EP3052233B1 - Dispositif et procédé de fractionnement aliquote d'un liquide - Google Patents

Dispositif et procédé de fractionnement aliquote d'un liquide Download PDF

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Publication number
EP3052233B1
EP3052233B1 EP14772107.0A EP14772107A EP3052233B1 EP 3052233 B1 EP3052233 B1 EP 3052233B1 EP 14772107 A EP14772107 A EP 14772107A EP 3052233 B1 EP3052233 B1 EP 3052233B1
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EP
European Patent Office
Prior art keywords
measuring chamber
liquid
chamber
fluid
fluid outlet
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EP14772107.0A
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German (de)
English (en)
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EP3052233A1 (fr
Inventor
Frank Schwemmer
Steffen ZEHNLE
Nils Paust
Pierre Dominique Kosse
Daniel Mark
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Hann-Schickard-Gesellschaft fuer Angewandte Forschung eV
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Hann-Schickard-Gesellschaft fuer Angewandte Forschung eV
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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
    • 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
    • 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
    • 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
    • B01L2200/06—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
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • 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
    • B01L2300/08—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
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0867—Multiple inlets and one sample wells, e.g. mixing, dilution
    • 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
    • B01L2300/087—Multiple sequential 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
    • B01L2400/04—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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0481—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure squeezing of channels or chambers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/08—Regulating or influencing the flow resistance
    • B01L2400/084—Passive control of flow resistance

Definitions

  • the present invention relates to a fluidics module, a device for aliquoting a liquid and a method for aliquoting a liquid. Examples of embodiments relate to parallel pneumatic measuring and aliquoting.
  • centrifugal microfluidics In centrifugal microfluidics, rotors are used to process liquids. Corresponding rotors contain chambers for collecting liquid and channels for fluid guidance. With centripetal acceleration of the rotor, the liquid is pressed radially outwards and can thus reach a radially outer position through appropriate fluid guidance. Centrifugal microfluidics is used, for example, in the field of life sciences, especially in laboratory analysis. Centrifugal microfluidics is used to automate processes and replace processes such as pipetting, mixing, measuring, aliquoting and centrifuging.
  • Aliquoting liquids is particularly necessary at the beginning, during or at the end of a process chain in order to carry out several independent detection reactions with one sample. Aliquoting processes are therefore essential for the fully automated parallelization of laboratory processes in a centrifugal-microfluidic rotor. For certain analysis methods, not only the aliquoting of a single volume of liquid into several aliquots is required, but also the aliquoting of several different liquid volumes, the aliquots of which in turn have to be further processed - e.g. mixed together. Quantitatively meaningful analysis processes can only be carried out if the aliquots have volumes that are as precisely defined as possible. For this reason, every aliquoting step should always be combined with a measuring step. This also applies if different aliquoting steps take place in parallel in a centrifugal microfluidic rotor.
  • Godino et al. [Lab Chip, 2013, 13, 685-69 , illustration 1 ] describes a dimensional structure containing a single compression chamber with an inlet and an outlet channel.
  • the compression chamber consists of two sections running radially on the outside (left & right) and a radially inner section.
  • a defined partial volume can be recorded from the left section. Excess liquid volume that exceeds the volume of the left section does not remain in the left section and therefore cannot be separated.
  • end cavities in a centrifugal microfluidic rotor can be filled via a supply channel running radially outward with ends extending radially inward.
  • the end cavities are vented so that air can escape from the end cavities during the filling process.
  • the excess liquid is then drained away from the end cavities via the supply channel and a siphon.
  • the liquid-gas interface between the liquid in the measuring channels and the air in the end cavities becomes unstable, so that the compressed gas escapes from the end cavity through the liquid phase in the measuring channel, and this can be transferred into the end cavity.
  • the US 6,632,399 B1 discloses a microfluidic array for separating glycohemoglobin from a blood sample.
  • the EP 1 832 872 A1 discloses a biological sample analysis plate on which, when a biological sample is transferred by rotating the plate, the biological sample can be easily transferred from an outer peripheral side to an inner peripheral side with respect to a rotation center.
  • the WO 2004/113871 A2 discloses a fluid circuit for receiving a fluid and separating a component of a fluid from the fluid.
  • the present invention is therefore based on the object of creating an improved concept for aliquoting a liquid.
  • Embodiments provide methods for aliquoting a liquid with a fluidic module, the fluidic module having a first measuring chamber and a second measuring chamber, a first fluid inlet channel connected to the first measuring chamber, and a second fluid inlet channel connected to the second measuring chamber, a first fluid outlet channel , which is connected to the first measuring chamber, and a second fluid outlet channel, which is connected to the second measuring chamber, wherein the fluidic module is designed such that when the fluidic module rotates about a center of rotation, a liquid centrifugally enters the first measuring chamber via the first fluid inlet channel and is driven into the second measuring chamber via the second fluid inlet channel, so that a compressible medium previously present in the first measuring chamber and in the second measuring chamber is compressed by the liquid driven into the first measuring chamber and the second measuring chamber, the fluidic module being designed in this way that when the rotation frequency is reduced and the compressible medium expands as a result, at least 80% of the liquid present in the first measuring chamber is discharged from the first measuring chamber via the first fluid outlet channel and
  • exemplary embodiments of the present invention are used in particular in the field of centrifugal microfluidics, which involves the processing of liquids in the nanoliter to milliliter range.
  • the fluidic structures can have suitable dimensions in the micrometer range for handling corresponding liquid volumes.
  • the fluidic structures (geometric structures) and the associated processes are suitable for measuring and/or aliquoting liquid in centrifuge rotors.
  • radial it is meant radially with respect to the center of rotation about which the fluidic module or the rotor is rotatable.
  • a radial direction away from the center of rotation is radially decreasing and a radial direction towards the center of rotation is radially increasing.
  • 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 further from the center of rotation than its end is radially rising.
  • Fig. 1 shows a device 8 with a fluidic module 10 in the form of a rotating body which has a substrate 12 and a lid 14.
  • the substrate 12 and the lid 14 can be circular in plan view, with a central opening via which the rotating body 10 can be attached to a rotating part 18 of a drive device via a conventional fastening device 16.
  • the rotating part 18 is rotatably mounted on a stationary part 22 of the drive device 20.
  • the drive device can be, for example, a conventional centrifuge with an adjustable rotation speed or a CD or DVD drive.
  • a control device 24 can be provided, which is designed to control the drive device 20 in order to apply rotations at different rotational frequencies to the rotating body 10.
  • the control device 24 can, as for those skilled in the art is obvious, for example, be implemented by an appropriately programmed computing device or a user-specific integrated circuit.
  • the control device 24 may further be designed to control the drive device 20 in response to manual input from a user in order to effect the required rotations of the rotating body.
  • the controller 24 is configured to control the drive device 20 to apply the rotating body to the rotational frequencies required to implement the invention as described herein.
  • a conventional centrifuge with only one direction of rotation can be used as the drive device 20.
  • the rotating body 10 has the required fluidic structures.
  • the required fluidic structures can 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 depicted in the substrate 12 while filling openings and vent openings are formed in the lid 14.
  • fluidic modules 32 are inserted into a rotor 30 and, together with the rotor 30, form the rotating body 10.
  • the fluidic modules 32 can each have a substrate and a cover, in which corresponding fluidic structures can in turn be formed.
  • the rotating body 10 formed by the rotor 30 and the fluidic modules 32 can in turn be subjected to rotation by a drive device 20, which is controlled by the control device 24.
  • the fluidic module or the rotating body that has the fluidic structures can be formed from any suitable material, for example a plastic, such as PMMA (polymethyl methacrylate, polycarbonate, PVC, polyvinyl chloride) or PDMS (polydimethylsiloxane) glass or similar.
  • a plastic such as PMMA (polymethyl methacrylate, polycarbonate, PVC, polyvinyl chloride) or PDMS (polydimethylsiloxane) glass or similar.
  • PMMA polymethyl methacrylate, polycarbonate, PVC, polyvinyl chloride
  • PDMS polydimethylsiloxane
  • FIG. 3a A top view of a section of a fluidic module 50 according to the invention, in which a cover is omitted so that the fluidic structures can be seen, is shown in Fig. 3a shown.
  • This in Fig. 3a Fluidic module 50 shown may have the shape of a disk, so that the fluidic structures are rotatable about a center of rotation 52.
  • the disk may have a central hole 54 for attachment to a drive device, for example as referred to above Figures 1 and 2 was explained.
  • the fluidic structures of the fluidic module 50 may include a measurement chamber 60, a compression chamber 66 connected to the measurement chamber 60 via a fluid overflow 68, a fluid inlet channel 70 connected to the measurement chamber 60, and a fluid outlet channel 72 connected to the measurement chamber 60 , exhibit.
  • the fluidic module 50 can be designed in such a way that when the fluidic module 50 rotates about the center of rotation 52, a liquid is driven centrifugally into the measuring chamber 60 via the fluid inlet channel 70 until liquid passes from the measuring chamber 60 into the compression chamber 66 via the fluid overflow 68, and until a compression of a compressible medium previously present in the measuring chamber 60, in the compression chamber 66 and the fluid overflow 68 caused by the liquid driven into the measuring chamber 60 is so great that when a rotation frequency is reduced and the resulting expansion of the compressible medium, a large part of the Liquid present in the measuring chamber 60 is driven out of the measuring chamber 60 via the fluid outlet channel 72.
  • the fluidic module 50 can be designed in such a way that when the rotation frequency is reduced and the resulting expansion of the compressible medium, a large part of the liquid present in the measuring chamber 60 is driven out of the measuring chamber 60 via the fluid outlet channel 72.
  • the measuring chamber 60, the compression chamber 66 and the fluid overflow 68 can be designed such that when the fluidic module 50 rotates about the center of rotation 52, the liquid is centrifugally driven into the measuring chamber 60 via the fluid inlet channel 70 until liquid is discharged from the fluid overflow 68 Measuring chamber 60 enters a section (e.g. collecting area) 67 of the compression chamber 66, in which the liquid that has entered the section of the compression chamber 66 is fluidically separated from the liquid present in the measuring chamber 60.
  • a section e.g. collecting area
  • the fluid overflow 68 can be arranged radially further inward than a radially outer end of the measuring chamber 60.
  • the fluid overflow 68 as in Fig. 3a can be seen, be arranged at a radially inner end of the measuring chamber 60 and / or the compression chamber 66.
  • the measuring chamber 60 is first (completely) filled before liquid passes from the measuring chamber 60 via the fluid overflow 68 into the section 67 of the compression chamber 66.
  • a radially outer end of the compression chamber 66 can be arranged radially further out than a radially outer end of the measuring chamber 60.
  • the fluidic module 50 can be designed such that when the fluidic module 50 rotates about the center of rotation 52, the liquid centrifugally driven into the measuring chamber 60 includes the compressible medium present in the measuring chamber 60, the compression chamber 66 and the fluid overflow 68.
  • the measuring chamber Before filling, i.e. before the liquid is centrifugally driven into the measuring chamber 60, the measuring chamber can also contain (dry or liquid) reagents in addition to the compressible medium. In other words, (dry or liquid) reagents can also be stored in the measuring chamber 60.
  • the measurement chamber 60 may include a fluid inlet 62 and a fluid outlet 64, with the fluid inlet channel 70 connected to the measurement chamber 60 via the fluid inlet 62, and the fluid outlet channel 72 connected to the measurement chamber 60 via the fluid outlet 64.
  • the measuring chamber 60 can also have a combined fluid inlet/fluid outlet 62,64, with the fluid inlet channel 70 and the fluid outlet channel 72 being connected to the measuring chamber 60 via the combined fluid inlet/fluid outlet 62,64.
  • the fluid outlet 64 of the measuring chamber 60 can be arranged such that the fluid outlet 64 of the measuring chamber 60 is sealed by the liquid centrifugally driven into the measuring chamber 60.
  • the fluid outlet 64 of the measuring chamber 60 can be arranged at a radially outer end of the measuring chamber 60 (bottom), as shown in FIG Fig. 3a according to a possible embodiment is shown.
  • the fluid inlet 62 of the measuring chamber is in the in Fig. 3a shown embodiment is also arranged at the radially outer end of the measuring chamber 60 (bottom).
  • the fluid inlet 62 of the measuring chamber 60 can also be arranged at a different position, such as at a radially inner end of the measuring chamber 60 (top) or between the radially inner end of the measuring chamber 60 and the radially outer end of the measuring chamber 60.
  • the fluidic module 50 can also be designed in such a way that when the fluidic module 50 rotates about the center of rotation 52, more liquid is driven centrifugally into the measuring chamber 60 than the measuring chamber 60 can hold, so that liquid flows via the fluid overflow 68 from the measuring chamber 60 into the compression chamber 66 arrived.
  • the fluid inlet channel 70 can be connected to an inlet region of the fluidic module 50.
  • the inlet area of the fluidic module 50 can be designed such that it can hold a larger volume of liquid (liquid volume) than the measuring chamber 60.
  • the inlet area of the fluidic module 50 can also be designed in such a way that a larger volume of liquid can be added to the inlet area of the fluidic module 50 than the measuring chamber 60 can hold.
  • the inlet region of the fluidic module 50 can be connected to a liquid chamber, so that liquid passes from the liquid chamber into the inlet region of the fluidic module 50 before and/or during the rotation of the fluidic module 50 about the center of rotation 52.
  • the inlet region of the fluidic module 50 can be designed as a liquid receptacle or can be connected to a liquid receptacle, so that liquid can be added to the liquid receptacle before and/or during the rotation of the fluidic module 50 about the rotation center 52.
  • the measuring chamber 60 can be designed to measure a defined volume of the liquid (liquid volume).
  • the measuring chamber 60 can therefore be designed in such a way that it can hold a defined and reproducible volume of liquid, which can then be driven, for example, via the fluid outlet channel 72 into a chamber connected to the fluid outlet channel 72.
  • the measuring chamber 60, the compression chamber 66 and the fluid overflow 68 can be designed in such a way that liquid only passes from the measuring chamber 60 via the fluid overflow 68 into the section 67 of the compression chamber 66 after the measuring chamber 60 has absorbed the volume of liquid to be measured ( e.g. after the measuring chamber 60 is (completely) filled). Liquid driven further centrifugally into the measuring chamber 60 thus flows after the measuring chamber 60 has absorbed the volume of liquid to be measured from the measuring chamber 60 via the fluid overflow 68 into the section 67 of the compression chamber 66, so that the fill level in the measuring chamber 60 does not change.
  • the volume of liquid (liquid volume) measured by the measuring chamber 60 can be defined by an overflow point between the measuring chamber 60 and the compression chamber 66.
  • the overflow point can be defined, for example, by an opening of the fluid overflow 68 into the measuring chamber 60 or by a geometric shape of the fluid overflow 68.
  • the fluid overflow 68 can be designed such that it covers at least one area (overflow point) between the Measuring chamber 60 and the compression chamber, which is arranged radially further inward (ie has a smaller distance from the center of rotation) than the mouths of the fluid overflow 68 to the measuring chamber 60 and the compression chamber 66.
  • liquid can be aliquoted using the measuring chamber, or in other words, at least an aliquot part (partial portion) of the liquid can be measured and then driven by the expansion of the compressible medium via the fluid outlet channel 72 into a chamber connected to the fluid outlet channel 72.
  • a quotient of the volume of liquid measured by the measuring chamber 60 and the volume of the liquid (to be measured or aliquoted) that the inlet region of the fluidic module 50 contains or that is added to the inlet region of the fluidic module 50 may be an integer or not can be an integer.
  • the fluidic module 50 can be designed in such a way that a fluidic resistance of the fluid inlet channel 70 is greater than a fluidic resistance of the fluid outlet channel 72.
  • the fluidic module 50 can also be designed such that a fluidic resistance of the fluid inlet 62 of the measuring chamber 60 is greater than a fluidic resistance of the fluid outlet 64 of the measuring chamber 60.
  • the fluidic module 50 can be designed in such a way that when the rotation frequency is reduced and the resulting expansion of the compressible medium, the liquid present in the measuring chamber 60 is (almost) completely driven out of the measuring chamber 60.
  • a (negligible) part of the liquid can remain or remain in the measuring chamber 60, so that the liquid is not completely but almost completely, for example at least 90% (or 80%, 85%, 95%, 99%), is driven out of the measuring chamber 60.
  • a (negligible) portion of the liquid can also be driven out of the measuring chamber 60 via the fluid inlet channel 70.
  • the fluidic module 50 can be designed in such a way that most of the liquid, for example at least 90% (or 80%, 85%, 95%, 99%), is driven out of the measuring chamber 60 via the fluid outlet channel 72.
  • the fluidic module 50 can be designed such that when the rotation frequency is reduced, the liquid that has entered the compression chamber 66 remains in the compression chamber 66, so that when the rotation frequency and the resulting expansion of the compressible medium are reduced, the liquid present in the measuring chamber 60 (almost) completely driven out of the measuring chamber 60.
  • the liquid remaining in the compression chamber 66 thus takes up part of the volume of the compression chamber 66.
  • the fluid overflow 68 can be designed as a fluid overflow channel that connects the measuring chamber 60 and the compression chamber 66.
  • the fluid overflow channel 68 can, for example, be arranged radially further inward than an outer end of the measuring chamber 60 and/or the compression chamber 66.
  • the fluid overflow channel 68 can be arranged at a radially inner end of the measuring chamber 60 and/or the compression chamber 68.
  • the overflow channel 68 can also be arranged at a radially outer end of the measuring chamber 60 and/or the compression chamber 66.
  • Fig. 3b shows a schematic top view of a section of a fluidic module 50 according to an exemplary embodiment of the present invention.
  • the fluidic module 50 can have a (first) measuring chamber 60 1 with a fluid inlet and a fluid outlet, a (first) compression chamber 66 1 , which has a (first) fluid overflow 68 1 with the (first) measuring chamber 60 1 is connected, a (first) fluid inlet channel 70 1 which is connected to the fluid inlet of the (first) measuring chamber 60 1 , and a (first) fluid outlet channel 72 1 which is connected to the fluid outlet of the (first) measuring chamber 60 1 , exhibit.
  • the fluidic module 50 can have a second measuring chamber 60 2 with a fluid inlet and a fluid outlet, a second compression chamber 66 2 , which is connected to the second measuring chamber 60 2 via a second fluid overflow 68 2 , a second fluid inlet channel 70 2 , which is connected to the Fluid inlet of the second measuring chamber 60 2 is connected, and a second fluid outlet channel 72 2 , which is connected to the fluid outlet of the second measuring chamber 60 2 .
  • the fluidic module 50 can have at least one further measuring chamber 60 2 to 60 n with a fluid inlet and a fluid outlet, at least one further compression chamber 66 2 to 66 n , which has at least one further fluid overflow 68 2 to 68 n with the at least one further measuring chamber 60 2 to 60 n is connected, at least one further fluid inlet channel 70 2 to 70 n , which is connected to the fluid inlet of the at least one further measuring chamber 60 2 to 60 n , and at least one further fluid outlet channel 72 2 to 72 n , which is connected to the fluid outlet of the at least another measuring chamber 60 2 to 60 n is connected.
  • the fluidic module 50 can have up to n measuring chambers 60 1 to 60 n with associated compression chambers 66 1 to 66 n , fluid overflows 68 1 to 68 n , fluid inlet channels 70 1 to 70 n and fluid outlet channels 72 1 to 72 n , where n is a natural number is greater than or equal to one, n ⁇ 1.
  • the fluid inlet channel 70 1 and the at least one further fluid inlet channel 70 2 to 70 n can have higher fluidic resistances than the fluid distribution channel 80 1 to 80 2 .
  • the fluid inlet channel 70 1 and the at least one further fluid inlet channel 70 2 to 70 n can each have a fluidic resistance that is at least a factor of 5 (or 10, 15, 20, or more) higher than the fluid distribution channel 80.
  • the fluidic module 50 can have a fluid inlet that is connected to the fluid distribution channel 80 via a fluid channel 82.
  • the fluid channel 82 can have a higher fluidic resistance than the fluid distribution channel 80.
  • the fluid channel 82 can have a fluidic resistance that is at least a factor of 5 (or 10, 15, 20, or more) higher than the fluid distribution channel 80.
  • the fluid channel (inlet channel) 82 can connect the filling channels to the fluidic inlet, wherein the fluid channel (inlet channel) 82 can have a high fluidic resistance (not necessarily high resistance).
  • Fig. 3c shows a schematic top view of a section of a fluidic module 50 according to an exemplary embodiment of the present invention.
  • the measuring chamber 60 1 has a fluid inlet 62 1 and a fluid outlet 64 1 , the fluid inlet channel 70 1 being connected to the measuring chamber 60 1 via the fluid inlet 62 1 , and the fluid outlet channel 72 1 being connected to the measuring chamber 60 1 via the fluid outlet 64 1 is connected.
  • the measuring chamber 60 2 has a combined fluid inlet/fluid outlet 62 2 , 64 2 , wherein the fluid inlet channel 70 and the fluid outlet channel 72 are connected to the measuring chamber 60 2 via the combined fluid inlet/fluid outlet 62 2 , 64 2 .
  • the fluid inlet channel 70 and the fluid outlet channel 72 can be connected directly to the combined fluid inlet/fluid outlet 62,64, i.e. each open directly into the measuring chamber 60 via the combined fluid inlet/fluid outlet 62,64.
  • the fluid inlet channel 70 and the fluid outlet channel 72 can also be brought together before the combined fluid inlet/fluid outlet 62,64.
  • the fluid inlet channel 70 and the fluid outlet channel 72 can be brought together by means of a fluid channel piece (e.g. T-piece or Y-piece), the fluid channel piece being directly connected to the combined fluid inlet/fluid outlet 62, 64.
  • a fluid channel piece e.g. T-piece or Y-piece
  • the fluid inlet channel 70 can be connected directly to the combined fluid inlet/fluid outlet 62, 64, while the fluid outlet channel 72 via the fluid inlet channel 70 is connected to the combined fluid inlet/fluid outlet 62, 64, that is to say that the fluid outlet channel 72 first opens into the fluid inlet channel 70.
  • the fluid outlet channel 72 can be connected directly to the combined fluid inlet/fluid outlet 62,64, while the fluid inlet channel 70 is connected to the combined fluid inlet/fluid outlet 62,64 via the fluid outlet channel, i.e. that the fluid inlet channel 70 first opens into the fluid outlet channel 72.
  • Fig. 3d shows a schematic top view of a section of a fluidic module 50 according to an exemplary embodiment of the present invention.
  • channels e.g. capillaries
  • Fig. 3e shows a schematic top view of a section of a fluidic module 50 according to an exemplary embodiment of the present invention.
  • the Fig. 4a to 4f show a schematic top view of the in Fig. 3b shown fluidic module 50 as well as liquid levels in the fluidic module 50 at six different times. However, it should be noted that the following description also refers to those in the Fig. 3a and 3b to 3e shown fluidic modules 50 is applicable.
  • Fluidic module 50 shown can be used to aliquot liquid.
  • Individual volumes (of the liquid to be aliquoted) can be measured under high centrifugation and separated from one another by a compressed, compressible medium (e.g. compressed air), which has been compressed from the liquid to be measured under centrifugation, and into chambers that are connected to the fluid outlet channels (e.g. follow-up chambers). , to be continued.
  • a compressed, compressible medium e.g. compressed air
  • Different output volumes create a different counterpressure through a different degree of compression of the compressible medium (e.g. air).
  • the compressible medium e.g. air volume
  • the various switching channels will not be exactly identical.
  • the fluidic module 50 for example by the in relation to the Fig. 1 and 2 drive 20 described, in a first phase ( 4a to 4c ) is subjected to a first rotation frequency f 1 , while the fluidic module 50 is in a second phase ( Fig. 4d to 4f ) is subjected to a second rotation frequency f 2 .
  • the second rotation frequency f 2 is smaller than the first rotation frequency f 1 , f 1 > f 2 .
  • Fig. 4a shows a schematic top view of the fluidic module 50 and a liquid level in the fluidic module 50 at a first point in time.
  • Fig. 4b shows a schematic top view of the fluidic module 50 and a liquid level in the fluidic module 50 at a second time.
  • Fig. 4c shows a schematic top view of the fluidic module 50 and a liquid level in the fluidic module 50 at a third time.
  • Fig. 4d shows a schematic top view of the fluidic module 50 and a liquid level in the fluidic module 50 at a fourth time.
  • Fig. 4e shows a schematic top view of the fluidic module 50 and a liquid level in the fluidic module 50 at a fifth time.
  • Fig. 4f shows a schematic top view of the fluidic module 50 and a liquid level in the fluidic module 50 at a sixth time.
  • the fluidic module 50 as in the Fig. 4a to 4f shown, can be filled under centrifugation (see Fig. 4a ).
  • the hermetically enclosed volume V of the compressible medium eg air volume
  • the compressible medium e.g.
  • Fig. 5 shows a schematic top view of a section of a fluidic module 100 according to an exemplary embodiment of the present invention.
  • the fluid inlet channels 70 1 to 70 4 of the first half of measuring chambers 60 1 to 60 4 are connected to a first inlet region 84 1 of the fluidic module 50 via a first distribution channel 80 1 and a first radially extending channel 82 1 , while the fluid inlet channels 70 5 to 70s the second half of measuring chambers 60 5 to 60s over one second distribution channel 80 2 and a second radially extending channel 82 2 are connected to a second inlet region 84 2 of the fluidic module 50.
  • the fluid outlet channels 70 1 to 70 4 of the first half of measuring chambers 60 1 to 60 4 and the fluid outlet channels 70 5 to 70 8 of the second half of measuring chambers 60 5 to 60 8 are each connected in pairs to a (downstream) chamber 86 1 to 86 4 .
  • first fluid outlet channel 72 1 and the fifth fluid outlet channel 72 5 are connected to the first (downstream) chamber 86 1
  • the second fluid outlet channel 72 2 and the sixth fluid outlet channel 72 6 are connected to the second (downstream) chamber 86 2
  • third fluid outlet channel 72 3 and the seventh fluid outlet channel 72 7 are connected to the third (downstream) chamber 86 3
  • the fourth fluid outlet channel 72 4 and the eighth fluid outlet channel 72 8 are connected to the fourth (downstream) chamber 86 4 .
  • the fluidic module 50 can be used to mix liquids by adding a first liquid to the first inlet region 84 1 and adding a second liquid to the second inlet region 84 2 , so that when the rotation frequency and the associated expansion of the Compressible medium is centrifugally driven into the (downstream) chambers 86 1 to 86 4 in each case an aliquot of the first liquid and an aliquot of the second liquid.
  • Fig. 6a shows a schematic top view of a partial section of the fluidic module 50 and a liquid level in the fluidic module 50 at a first point in time.
  • Fig. 6b shows a schematic top view of the partial section of the fluidic module 50 and a liquid level in the fluidic module 50 at a second time.
  • the fluidic module 50 continues to be subjected to the first rotation frequency f 1 , whereby the liquid is driven centrifugally via the fluid inlet channels 70 1 to 70 4 into the measuring chambers 60 1 to 60 4 , resulting in the in Fig. 4b fluid level shown.
  • Fig. 6c shows a schematic top view of the partial section of the fluidic module 50 and a liquid level in the fluidic module 50 at a third point in time.
  • the fluidic module 50 continues to be subjected to the first rotation frequency f 1 , whereby the liquid continues to be driven centrifugally via the fluid inlet channels 70 1 to 70 4 into the measuring chambers 60 1 to 60 4 , so that liquid is already flowing over at the third time the fluid overflows 68 1 to 68 4 from the measuring chambers 60 1 to 60 4 have reached the compression chambers 66 1 to 66 4 .
  • Fig. 6d shows a schematic top view of the partial section of the fluidic module 50 and a liquid level in the fluidic module 50 at a fourth point in time.
  • Fig. 6e shows a schematic top view of the partial section of the fluidic module 50 and a liquid level in the fluidic module 50 at a fifth time.
  • FIG. 6a to 6d show an example of the aliquoting process.
  • a first liquid flows under a high rotation frequency (centrifugation) of, for example, 90 Hz from an inlet region 84 1 through a channel 82 1 leading radially outwards via a distribution channel 80 1 into four measuring chambers 60 1 to 60 4 with a volume of approximately 5 ⁇ l.
  • the fluid inlet channel 70 1 to 70 4 to the measuring chamber 60 1 to 60 4 can be designed so that it starts at the upper end of the measuring chamber 60 1 to 60 4 (not absolutely necessary).
  • the fluid outlet channel 72 1 to 72 4 is then hermetically sealed by a first part of the inflowing liquid. Liquid flowing in further then compresses (at least partially) the enclosed compressible medium (e.g. gas volume) in the compression chamber (pressure chamber) 66 1 to 66 4 (see Fig. 6b ).
  • the enclosed compressible medium e.g. gas volume
  • a compression chamber (pressure chamber) 66 1 to 66 4 is connected to each of the measuring chambers 60 1 to 60 4 , in which a defined volume of the compressible medium (eg air volume) is enclosed. Excess liquid flows into the drain areas of the individual compression chambers (pressure chambers) 66 1 to 66 4 until the inlet area 84 1 is emptied (not absolutely necessary). Now a balance is established between centrifugal force and pneumatic counter pressure.
  • the enclosed compressible medium eg air volume
  • pressure chamber 206 expands under the lower centrifugal pressure.
  • the liquid column to rise in the radially running channel 82 1 and in the fluid outlet channel 72 1 to 72 4 , which can be designed, for example, as a siphon. From a certain filling level, the filling level exceeds the top of the siphon 72 1 to 72 4 and the liquid is transported further. Due to the centrifugal force and excess pressure, the liquid from the measuring chambers 60 1 to 60 4 is now completely transferred into the chambers 86 1 to 86 4 .
  • the fluid inlet channel (filling channel) 70 1 to 70 4 is located at the upper end of the measuring chamber 60 1 to 60 4 , the liquid remains in the fluid inlet channels 70 1 to 70 4 and is not distributed to the measuring chambers 60 1 to 60 4 .
  • the accuracy of the aliquoting process becomes particularly high when the fluid inlet channels 70 1 to 70 4 and the fluid outlet channels 72 1 to 72 4 are small compared to the measuring chamber 60 1 to 60 4 .
  • Measurement inaccuracies arise, for example, because different initial conditions, such as input volume, manufacturing tolerances, etc., lead to differences in the fill level during the measuring step.
  • the measurement accuracy is directly related to the dimensions of the fluid inlet channels 70 1 to 70 4 and the fluid outlet channels 72 1 to 72 4 . Smaller dimensions lead to more precise measurements.
  • the fluid outlet channel (e.g Siphon) 72 1 to 72 4 have a much smaller fluidic resistance than the sum of the resistances of the fluid inlet channels 70 1 to 70 4 , and on the other hand, the fluid inlet channel (filling channel) 70 1 to 70 4 can be at a radially inner point of the measuring chamber 60 1 set up to 60 4 .
  • the measuring chambers 60 1 to 60 4 are not in fluid communication, at least during a certain period of emptying. During this time, any pressure differences do not cause any additional errors.
  • the aliquoting concept described above can also be used, with small changes, to aliquot liquids from the radially outer to radially further inward (radially outer aliquoting).
  • the siphon 72 1 to 72 4 can be replaced by an inwardly leading fluid outlet channel 72 5 to 72 8 (see Fig. 5 ).
  • the inlet volume of the liquid per measuring chamber (aliquoting chamber) 60 1 to 60 4 can be designed so that (practically) all of the liquid in the measuring chamber 60 1 to 60 4 and all of the liquid in the fluid outlet channel 72 5 to 72 8 flows into a subsequent, further internal chamber 86 1 to 864 is transferred.
  • an aliquoting concept can be created that aliquots two liquids on a fluidic layer.
  • the overall structure can then, for example, look like this: an aliquot from a first aliquoting structure (first half of measuring chambers 60 1 to 60 4 ) and an aliquot from a second aliquoting structure (second half of measuring chambers 60s to 60s) are placed in a common chamber (cavity ) 86 1 to 86 4 are transferred.
  • the subsequent (cavity) 86 1 to 86 4 can be a mixing chamber 86 1 to 86 4 .
  • the entire circumference around the axis of rotation can potentially be used for fluidic structures.
  • the aliquoting concept presented here is generally also suitable for aliquoting on a multi-layer structured disk.
  • the disk can be designed in such a way that the liquid can be guided over a fluidic layer A for filling and can potentially be guided past crossing channels.
  • the chamber is now emptied via a channel on the fluidic layer B.
  • This channel can be either a siphon (eg 72 1 to 72 4 ) or another channel that leads, for example, radially inwards (eg 72 5 to 72s). Otherwise, the aliquoting process takes place as described with regard to radially inner aliquoting. This is possible, for example: B.
  • each measuring chamber 60 1 to 60 8 can be provided with its own fluidic breakthrough, or several measuring chambers 60 1 to 60 8 can have a fluidic breakthrough together.
  • Embodiments of the present invention enable simultaneous, parallel aliquoting of two liquids on a fluidic layer.
  • the measuring or measuring of the volumes takes place at high pressures, which means that capillary forces have little influence.
  • exemplary embodiments enable a potentially high level of accuracy since the measuring of the liquids takes place at high rotational frequencies.
  • embodiments do not require any sharp edges.
  • the measuring step is carried out at "high" rotation frequencies (rotation frequencies) and then switched on at low rotation frequencies (rotation frequencies).
  • the fluidic structure described here is still functional even when heavily overfilled (> 50% of the measured volume).
  • the aliquoting concept described here allows two liquids to be aliquoted and combined on a fluidic layer.
  • the liquid in the fluidic structure described here, the liquid can be supplied to the measuring chambers from the outside and, moreover, the liquid can then be further processed.
  • At least two aliquots can have a waste cavity connected to this measuring chamber (directly or via a channel); this can be used, for example, for individual quality control of each individual aliquot by reading out the fill level in the waste cavity.
  • the measuring chambers are separated from one another by a fluidic resistance that is higher than the channel used to advance the aliquots.
  • FIG. 1 For exemplary embodiments create a fluidic structure and a method for aliquoting multiple aliquots, where the measuring step is carried out at "high" rotational frequencies (rotational frequencies) and the continuation of the liquids takes place at low rotational frequencies.
  • the fluidic structure can be designed in such a way that a compressible medium (e.g. air) is compressed in the compression chamber when the measuring chamber is filled.
  • the fluidic structure can be designed such that the fluid inlet of the measuring chamber has a fluidically higher resistance than the
  • the fluidic structure can be designed in such a way that in the volume-determining measuring step the meniscus is only in channels that are small compared to the measuring chamber. Furthermore, the fluidic structure can be designed in such a way that the volume-determining measuring chamber is filled to over 50% (70%, 90%, completely). Furthermore, the fluidic structure can be designed such that an interface between the compressible medium and the liquid (e.g. air-water interface) migrates radially inwards during emptying. In addition, the fluidic structure can be designed such that at least one measuring chamber is filled from radially further in and is emptied radially further out.
  • Fig. 7 shows a schematic top view of a section of a fluidic module 100.
  • the fluidic module 100 comprises a fluid inlet channel 102, at least one measuring chamber 104 1 to 104 i with a fluid inlet 106 1 to 106 i and a fluid outlet 108 1 to 108 i , at least one fluid resistance element 110 1 to 110 i , and an overflow 112, wherein the fluid inlet channel 102 is connected to the at least one measuring chamber 104 1 to 104 i via the fluid inlet 106 1 to 106 i and to the overflow 112, and wherein the at least one fluid resistance element 110 1 to 110 i is connected to the at least one measuring chamber 104 1 to 104 i is connected via the fluid outlet 108 1 to 108 i .
  • the fluidic module 100 is designed in such a way that when the fluidic module rotates about a center of rotation 114 and the resulting centrifugal pressure, a liquid is driven centrifugally via the fluid inlet channel 102 into the at least one measuring chamber 104 1 to 104 i , the at least one fluid resistance element 110 1 to 110 i has a fluidic resistance that is greater than a fluidic resistance of the Fluid inlet channel 102 and as a fluidic resistance of the fluid inlet 104 1 to 104 i , so that more liquid is driven into the at least one measuring chamber 104 1 to 104 i than from the at least one measuring chamber 104 1 to 104 i via the at least one fluid resistance element 110 1 to 110 i arrives, so that the at least one measuring chamber 104 1 to 104 i is filled and excess liquid reaches the overflow 112.
  • the fluidic module 100 can also be designed in such a way that when the rotation frequency increases (eg at least by a factor of 2 (or 3, 4, 5, 7, 10)) and a resulting increase in the centrifugal pressure in the at least one measuring chamber 104 1 to 104 i existing liquid is driven out of the measuring chamber 104 1 to 104 i faster via the at least one variable fluid resistance element 110 1 to 110 i than before the increase in the rotation frequency.
  • the rotation frequency increases (eg at least by a factor of 2 (or 3, 4, 5, 7, 10)) and a resulting increase in the centrifugal pressure in the at least one measuring chamber 104 1 to 104 i existing liquid is driven out of the measuring chamber 104 1 to 104 i faster via the at least one variable fluid resistance element 110 1 to 110 i than before the increase in the rotation frequency.
  • the rotation frequency does not have to be increased so that the liquid present in the at least one measuring chamber 104 1 to 104 i is centrifugally driven out of the same.
  • the centrifugal pressure increases, so that the liquid present in the at least one measuring chamber 104 1 to 104 i can be driven out of it more quickly.
  • the fluidic module 100 may have an inlet region 116 that is connected to the fluid inlet channel 102.
  • a first section 102a of the fluid inlet channel 102 may be connected to the inlet region 116 and extend from radially further inwards to radially further outwards.
  • a second section 102b of the fluid inlet channel 102, to which the at least one measuring chamber 104 1 to 104 i can be connected, can run laterally (ie have a uniform radial distance from the center of rotation 114).
  • a third section 102c of the fluid inlet channel 102 can run from radially further inwards to radially further outwards and be connected to the overflow 112.
  • the fluidic module 100 can have at least one further chamber 118 1 to 118 4 , which is connected to an output of the at least one variable fluid resistance element 110 1 to 110 i , wherein the at least one measuring chamber 104 1 to 104 i is connected to the at least one variable fluid resistance element 110 1 to 110 i is connected via an input of the at least one variable fluid resistance element 110 1 to 110 i .
  • FIG. 7 shows a fluidic structure 100 (measuring structure or aliquoting structure) with an inlet area 116, a filling and overflow channel 102, a measuring chamber 104 1 to 104 i , a valve 110 1 to 110 i and an overflow 112, whereby the valve 110 1 to 110 i does not close completely but is continuously flowed through by liquid.
  • the flow resistance of the valve 110 1 to 110 i is so high that at a first rotation frequency f1, the liquid fills the measuring chamber 104 1 to 104 i much more quickly and excess liquid flows out of the inlet area 116 via the overflow channel 102 into the overflow area 112, than in a subsequent chamber 118 1 to 118 i , which is connected downstream of the valve 110 1 to 110 i .
  • the process of splitting the liquid would be at least 10x (better 100x) faster compared to moving the liquid forward. This ensures the volumetric accuracy of the measuring without requiring a valve 110 1 to 110 i which completely prevents the flow of liquid during the filling process.
  • aspects have been described in connection with a device, it is understood that these aspects also represent a description of the corresponding method, so that a block or a component of a device is also to be understood as a corresponding method step or as a feature of a method step. Similarly, aspects described in connection with or as a method step also represent a description of a corresponding block or detail or feature of a corresponding device.
  • Some or all of the method steps may be performed by a hardware apparatus (or using a hardware device). Apparatus), such as a microprocessor, a programmable computer or an electronic circuit. In some embodiments, some or more of the key process steps may be performed by such apparatus.

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Claims (14)

  1. Procédé de fractionnement en parties aliquotes d'un liquide à l'aide d'un module fluidique (50), dans lequel le module fluidique présente une première chambre de mesure (601) et une deuxième chambre de mesure (602), un premier canal d'admission de fluide (701) qui est connecté à la première chambre de mesure (601), et un deuxième canal d'admission de fluide (702) qui est connecté à la deuxième chambre de mesure (602), un premier canal de sortie de fluide (721) qui est connecté à la première chambre de mesure (601), et un deuxième canal de sortie de fluide (722) qui est connecté à la deuxième chambre de mesure (602), dans lequel le module fluidique (50) est conçu de sorte que, lors d'une rotation du module fluidique (50) autour d'un centre de rotation (52), un liquide soit poussé de manière centrifuge, à travers le premier canal d'admission de fluide (701), dans la première chambre de mesure (601) et, à travers le deuxième canal d'admission de fluide (702), dans la deuxième chambre de mesure (602), de sorte que par le liquide poussé dans la première chambre de mesure (601) et dans la deuxième chambre de mesure (602) soit comprimé un milieu compressible présent auparavant dans la première chambre de mesure (601) et dans la deuxième chambre de mesure (602), dans lequel le module fluidique (50) est conçu de sorte que, lors d'une réduction de la fréquence de rotation et d'une dilatation qui en résulte du milieu compressible, au moins 80% du liquide présent dans la première chambre de mesure (601) soit poussé, à travers le premier canal de sortie de fluide (721), hors de la première chambre de mesure (601) et au moins 80% du liquide présent dans la deuxième chambre de mesure (602) soit poussé, à travers le deuxième canal de sortie de fluide (722), hors de la deuxième chambre de mesure (602), dans lequel le module fluidique (50) présente un canal de répartition de fluide (80), dans lequel le premier canal d'admission de fluide (701) et le deuxième canal d'admission de fluide (702) sont connectés au canal de répartition de fluide (80), dans lequel le procédé présente le fait de:
    soumettre le module fluidique à une fréquence de rotation, de sorte que le liquide soit poussé de manière centrifuge, à travers le premier canal d'admission de fluide (701), dans la première chambre de mesure (601) et, à travers le deuxième canal d'admission de fluide (702), dans la deuxième chambre de mesure (602), de sorte que par le liquide poussé dans la première chambre de mesure (601) et dans la deuxième chambre de mesure (602) soit comprimé un milieu compressible présent auparavant dans la première chambre de mesure (601) et dans la deuxième chambre de mesure (602); et
    réduire la fréquence de rotation à laquelle est soumis le module fluidique, de sorte que, par la réduction de la fréquence de rotation et la dilatation qui en résulte du milieu compressible, au moins 80% du liquide présent dans la première chambre de mesure (601) soit poussé, à travers le premier canal de sortie de fluide (721), hors de la première chambre de mesure (601) et au moins 80% du liquide présent dans la deuxième chambre de mesure (602) soit poussé, à travers le deuxième canal de sortie de fluide (722), hors de la deuxième chambre de mesure (602),
    dans lequel le module fluidique présente par ailleurs une première chambre de compression (661) et une deuxième chambre de compression (662), dans lequel la première chambre de compression (661) et la première chambre de mesure (601) sont connectées l'une à l'autre par l'intermédiaire d'un premier trop-plein de fluide (681), et dans lequel la deuxième chambre de compression (662) et la deuxième chambre de mesure (602) sont connectées l'une à l'autre par l'intermédiaire d'un deuxième trop-plein de fluide (682);
    dans lequel, lors de la soumission du module fluidique à une fréquence de rotation et de la rotation qui en résulte du module fluidique (50) autour du centre de rotation (52), le liquide est poussé à travers le premier canal d'admission de fluide (701) dans la première chambre de mesure (601) et à travers le deuxième canal d'admission de fluide (702) dans la deuxième chambre de mesure (602) jusqu'à ce que le liquide arrive à travers le premier trop-plein de fluide (681) de la première chambre de mesure (601) dans un segment de la première chambre de compression (661), dans lequel il est séparé du liquide présent dans la première chambre de mesure (601), et à travers le deuxième trop-plein de fluide (682) de la deuxième chambre de mesure (602) dans un segment de la deuxième chambre de compression (662), dans lequel il est séparé du liquide présent dans la deuxième chambre de mesure (602), et jusqu'à ce qu'une compression provoquée par le liquide poussé dans la première chambre de mesure (601) d'un milieu compressible présent auparavant dans la première chambre de mesure (601), dans la première chambre de compression (661) et dans le premier trop-plein de fluide (681) et une compression provoquée par le liquide poussé dans la deuxième chambre de mesure (602) d'un milieu compressible présent auparavant dans la deuxième chambre de mesure (602), dans la deuxième chambre de compression (662) et dans le deuxième trop-plein de fluide (682) soit si grande que, lors d'une réduction de la fréquence de rotation et d'une dilatation qui en résulte du milieu compressible, au moins 80% du liquide présent dans la première chambre de mesure (601) soit poussé, à travers le premier canal de sortie de fluide (721), hors de la première chambre de mesure (601) et au moins 80% du liquide présent dans la deuxième chambre de mesure (602) soit poussé, à travers le deuxième trop-plein de fluide (722), hors de la deuxième chambre de mesure (602).
  2. Procédé selon la revendication 1, dans lequel les résistances fluidiques du premier canal d'admission de fluide (701) et du deuxième canal d'admission de fluide (702) sont, du fait de la conception géométrique du premier canal d'admission de fluide (701), du deuxième canal d'admission de fluide (702), de la première chambre de mesure (601) et de la deuxième chambre de mesure (602), supérieures aux résistances fluidiques du premier canal de sortie de fluide (721) et du deuxième canal de sortie de fluide (722).
  3. Procédé selon l'une des revendications 1 à 2, dans lequel, lors de soumission du module fluidique à une fréquence de rotation et de la rotation qui en résulte du module fluidique (50) autour du centre de rotation (52), le liquide poussé de manière centrifuge dans la première chambre de mesure (601) comporte le milieu compressible présent dans la première chambre de mesure (601), la première chambre de compression (661) et le premier trop-plein de liquide (681) et que le liquide poussé de manière centrifuge dans la deuxième chambre de mesure (602) comporte le milieu compressible présent dans la deuxième chambre de mesure (602), la deuxième chambre de compression (662) et le deuxième trop-plein de fluide (682).
  4. Procédé selon l'une des revendications 1 à 3, dans lequel, lors de la soumission du module fluidique à une fréquence de rotation et de la rotation qui en résulte du module fluidique (50) autour du centre de rotation (52), plus de liquide est poussé de manière centrifuge dans la première chambre de mesure (601) et la deuxième chambre de mesure (602) que ce que peuvent contenir la première chambre de mesure (601) et la deuxième chambre de mesure (602), de sorte que du liquide arrive, à travers le premier trop-plein de liquide (681), de la première chambre de mesure (601) dans la première chambre de compression (661) et, à travers le deuxième trop-plein de fluide (682), de la deuxième chambre de mesure (602) dans la deuxième chambre de compression (662).
  5. Procédé selon l'une des revendications 1 à 4, dans lequel, lors de la réduction de la fréquence de rotation à laquelle est soumis le module fluidique et de la dilatation qui en résulte du milieu compressible, le liquide présent dans la première chambre de mesure (601) est poussé, à travers le premier canal de sortie de fluide (721) hors de la première chambre de mesure (601) et le liquide présent dans la deuxième chambre de mesure (602) est poussé, à travers le deuxième canal de sortie de fluide (722), jusqu'à ce qu'au moins une partie d'une part de volume en excès du milieu compressible arrive, à travers le premier canal de sortie de fluide (721), hors de la première chambre de mesure (601) et, à travers le deuxième canal de sortie de fluide (722), hors de la deuxième chambre de mesure (602).
  6. Procédé selon l'une des revendications 1 à 5, dans lequel, lors de la réduction de la fréquence de rotation à laquelle est soumis le module fluidique, le liquide arrivé dans la première chambre de compression (661) reste dans la première chambre de compression (661) et le liquide arrivé dans la deuxième chambre de compression (662) reste dans la deuxième chambre de compression (662).
  7. Procédé selon la revendication 6, dans lequel, lors de la réduction de la fréquence de rotation à laquelle est soumis le module fluidique, le liquide arrivé dans la première chambre de compression (661) reste dans la première chambre de compression (661) et le liquide arrivé dans la deuxième chambre de compression (662) reste dans la deuxième chambre de compression (662), de sorte que, lors de la réduction de la fréquence de rotation et de la dilatation qui en résulte du milieu compressible dans la première chambre de mesure (601), le liquide présent dans la première chambre de mesure (601) est poussé, à travers le premier canal de sortie de fluide (721), hors de la première chambre de mesure (601) et le liquide présent dans la deuxième chambre de mesure (602) est poussé, à travers le deuxième canal de sortie de fluide (722), hors de la deuxième chambre de mesure (602) jusqu'à ce qu'au moins une partie d'une part de volume en excès du milieu compressible arrive, à travers le premier canal de sortie de fluide (721), hors de la première chambre de mesure (601) et, à travers le deuxième canal de sortie de fluide (722), hors de la deuxième chambre de mesure (602).
  8. Procédé selon la revendication 6 ou 7, dans lequel, lors de la réduction de la fréquence de rotation à laquelle est soumis le module fluidique et de la dilatation du milieu compressible qui en résulte, une part de volume en excès du milieu compressible qui résulte du liquide restant dans la première et la deuxième chambre de compression (661:662) arrive en une quantité d'au moins 70%, à travers le premier canal de sortie de fluide (721), hors de la première chambre de mesure (601) et, à travers le deuxième canal de sortie de fluide (722), hors de la deuxième chambre de mesure (602).
  9. Procédé selon l'une des revendications 6 à 8, dans lequel, lors de la réduction de la fréquence de rotation à laquelle est soumis le module fluidique, le liquide arrivé dans la première chambre de compression (661) reste dans la première chambre de compression (661) et le liquide arrivé dans la deuxième chambre de compression (662) reste dans la deuxième chambre de compression (662), de sorte que, lors de la réduction de la fréquence de rotation et de la dilatation qui en résulte du milieu compressible, le liquide présent dans la première chambre de mesure (601) est poussé, à travers le premier canal de sortie de fluide (721), dans une première chambre (861) connectée au premier canal de sortie de fluide (721) et le liquide présent dans la deuxième chambre de mesure (602) est poussé, à travers le deuxième canal de sortie de fluide (722), dans une deuxième chambre (862) connectée au deuxième canal de sortie de fluide (722).
  10. Procédé selon l'une des revendications 1 à 9, dans lequel la première chambre de mesure (601) présente une première entrée de fluide (621) et une première sortie de fluide (641) et la deuxième chambre de mesure (602) présente une deuxième entrée de fluide (622) et une deuxième sortie de fluide (642), dans lequel la première entrée de fluide (621) et la deuxième entrée de fluide (622) sont disposées radialement plus à l'intérieur que la première sortie de fluide (641) et la deuxième sortie de fluide (642), dans lequel le premier canal d'admission de fluide (701) est connecté, à travers la première entrée de fluide (621), à la première chambre de mesure (601), dans lequel le deuxième canal d'admission de fluide (702) est connecté, à travers la deuxième entrée de fluide (621), à la deuxième chambre de mesure (602), dans lequel le premier canal de sortie de fluide (721) est connecté, à travers la première sortie de fluide (641), à la première chambre de mesure (601), et dans lequel le deuxième canal de sortie de fluide (722) est connecté, à travers la deuxième sortie de fluide (642), à la deuxième chambre de mesure (602).
  11. Procédé selon la revendication 13, dans lequel la première sortie de fluide (641) est disposée radialement à une extrémité extérieure de la première chambre de mesure (601) et la deuxième sortie de fluide (642) est disposée radialement à une extrémité extérieure de la deuxième chambre de mesure (602), et/ou dans lequel la première entrée de fluide (621) est disposée radialement à une extrémité intérieure de la première chambre de mesure (601) et la deuxième entrée de fluide (622) est disposée radialement à une extrémité intérieure de la deuxième chambre de mesure (602).
  12. Procédé selon l'une des revendications 1 à 11, dans lequel, lors de la soumission du module fluidique à une fréquence de rotation et de la rotation qui en résulte du module fluidique (50) autour du centre de rotation (52), un premier liquide est poussé dans la première chambre de mesure (601) et un deuxième liquide est poussé dans la deuxième chambre de mesure (602), dans lequel le premier canal de sortie de fluide (721) et le deuxième canal de sortie de fluide (722) sont connectés à une chambre de mélange (861:86n).
  13. Procédé selon la revendication 12, dans lequel la première chambre de mesure (601) et la première chambre de compression (661) sont disposées radialement plus à l'intérieur que la deuxième chambre de mesure (602) et la deuxième chambre de compression (662:660).
  14. Dispositif (8) de fractionnement en parties aliquotes d'un liquide avec un module fluidique (50), dans lequel le module fluidique présente une première chambre de mesure (601) et une deuxième chambre de mesure (602), un premier canal d'admission de fluide (701) qui est connecté à la première chambre de mesure (601), et un deuxième canal d'admission de fluide (702) qui est connecté à la deuxième chambre de mesure (602), un premier canal de sortie de fluide (721) qui est connecté à la première chambre de mesure (601), et un deuxième canal de sortie de fluide (722) qui est connecté à la deuxième chambre de mesure (602), dans lequel le module fluidique (50) est conçu de sorte que, lors d'une rotation du module fluidique (50) autour d'un centre de rotation (52), un liquide soit poussé de manière centrifuge, à travers le premier canal d'admission de fluide (701), dans la première chambre de mesure (601) et, à travers le deuxième canal d'admission de fluide (702), dans la deuxième chambre de mesure (602), de sorte que par le liquide poussé dans la première chambre de mesure (601) et dans la deuxième chambre de mesure (602) soit comprimé un milieu compressible présent auparavant dans la première chambre de mesure (601) et dans la deuxième chambre de mesure (602), dans lequel le module fluidique (50) est conçu de sorte que, lors d'une réduction de la fréquence de rotation et d'une dilatation qui en résulte du milieu compressible, au moins 80% du liquide présent dans la première chambre de mesure (601) soit poussé, à travers le premier canal de sortie de fluide (721), hors de la première chambre de mesure (601) et au moins 80% du liquide présent dans la deuxième chambre de mesure (602) soit poussé, à travers le deuxième canal de sortie de fluide (722), hors de la deuxième chambre de mesure (602), dans lequel le module fluidique (50) présente un canal de répartition de fluide (80), dans lequel le premier canal d'admission de fluide (701) et le deuxième canal d'admission de fluide (702) sont connectés au canal de répartition de fluide (80), dans lequel le dispositif présente:
    un moyen d'entraînement (20) avec un moyen de commande (24);
    dans lequel le moyen de commande (24) est configuré pour commander le moyen d'entraînement (20) pour soumettre, dans une première phase, le module fluidique (50) à une fréquence de rotation telle que du liquide soit poussé de manière centrifuge, à travers le premier canal d'admission de fluide (701), dans la première chambre de mesure (601) et, à travers le deuxième canal d'admission de fluide (702), dans la deuxième chambre de mesure (602), de sorte que, par le liquide poussé dans la première chambre de mesure (601) et dans la deuxième chambre de mesure (602), soit comprimé un milieu compressible présent auparavant dans la première chambre de mesure (601) et dans la deuxième chambre de mesure (602); et
    dans lequel le moyen de commande (24) est configuré pour commander le moyen d'entraînement (20) pour réduire, dans une deuxième phase, la fréquence de rotation à laquelle est soumis le module fluidique (50) de sorte que, par la réduction de la fréquence de rotation et de la dilatation qui en résulte du milieu compressible, au moins 80% du liquide présent dans la première chambre de mesure (601) soit poussé, à travers le premier canal de sortie de fluide (721), hors de la première chambre de mesure (601) et au moins 80% du liquide présent dans la deuxième chambre de mesure (602) soit poussé, à travers le deuxième canal de sortie de fluide (722), hors de la deuxième chambre de mesure (602);
    dans lequel le module fluidique présente par ailleurs une première chambre de compression (661) et une deuxième chambre de compression (662), dans lequel la première chambre de compression (661) et la première chambre de mesure (601) sont connectées l'une à l'autre à travers un premier trop-plein de fluide (681), et dans lequel la deuxième chambre de compression (662) et la deuxième chambre de mesure (602) sont connectées l'une à l'autre à travers un deuxième trop-plein de fluide (682);
    dans lequel, lors de la soumission du module fluidique à une fréquence de rotation et de la rotation qui en résulte du module fluidique (50) autour du centre de rotation (52), le liquide est poussé à travers le premier canal d'admission de fluide (701) dans la première chambre de mesure (601) et à travers le deuxième canal d'admission de fluide (702) dans la deuxième chambre de mesure (602) jusqu'à ce que le liquide arrive à travers le premier trop-plein de fluide (681) de la première chambre de mesure (601) dans un segment de la première chambre de compression (661), dans lequel il est séparé du liquide présent dans la première chambre de mesure (601), et à travers le deuxième trop-plein de fluide (682) de la deuxième chambre de mesure (602) dans un segment de la deuxième chambre de compression (662), dans lequel il est séparé du liquide présent dans la deuxième chambre de mesure (602), et jusqu'à ce qu'une compression provoquée par le liquide poussé dans la première chambre de mesure (601) d'un milieu compressible présent auparavant dans la première chambre de mesure (601), dans la première chambre de compression (661) et dans le premier trop-plein de fluide (681) et une compression provoquée par le liquide poussé dans la deuxième chambre de mesure (602) d'un milieu compressible présent auparavant dans la deuxième chambre de mesure (602), dans la deuxième chambre de compression (662) et dans le deuxième trop-plein de fluide (682) soit si grande que, lors d'une réduction de la fréquence de rotation et d'une dilatation qui en résulte du milieu compressible, au moins 80% du liquide présent dans la première chambre de mesure (601) soit poussé, à travers le premier canal de sortie de fluide (721), hors de la première chambre de mesure (601) et au moins 80% du liquide présent dans la deuxième chambre de mesure (602) soit poussé, à travers le deuxième trop-plein de fluide (722), hors de la deuxième chambre de mesure (602).
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CN105939784A (zh) 2016-09-14
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