WO2024068291A1 - Composant microfluidique - Google Patents

Composant microfluidique Download PDF

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Publication number
WO2024068291A1
WO2024068291A1 PCT/EP2023/075287 EP2023075287W WO2024068291A1 WO 2024068291 A1 WO2024068291 A1 WO 2024068291A1 EP 2023075287 W EP2023075287 W EP 2023075287W WO 2024068291 A1 WO2024068291 A1 WO 2024068291A1
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WO
WIPO (PCT)
Prior art keywords
microfluidic
channels
channel
sub
connecting channel
Prior art date
Application number
PCT/EP2023/075287
Other languages
German (de)
English (en)
Inventor
Stefan Jacob
Melanie Colditz
Andreas Winkler
Stefanie HARTMANN
Uhland WEISSKER
Original Assignee
Leibniz-Institut Für Festkörper- Und Werkstoffforschung Dresden E. V.
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 Leibniz-Institut Für Festkörper- Und Werkstoffforschung Dresden E. V. filed Critical Leibniz-Institut Für Festkörper- Und Werkstoffforschung Dresden E. V.
Publication of WO2024068291A1 publication Critical patent/WO2024068291A1/fr

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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
    • B01L3/502746—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
    • B01L3/502761—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 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
    • 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
    • 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
    • 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
    • B01L2200/0668—Trapping microscopic beads
    • 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
    • B01L2300/0864—Configuration of multiple channels and/or chambers in a single devices comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
    • 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
    • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • 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
    • B01L2400/086—Passive control of flow resistance using baffles or other fixed flow obstructions

Definitions

  • the invention relates to the fields of microsystems technology and microfluidics and relates to a microfluidic component, such as for actuator or sensory lab-on-a-chip systems, for portable microfluidic systems for field use in agriculture, bioanalytics, etc Medical technology for which impedance spectroscopy, surface plasmon resonance or electromagnetic separation can be used in medical technology or in analytical chemistry and biochemistry.
  • a microfluidic component such as for actuator or sensory lab-on-a-chip systems, for portable microfluidic systems for field use in agriculture, bioanalytics, etc
  • Medical technology for which impedance spectroscopy, surface plasmon resonance or electromagnetic separation can be used in medical technology or in analytical chemistry and biochemistry.
  • Microfluidics deals with the behavior of liquids and gases in the smallest of spaces (Wikipedia, search term “microfluidics”). Microfluidics is also increasingly used for the analysis or manipulation of fluids, for example for the synthesis of particles and medically effective biological molecules/particles/cells.
  • so-called lab-on-a-chip systems also known as micro total analysis systems, pTAS
  • pTAS micro total analysis systems
  • All lab-on-a-chip systems can also perform the necessary tasks that are carried out on a macroscopic scale. These include, for example, mixing, measuring, reacting, transporting, filtering, analyzing (for example optically, electrically or acoustically), etc.
  • microfluidic microchemomechanical system with at least one structural support with at least a first channel, a cover which at least partially covers the structural support and at least one second channel, the second channel being arranged on the structural support or the cover .
  • the channels each form reservoirs delimited by active elements, which are arranged in such a way that they have at least one superposition area to one another and together form a reaction chamber.
  • a microfluidic chip that includes at least one microfluidic channel system, which includes at least one horizontal channel and at least one horizontal chamber, wherein the at least one channel and the at least one chamber are separated by a membrane and the at least one channel can be flowed through by a cell-containing liquid, and has a width of at least 10 pm and a maximum of 300 pm and a depth of at least 10 pm and a maximum of 100 pm.
  • microfluidic processor which has at least one fluidic mixing unit, which has hydrogel actuator-based pumps connected on the output side and produces mixing ratios for various process media, which can be structurally specified by the respective volumes of the pump chambers of the pumps and transport the resulting mixture into reaction or analysis units.
  • At least one polymer layer is applied to a substrate at least at the positions of connecting elements and subsequently brought the connecting element into position on the polymer layer. Subsequently, at least one further polymer layer is applied at least partially over the connecting element at least with a thickness that is at least greater than the height of the connecting element, and then structuring and curing of the at least second polymer layer is realized.
  • the flow resistance in the microfluidic channel can be calculated taking into account the channel dimensions and the cross-sectional shape and then adjusted by changing the geometry (e.g. walls, floors, lids) and surfaces (e.g. roughness, surface chemistry).
  • a disadvantage of the solutions of the prior art is that in the known solutions for microfluidic systems, in particular external events that affect the microfluidic system or internal events, for example in a sub-area of the microfluidic system that affect other sub-areas of the microfluidic system ("crosstalk"), cause disturbances to at least the main function of the microfluidic system, which hinder and/or prevent the desired result that is to be achieved by the microfluidic system, and thus the functionality of the microfluidic system as a whole cannot be reliably guaranteed.
  • crosstalk sub-area of the microfluidic system that affect other sub-areas of the microfluidic system
  • the object of the present invention is to provide a microfluidic component that compensates for, suppresses and/or terminates disturbances in microfluidic systems and thus at least the main function of the microfluidic system is guaranteed to be essentially trouble-free.
  • the microfluidic component according to the invention in a microfluidic system contains at least one channel-shaped component which is connected to the microfluidic system at least with an opening, the channel-shaped component being split into at least two sub-channels, and at least two sub-channels being directly connected by at least one connecting channel, and wherein the connecting channel(s) may have inlets and/or outlets, and wherein a lower flow resistance is realized in the interior of the connecting channels than in the respective sub-channels, and wherein the sub-channels have inlets and/or outlets.
  • the channel-shaped component(s) and/or the sub-channels and/or the connecting channel(s) have dimensions in the micrometer and/or nanometer range, even more advantageously dimensions between 0.1 and 1000 pm. Furthermore advantageously, due to the geometry and/or the surface properties of the surfaces in contact with the fluid, the channel-shaped components have a flow resistance for forming a continuous and/or laminar flow of the fluid.
  • the at least one channel-shaped component is split into 3 to 5 sub-channels.
  • the flow resistance inside a connecting channel is 10 to 100 times lower than in the sub-channels that the connecting channel connects.
  • microfluidic components are integrated into microfluidic systems that are actuator or sensor lab-on-a-chip systems or microfluidic systems.
  • the at least one channel-shaped component and/or the at least two sub-channels and/or the at least one connecting channel and/or the inlets and/or outlets consist at least partially of elastomers such as polydimethylsiloxane (PDMS), glass-based microfluid systems such as silicon, glass, (amorphous) SiO2, polymers such as cycloolefin copolymers (COC), epoxy resins, acrylic resins, PTFE, PMMA, PC, PS and/or PEEK, piezoelectric materials, TOPAS, ceramics, ultra-thin and/or thin glassy or polymeric plates or films and/or dry photoresists.
  • elastomers such as polydimethylsiloxane (PDMS), glass-based microfluid systems such as silicon, glass, (amorphous) SiO2, polymers such as cycloolefin copolymers (COC), epoxy resins, acrylic resins, PTFE, PMMA, PC, PS and/or PEEK
  • microfluidic component in a microfluidic system that has at least one channel-shaped component that is connected to the microfluidic system at least via an opening.
  • the channel-shaped component is further split into at least two sub-channels. Furthermore, the at least two sub-channels are connected by at least one connecting channel, which directly connects the at least two sub-channels to one another.
  • the connecting channel can have inlets and/or outlets.
  • sub-channels have inlets and/or outlets.
  • microfluidic components In a microfluidic system, functional microfluidic components must generally be connected to channel-shaped microfluidic components and channel-shaped microfluidic components must also be present from the inlet and to the outlet of the fluid and other components from and into the microfluidic system. These are also generally referred to as microfluidic channels.
  • fluids in gaseous and/or liquid form are present within a microfluidic system.
  • the fluids can also contain gas bubbles, fluid droplets and/or solids that can be moved in the microfluidic system, or can be mixtures of gaseous or liquid components with solids, such as suspensions, dispersions or emulsions.
  • the channel-shaped components, the sub-channels and/or the connecting channels have dimensions in the micrometer and/or nanometer range, even more advantageously dimensions between 0.1 and 1000 pm.
  • channel-shaped components have geometries and/or surface properties of the surfaces in contact with the fluid, through which they have a flow resistance for forming a continuous and/or laminar flow of the fluid.
  • the at least one channel-shaped component is split into 3 to 5 sub-channels.
  • the at least one connecting channel has dimensions in the micrometer and/or nanometer range, but partially has smaller dimensions of its length and/or larger dimensions of its cross-sectional area than the channel-shaped component before separation.
  • the flow velocity and the associated friction losses on the connecting channel walls are lower and the momentum compensation is considerably smaller.
  • a further advantageous embodiment of the solution according to the invention is that a flow resistance that is 10 - 100 times lower is realized inside a connecting channel than in the sub-channels that the connecting channel connects.
  • microfluidic components are integrated into microfluidic systems, which are actuator or sensory lab-on-a-chip systems or microfluidic systems.
  • microfluidic systems require that inlets and outlets are available on the microfluidic systems, which in turn are usually Connectors, cannulas and tubes connected to peripheral devices for fluid supply, to reservoirs or upstream and/or downstream passive or active (micro-)fluidic elements, or to sampling devices.
  • Connectors cannulas and tubes connected to peripheral devices for fluid supply, to reservoirs or upstream and/or downstream passive or active (micro-)fluidic elements, or to sampling devices.
  • All of these upstream and downstream components in the microfluidic system and in particular the formation of drops at fluid outlets and/or the presence of more than two inlets and outlets of the microfluidic component can cause disruptions to at least the main function of the microfluidic system due to external events such as movements and/or vibrations.
  • movements and vibrations can cause pressure fluctuations in the microfluidic system, which are passed on directly to the fluid in the microfluidic systems due to the low compressibility of fluids.
  • Such disruptions can be bubbles, blockages, temperature fluctuations, pressure fluctuations, the effects of which can be compensated, suppressed and/or stopped by the solution according to the invention.
  • Such disturbances caused by external events also enter the channel-like microfluidic components via the inlets and/or outlets, spread through the fluid and interact with the components through friction on the component walls, through friction in the flow of the fluid, through geometric scattering, through momentum transfer to the flow of the fluid and/or through momentum transfer to the component walls and, if present, to particles in the fluid.
  • the compensation, suppression and/or termination of these disturbances in the microfluidic component takes place proportionately according to the respective flow-mechanical resistances.
  • the disturbances are often not predictable or externally controllable.
  • microfluidic component according to the invention it is now possible for the first time to use the microfluidic component according to the invention to detect such disturbances that are caused by external events or by internal events in the microfluidic system, such as for example in downstream microfluidic components, can be compensated, suppressed and/or terminated in the microfluidic systems and thus at least the main function of the microfluidic system can be ensured essentially without disruption.
  • the solution according to the invention enables a secure, stable operation of the microfluidic systems, in particular independently of downstream microfluidic components.
  • the microfluidic component according to the invention can also ensure that disturbances caused by external and/or internal events do not reach the areas of the microfluidic systems that are present for the respective desired function of the microfluidic systems, but are compensated, suppressed and/or terminated in the microfluidic components according to the invention.
  • the channel-shaped component of the microfluidic component is split into at least two sub-channels after an inlet and/or before an outlet.
  • the at least two sub-channels are then directly connected to one another after and/or before the inlets and/or outlets of the microfluidic system via at least one connecting channel.
  • the connecting channel contains a fluid of the same composition as the at least two sub-channels that the connecting channel connects to one another.
  • connecting channel itself can have inlets and/or outlets.
  • the connecting channel can also be filled with a gas or gas mixture, such as air, which prevents fluid from the sub-channels from penetrating into the connecting channel and further compensates, suppresses or terminates disturbances, for example in the form of pressure fluctuations, due to the compressibility of the gas or gas mixture.
  • a gas or gas mixture such as air
  • At least one partial channel is required for the discharge of the particles after the particles have been separated from the liquid.
  • the liquid can be from the separation point of particle-free liquid and more concentrated Dispersion continues two sub-channels and are subsequently connected to a connecting channel in front of the outlets.
  • the structure of the microfluidic systems for example on chips, can be essentially retained by splitting into sub-channels and integrating connecting channels, since only little space is required for production and/or integration into existing systems and no other production processes are necessary.
  • the solution according to the invention compensates for, suppresses or stops the coupling of interference caused by external or internal influences into microfluidic systems and improves the functionality of the microfluidic components of the microfluidic systems. This also makes it possible to change media or rinse the system without deactivating one or more inlets and/or outlets due to excessive flow resistance. This is also the case if air bubbles occur in the system. Larger volumes of fluid can also be introduced and/or discharged from or into different reservoirs via more than two inlets and/or outlets. Contamination of different fluids in the microfluidic system is also counteracted by avoiding the effects of interference on the function of the microfluidic system.
  • microfluidic systems can be implemented without additional effort in chip production and is compatible with conventional microfluidic systems, such as polymer fluidic chips, microfluidic systems based on elastomers, such as PDMS, or glass-based microfluidic systems.
  • conventional microfluidic systems such as polymer fluidic chips, microfluidic systems based on elastomers, such as PDMS, or glass-based microfluidic systems.
  • the components according to the invention can also be installed as a module in microfluidic systems.
  • the at least one channel-shaped component and/or the at least two partial channels and/or the at least one connecting channel and/or the inlets and/or outlets can be made of elastomers, such as polydimethylsiloxane (PDMS), glass-based microfluid systems, such as silicon, glass, (amorphous ) SiC>2, polymers such as cycloolefin copolymers (COC), epoxy resins, acrylic resins, PTFE, PMMA, PC, PS and/or PEEK, piezoelectric materials, TOPAS, ceramics, ultra-thin and/or thin glassy or polymeric plates or films and / or dry photoresists at least partially consists.
  • elastomers such as polydimethylsiloxane (PDMS), glass-based microfluid systems, such as silicon, glass, (amorphous ) SiC>2, polymers such as cycloolefin copolymers (COC), epoxy resins, acrylic resins, PTFE, PMMA
  • microfluidic component according to the invention can be produced using known processes such as laminating, hot pressing, hot stamping, deep drawing, injection molding, additive manufacturing processes such as inkjet, piezojet, aerosol jet printing, stereolithography, aerosol printing, 3D printing, lithography, (nano) imprinting - Lithography, microtechnology, microcontact printing, wafer bonding, dispensing technologies, CNC processing, laser application processes, milling and/or grinding.
  • additive manufacturing processes such as inkjet, piezojet, aerosol jet printing, stereolithography, aerosol printing, 3D printing, lithography, (nano) imprinting - Lithography, microtechnology, microcontact printing, wafer bonding, dispensing technologies, CNC processing, laser application processes, milling and/or grinding.
  • Fig. 1 is a schematic sketch of a microfluidic component according to the invention.
  • a microfluidic component for separating ceramic particles 600 from water as a fluid consists of a substrate 100 on which the microfluidic component is arranged in a microfluidic system.
  • the water-particle mixture is introduced as a fluid into the channel-shaped component 300.
  • the channel-shaped component 300 is then split into three sub-channels 301, 302, 303 at the location of the split 401.
  • the ceramic particles 600 are discharged from the microfluidic system from a sub-channel 301 with an outlet 501.
  • the particle-free water is discharged from the microfluidic system via the two sub-channels 302/304 and 303/305 via the outlets 502 and 503. Before the water is discharged, the sub-channels 302 and 303 filled with water are directly connected to a connecting channel 504.
  • the channel-shaped component 300 is divided into three sub-channels 301 with the dimensions 100 pm x 50 pm x 75 pm (W x H x L) and 302, 303 with the dimensions 100 pm x 50 pm x 100 pm (W x H x L).
  • the connecting channel 504 has a significantly lower flow resistance inside in relation to R302 and R303.
  • the sub-channels 304 and 305 each have a lower flow resistance in relation to R302 and R303 and a higher flow resistance in relation to R504.
  • the dripping of water from the two outlets 502 and 503 of the two partial channels 304 and 305 triggers a movement which, as an external disturbance, causes a pressure fluctuation in the microfluidic component.

Abstract

L'invention se rapporte au domaine de la technologie des microsystèmes et concerne un composant microfluidique qui peut être utilisé, par exemple, pour des systèmes de laboratoire sur puce d'actionneur ou de capteur. L'objet de la présente invention est de fournir un composant microfluidique qui égalise, supprime et/ou arrête l'interférence dans des systèmes microfluidiques et garantit ainsi qu'au moins la fonction principale du système microfluidique est essentiellement exempte d'interférence. L'objet est atteint par un composant microfluidique dans un système microfluidique, contenant au moins un composant en forme de canal relié au système microfluidique par au moins une ouverture ; ledit composant en forme de canal est divisé en au moins deux sous-canaux, et au moins deux sous-canaux sont directement reliés par au moins un canal de liaison pouvant avoir des entrées et/ou des sorties ; une résistance à l'écoulement inférieure est réalisée à l'intérieur des canaux de liaison que dans les sous-canaux respectifs ; et les sous-canaux présentent des entrées et/ou des sorties.
PCT/EP2023/075287 2022-09-28 2023-09-14 Composant microfluidique WO2024068291A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102022125010.5A DE102022125010A1 (de) 2022-09-28 2022-09-28 Mikrofluidisches Bauteil
DE102022125010.5 2022-09-28

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WO2024068291A1 true WO2024068291A1 (fr) 2024-04-04

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WO2008036083A1 (fr) * 2006-09-19 2008-03-27 Vanderbilt University Cytomètre de flux microfluidique et ses applications
US20170052107A1 (en) * 2010-11-18 2017-02-23 The Regents Of The University Of California Method and device for high-throughput solution exchange for cell and particle suspensions
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