EP3978132A1 - Dispositif de transport d'un fluide dans un canal d'un élément microfluidique - Google Patents

Dispositif de transport d'un fluide dans un canal d'un élément microfluidique Download PDF

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Publication number
EP3978132A1
EP3978132A1 EP21204270.9A EP21204270A EP3978132A1 EP 3978132 A1 EP3978132 A1 EP 3978132A1 EP 21204270 A EP21204270 A EP 21204270A EP 3978132 A1 EP3978132 A1 EP 3978132A1
Authority
EP
European Patent Office
Prior art keywords
fluid
pressure
transport
pressure source
face
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.)
Pending
Application number
EP21204270.9A
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German (de)
English (en)
Inventor
Lutz Weber
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.)
Thinxxs Microtechnology GmbH
Original Assignee
Thinxxs Microtechnology 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 Thinxxs Microtechnology GmbH filed Critical Thinxxs Microtechnology GmbH
Publication of EP3978132A1 publication Critical patent/EP3978132A1/fr
Pending 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
    • B01L3/50273—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
    • 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
    • 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
    • B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
    • 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
    • B01L2200/16—Reagents, handling or storing thereof
    • 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
    • B01L2300/0864—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
    • B01L2300/00—Additional constructional details
    • B01L2300/14—Means for pressure control
    • 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
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0694—Valves, specific forms thereof vents used to stop and induce flow, backpressure 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

Definitions

  • the invention relates to a device for transporting a fluid in a duct system of a microfluidic element, in particular a flow cell.
  • liquids e.g. blood to be examined
  • reagents for example, or / and feed a detection area
  • a common task is to separate a specific amount of liquid from a larger bulk sample fed into the flow cell and transport the separated amount of liquid onward.
  • the separated quantity of liquid often has to be divided further into partial quantities of the same or different sizes, with the partial quantities having to be transported further.
  • the invention is based on the object of creating a new device of the type mentioned at the outset, which makes it possible to control transport processes in microfluidic elements more precisely and reliably than in the prior art and at the same time reduce the production costs for the microfluidic elements.
  • the device according to the invention that achieves this object is characterized by a pressure source for pressurizing a front end face in the transport direction of the fluid that fills the cross-section of the channel section.
  • the fluid is not only moved through the channel strand of the microfluidic element by overcoming a resistance caused by friction and capillary forces, but also by overcoming a counterforce generated by the said pressurization.
  • the pressure applied according to the invention at the front end face of the fluid in particular a front liquid meniscus, prevents unwanted detachment of small amounts of fluid from the end face and wetting-related advances or lagging of parts of the amount of fluid close to the delimiting channel walls and thus ensures that the transported fluid is precisely delimited at its Front.
  • the microfluidic element can be closed off in a fluid-tight manner from the outside and environmental contamination by escaping fluid can be prevented. Since coatings for hydrophilization or hydrophobicization, valves for fluid control and/or extremely high accuracy requirements for the microstructures are no longer required, the manufacturing effort is reduced.
  • the pressure source which is preferably a compressed gas source, can be an integral component of the microfluidic element or, for example, a component of an operator device to which the microfluidic element can be coupled.
  • the pressure source comprises a closed space in which a pressurized gas, eg air, is introduced by displacement of the front end face of the fluid transported in the ductwork is compressible.
  • a pressurized gas eg air
  • the pressure built up in the closed space depending on the position of the end surface in the ductwork is applied to the end surface, and the force generated by this pressure must be overcome in addition to the flow resistance when transporting the fluid.
  • the force used to transport the fluid within the microfluidic element can be of different types. While an inertial force, in particular centrifugal force, can be used to shift the fluid in the duct system, in a preferred embodiment of the invention the duct system can be connected to a transport pressure source that acts on the fluid in the transport direction.
  • the transport pressure source can also be an integral part of the microfluidic element.
  • This transport pressure source can be used to apply a compressed gas, e.g.
  • the pressure force generated must overcome the flow resistance and the pressure force applied at the opposite end against the plug-like quantity of fluid according to the invention.
  • the pressure generated by the pressure source at the front end face is clearly functionally related to the position of the front end face in the duct line. This condition is approximately met by the previously mentioned pressure source comprising a closed space. If necessary, a correction factor that takes the ambient temperature into account is determined.
  • a device that detects the pressure on the front end face e.g. a pressure sensor, can advantageously be provided, which uses the functional relationship to determine the position of the front end face in the duct line.
  • the position of a quantity of fluid filling the duct line like a plug within the flow cell can also be determined and its transport precisely controlled.
  • the transport of the fluid can be interrupted by setting the pressure P1 of the transport pressure source equal to the pressure P2 at the front end face.
  • the transport direction can even be reversed.
  • a quantity of fluid that fills the duct line in the manner of a plug can therefore be pushed back and forth as desired within a duct line and positioned at the desired locations eg in reaction areas, detection areas, filters or areas in which it comes into contact with a reagent stored in the microfluidic element or with a test strip known from diagnostics.
  • the pressure rise characteristic of the compressed gas source having the closed space can advantageously be influenced in a desired manner in that the closed space can be expanded by the compressed gas compressed therein.
  • the closed space can have a wall on one side formed by a stretchable film.
  • the closed space of the pressure source can be accommodated in a plate that forms the microfluidic element and/or can be formed by a separate container that can be connected to the plate.
  • the duct line advantageously has at least one cross-sectional widening to form a chamber, e.g. a detection chamber, a mixing chamber, a reaction chamber or the like.
  • the chamber may contain dry reagents, e.g., substances for performing a PCR or for capturing analytes of the fluid sample, filters, membranes, test strips, mixing blades, detection means such as optical windows, prisms and electrical conductors, and other means for analysis and synthesis.
  • a plurality of duct lines can run together in a single duct line which is connected or can be connected to a pressure source.
  • the multiple duct lines can each be connected or can be connected to a transport pressure source, so that a sequence or mixture of different fluids can be generated and transported in the single duct line by sequential activation of the transport pressure sources.
  • a duct line can also branch into a plurality of duct lines that are each connected or can be connected to a pressure source, and in this way can further divide a quantity of fluid into partial quantities without using a plurality of pressure sources or valves.
  • the back pressure applied according to the invention at the front end surfaces of the partial amounts of fluid allows not only an even division of the total amount into partial amounts, but also the spatial separation of the partial amounts by the transport gas flowing after the partial amounts of fluid in the channel strands.
  • the application of back pressure to the fluid to be transported according to the invention also ensures that channel sections with different cross-sectional dimensions are completely filled. Especially in the case of cracks and dimensional changes within a duct run, zones usually occur that are not completely flown through or wetted, which can lead to air bubbles being trapped. This is avoided by the invention.
  • a plate-shaped flow cell has an inlet opening 1 for a fluid, eg a blood sample.
  • the inlet opening 1 is located in the bottom of a pot-like storage vessel 2 molded onto the flow cell.
  • a channel 3 extends from the inlet opening, which runs in a meandering manner up to a widening 4 and is led further from the widening 4 to a branch 5 .
  • a duct 6 opens into the duct 9, which is in communication with an opening to which a source of air pressure can be connected, as will be explained below.
  • a channel 8 leading to a ventilation opening branches off from the channel 3.
  • the cross section of channel 8 is significantly smaller than the cross section of channel 3.
  • the channel 3 divides into two branch channels 9 and 9', which are symmetrical to the longitudinal central axis of the flow cell and divide again at two further junctions 10 and 10'.
  • the channel 3 thus merges into a total of four branches 11, 11', 11" and 11'".
  • the four branches have the same design and have identical volumes.
  • Each of the four branches 11, 11′, 11′′ and 11′′′ contains a first meandering channel section 12, which is followed by a channel widening 13.
  • the channel widening 13 contains a dry reagent.
  • the channel widening 13 is followed by a second meandering channel section 14
  • the channel section 14 is followed by a further widened channel 15, which in the relevant exemplary embodiment serves as a reaction chamber and can contain a further dry reagent, e.g.
  • each branch 11, 11′, 11′′, 11′′′′ forms a chamber 17 with a volume that is significantly larger than the volume of the widenings 13, 15 and 16.
  • the plate-shaped flow cell consists of a plastic plate in which recesses are incorporated to form the channels and cavities described above, and a film sealing the recesses and welded or glued to the plastic plate in a fluid-tight manner.
  • the known plastic processing methods in particular injection molding, can be used to produce the plate.
  • a substrate having a plurality of layers and laminated foils could be provided.
  • Other materials include glass, silicon and metal and composite materials.
  • Other processing methods include hot stamping and laser cutting.
  • a fluid sample for example a blood sample, is introduced into the reservoir 2 at the inlet port 1 .
  • the channel 3 fills up to the widening 4 by capillary action.
  • the channel 3 can be made hydrophilic by plasma treatment or wet-chemical pretreatment.
  • the blood sample could be introduced into the channel 3 by applying pressure, e.g. with the aid of a pipette or syringe.
  • This task could also be performed by an operator facility provided for the flow cell. Air can escape from the channel 3 via the ventilation channel 8 .
  • the widening 4 limits the filling of the channel 3 and thus the precise measurement of a sample quantity, as is shown in Figure 3a is shown.
  • the inlet opening 1 and the channel 8 are closed and the opening 7 is connected to an air pressure source 18 which can be part of an operating device provided for the flow cell.
  • the measured amount of sample can be conveyed beyond the widening 4 in the channel 3 to the branch 5, where the amount of sample is divided into halves.
  • a further division into halves takes place at the branches 10 and 10', so that each of the branches 11, 11', 11" and 11′′′ receives a quarter of the measured sample quantity.
  • the pressure in the chambers 17 increases as a result of compression as the fluid is transported through the channel 3.
  • the air pressure P1 exerted by the compressed air source 18 must be greater than the respective air pressure P2 in the chambers 17, which is applied to the front end surfaces 42 of the fluid quantities in the transport direction.
  • Each position of the sub-sample quantities filling the duct line like plugs corresponds to a specific pressure P2 in the chambers 17. If the pressure P1 of the compressed air source 18 is equal to the pressure P2, the sub-sample quantities remain in place.
  • Figure 3b are the sub-sample amounts just in the channel section 12.
  • the sub-sample amounts according to 3c are transferred to the expansions 13, where they each come into contact with a dry reagent. Reducing the pressure P1 causes the sub-sample quantities to flow back into the meandering channel sections 12, where mixing takes place. Another increase in pressure leads the sub-sample quantity via the widened channels 13 into the next meandering channel section 14. In the channel sections 14, the mixing is completed.
  • a further increase in the pressure P1 results in a transfer to the expansions 15, where a reaction takes place in the exemplary embodiment shown, for example a PCR. Sample testing is completed in the flares 16 where measurements are performed on the processed samples.
  • the compressed air source 18 can have a measuring device for determining the respective pressure P2, which uses a predetermined relationship between the pressure P2 and the positions of the subsets to determine their position and, if necessary, automatically controls the transport of the subsets.
  • the structure of the flow cell shown largely corresponds to that of the flow cell described above. Only the ventilation channel 8 and the channel 6 with the opening 7 are missing.
  • the sample inlet 1 can be connected to a pressure source and a sample quantity filling the storage vessel 2 can be pressed into the channel 3 .
  • the volume of the measured amount of sample thus corresponds approximately to the volume of the storage vessel 2 or to a partial amount predetermined by the person entering it.
  • the sample quantity measured in this way is processed further as described above.
  • FIG figure 5 shows that a pressure source can also be integrated into a flow cell.
  • a pressure source can also be integrated into a flow cell.
  • such an integrated pressure source is formed by a recess 19 which is covered by a flexible membrane 20.
  • the pressure in a pressure line 21 can be increased by a defined amount.
  • the recess 19 could also contain a liquid.
  • a sample liquid could flow through the space formed by the recess 19 .
  • a blister with a curved, compressible foil hood could also be used.
  • an "air spring” is formed by the closed chamber 17 integrated into the flow cell plate.
  • FIG. 6 shows an embodiment of an "air spring” with a chamber 22 which is covered by a flexible membrane 23.
  • the membrane which is made of plastic, an elastomer, silicone or TPE, for example, can be expanded in such a way that a desired increase in pressure occurs in the chamber 22 .
  • the dimensions of the “air spring” are therefore advantageously smaller when the flow cell is not in use than when it is in operation.
  • the bulging of the flexible membrane 23 delimiting the chamber 22 can be determined, for example, with the aid of a simple distance sensor and used to determine the pressure P2 and thus the position of the front fluid meniscus and thus set up a regulation for the fluid transport.
  • the volume of the chamber 22 can be adjusted in the desired manner via the position of the plunger.
  • the stamp can be part of an operator facility.
  • FIG. 7 12 shows a variant of an "air spring” with a separate vessel component 25 that can be attached to a flow cell, with a sealing ring 26 surrounding an opening formed on the flow cell plate.
  • a separate vessel component 27 can be plugged onto a flow cell, in which case, for example, a plug-in crown, a press fit and/or a LUER connection can be used.
  • the slab-shaped flow cell need not have a "spring chamber" itself.
  • the space required for the integrated chamber can be used for other purposes.
  • the vessel component 27 has an adjustable stopper 28, through which the air volume of the vessel component can be varied, so that different conditions for the transport of a fluid within a flow cell can be set.
  • air spring can be part of an operator's facility and a corresponding connection to the flow cell corresponding to the connection of 7 can be made with the help of a ring seal.
  • FIG 9 Flow cell shown three channel strands 29, 30 and 31 for transporting different fluids.
  • Each of the channel strands 29, 30, 31 can be connected to an inlet opening for the relevant fluid and a pressure source.
  • a pressure source common to all three duct lines could be used.
  • the duct runs 29 to 31 converge at a mixing point 32 from which a single duct 33 runs to a closed chamber 34 .
  • sequences of the different fluids contained in the duct lines 29 to 31 can be generated in the duct 33, the size of the subsets being controllable via the pressure applied to the respective duct line.
  • the channel 33 can branch again, with branches 35, 35' each being connected to an air spring chamber 36 or 36'.
  • a fluid sequence generated in the channel 33 at the mixing point 32 can be divided further, with a sequence each reaching the branches 35 and 35 ′, the components of which each have half the fluid quantity of the sequence in the channel 33 .
  • This can be advantageous in order to limit the sequential pressurization of channels 29-31 simplify. If fluid sequences with particularly small subsets are to be generated, this would require a very short and precise pressurization.
  • their accuracy is decisive and this accuracy can be adjusted very precisely during production of the microfluidic element by injection molding.
  • Figure 10b shows a branching duct with one branch 37 connected to a chamber 38 and another branch 39 connected to a chamber 40.
  • the volume of chamber 38 is greater than the volume of chamber 40.
  • the pressure in the smaller chamber 40 increases faster than in chamber 38. Accordingly, a larger partial package is formed at the branching point in branch 37 than in branch 39.
  • the ratio can be adjusted vary as appropriate with the splitting of the fluid packet at the bifurcation point.
  • FIG. 11 shows further exemplary embodiments for flow cells, wherein in the exemplary embodiment of FIG Figure 11a a canal branch with a matrix-like branching and in Figure 11b a ductwork with a star-shaped branching is shown.
  • the duct line has a central inlet opening 41, which at the same time forms a branching point.
  • a pneumatic pressure source for example, can be connected to the branching point.
  • the embodiment of Figure 11b is particularly suitable for the transport of fluid by centrifugal force.
  • the flow cell is rotated around the inlet opening 41 .
EP21204270.9A 2009-06-05 2010-05-14 Dispositif de transport d'un fluide dans un canal d'un élément microfluidique Pending EP3978132A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE202009008052U DE202009008052U1 (de) 2009-03-23 2009-06-05 Vorrichtung zum Transportieren eines Fluids in einem Kanalstrang eines Mikrofluidelements
PCT/DE2010/000541 WO2010139295A1 (fr) 2009-06-05 2010-05-14 Dispositif pour transporter un fluide dans un canal d'élément microfluidique
EP10725960A EP2437890A1 (fr) 2009-06-05 2010-05-14 Dispositif pour transporter un fluide dans un canal d'élément microfluidique

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
EP10725960A Division EP2437890A1 (fr) 2009-06-05 2010-05-14 Dispositif pour transporter un fluide dans un canal d'élément microfluidique

Publications (1)

Publication Number Publication Date
EP3978132A1 true EP3978132A1 (fr) 2022-04-06

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Family Applications (3)

Application Number Title Priority Date Filing Date
EP21204270.9A Pending EP3978132A1 (fr) 2009-06-05 2010-05-14 Dispositif de transport d'un fluide dans un canal d'un élément microfluidique
EP10725960A Ceased EP2437890A1 (fr) 2009-06-05 2010-05-14 Dispositif pour transporter un fluide dans un canal d'élément microfluidique
EP21204273.3A Pending EP3978133A1 (fr) 2009-06-05 2010-05-14 Dispositif de transport d'un fluide dans un canal d'un élément microfluidique

Family Applications After (2)

Application Number Title Priority Date Filing Date
EP10725960A Ceased EP2437890A1 (fr) 2009-06-05 2010-05-14 Dispositif pour transporter un fluide dans un canal d'élément microfluidique
EP21204273.3A Pending EP3978133A1 (fr) 2009-06-05 2010-05-14 Dispositif de transport d'un fluide dans un canal d'un élément microfluidique

Country Status (4)

Country Link
US (1) US10315197B2 (fr)
EP (3) EP3978132A1 (fr)
DE (2) DE102009015395B4 (fr)
WO (1) WO2010139295A1 (fr)

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DE102009015395B4 (de) 2022-11-24
US10315197B2 (en) 2019-06-11
DE202009008052U1 (de) 2009-08-27
EP3978133A1 (fr) 2022-04-06
DE102009015395A1 (de) 2010-09-30
US20120082599A1 (en) 2012-04-05
EP2437890A1 (fr) 2012-04-11

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