WO2014198703A1 - Dispositif de manipulation de fluide et procédé pour le traitement d'un liquide en utilisant une barrière de diffusion - Google Patents

Dispositif de manipulation de fluide et procédé pour le traitement d'un liquide en utilisant une barrière de diffusion Download PDF

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Publication number
WO2014198703A1
WO2014198703A1 PCT/EP2014/061990 EP2014061990W WO2014198703A1 WO 2014198703 A1 WO2014198703 A1 WO 2014198703A1 EP 2014061990 W EP2014061990 W EP 2014061990W WO 2014198703 A1 WO2014198703 A1 WO 2014198703A1
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WIPO (PCT)
Prior art keywords
compression chamber
liquid
fluid
chamber
gas
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PCT/EP2014/061990
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German (de)
English (en)
Inventor
Nils Paust
Simon Wadle
Gregor CZILWIK
Original Assignee
Hahn-Schickard-Gesellschaft für angewandte Forschung e.V.
Albert-Ludwigs-Universität Freiburg
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Publication of WO2014198703A1 publication Critical patent/WO2014198703A1/fr

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
    • 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
    • B01L3/502723—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 venting arrangements
    • 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
    • B01L3/502738—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 integrated valves
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • 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
    • B01L2200/0605—Metering of 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
    • B01L2200/0621—Control of the sequence of chambers filled or emptied
    • 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
    • B01L2200/0684—Venting, avoiding backpressure, avoid gas bubbles
    • 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
    • B01L2200/14—Process control and prevention of errors
    • B01L2200/142—Preventing evaporation
    • 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
    • B01L2200/14—Process control and prevention of errors
    • B01L2200/143—Quality control, feedback systems
    • B01L2200/146—Employing pressure sensors
    • 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
    • B01L2300/0803—Disc shape
    • 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
    • B01L2300/10—Means to control humidity and/or other gases
    • 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
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B01L2300/1855—Means for temperature control using phase changes in a medium
    • 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
    • B01L2300/18—Means for temperature control
    • B01L2300/1861—Means for temperature control using radiation
    • 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
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0409—Moving fluids with specific forces or mechanical means specific forces centrifugal forces

Definitions

  • the present invention relates to a fluid handling apparatus and method for processing a fluid in which a liquid disposed in a compression chamber is heated to process the same.
  • Such devices and methods can be used in particular in biochemical methods, such as temperature-controlled, biochemical analysis methods (eg, those known as Sanger Sequencing, Ligase Chain Reaction, DNA Restriction, S nger Sequencing, Enzyme Kinetic Monitoring), and in particular a PCR ( Polymerase chain reaction) can be used.
  • biochemical analysis methods eg, those known as Sanger Sequencing, Ligase Chain Reaction, DNA Restriction, S nger Sequencing, Enzyme Kinetic Monitoring
  • PCR Polymerase chain reaction
  • US 812,893 B2 describes the use of an overpressure due to a temperature increase for switching liquids by means of a thermal control. By locally heating air is expanded and thus liquids are transported on.
  • the object underlying the present invention is to provide a fluid handling device and a method for processing a fluid, which allow pressure reduction in order to realize unitary fluid operations, such as in-pumping, even at elevated temperatures.
  • Embodiments of the invention provide a fluid handling device comprising: a compression chamber having a first compression chamber portion and a second compression chamber portion, the first compression chamber portion having a fluid inlet through which a fluid is insertable into the compression chamber; a vapor diffusion barrier between the first compression chamber portion and the second compression chamber portion; and a heater configured to heat at least the first compression chamber portion and the contents thereof, wherein the steam diffusion barrier is configured to heat an evaporating rate of a liquid disposed in the first compression chamber portion to a temperature at which the first compression chamber portion and its contents heat up At least reduce second compression chamber portion arranged gas and thus to reduce a pressure increase in the compression chamber.
  • Processing the liquid in the first compression chamber portion comprises heating at least the liquid disposed in the first compression chamber portion, wherein a vapor diffusion barrier is disposed between the compression chamber portion and the second compression chamber portion, such that when heated, an evaporation rate of the liquid disposed in the first compression chamber portion is at least reduced in the arranged in the second compression chamber section gas and thus a pressure increase in the compression chamber is reduced.
  • Embodiments of the invention are based on the recognition that by separating a liquid volume from an enclosed gas volume in a compression chamber by a diffusion barrier, the total pressure for the duration of a processing (for example, according to a processing protocol) can be significantly reduced because the total amount of water vapor produced is reduced or reduced can be minimized.
  • the vapor diffusion barrier is one way to reduce or regulate the total pressure in a closed reaction space. By reducing and controlling the total pressure, a completely closed system can be realized whose function is not affected by the elevated temperatures and in which no external elements are necessary to build up a back pressure.
  • the compression chamber is not vented, wherein the fluid is introduced into the compression chamber via the fluid inlet to compress a volume of gas trapped in the compression chamber.
  • one of the compression chamber sections is provided with a valve which can be selectively opened to allow venting of the compression chamber or closed to prevent venting of the compression chamber.
  • Embodiments may include a controller configured to open the valve during introduction of the liquid to establish pressure equalization in the compression chamber, and after insertion of the liquid or after introduction of the liquid and at least partial heating of the liquid, the valve in order to subsequently reduce, with the valve closed, during periods of elevated temperature, an increase in pressure in the compression chamber caused by evaporation through the diffusion barrier.
  • the vapor diffusion barrier has a capillary channel fluidly connecting the first compression chamber portion to the second compression chamber portion.
  • the total pressure in the closed system i. the non-vented compression chamber, by the choice of geometric parameters, such as channel cross-section or channel length of the capillary channel, are regulated.
  • the capillary channel has a length which is at least 3 times, 5 times or 10 times greater than the hydraulic diameter of the capillary channel and / or in which the volume of the second compression chamber portion at least 5 times 10 times or 20 times larger than the product of cross section and length of the capillary channel.
  • the vapor diffusion barrier comprises a gas-permeable and liquid-impermeable membrane that separates the first compression chamber portion and the second compression chamber portion.
  • a capillary channel between two compression chamber sections is not necessary.
  • Alternati can also be a vapor diffusion barrier a combination of a capillary channel and a gas permeable and liquid impermeable membrane may be implemented.
  • the fluid handling device further includes a collection chamber fluidly connected to the compression chamber via an outlet fluid channel, the outlet fluid channel having an outlet fluid channel inlet opening into the compression chamber and located radially outward than an outlet fluid channel outlet of the outlet fluid channel flows into the catch chamber, wherein liquid from the first compression chamber portion is drivable by expanding the gas arranged in the compression chamber through the Auslassfluidkanal into the catch chamber.
  • a collection chamber fluidly connected to the compression chamber via an outlet fluid channel
  • the outlet fluid channel having an outlet fluid channel inlet opening into the compression chamber and located radially outward than an outlet fluid channel outlet of the outlet fluid channel flows into the catch chamber, wherein liquid from the first compression chamber portion is drivable by expanding the gas arranged in the compression chamber through the Auslassfluidkanal into the catch chamber.
  • the fluid inlet is fluidically connected to an inlet chamber, wherein the compression chamber and the inlet chamber are formed in a rotary body or a fluidic module that is insertable into a rotary body, so that by rotation of the rotary body, the liquid by centrifugal force from the inlet chamber into the first compression chamber section can be introduced.
  • the corresponding fluidic structures may be implemented in a non-centrifugal system, such as a gravitational force-based system or a pressure-driven system.
  • a ratio between flow resistance of the outlet fluid channel for fluid flow from the compression chamber to the collection chamber and flow resistance of an inlet fluid channel between the compression chamber and the inlet chamber for fluid flow from the compression chamber to the inlet chamber may be adjusted by a particular ratio between volume flow into the collecting chamber and a volume flow into the inlet chamber.
  • the corresponding flow resistance of the Auslassfluidkanals may be smaller than the corresponding flow resistance of the inlet fluid channel, so that a targeted emptying of the liquid from the compression chamber can be effected in the collecting chamber.
  • the fluid handling device further includes a drive device configured to apply rotation to the fluid handling device.
  • the drive device can be designed in such a way that, in a first phase, the rotational body is subjected to a rotation frequency such that the gas in the compression chamber is compressed by the introduced liquid, and in a second phase, after a temperature treatment of the fluid, to reduce the rotational frequency, in order to drive at least parts of the liquid out of the compression chamber into the collecting chamber via the outlet channel.
  • a passive inward pumping can be achieved only by changing the rotational frequency
  • Figure 1 is a schematic representation of a closed system with a gas-liquid mixture.
  • FIG. 2 is a schematic plan view of a fluid handling device
  • Fig. 3 is a diagram for explaining the operation of the fluid handling device shown in Fig. 2;
  • FIG. 4 is a schematic plan view of fluidic structures of an alternative embodiment
  • a vapor diffusion barrier is understood to mean a device which reduces evaporation of a liquid into a gas compared to a case in which the diffusion barrier is absent, when the liquid and the gas are arranged in a fluidic system, the gas is trapped by the liquid in a non-vented fluidic structure.
  • the gas is in a space that is closed by mechanical structures and the liquid.
  • the fluidic structures on the side of the liquid away from the gas may be vented.
  • a vapor diffusion barrier may be formed by a geometric structure in the form of a capillary channel.
  • inward pumping herein is meant a transport of liquid in a tube. Tor or rotational body of a respect to a rotational axis radially outer position to a radially inner position understood.
  • Embodiments of the invention may be implemented in lab-on-a-chip systems wherein a vapor diffusion barrier is used to reduce the pressure in closed reaction spaces in which a liquid-gas mixture is located for temperature-controlled biochemical analysis methods.
  • Such methods may, for example, be methods such as Sanger Sequencing, Ligase Chain Reaction, DNA Restriction,, Enzymes Kinetic Monitoring, and in particular a PCR.
  • the fluidic operation of passive radial inward pumping at elevated temperatures is not limited, as a pressure increase in the trapped liquid-gas mixture can be reduced or avoided, which could otherwise lead to fluid loss , For example, by early venting or by delamination of a lidding film.
  • the controlled overpressure can be used selectively, for example, to pump an amplificate volume after the thermocycling to a further process module, for example a DNA array.
  • Embodiments of the present invention thus allow the performance of temperature-regulated, biochemical assays, the processing of elevated temperatures up to 99 ° C are necessary, with such a temperature increase leads to an increased pressure in the trapped volume of a liquid-gas mixture.
  • the invention makes it possible to reduce and regulate the existing pressure at such elevated temperatures in an enclosed volume through a passive diffusion barrier, so that the reaction spaces can be closed, for example, to avoid cross-contamination from the environment or parallel reactions. In this case, an increase in pressure, which can lead to delamination or uncontrolled ventilation in I, ab-on-a-chip systems, can be avoided. Venting the reaction space, in which by using a valve, the pressure could be regulated in principle, but with the risk of DNA contamination, is therefore not necessary.
  • Embodiments of the invention thus use a Dampfdi ffusionsbarriere to reduce pressure or pressure control.
  • Available systems use diffusion barriers, for example in the form of a capillary, only to reduce fluid losses, but not to reduce and regulate pressure or to switch fluid.
  • the capillary is not closed, so that there is a risk of leakage of molecules, for example of synthetic molecules.
  • Fig. La shows schematically a closed container 2a, in which a gas-liquid mixture is arranged.
  • Fig. 1b shows schematically a closed container 2b having a first container portion 3a and a second container portion 3b, between which a vapor diffusion barrier 4 is arranged in the form of a capillary channel.
  • Embodiments of the invention are based, as shown in FIG. 1b, on the spatial separation of the liquid and the gas through the vapor diffusion barrier, wherein the liquid is disposed in the container portion 3a and the gas is disposed in the container portion 3b.
  • the volume of the liquid is thus spatially separated from the volume of trapped gas, but there is a connection of the two volumes across the vapor diffusion barrier.
  • a vapor diffusion barrier in the form of a capillary prevents the propagation of the vapor, so that the equilibrium is reached only after a very long time, depending on the design of the capillary.
  • a capillary which acts as a vapor barrier, the diffusion length can be chosen very far.
  • the formation of steam in this case depends on the slow diffusion rate of the vapor along the capillary or vapor barrier.
  • a convective mass transport along a capillary can be neglected. From this Grand can be controlled by the choice of the cross-sectional area and the length of the capillary, the time course of the increase in the vapor content and thus the pressure increase in the entire volume.
  • gas gas designates the pressure which prevails in the gas when the vapor-liquid equilibrium is reached.
  • a water-air mixture is considered, which is located in a closed room. It is heated to 95 ° C. This temperature is used, for example, as Denaturierangstemperatur in a polymerase chain reaction (PCR). Assuming that the vapor pressure of water in the water-air mixture depends only on temperature, the air consists only of oxygen (0 2 ) and nitrogen ( 2 ) and both gases in the mixture can behave as ideal gases the effect of the diffusion barrier can be described as follows:
  • J is the material flow
  • A is the cross-sectional area of the capillary
  • D is the diffusion coefficient
  • the length L is included in the estimation via the concentration gradient ⁇ .
  • a vapor diffusion barrier may be used to reduce an evaporation rate in a closed system and thereby to reduce a pressure increase in a compression chamber upon heating of an air-liquid mixture disposed in the chamber.
  • FIG. 2 shows a schematic plan view of fluidic structures of a fluid handling device.
  • FIG. 2 shows a schematic plan view of fluidic structures of a fluid handling device.
  • FIG. 5 shows a device with a fluidic module 10 in the form of a rotational body, which has a substrate 12 and a cover 14.
  • the substrate 12 and the lid 14 may be circular in plan view, with a central opening through which the rotary body 10 may be attached via a conventional fastening means 16 to a rotating part 18 of a drive device.
  • the rotating part 18 is rotatably supported on a stationary part 22 of the drive device 20.
  • the drive device may be, for example, a conventional centrifuge with adjustable rotational speed or a CD or DVD drive.
  • a controller 24 may be provided which is configured to control the drive unit 20 to apply rotation to the rotary body 10 at different rotational frequencies.
  • controller 24 may be implemented by, for example, a suitably programmed computing device or custom integrated circuit.
  • the controller 24 may be further configured to control the drive device 20 upon manual inputs by a user to effect the required rotations of the rotating body. In either case, the controller 24 is configured to control the drive device 20 to apply the rotational body at the required rotational frequencies to implement the invention as described herein.
  • drive device 20 a conventional centrifuge with only one direction of rotation can be used.
  • the rotary body 10 has the required fluidic structures.
  • the required fluidic structures may be formed by cavities and channels in the lid 14, the substrate 12 or in the substrate 12 and the lid 14.
  • fluidic structures may be imaged in the substrate 12 while fill openings and vents are formed in the lid 14.
  • fluidic modules 32 are inserted into a rotor 30 and together with the rotor 30 form the rotary body 10.
  • the fluidic modules 32 can each have a substrate and a lid, in which corresponding fluidic structures can be formed ,
  • the through the rotor 30th and the fluid body module 32 formed rotational body 10 is in turn by a drive device 20 which is controlled by the control device 24, acted upon by a rotation.
  • the fluidic module or body having the fluidic structures may be formed of any suitable material, for example, a plastic such as PMMA (polymethylmethacrylate, polycarbonate, PVC, polyvinyl chloride) or PDMS (polydimethylsiloxane ) Glass or the like.
  • a plastic such as PMMA (polymethylmethacrylate, polycarbonate, PVC, polyvinyl chloride) or PDMS (polydimethylsiloxane ) Glass or the like.
  • the rotary body 10 may be considered as a centrifugal microfluidic platform.
  • a heating device 40 is shown, which is designed to heat at least portions of the rotational body 10 in FIG. 5 or the fluidic module 32 in FIG. 6, such that at least one first compression chamber portion and whose contents are heated.
  • the heating device 40 can be designed as an external heating device, for example jet heating, or can be integrated into the fluidic module or the drive device.
  • FIG 2 shows a plan view of a rotary body 50 having a rotation axis 52.
  • the rotational axis is in each case radial with respect to the center of rotation about which the fluidic module or the rotor is rotatable, that is to say in FIG
  • a radial direction is radially sloping away from the center of rotation, and a radial direction toward the center of rotation is radially increasing, and a fluid channel whose beginning is closer to the center of rotation than its end is thus radially sloping while a fluid channel whose beginning is farther from the center of rotation than the end of which is radially increasing.
  • Embodiments of the present invention may find particular application in the field of centrifugal micro-scrolling, which involves the processing of liquids in the nanoliter to milliliter range.
  • the fluidic structures can have suitable dimensions in the micrometer range for the corresponding liquid volumes.
  • the fluidic structures formed in a rotary body 50 have an inlet chamber 54, which can be vented via a vent opening 56.
  • the inlet chamber 54 is fluidly connected to a compression chamber 60 via an inlet channel 58.
  • the compression chamber 60 has a first compression chamber section 62, a second compression chamber section 64 and an intermediate compression chamber section 64. see Dampfdi ff usions Barriere 66 in the form of a capillary channel arranged on the first compression chamber section 62 and the second compression chamber section 64.
  • the structures 62, 64, and 66 form a compression chamber because a volume of gas trapped therein can be trapped and compressed by a liquid introduced into the first compression chamber portion 62 via the inlet chamber 54 and the inlet channel 58.
  • the first compression chamber section 62 is fluidically connected via a discharge channel 68 to a collecting chamber 70.
  • the collecting chamber 70 has a vent 72.
  • the inlet passage 58 is fluidly coupled to a valve outlet of the first compression chamber section 62.
  • the outlet channel 68 is also fluidly coupled to the fluid inlet of the first compression chamber section 62, wherein the inlet channel 58 and the outlet channel 68 have a common channel section.
  • the first compression chamber portion may include a separate fluid outlet to which the outlet channel is fluidically coupled.
  • the compression chamber is a non-vented chamber in embodiments to facilitate compression of the compressible medium.
  • the compression chamber with the exception of the fluid inlet or a plurality of fluid inlets, which are connected to inlet chambers and / or collecting chambers, no fluid openings.
  • the compression chamber may have additional fluid openings, but with respect to the gas in the compression chamber have such a high flow resistance that compression of the gas is possible and thus no venting of the compression chamber takes place in the sense of pressure equalization.
  • the compression chamber may have at least one additional fluid opening, which can be optionally closed, for example by a valve that can be actively actuated, so that in the closed state of the additional fluid opening, a gas in the compression chamber can be compressed.
  • the diffusion barrier is in the form of a capillary channel having a length that is at least 3, 5 or 10 times greater than the hydraulic diameter of the capillary channel.
  • the capillary channel may have a length which is at least 20 times greater than the hydraulic diameter of the capillary channel.
  • the volume of the second compression chamber portion 64 may be at least 5 times, 10 times or at least 20 times greater than the product of a cross-section and length of the capillary channel.
  • the collection chamber 70 is located radially further inward than the first compression chamber portion 62 so that liquid from the first compression chamber portion 62 can be pumped radially inward into the collection chamber 70 via a pumping height 80.
  • the capillary channel 66 may, for example, have a cross section of ⁇ x 1 ⁇ and separates a disposed in the second compression chamber section 64 gas volume of a arranged in the first compression chamber section 62 liquid volume.
  • the volume of liquid disposed in the second compression chamber portion is thereby heated by means of the heater, which is also shown schematically in phantom in Fig. 2, to effect, for example, a biochemical reaction (e.g., a PCR reaction) in the liquid phase.
  • the second compression chamber portion 62 may therefore also be referred to as a reaction chamber.
  • the fluidics shown in FIG. 2 provide a pneumatic pumping structure that allows radial inward pumping in combination with a diffusion pressure barrier.
  • liquid is introduced into the engagement chamber 54, which can be done for example via the vent opening 56. This can be done at room temperature.
  • the sample liquid at room temperature of, for example, 25 ° C is forced by centrifugal force from the inlet chamber 54 through the inlet channel 58 into the compression chamber 60, in particular the first compression chamber portion 62, and the outlet channel.
  • gas arranged in the second compression chamber section 64 for example air, which represents a compressible medium, is compressed.
  • an overpressure p is generated in the gas, as shown in phase 1 in FIG.
  • the increase in the rotational frequency can take place, for example, with an acceleration of 10 Hz / s.
  • the rotational frequency is kept constant, with the liquid levels in the inlet channel 58, the compression chamber 60 and the outlet channel 68 assuming an equilibrium position, while the gas in the second compression Chamber section 64 is still compressed.
  • the constant rotational frequency can be 35 Hz.
  • the temperatures are cycled using the heater, for example between 50 ° C and max. 99 ° C, as shown in Fig. 3.
  • the excess pressure between the compression chamber 60 and the ambient pressure in this case the atmospheric pressure, is reduced by an overall low formation of steam, so that the fluidic functionality can be ensured.
  • the low vapor formation is achieved by the vapor diffusion barrier 66, wherein in phase 2 schematically diffusing vapor molecules in an enlarged portion of the interface between liquid in the first compression chamber portion 62 and gas in the diffusion barrier 60 are shown.
  • the outlet channel 68 and the inlet channel 58 are designed such that the flow resistance of the outlet channel 68 for a liquid flow from the compression chamber 60 to the collection chamber 70 is less than a flow resistance of the inlet channel 58 for a liquid flow from the compression chamber 60 to the inlet chamber 54
  • the liquid escapes from the second compression chamber section 62 through the outlet channel 68 into the catch chamber 70, as shown by phase 3 in FIG.
  • the rotation frequency is lowered to 10 Hz.
  • the lower rotational frequency may also become zero or assume negative values (reverse rotational direction).
  • the temperature of discharging the liquid into the catching chamber which is 70 ° in the example shown, may be selected in a range from room temperature to 99 ° C. In addition, temperatures below room temperature are possible, because then the pressure is reduced.
  • the implementation outlined in these embodiments may be implemented monolithically. It has been shown that, under the conditions described above, after a PCR thermocycling of a 40 ⁇ sample, more than 90% can be pumped radially inwards over a pump height of 30 mm within one second.
  • FIG. 4 shows fluidic structures of an alternative embodiment which includes a compression chamber 60 'having a first compression chamber portion 62' and a second compression chamber portion 62 ' Compression chamber section 64% have an inlet channel 58 'and a diffusion barrier 66' in the form of a fluid channel.
  • the first compression chamber portion 62 ' has a valve 90 which may be open during a case of zero action to achieve pressure equalization and then closed.
  • the inlet (inlet channel 58 ') of the reaction chamber (compression chamber 60') can also have a valve 92 which is open during filling and can subsequently be closed.
  • one of the compression chamber sections has a valve which can be selectively opened during the Befiilvorgangs or even during heating to produce a pressure equalization.
  • the valve can be closed.
  • a pressure increase due to evaporation across the vapor diffusion barrier is reduced.
  • the heater may be configured in embodiments of the invention to locally heat the first compression chamber portion and the liquid disposed therein.
  • the insulating means may also be configured to globally heat the entire rotary body or the entire fluidic module.
  • exemplary embodiments of the invention allow a simple construction, since no specific etching device is required for heating only a part of the rotary body or of the fluidic module.
  • the heater may be a global heater configured to heat the entire rotary body by heating the rotary part of the drive device to which the rotary body is attached.
  • Embodiments of the present invention thus provide a passive method of reducing and regulating a pressure increase through vapor formation in an enclosed volume of gas.
  • Embodiments of the invention can be used for completely closed systems and also for partially ventilated systems in which fluid structures associated with the liquid, but not with the enclosed gas, are vented.
  • a vapor diffusion barrier is used for the first time to reduce or minimize the total pressure in a completely or partially closed system with gas-liquid mixture by reducing the formation of steam at elevated temperatures up to 99 ° C.
  • the pressure can be regulated.
  • the use of vapor diffusion barriers to reduce the pressure in closed systems is not known in the prior art.
  • embodiments of the invention provide geometric structures and methods that reduce the overall pressure globally in a closed or locally partially closed system liquid-gas mixture by using a vapor diffusion barrier.
  • Embodiments provide geometric structures and methods in which the pressure can be regulated by selecting the geometric parameters of the diffusion barrier.
  • the present invention can be used everywhere, where a gas / liquid mixture is exposed during a temperature treatment to a pressure and an additional pressure due to evaporation of the liquid is to be reduced in the gas.

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  • Analytical Chemistry (AREA)
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Abstract

L'invention concerne un dispositif de manipulation de fluide comportant une chambre de compression pourvue d'une première partie de chambre de compression et d'une deuxième partie de chambre de compression. La première partie de chambre de compression comporte une entrée de fluide, par laquelle un liquide peut être amené dans la chambre de compression. Une barrière à la diffusion de vapeur est prévue entre la première partie de chambre de compression et la deuxième partie de chambre de compression. Un système de chauffage est configuré pour chauffer au moins la première partie de la chambre de compression et son contenu. La barrière à la diffusion de vapeur est configurée au moins pour réduire lors d'un chauffage de la première partie de la chambre de compression et de son contenu, un taux d'évaporation d'un liquide disposé dans la première partie de la chambre de compression en un gaz disposé dans la deuxième partie de la chambre de compression et ainsi, réduire une augmentation de pression dans la chambre de compression.
PCT/EP2014/061990 2013-06-10 2014-06-10 Dispositif de manipulation de fluide et procédé pour le traitement d'un liquide en utilisant une barrière de diffusion WO2014198703A1 (fr)

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DE102013210818.4 2013-06-10
DE201310210818 DE102013210818B3 (de) 2013-06-10 2013-06-10 Fluidhandhabungsvorrichtung und Verfahren zum Prozessieren einer Flüssigkeit unter Verwendung einer Diffusionsbarriere

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CN109975102A (zh) * 2019-04-11 2019-07-05 石家庄禾柏生物技术股份有限公司 一种分离流体中悬浮固体的装置
WO2020190138A1 (fr) 2019-03-19 2020-09-24 Stichting Euroclonality Moyens et procédés d'évaluation précise de réarrangements génétiques d'immunoglobuline (ig)clonale/récepteur de lymphocytes t (tr)
WO2024194145A1 (fr) 2023-03-23 2024-09-26 Hahn-Schickard-Gesellschaft für angewandte Forschung e.V. Module fluidique, dispositif de traitement fluidique et procédé impliquant une égalisation de pression temporaire dans une chambre pneumatique

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DE102014211121A1 (de) 2014-06-11 2015-12-17 Hahn-Schickard-Gesellschaft für angewandte Forschung e.V. Fluidikmodul, vorrichtung und verfahren zum handhaben von flüssigkeit
DE102016207845B4 (de) * 2016-05-06 2018-04-12 Hahn-Schickard-Gesellschaft für angewandte Forschung e.V. Fluidhandhabungsvorrichtung und Verfahren zur Fluidhandhabung
DE102016208972A1 (de) * 2016-05-24 2017-11-30 Hahn-Schickard-Gesellschaft für angewandte Forschung e.V. Fluidikmodul, Vorrichtung und Verfahren zum biochemischen Prozessieren einer Flüssigkeit unter Verwendung von mehreren Temperaturzonen
DE102023202206A1 (de) 2023-03-10 2024-09-12 Hahn-Schickard-Gesellschaft für angewandte Forschung e.V. Sequentielles Pumpen mittels eines Aktuators

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Cited By (4)

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Publication number Priority date Publication date Assignee Title
WO2020190138A1 (fr) 2019-03-19 2020-09-24 Stichting Euroclonality Moyens et procédés d'évaluation précise de réarrangements génétiques d'immunoglobuline (ig)clonale/récepteur de lymphocytes t (tr)
CN109975102A (zh) * 2019-04-11 2019-07-05 石家庄禾柏生物技术股份有限公司 一种分离流体中悬浮固体的装置
WO2024194145A1 (fr) 2023-03-23 2024-09-26 Hahn-Schickard-Gesellschaft für angewandte Forschung e.V. Module fluidique, dispositif de traitement fluidique et procédé impliquant une égalisation de pression temporaire dans une chambre pneumatique
DE102023202639A1 (de) 2023-03-23 2024-09-26 Hahn-Schickard-Gesellschaft für angewandte Forschung e.V. Fluidikmodul, Fluidhandhabungsvorrichtung und Verfahren mit vorübergehendem Druckausgleich in einer Pneumatikkammer

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