundreds of units, enabling high throughput by highly parallel and automated liquid handling.
  • centrifugal valving relies on some strategies also employed by paper microfluidics, such as paper channels, dissolvable materials, or hydro-phobic/philic surface treatments.
  • Some active valves have been proposed based on employing a laser to melt a wax plug, but utilization of such valving means requires additional fabrication steps and can increase the fabrication costs.
  • Siphon valves have also been proposed as a valving alternative not requiring extra fabrication steps.
  • Centrifugally driven devices offer a separation between the fluid and driving force since no connection between the motor and the fluidic circuit is necessary.
  • Disposable modular cartridges can be used for rapid on-site testing requiring nearly no user expertise.
  • the fabrication costs of these cartridges are determined by the complexity of the steps required to fabricate the embedded unit operators.
  • the accuracy of the driving force in centrifugal microfluidics is imposed by the precision with which the turning velocity of the disk can be controlled, i.e. how finely a motor can be driven.
  • the disk radius limits the length of the fluidic circuits since the centrifugal force can only drive the fluid radially outwards.
  • the required disk surface increases quadratically with the number of embedded unit operations (proportional to the radial length).
  • the platform also lacks flexibility compared to pressure-driven devices and is more expensive than paper-driven microfluidics.
  • US7258774 describes various microfluidic devices in which flexible wall elements of a conduit are actuated by an overpressure in corresponding control channels. This device is complex and requires an arrangement for generating this control channel overpressure.
  • W02022/010987 discloses a microfluidic device comprising a chamber partially defined by a single flexible membrane that can be actuated magnetically, pneumatically or mechanically. This membrane returns to its initial position by elastic return as soon as the actuation force is released. This device requires an arrangement for magnetic, pneumatic or mechanical actuation.
  • US11117135 discloses a sealed cartridge in which chambers are successively opened by irreversibly breaking a seal through a flexible wall. The liquid they contain is transported by centrifugal force into successive reaction chambers, where they are combined and blended by acceleration generated by the centrifuge in which the cartridge is placed. Since the seal is destroyed in use, this device has very limited applications.
  • EP2352036 discloses a device wherein several fluids successively reach different chambers, linked together by channels that are closed or opened as the fluid progresses. The driving force for transporting the fluid is again centrifugal.
  • Figure 4 of this document discloses a first embodiment wherein the upper wall of the channels is formed by two flexible layers with two different levels of adhesion, which enables the channels to be opened or closed, depending on pressure applied on the outermost layer. This device requires external application of pressure to function, and is very limited in its application.
  • US2002/155010 discloses a microfluidic valve device with pressure, magnetic or electromechanical actuation of a flexible element. Again, this device requires this external actuation to function.
  • US8852529 describes a microfluidic device in which fluid is driven through a conduit centrifugally, and one or more flexible elements are used to vary the effective cross-sectional area of the conduit in response to rotation.
  • this device does not require external actuation by means of pressure, mechanical actuation, magnetism, electromagnetism or similar, it is limited to very specific applications, notably in respect of the interplay between fluid driving and actuation of the flexible element.
  • the actuation of the flexible element(s) is coupled with the centrifugal driving of the fluid flow, which is of very limited application.
  • the aim of the present invention is to at least partially overcome the drawbacks of the prior art.
  • the invention relates to a microfluidic device as defined in claim 1.
  • This microfluidic device comprises at least one conduit arranged for the transport of a liquid, wherein said conduit comprises at least one flexible element arranged to be reversibly movable between at least a first position and a second position (and back again) in response to an Euler force or a linear force, this Euler force or linear force resulting from an acceleration to which said microfluidic device is subject, the at least one flexible element hence being bistable or multistable. Accelerations produce so-called fictitious or apparent forces, and the present invention exploits these to cause the flexible element to be moved between at least two positions in response to them, without recourse to active components (e.g. actuators).
  • active components e.g. actuators
  • Such accelerations can be linear, related to a linear acceleration or deceleration (which is of course an acceleration with a negative value), or related to circular motion, the fictitious forces in question being in particular so-called Euler forces (acting tangentially in response to angular accelerations or decelerations).
  • the flexible elements may be arranged to form valves, mixing elements, liquid switches or similar.
  • said at least one flexible element is a flexible wall section integrated with the conduit (i.e. helping to define it rather than being attached inside an otherwise fully-integral conduit) arranged to open said conduit when in its first position and to restrict or block said conduit in its second position, or vice-versa.
  • the flexible wall section hence acts as a valve, and is bistable (i.e. it can adopt two stable states, an action being required to transition between said stable states), in which case accelerations causing apparent forces in opposite directions will switch the valve from open to closed and vice-versa.
  • Such flexible wall section based valves can be arranged in a row of three, such that at least one of said flexible wall sections substantially closes off said conduit at a predetermined level of acceleration, so as to act as a peristaltic pump.
  • liquid can be pumped against any apparent forces (gravitational, centrifugal etc.) by manipulating the accelerations of the device so as to cause the valves to change state in sequence.
  • outermost said flexible wall sections are arranged in opposite side walls of said conduit, the middle flexible wall section being arranged in one or other of said side walls.
  • said conduit is split into at least two branches, said flexible element being arranged in said conduit so as to direct flow into or out of one of said branches depending on said acceleration.
  • the flexible element hence acts as a liquid switch to bring either of the conduit branches into fluidic connection with the main conduit.
  • said conduit comprises a plurality of said flexible elements disposed therein and each arranged so as to move from its first position to its second position and vice-versa at a different, predetermined acceleration for each flexible element.
  • This can be achieved e.g. by varying the shape and/or thickness of the various flexible elements, exploiting contact with rigid elements, angles of clamping, use of pinned connections or any other suitable means, and is within the ability of the skilled person.
  • the flexible elements move in the liquid flow as the acceleration is varied, and hence mix the fluid. This is particularly useful when two different fluid flows are brought together.
  • said flexible element is disposed in said conduit attached to a side wall thereof and is arranged to move from a first position parallel to said side wall to a second position in which its tip is proximate to an opposite side wall, in response to an acceleration.
  • This arrangement is useful as an analogue valve which is normally open until subject to an acceleration.
  • said flexible element is disposed in said conduit attached to a sidewall thereof and is arranged to move from a first position extending across said conduit to a second position, curved within said conduit.
  • This arrangement is useful as an analogue valve which is normally closed until subject to an acceleration.
  • At least two of said flexible elements are provided and arranged to direct fluid into or out of one of at least two branches of said conduit, the branch being determined by said acceleration. This enables bringing one of two or more branches into fluidic communication with the main part of the conduit and thereby select where fluid flows from or to.
  • At least two of said flexible elements are provided extending towards each other from opposite side walls of said conduit and arranged to flex in mirror image to each other in response to said acceleration.
  • a nozzle of varying section is hence provided, the second stable position of the flexible elements typically defining a smaller nozzle than the first stable position.
  • At least two of said flexible elements are provided, extending in opposite directions from a common attachment point on a side wall of said conduit, a first of said flexible elements extending in an upstream direction and having a first position parallel to said side wall and a second position touching or proximate to the opposite side wall, a second of said flexible elements extending in a downstream direction and having a first position touching or proximate to said opposite side wall and having a second position parallel to said side wall.
  • the microfluidic device of the invention may be adapted to be placed in a centrifuge or in a system arranged to impose a linear acceleration.
  • the flexible element is arranged such that the Euler or linear force resulting from an acceleration acts directly thereupon.
  • one or more auxiliary actuators situated externally to the conduit and mechanically connected with the flexible element, the actuator being arranged to respond to the Euler or linear force acting thereupon, this being then transmitted to the flexible element, e.g. via a linkage. This permits decoupling the design of the flexible element from the responsiveness to the Euler or linear force, e.g. so as to provide a greater response than may be possible if the force acts directly on the flexible element.
  • the invention also relates to a centrifuge system comprising a centrifuge adapted to receive a microfluidic device as defined above, a controllable motor arranged to rotate said centrifuge, and a controller arranged to control said motor.
  • a centrifuge system comprising a centrifuge adapted to receive a microfluidic device as defined above, a controllable motor arranged to rotate said centrifuge, and a controller arranged to control said motor.
  • FIG. 1 is a cross-sectional schematic view of a microfluidic device according to a nonlimiting embodiment of the invention
  • FIGS. 2 to 10 are schematic cross-sectional views of nonlimiting variants of conduits suitable for use in a microfluidic device according to the invention.
  • FIG. 11 is a schematic view of a centrifuge system provided with a microfluidic device according to the invention and illustrating the apparent forces acting on the microfluidic device;
  • FIG. 12 is a further cross-sectional schematic view of a microfluidic device according to a nonlimiting embodiment of the invention, where the Euler or linear force acts on an auxiliary actuator.
  • Figures 1 to 10 illustrate a number of non-limiting embodiments of microfluidic devices 1 according to the invention, which all contain at least one flexible element which is arranged to be actuated by an apparent force resulting from an acceleration.
  • This force may be engendered by a linear acceleration (such as by shaking, tapping the device 1 against a surface, or subjecting it to any other linear acceleration or deceleration, whether it be manually or by use of a system adapted to cause the device to be accelerated or decelerated linearly or with at least one linear component), or may be the result of an Euler force resulting from an angular acceleration or deceleration.
  • a linear acceleration such as by shaking, tapping the device 1 against a surface, or subjecting it to any other linear acceleration or deceleration, whether it be manually or by use of a system adapted to cause the device to be accelerated or decelerated linearly or with at least one linear component
  • Euler force resulting from an angular acceleration or deceleration Firstly, the structure of these
  • Microfluidic device 1 comprises a unitary or multi-part substrate of any convenient shape (here illustrated as rectangular, but other shapes such as discs are known in the art and are equally applicable) in which fluid pathways are formed, namely a first reservoir 5, filled with a liquid, a second reservoir 7, which is empty as illustrated but may also contain a liquid, and a conduit 9 linking the interior of the first reservoir 5 with the interior of the second reservoir 7 such that liquid may pass from one to the other.
  • One sidewall of the conduit 9 comprises a flexible element 11 , which is a flexible wall section 11 , defining a valve 13.
  • This wall section 11 is arranged as a clamped-clamped beam which is integrated with the conduit 9 and helps to define its envelope, and when it is in the position illustrated with a solid line, which is a stable position, it is in contact with the opposite wall of the conduit 9, seals the conduit 9 and prevents fluid flow from the first reservoir 5 to the second reservoir 7.
  • the valve 13 opens and allows fluid to flow from the first reservoir 5 to the second reservoir 7.
  • a pre-compressed plate or other bistable structures can be used.
  • the flexible wall section 11 is bistable, that is to say that the flexible wall section 11 will adopt the form indicated with a dotted line 1 T (i.e. its second position) stably until such time as the microfluidic device is subjected to a sufficient acceleration in the opposite direction to return it to its first position as indicated with the solid line.
  • “bistable” simply means that the element concerned has two stable equilibrium states, i.e. that its first position and its second position are both stable, and the element will remain in its present state in the absence of actuation (see, for instance, Morris, Christopher G. (1992), Academic Press Dictionary of Science and Technology, Gulf Professional publishing, p. 267, ISBN 978-0122004001).
  • energy is required, supplied in the present invention by means of the linear or Euler force resulting from an acceleration.
  • a threshold energy level is required to switch from a first stable equilibrium state or position to a second stable equilibrium state or position, and vice-versa.
  • reservoirs 5, 7 may be open to ambient conditions or closed, and are only provided as nonlimiting examples; the conduit 9 may join two other conduits, a reservoir to another conduit, or any two other fluid handling structures of a microfluidic device 1. Since these reservoirs 5, 7 (or other structures as the case may be) are not important to the definition of the present invention, they have been omitted from the remaining figures to focus on the conduit 9.
  • Figure 2 illustrates a conduit 9 provided with three valves 13a, 13b, 13c arranged in sequence, each defined by a flexible wall section 11a, 11b, 11c respectively as described in the context of figure 1 .
  • the outermost flexible wall sections 11a, 11c are situated on opposite sides of the conduit 9, and in the illustrated variant the middle flexible wall section 11 b is situated on the same side of the conduit 9 as the downstream flexible wall section 13c, although other arrangements are possible.
  • the upstream valve 13a and the middle valve 13b are open, and the downstream valve 13c is closed.
  • These valves are arranged such that each valve 13a, 13b, 13c changes state (i.e.
  • a non-limiting sequence of opening (o) and closing (c) the three valves 13a, 13b, 13c so that the arrangement acts as a peristaltic pump is given as follows: Step 1 - 13a(c)13b(o)13c(o), Step 2 - 13a(c)13b(c)13c(o), Step 3 - 13a(o) 13b(c) 13c(c) , Step 4 - 13a(o) 13b(o) 13c(c) , Step 5 - idem Step 1 .
  • FIG. 3 illustrates a conduit 9 which has branches 9a and 9b arranged in a Y- type configuration, although the same principle applies to a T-type configuration.
  • a flexible element 15 is arranged inside the conduit 9 and attached between the branches 9a, 9b to an attachment point 10 on a sidewall so as to be able to connect the main part of the conduit 9 to either of the branches 9a, 9b, while shutting off the other.
  • the flexible element cooperates with the walls of the conduit 9 so as to form a distribution valve, such that the section of conduit 9, 9a, 9b can act as a sorter or a switch, directing fluid from the main part of the conduit 9 into one or other branch 9a, 9b, or vice-versa.
  • the bistability of flexible elements 15 is obtained by their shape and/or boundary conditions, which is within the ability of the skilled person to determine. This applies equally to the embodiments of figures 4-10.
  • Figure 4 illustrates a conduit which is split into two parallel branches 9a, 9b on the left side by a dividing wall 17, and is provided with a number of flexible elements 15 facing the two parallel branches 9a, 9b and mounted at corresponding attachment points 10 provided on the base of the conduit 9 and arranged at various ad hoc positions.
  • the flexible elements 15 may or may not be aligned and may or may not have the same initial angle with respect to the flow, and typically they would be arranged to respond differently to varying accelerations. By varying the acceleration so as to subject the flexible elements 15 to various apparent forces (whether Euler or linear), they can be made to move in the flow path and mix the two different liquids arriving down each parallel branch 9a, 9b.
  • Figure 5 illustrates a conduit 9 provided with a flexible element 15 attached to a sidewall of the conduit 9 at a corresponding attachment point 10 and extending parallel thereto when in its first stable position.
  • An apparent force caused by an acceleration causes the flexible element 15 to flex and close off the conduit 9 completely when the flexible element 15 has transitioned into its second stable position, closing the conduit 9 completely when it touches the opposite side wall.
  • the direction of flow is immaterial, however it must be borne in mind that a too-strong flow from left to right (in the orientation of the figure) may cause the valve 13 to block in its closed position, whereas a too-strong flow from right to left may not allow the valve 13 to close completely.
  • Figure 6 illustrates a conduit 9 which differs from that of figure 5 in that the flexible element 15 is attached to a side wall of the conduit 9 at an attachment point 10 and extends substantially perpendicular thereto in its first stable position, and flexes to open the conduit in its second stable position in response to forces caused by an acceleration.
  • Figure 7 is a conduit 9 arranged as a two-way switch, in which the conduit 9 is divided into two branches 9a, 9b in a T-configuration.
  • a pair of flexible elements 15a, 15b are attached to the walls of the conduit 9 at respective attachment points 10a, 10b, and are arranged such that their free ends rest against respective abutments 19 in their first stable positions, so as to close off each branch 9a, 9b and hence form respective valves 13a, 13b.
  • Apparent forces arising from an acceleration result in one or other of the branches 9a, 9b opening and adopting its second stable position.
  • the direction of the apparent forces caused by accelerations determines which valve 13a, 13b is opened or closed, the positioning of the abutments 19 determining the direction in which the flexible elements 15a, 15b respond to accelerations.
  • Figure 8 illustrates a conduit 9 arranged as a multi-way flow director, which uses a pair of flexible elements 15a, 15b arranged in parallel either side of the main part of the conduit 9 so as to be able to direct flow into a plurality of branches 9a, 9b, 9c, 9d, 9e (here there are five illustrated, but this could also be two, three or four, or more than five) depending on the position of the two flexible elements 15a, 15b, as determined by the apparent forces to which the system was subjected. No abutments are provided, so that the flexible elements can flex in either direction, and the attachment points 10a, 10b are as illustrated.
  • Figure 9 illustrates a conduit 9 provided by two flexible elements 15a, 15b attached to opposite side walls of the conduit 9 and extending towards each other from respective attachment points 10a, 10b. Apparent forces resulting from accelerations cause the flexible elements 15a, 14b to flex in the downstream direction in mirror image to each other, so as to form a nozzle with at least two different sections.
  • Figure 10 illustrates a conduit 9 provided with two flexible elements 15a, 15b attached to the same attachment point 10 on the same side wall and extending in opposite directions.
  • the upstream flexible element 15a extends upstream parallel to the side wall of the conduit 9, and the downstream flexible element 15b curves upwards and substantially touches, or is at least proximate to, the opposite side wall so as to block the flow.
  • An apparent acceleration to the left causes the upstream flexible element 15a to adopt its second position, where it curves and touches or is proximate to the opposite side wall, and the downstream flexible element 15b adopts its second position parallel to the side wall. This is illustrated by the dotted lines 15a’, 15b’.
  • This arrangement causes fluid plugs, droplets or aliquots to be allowed past the arrangement of flexible elements 15a, 15b.
  • Figure 12 illustrates a variant of the arrangement of figure 1 , which differs therefrom in that an auxiliary actuator 21 is provided.
  • This auxiliary actuator 21 is bistable, and is illustrated here in the form of a built-in, pre-buckled beam, although other structures (discs or similar) are equally possible.
  • This is operatively connected with the flexible element 11 by a linkage 23 such that the flexible element 11 moves in synchronicity with the auxiliary actuator 21 when it changes from its first to its second stable state in response to a sufficient, threshold linear or Euler force.
  • the flexible element 11 does not have to have symmetrical stable states. For instance, in the dashed configuration, it may be in line with the remainder of the conduit wall, and this flexibility of design is a further advantage of the use of an auxiliary actuator 21.
  • This arrangement enables decoupling of the actuation from the design of the flexible element 11 , enabling both the auxiliary actuator 21 and the flexible element 11 to be individually optimized rather than having to design the flexible section 11 to also respond to the linear or Euler force on its own.
  • the auxiliary actuator could be stiffer than may be desirable with a flexible wall element 11 , to give a higher force/acceleration threshold for changing from the first to the second positions.
  • the length of the auxiliary actuator could be longer than desirable for a flexible wall section 11.
  • An auxiliary actuator 21 may also be used with any of the other embodiments, provided that the linkage 23 can pass through the wall of the conduit.
  • the conduit 9 and branches 9a, 9b, 9c, 9d, 9e may be of round, oval, square or rectangular cross-section, fabricated using the usual techniques known in the art and typically of polymer materials, though any other suitable materials are of course possible.
  • the cross-section typically has a maximum width of 2mm or less, typically 1 mm or less.
  • the flexible wall sections 11 , 11a, 11 b, 11 may be integrally formed, or may be separate elements glued or welded to the remainder of the conduit wall.
  • Flexible elements 15, 15a, 15b may be integrally formed by 3D printing or by soft lithography-based fabrication methods, or positioned in the conduit before a closure plate is provided thereupon. In the case of an auxiliary actuator 21 , this may for instance be made of polymer materials, metallic materials or any other convenient materials.
  • Microfluidic device 1 may be a pharmacological, chemical or other test device, a lab-on-chip arrangement or part thereof, a microfluidic acceleration detector (e.g. a detector that lets aliquot of liquid flow in response to a certain acceleration or deceleration), an acceleration logic operator (sequencing droplets or aliquots in different manners according to accelerations), microfluidic based protecting equipment (acceleration moving elastic components, moving a highly viscous (low Re) fluid while dissipating part of the energy of an impact or any other kind of microfluidic device.
  • a microfluidic acceleration detector e.g. a detector that lets aliquot of liquid flow in response to a certain acceleration or deceleration
  • an acceleration logic operator quencing droplets or aliquots in different manners according to accelerations
  • microfluidic based protecting equipment acceleration moving elastic components, moving a highly viscous (low Re) fluid while dissipating part of the energy of an impact or any other kind of micro
  • Centrifugal force F Centrifugai is the fictitious force which acts radially outwards from the axis of rotation, and has the formula, for mass m, angular velocity a) and radius r:
  • the apparent force can be varied to actuate a flexible element 11 , 15 which is aligned substantially tangentially to the radius r, although centrifugal actuation used on its own does not form part of the present invention.
  • the fictitious Euler force operates when there is an angular acceleration, as in when the centrifuge is angularly accelerated or decelerated.
  • This force F Euier has the formula, for mass m, angular velocity a) and radius r: da)
  • This fictitious force can be used to manipulate flexible elements 11 , 15 which are aligned substantially radially, by accelerating the motor M or braking the centrifuge 100.
  • a large variety of microfluidic devices can be created by arranging conduits at various angles, and by arranging flexible elements 11 , 15, reservoirs and other elements as appropriate to form the microfluidic circuits required.
  • the centrifugal force can be used as a driving force for driving liquid flow radially outwards, and furthermore the arrangement of figure 2, if the valves 13a, 13b, 13c are arranged to be opened and closed at varying levels of Euler force, can be used to pump liquid against the effect of the centrifugal force, i.e. with a component radially inwards, or with a tangential component.
  • microfluidic devices 1 can be fabricated with only flexible elements 11 , 15 as described above, it is also possible to add active actuator components, e.g. made of magneto-active elastomers. Magneto-active materials can be used to fabricate bi- or multistable structures (which may be the flexible elements 11 , 15), which switch between stable modes under the appropriate magnetic field. These structures can be embedded in microfluidic devices 1 , and can be switched on demand before running a test by applying external magnetic fields generated via external electromagnets. The microfluidic devices 1 can therefore be created with programmable fluidic circuitry, controlled via such magneto-active valves.
  • Figures 1 , 2, 7, 8, 12 actuation with Euler force, tuned with centrifugal force, or y actuation, possibly tuned by x acceleration forces;
  • Figures 3, 5, 6 Euler and/or centrifugal and/or x and/or y forces;
  • Figure 4 Euler and/or centrifugal and/or x and/or y forces at varying apparent force loads for each flexible element 15;

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • General Engineering & Computer Science (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Mechanical Engineering (AREA)
  • Micromachines (AREA)

Abstract

Le dispositif microfluidique (1) comprend au moins un conduit (9) agencé pour le transport d'un liquide, ledit conduit (9) comprenant au moins un élément flexible (11; 11a; 11b; 11c; 15; 15a; 15b) agencé pour être mobile de manière réversible entre au moins une première position et une seconde position en réponse à une force d'Euler ou une force linéaire résultant d'une accélération à laquelle ledit dispositif microfluidique (1) est soumis, chacune de ladite première position et de ladite seconde position étant une position stable.
PCT/EP2024/054220 2023-02-23 2024-02-20 Dispositif microfluidique Ceased WO2024175560A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP23158308 2023-02-23
EP23158308.9 2023-02-23

Publications (1)

Publication Number Publication Date
WO2024175560A1 true WO2024175560A1 (fr) 2024-08-29

Family

ID=85381121

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2024/054220 Ceased WO2024175560A1 (fr) 2023-02-23 2024-02-20 Dispositif microfluidique

Country Status (1)

Country Link
WO (1) WO2024175560A1 (fr)

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6123316A (en) * 1996-11-27 2000-09-26 Xerox Corporation Conduit system for a valve array
US20020155010A1 (en) 2001-04-24 2002-10-24 Karp Christoph D. Microfluidic valve with partially restrained element
US20050205136A1 (en) * 2000-02-29 2005-09-22 Freeman Alex R Integrally manufactured micro-electrofluidic cables
US20070189910A1 (en) * 2006-01-20 2007-08-16 Albert-Ludwigs-Universitaet Freiburg Fluid handling apparatus and method of handling a fluid
US7258774B2 (en) 2000-10-03 2007-08-21 California Institute Of Technology Microfluidic devices and methods of use
EP2352036A1 (fr) 2008-10-28 2011-08-03 Fujikura Kasei Co., Ltd. Dispositif de trajet d'écoulement de liquide et son procédé de fabrication
US8852529B2 (en) 2010-03-10 2014-10-07 Nexvivo Co., Ltd. Particle processing device using centrifugal force
US11117135B2 (en) 2016-10-28 2021-09-14 Sysmex Corporation Liquid-sealed cartridge and liquid transferring method
WO2022010987A1 (fr) 2020-07-07 2022-01-13 Redbud Labs, Inc. Dispositifs microfluidiques et procédés comprenant des membranes souples

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6123316A (en) * 1996-11-27 2000-09-26 Xerox Corporation Conduit system for a valve array
US20050205136A1 (en) * 2000-02-29 2005-09-22 Freeman Alex R Integrally manufactured micro-electrofluidic cables
US7258774B2 (en) 2000-10-03 2007-08-21 California Institute Of Technology Microfluidic devices and methods of use
US20020155010A1 (en) 2001-04-24 2002-10-24 Karp Christoph D. Microfluidic valve with partially restrained element
US20070189910A1 (en) * 2006-01-20 2007-08-16 Albert-Ludwigs-Universitaet Freiburg Fluid handling apparatus and method of handling a fluid
EP2352036A1 (fr) 2008-10-28 2011-08-03 Fujikura Kasei Co., Ltd. Dispositif de trajet d'écoulement de liquide et son procédé de fabrication
EP2352036B1 (fr) * 2008-10-28 2019-09-11 Fujikura Kasei Co., Ltd. Dispositif de trajet d'écoulement de liquide
US8852529B2 (en) 2010-03-10 2014-10-07 Nexvivo Co., Ltd. Particle processing device using centrifugal force
US11117135B2 (en) 2016-10-28 2021-09-14 Sysmex Corporation Liquid-sealed cartridge and liquid transferring method
WO2022010987A1 (fr) 2020-07-07 2022-01-13 Redbud Labs, Inc. Dispositifs microfluidiques et procédés comprenant des membranes souples

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
BOHM S ET AL: "A micromachined silicon valve driven by a miniature bi-stable electro-magnetic actuator", SENSORS AND ACTUATORS A: PHYSICAL, ELSEVIER BV, NL, vol. 80, no. 1, 1 March 2000 (2000-03-01), pages 77 - 83, XP004189238, ISSN: 0924-4247, DOI: 10.1016/S0924-4247(99)00298-8 *
CLIME LIVIU ET AL: "Active pumping and control of flows in centrifugal microfluidics", MICROFLUIDICS AND NANOFLUIDICS, SPRINGER BERLIN HEIDELBERG, BERLIN/HEIDELBERG, vol. 23, no. 3, 2 February 2019 (2019-02-02), pages 1 - 22, XP036728862, ISSN: 1613-4982, [retrieved on 20190202], DOI: 10.1007/S10404-019-2198-X *
MORRIS, CHRISTOPHER G.: "Academic PressDictionary of Scienceand Technology", 1992, GULF PROFESSIONAL PUBLISHING, pages: 267
SCHOMBURG W K ET AL: "AMANDA - Low-cost production of microfluidic devices", SENSORS AND ACTUATORS A: PHYSICAL, ELSEVIER BV, NL, vol. 70, no. 1-2, 1 October 1998 (1998-10-01), pages 153 - 158, XP004140126, ISSN: 0924-4247, DOI: 10.1016/S0924-4247(98)00126-5 *

Similar Documents

Publication Publication Date Title
US6431212B1 (en) Valve for use in microfluidic structures
Gorkin III et al. Pneumatic pumping in centrifugal microfluidic platforms
US6981518B2 (en) Latching micro-regulator
US20050224351A1 (en) Microfluidic devices for introducing and dispensing fluids from microfluidic systems
EP2344938B1 (fr) Dispositif de déviation de jet
US8309039B2 (en) Valve structure for consistent valve operation of a miniaturized fluid delivery and analysis system
US20080271799A1 (en) Microfluidic Regulating Device
Lai et al. Design and dynamic characterization of “single-stroke” peristaltic PDMS micropumps
Aeinehvand et al. Reversible thermo-pneumatic valves on centrifugal microfluidic platforms
WO2004034028A2 (fr) Systemes et composants microfluidiques
WO2002001081A2 (fr) Valve pour structures microfluidiques
Ni et al. An integrated planar magnetic micropump
Churski et al. Droplet on demand system utilizing a computer controlled microvalve integrated into a stiff polymeric microfluidic device
Carpentras et al. A novel magnetic active valve for lab-on-CD technology
WO2024175560A1 (fr) Dispositif microfluidique
Tice et al. Control of pressure-driven components in integrated microfluidic devices using an on-chip electrostatic microvalve
US9791068B2 (en) Lifting gate polydimethylsiloxane microvalves and pumps for microfluidic control
Shikida et al. A palmtop-sized rotary-drive-type biochemical analysis system by magnetic bead handling
Xiang et al. Mechanically programmed valving technology and the active flow switching application in centrifugal microfluidics
KR100846489B1 (ko) 미세유체 칩 및 그를 구비한 미세유체 조작장치
Johnston et al. Elastomer-glass micropump employing active throttles
CN1521499A (zh) 多方向逻辑式微流体控制系统及其方法
Li et al. Pneumatic pumps
US20190024648A1 (en) Architecture for a system of integrated pumps, mixers, and gates for microfluidic devices
Morimoto et al. Layer-to-layer parallel fluidic transportation system by addressable fluidic gate arrays

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 24706114

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE