EP4196270A1 - Cuve à circulation pour intégrer une unité de traitement dans un dispositif microfluidique et procédé de traitement d'un fluide échantillon - Google Patents

Cuve à circulation pour intégrer une unité de traitement dans un dispositif microfluidique et procédé de traitement d'un fluide échantillon

Info

Publication number
EP4196270A1
EP4196270A1 EP21758317.8A EP21758317A EP4196270A1 EP 4196270 A1 EP4196270 A1 EP 4196270A1 EP 21758317 A EP21758317 A EP 21758317A EP 4196270 A1 EP4196270 A1 EP 4196270A1
Authority
EP
European Patent Office
Prior art keywords
flow cell
fluid
capillary gap
sample liquid
processing unit
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
EP21758317.8A
Other languages
German (de)
English (en)
Inventor
Daniel Sebastian Podbiel
Hannah Bott
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Robert Bosch GmbH
Original Assignee
Robert Bosch GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Robert Bosch GmbH filed Critical Robert Bosch GmbH
Publication of EP4196270A1 publication Critical patent/EP4196270A1/fr
Pending 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
    • B01L3/502715—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 interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
    • 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
    • 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
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • B01L2200/027—Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
    • 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
    • B01L2200/12—Specific details about manufacturing devices
    • 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
    • B01L2300/04—Closures and closing means
    • B01L2300/046—Function or devices integrated in the closure
    • B01L2300/047—Additional chamber, reservoir
    • 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
    • B01L2300/0877—Flow 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
    • B01L2400/08—Regulating or influencing the flow resistance
    • B01L2400/084—Passive control of flow resistance

Definitions

  • the invention is based on a flow cell for integrating a processing unit in a microfluidic device and a method for processing a sample liquid with a flow cell according to the species of the independent claims.
  • the subject matter of the present invention is also a computer program.
  • Microfluidic devices or systems allow a decentralized analysis of patient samples using modern molecular diagnostic methods.
  • both a suitable design of the structures and a suitable implementation of the process steps are generally necessary in order to ensure the desired functionalities.
  • a suitable design of the microfluidic structures and the use of capillary effects for example through the realization of so-called phase guides for the complete filling of the microfluidic structures.
  • the invention presented here compensates for possible impairments in the functionality of microfluidic structures due to structural or chemical inhomogeneities, such as a rough surface, on a surface to be wetted with a sample liquid. Pinning of phase interfaces, which is undesired due to such inhomogeneities, is prevented or reduced, as a result of which the fluid guidance in the microfluidic device is promoted.
  • the filling characteristics of the microfluidic device are also influenced in a positive way, which has an advantageous effect on reproducibility.
  • a flow cell for integrating a processing unit into a microfluidic device having a receiving device with a depression, the processing unit being arranged or arrangable in the depression.
  • the flow cell has a cover device for covering the depression and at least one capillary gap for (e.g. capillary) receiving a fluid, the capillary gap being formed between an edge region of the cover device and the receiving device and additionally or alternatively between the cover device and the processing unit.
  • the microfluidic device can be a so-called lab-on-chip system, for example, which can be used for the preparation and analysis of different sample liquids by means of various integrated components.
  • an aqueous solution can be used as the sample liquid, for example for carrying out chemical, biochemical, medical or molecular diagnostic analyses.
  • This can be, for example, a so-called PCR master mix or rITA master mix, in particular with sample material contained therein, for example of human origin, obtained, for example, from body fluids, swabs, secretions, sputum or tissue samples.
  • the targets to be detected in the sample liquid can, for example, be of medical, clinical, therapeutic or diagnostic relevance and can be, for example, bacteria, viruses, specific cells such as circulating tumor cells, cell-free DNA, proteins or other biomarkers.
  • a processing unit can be integrated into the flow cell presented here, which is, for example, an aliquoting structure, for example a multi-cavity array for introducing a sample liquid, or microfluidic separation structures, for example a net or a filter. can act.
  • the processing unit is arranged in the recess of the receiving device, wherein the recess can have dimensions of 3 x 3 x 0.1 mm 3 to 30 x 30 x 3 mm 3 , preferably 3 x 3 x 0.3 mm 3 to 10, for example x 10 x 1mm 3 .
  • a capillary gap is created which is designed to receive and enclose a fluid, for example the sample liquid, by means of capillary forces.
  • a phase interface can thus be created between the sample liquid in the capillary gap and another fluid, which can be conducted to the processing unit for a reaction, for example.
  • the cover device can have a recess, in which case a receiving chamber for receiving the fluid can be provided between the processing unit that is arranged or can be arranged in the recess and the recess.
  • the receiving chamber can have a volume of 1 pl to 1 ml, preferably 3 pl to 100 pl and in particular 20 pl.
  • Such a receiving chamber has the advantage that an introduced fluid can be easily received and evenly distributed over the processing unit.
  • the cover unit can be made transparent, for example, so that the distribution and the reaction occurring in the receiving chamber can be observed from outside the flow cell.
  • a capillary gap height can be smaller than a height of a central area of the receiving chamber, in which case the capillary gap height can in particular be at least no more than 10% of the height of the central area of the receiving chamber.
  • the height of the capillary gap can be, for example, 10 ⁇ m to 500 ⁇ m, in particular 100 to 150 ⁇ m.
  • this allows the absorption of fluids to be optimized by means of capillary forces.
  • the flow cell can comprise a further capillary gap which can be arranged on a further edge region of the cover unit opposite the capillary gap.
  • the capillary gap and the further capillary gap can run along the receiving chamber in the direction of flow, as a result of which the receiving chamber can advantageously be almost completely sealed laterally by a fluid and an undesired pinning effect can be avoided.
  • any undesired structural inhomogeneities in the structure surface can be wetted or filled with the liquid, so that pinning, for example, of the sample liquid to these inhomogeneities can be prevented or significantly reduced.
  • the cover device can have an elevation along the edge region, with between the elevation and a capillary channel can be formed in the edge area, in particular wherein the capillary gap can be formed between the elevation and the processing unit.
  • the elevation can run parallel to the edge area of the cover device, similar to a step or a bulge, and thus form the capillary channel.
  • a fluid is introduced into the receiving chamber, it can be drawn directly into the capillary channel by capillary forces, for example, or it can be drawn into the capillary channel by capillary forces during the course of filling the receiving chamber through the capillary gap formed between the elevation and the processing unit.
  • the formation of such an elevation in addition to a saving in material, can also result in an optical marking for centering the cover device on the receiving device.
  • the flow cell can have an inlet opening for introducing the fluid into the receiving chamber in a direction of flow, wherein the receiving chamber can be delimited laterally in the direction of flow by the capillary gap and the further capillary gap.
  • the flow cell can be designed, for example, to take in a fluid through the inlet opening and to release it again through an outlet opening, for example arranged opposite the inlet opening. Due to the lateral delimitation by the capillary gap and the further capillary gap, a fluid located in the receiving chamber, for example a sample liquid, can advantageously be completely displaced by a subsequently introduced fluid, with an undesired pinning of the phase interface adjoining the sample liquid to inhomogeneities of the structural surface being prevented can.
  • the capillary gap can adjoin the recess.
  • the capillary gap can, for example, along a side portion of the Deepening run, at the same time being in direct proximity to the processing unit arranged in the deepening.
  • Such an arrangement has the advantage that the spatial volume of the receiving chamber, including the capillary gap, can be kept as small as possible, as a result of which only a small amount of fluid can be used.
  • a surface-independent microfluidic processing is made possible by the capillary enclosed fluid defining the surface properties of the structure and thus the fluidic processing.
  • a method for processing a sample liquid with a variant of the flow cell presented above including a step of wetting the at least one capillary gap with the fluid, a step of enclosing part of the fluid in the capillary gap and a step of introducing a sample liquid included in the receiving chamber.
  • the step of wetting the at least one capillary gap with the fluid can also be referred to as priming of structures, with these structures being pre-wetted by the fluid to be processed or by an additional fluid.
  • a gas for example CO2, or another fluid, for example ethanol, can be used for this purpose.
  • the sample liquid can be used as the fluid in the method for the wetting, enclosing and introducing steps.
  • the use of the sample liquid for priming the microfluidic structure is particularly advantageous if the flow cell must not be wetted with additional fluids before the sample analysis, in particular in predetermined partial areas.
  • a portion of the sample liquid can thus advantageously be enclosed in the at least one capillary gap and thus prevent subsequent fluids from being pinned to surface inhomogeneities of the receiving chamber.
  • the method can additionally include a step of displacing at least part of the fluid with the sample liquid and additionally or alternatively with another fluid.
  • sequential process steps can also be carried out in the previously presented flow cell with this method which successively different fluids are introduced into a microfluidic structure.
  • a requirement in the sequential process management can therefore also be the complete displacement of one fluid from the receiving chamber by another fluid in order to avoid inclusions of the first fluid and to ensure complete filling, in particular of predetermined partial areas, with the second fluid.
  • the method can additionally include a step of evaluating a reaction of the sample liquid on the processing unit after part of the sample liquid introduced into the receiving chamber has been discharged from the receiving chamber.
  • the fluid following the sample liquid can be made transparent, so that in particular optical reactions of the sample liquid remaining in the processing unit can be clearly recognized.
  • a method for producing a variant of the flow cell presented above comprising a step of providing the receiving device and the cover device and a step of assembling the receiving device and the cover device to produce a variant of the flow cell presented above.
  • the receiving device and the cover device can be formed from a polymer substrate, for example polycarbonate (PC), polypropylene (PP), polyethylene (PE), cycloolefin copolymer (COP, COC), polymethyl methacrylate (PMMA) or polydimethylsiloxane (PDMS).
  • the components produced can, for example, have a thickness of 0.6 mm to 30 mm, in particular 1 mm to 10 mm.
  • Variants of these methods can be implemented, for example, in software or hardware or in a mixed form of software and hardware, for example in a control unit.
  • control unit can operate at least one microfluidic pump unit for processing at least one fluid.
  • control unit can have at least one computing unit for processing signals or data, at least one memory unit for storing signals or data, at least one interface to a sensor or an actuator for reading in sensor signals from the sensor or for outputting control signals to the actuator and/or or have at least one communication interface for reading in or outputting data that are embedded in a communication protocol.
  • the arithmetic unit can be, for example, a signal processor, a microcontroller or the like, with the memory unit being able to be a flash memory, an EEPROM or a magnetic memory unit.
  • the communication interface can be designed to read in or output data wirelessly and additionally or alternatively by wire, wherein a communication interface that can read in or output wire-bound data can, for example, read this data electrically or optically from a corresponding data transmission line or can output it to a corresponding data transmission line.
  • a control device can be understood to mean an electrical device that processes sensor signals and outputs control and/or data signals as a function thereof.
  • the control unit can have an interface that can be designed in terms of hardware and/or software.
  • the interfaces can be part of what is known as a system ASIC, for example, which contains a wide variety of functions of the control unit.
  • the interfaces can be separate integrated circuits or to consist at least partially of discrete components.
  • the interfaces can be software modules which are present, for example, on a microcontroller alongside other software modules.
  • a computer program product or computer program with program code which can be stored on a machine-readable carrier or storage medium such as a semiconductor memory, a hard disk memory or an optical memory and for carrying out, implementing and/or controlling the steps of the method according to one of the embodiments described above, is also advantageous used, especially when the program product or program is run on a computer or device.
  • FIG. 1 shows a schematic cross-sectional representation of an exemplary embodiment of a flow cell
  • FIG. 2 shows a schematic representation of an exemplary embodiment of a flow cell
  • FIG. 3 shows a schematic cross-sectional illustration of an embodiment of a flow cell with a capillary channel
  • FIG. 4 shows a schematic representation of an exemplary embodiment of a flow cell during the introduction of the sample liquid
  • FIG. 5 shows a schematic representation of an embodiment of a flow cell during the filling of the capillary gap and the further capillary gap
  • FIG. 6 shows a schematic representation of an exemplary embodiment of a flow cell during the filling of the processing unit
  • FIG. 7 shows a schematic representation of an embodiment of a flow cell completely filled with sample liquid
  • 8 shows a schematic representation of an exemplary embodiment of a flow cell during the introduction of a sealing fluid
  • FIG. 9 shows a schematic representation of an exemplary embodiment of a flow cell during displacement of the sample liquid by the sealing fluid
  • FIG. 10 shows a schematic cross-sectional illustration of an exemplary embodiment of a flow cell with a capillary gap
  • FIG. 11 shows a flowchart of an embodiment of a method for processing a sample liquid
  • FIG. 12 shows a flow chart of an embodiment of a method for processing a sample liquid with an additional displacement step
  • FIG. 13 shows a flow chart of an embodiment of a method for processing a sample liquid with an additional step of evaluation
  • FIG. 14 shows a flow chart of an embodiment of a method for producing a flow cell
  • FIG. 15 shows a block diagram of an embodiment of a control device for controlling steps of an embodiment of a method for processing a sample liquid
  • 16 shows a block diagram of an embodiment of a control device for controlling steps of an embodiment of a method for producing a flow cell.
  • an embodiment includes an "and/or" link between a first feature and a second feature, this should be read in such a way that the embodiment according to one embodiment includes both the first feature and the second feature and according to a further embodiment either only that having the first feature or only the second feature.
  • the flow cell 100 comprises a receiving device 105 with a depression 110 in which a processing unit 115 is arranged.
  • the processing unit 115 is in the form of a silicon microcavity array for aliquoting a sample of liquid.
  • a cover device 120 which can also contain fluidic structures of the microfluidic system and is also formed with a recess 125, is arranged above receiving device 105 and thus also above processing unit 115, with a receiving chamber 130 being formed between recess 125 and depression 110 .
  • the receiving chamber 130 is designed to receive a fluid, with the processing unit 115 and other areas of the receiving chamber 130 being wetted with the fluid.
  • the fluid also penetrates into the capillary gap 135 which is formed between an edge area 140 of the cover device 120 and the processing unit 115 .
  • the capillary gap is formed laterally offset between the cover device 120 and the receiving device 105 .
  • a further capillary gap 145 is arranged opposite the capillary gap 135 and is formed between a further edge area 150 of the cover device 120 and the receiving device 105 .
  • So-called priming of the structures can be carried out in the flow cell 100 shown here, with regions of the receiving chamber 130 being pre-wetted by a sample liquid, which can also be referred to as the fluid to be processed, or by an additional fluid.
  • a gas for example CO 2
  • another fluid for example ethanol
  • the flow cell 100, into which the processing unit 115, which can also be referred to as an additional component, is integrated is fluidically designed in this exemplary embodiment such that the processing unit 115 can be integrated and processed, so that priming-free, sequential fluidic processing of the processing unit 115 is enabled.
  • the flow cell 100 is designed such that the integration of the processing unit 115 and the joining of the receiving device 105 to the cover device 120 creates a capillary gap 135, which can also be referred to as a gap, which can be filled capillary, resulting in a capillary guide.
  • the capillary gap 135 arranged between the processing unit 115 and the cover device 120 is significantly smaller than a middle region of the receiving chamber 130, which can also be referred to as the headspace of the flow cell 100.
  • the height of the capillary gap is therefore less than the height between the functional part of the processing unit 115 that is to be filled and the cover device 120 of the flow cell 100.
  • FIG. 2 shows a schematic representation of a flow cell 100 according to an exemplary embodiment. This can be the flow cell described in FIG.
  • the flow cell 100 is arranged in a microfluidic device 200 and is designed to receive a fluid through an inlet opening 205 . From the inlet opening 205 , an elevation 210 and an additional elevation 215 each run along two opposite sides of the processing unit 115 , delimiting a capillary channel 220 and another capillary channel 225 from an area of the receiving chamber 130 . In this exemplary embodiment, the flow cell 100 is designed to pass the fluid between the processing unit 115 and the elevation 210 into the capillary channel 220 and between the processing unit 115 and the further elevation 215 through a capillary gap, as was described in Figure 1 further capillary channel 225 to draw.
  • the receiving chamber 130 is wetted by the fluid, as a result of which inhomogeneities in the material of the flow cell 100 are compensated for.
  • An inclusion of the fluid in the capillary gaps and the capillary channel 220 and the further capillary channel 225 is achieved, so that a subsequent filling of the receiving chamber with a sample liquid is possible.
  • the elevation 210 and the further elevation 215 lead to an outlet opening 230 for dispensing the previously absorbed fluid or part of the previously absorbed fluid.
  • FIG 3 shows a schematic cross-sectional illustration of an exemplary embodiment of a flow cell 100 with a capillary channel 220.
  • the receiving chamber 130 is delimited on both sides by the elevation 210 and the further elevation 215, so that the actual receiving chamber 130 is shown on a smaller scale than the receiving chamber described in FIG.
  • a capillary channel 220 is formed between the elevation 210 and the edge region 140, and a further capillary channel 225 is formed between the further elevation 215 and the further edge region 150.
  • the capillary channel 220 and the further capillary channel 225 are formed in order to enter the receiving chamber 130 absorb introduced fluids.
  • an introduced fluid which can be the sample liquid only by way of example, is drawn through the capillary gap 135 into the capillary channel 220 and through the capillary gap 145 into the capillary channel 225 by means of capillary forces.
  • the fluid enclosed in the capillary gap 135 and in the further capillary gap 145 seals the receiving chamber 130 on both sides and undesired pinning of subsequently introduced fluids into the receiving chamber 130 is avoided.
  • FIG. 4 shows a schematic representation of an exemplary embodiment of a flow cell 100 during the introduction of the sample liquid 400.
  • This can be the flow cell described in the previous figures.
  • FIG. 4 shown here is divided into a left-hand sub-figure and a right-hand sub-figure, with the right-hand sub-figure showing an enlargement of part of the schematic representation of the left-hand sub-figure.
  • the flow cell 100 comprises a processing unit 115, which can also be referred to as an aliquoting structure and is formed with a silicon microcavity array only by way of example.
  • the sample liquid 400 is introduced into the flow cell 100 through the inlet opening 205 .
  • FIG. 5 shows a schematic representation of an exemplary embodiment of a flow cell 100 during the filling of the capillary gap 135 and the further capillary gap 145.
  • This can be the flow cell described in the previous figures and the sample liquid described in FIG. Similar to FIG. 4, FIG. 5 shown here is also divided into two sub-figures, with the right-hand sub-figure showing an enlargement of part of the schematic representation of the left-hand sub-figure.
  • the sample liquid 400 reaches the capillary gap 135 and the further capillary gap 145, which can each also be referred to as capillary guides. Due to capillary forces, the sample liquid 400 is drawn into the capillary gap 135 and the further capillary gap 145 and fills them before the receiving chamber 130 is completely filled.
  • FIG. 6 shows a schematic representation of an exemplary embodiment of a flow cell 100 during the filling of the processing unit 115. This can be the flow cell and the processing unit described in the previous figures. Similar to FIG. 4 and FIG. 5, FIG. 6 shown here is also divided into two sub-figures, with the right-hand sub-figure showing an enlargement of part of the schematic representation of the left-hand sub-figure. In the representation shown here, the capillary gap 135 and the further capillary gap 145 are completely filled with the sample liquid 400 and the sample liquid 400 reaches the processing unit 115 and fills the compartments to be aliquoted.
  • FIG. 7 shows a schematic representation of an exemplary embodiment of a flow cell 100 completely filled with sample liquid 400. This can be the flow cell described in the previous figures. Similar to FIG. 4, FIG. 5 and FIG. 6, FIG. 7 shown here is also divided into two sub-figures, with the right-hand sub-figure showing an enlargement of part of the schematic representation of the left-hand sub-figure. In the here shown representation, the entire flow cell 100 is wetted with the sample liquid 400 .
  • FIG. 8 shows a schematic representation of an exemplary embodiment of a flow cell 100 during the introduction of a sealing fluid 800.
  • This can be the flow cell described in the previous figures. Similar to FIG. 4, FIG. 5, FIG. 6 and FIG. 7, FIG. 8 shown here is also divided into two sub-figures, with the right sub-figure showing an enlargement of part of the schematic illustration of the left sub-figure.
  • a sealing fluid 800 which can also be referred to as fluid 2 or displacement fluid, is introduced into the flow cell 100 to displace the sample liquid 400, which can also be referred to as fluid 1, and to seal the processing unit 115.
  • the sealing fluid is a mineral oil.
  • silicone oils, fluorinated hydrocarbons such as 3M Fluorinert or Fomblin can also be used in a suitable combination, with the two phases being immiscible or only slightly miscible, for example 3M Fluorinert FC40, FC-70 and/or silicone oil.
  • FIG. 9 shows a schematic representation of an exemplary embodiment of a flow cell 100 during the displacement of the sample liquid 400 by the sealing fluid 800.
  • This can be the flow cell described in the previous figures. Similar to FIG. 4, FIG. 5, FIG. 6, FIG. 7 and FIG. 8, FIG. 9 shown here is also divided into two partial figures, with the right partial figure showing an enlargement of part of the schematic illustration of the left partial figure.
  • the receiving chamber 130 is largely filled with the sealing fluid 800 , as a result of which the sample liquid 400 is displaced from the receiving chamber 130 .
  • the sample liquid 400 enclosed in the capillary gap 135 and in the further capillary gap 145 remains there and serves as a phase shaper of the resulting interface between the sample liquid 400 and the sealing fluid 800 in the sequential process of the aliquoting structure with the sealing fluid 800. This ensures a complete, pinning-free displacement of the Sample liquid 400 from the functional area of the processing unit 115 is reached with the compartments to be aliquoted.
  • FIG. 10 shows a schematic cross-sectional illustration of an exemplary embodiment of a flow cell 100 with a capillary gap 135. This can be the flow cell described in the previous figures.
  • FIG. 10 shown here is divided into two sub-figures, with the lower sub-figure showing an enlargement of part of the schematic representation of the upper sub-figure.
  • the capillary gap 135 is arranged between the cover device 120, which can also be referred to as a microfluidic component—top side, and the processing unit 115, which can also be referred to as a silicon component.
  • both the processing unit 115 and the capillary gap 135 are surrounded by the receiving device 105, which can also be referred to as a microfluidic component—bottom side.
  • the capillary gap 135 can also be placed to the side of the processing unit 115, which can also be referred to as a component to be integrated, and/or only in partial areas of the flow cell 100.
  • the preceding figures 1 to 10 show a flow cell 100, which allows a continuous pinning-free wetting of partial areas of the flow cell 100 with a sample liquid 400, using a further liquid, or a sealing fluid 800, and utilizing a capillary force induced retention or inclusion of the additional liquid on a surface provided for this purpose or in sub-areas of the flow cell 100 provided for this purpose.
  • the flow cell 100 is therefore configured in such a way that the additional liquid remains or is included in sub-areas provided for this purpose, such as in capillary gaps, for example, in order to achieve a particularly defined filling of other partial areas of the flow cell 100 with a sample liquid 400.
  • the method 1100 includes a step 1105 of wetting the at least one capillary gap with the fluid. In other words, in this first step, partial areas of the flow cell are wetted with a liquid.
  • the method 1100 includes a step 1110 of enclosing part of the fluid in the capillary gap and a step 1115 of introducing a sample liquid into the receiving chamber. Step 1110 of enclosing and step 1115 of introducing can also be carried out in reverse order or simultaneously. In other words, the sample liquid is introduced into the flow cell.
  • the fluid When the sample liquid is introduced, the fluid is left behind or trapped on a surface or in partial areas of the flow cell, induced by capillary forces, so that continuous pinning-free filling of partial areas of the flow cell with the sample liquid can be achieved, i.e. in particular filling , in which a continuous progression of a phase boundary surface adjoining the sample liquid through the flow cell is achieved.
  • the wetting behavior of the sample liquid can be advantageously adjusted when filling partial areas of the flow cell.
  • FIG. 12 shows a flow chart of an embodiment of a method 1100 for processing a sample liquid with a flow cell with an additional step 1200 of displacing at least part of the fluid with the sample liquid.
  • step 1200 of displacing a portion of the fluid with another fluid may be performed.
  • sequential processing with multiple fluids in the flow cell is made possible. This is desirable in particular when it is necessary for the analysis of a sample to completely fill and again empty a microfluidic structure at least in partial areas, or to completely displace a fluid from the structure.
  • FIG. 13 shows a flow chart of an embodiment of a method 1100 for processing a sample liquid with a flow cell with an additional step 1300 of evaluation. In step 1300 of evaluation, a reaction of the sample liquid on the processing unit is evaluated after part of the sample liquid introduced into the receiving chamber has been discharged from the receiving chamber.
  • the method 1400 comprises a step 1405 of providing the receiving device and the cover device and a step 1410 of assembling the receiving device and the cover device.
  • FIG. 15 shows a block diagram of an embodiment of a control device 1500 for controlling steps of an embodiment of a method 1100 for processing a sample liquid.
  • the control unit 1500 includes a device 1510 for wetting the at least one capillary gap with the fluid.
  • the control unit 1500 includes a device 1520 for enclosing part of the fluid in the capillary gap and a device 1530 for introducing a sample liquid into the receiving chamber.
  • FIG. 16 shows a block diagram of an embodiment of a control device 1600 for controlling steps of an embodiment of a method 1400 for manufacturing a flow cell.
  • the control unit 1600 includes a device 1610 for providing the receiving device and the cover device and a device 1620 for joining the receiving device and the cover device.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Abstract

L'invention concerne une cuve à circulation (100) pour intégrer une unité de traitement (115) dans un dispositif microfluidique (200), la cuve à circulation (100) comportant une unité de réception (105) avec un évidement (110), l'unité de traitement (115) étant/pouvant être disposée dans l'évidement (110). La cuve à circulation (100) comprend en outre une unité de couvercle (120) destiné à recouvrir l'évidement (110) et au moins un espace capillaire (135) pour recevoir un fluide, l'espace capillaire (135) est formée entre une région de bord (140) de l'unité de couvercle (120) et l'unité de réception (105) et, de plus ou en variante, entre l'unité de couvercle (120) et l'unité de traitement (115).
EP21758317.8A 2020-08-12 2021-07-27 Cuve à circulation pour intégrer une unité de traitement dans un dispositif microfluidique et procédé de traitement d'un fluide échantillon Pending EP4196270A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102020210219.8A DE102020210219A1 (de) 2020-08-12 2020-08-12 Flusszelle zum Integrieren einer Prozessierungseinheit in eine mikrofluidische Vorrichtung und Verfahren zum Prozessieren einer Probenflüssigkeit
PCT/EP2021/070915 WO2022033858A1 (fr) 2020-08-12 2021-07-27 Cuve à circulation pour intégrer une unité de traitement dans un dispositif microfluidique et procédé de traitement d'un fluide échantillon

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EP4196270A1 true EP4196270A1 (fr) 2023-06-21

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EP21758317.8A Pending EP4196270A1 (fr) 2020-08-12 2021-07-27 Cuve à circulation pour intégrer une unité de traitement dans un dispositif microfluidique et procédé de traitement d'un fluide échantillon

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US (1) US20230347340A1 (fr)
EP (1) EP4196270A1 (fr)
CN (1) CN116075366A (fr)
DE (1) DE102020210219A1 (fr)
WO (1) WO2022033858A1 (fr)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10326607A1 (de) 2003-06-13 2005-01-05 Steag Microparts Gmbh Vorrichtung zum Handhaben von Flüssigkeiten
GB0614297D0 (en) * 2006-07-19 2006-08-30 Shaw Water Engineering Ltd Apparatus, system and method for detecting particles
DE102006038271A1 (de) 2006-08-11 2008-02-14 Senslab-Gesellschaft Zur Entwicklung Und Herstellung Bioelektrochemischer Sensoren Mbh Sensorvorrichtung mit strukturierter Durchflusszelle
US9803239B2 (en) * 2012-03-29 2017-10-31 Complete Genomics, Inc. Flow cells for high density array chips
US11351548B2 (en) * 2017-10-13 2022-06-07 Maxim Integrated Products, Inc. Analyte sensor package with dispense chemistry and microfluidic cap

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US20230347340A1 (en) 2023-11-02
CN116075366A (zh) 2023-05-05
DE102020210219A1 (de) 2022-02-17
WO2022033858A1 (fr) 2022-02-17

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