EP3154692B1 - Module fluidique, dispositif et procédé de manipulation de fluide - Google Patents

Module fluidique, dispositif et procédé de manipulation de fluide Download PDF

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Publication number
EP3154692B1
EP3154692B1 EP15731267.9A EP15731267A EP3154692B1 EP 3154692 B1 EP3154692 B1 EP 3154692B1 EP 15731267 A EP15731267 A EP 15731267A EP 3154692 B1 EP3154692 B1 EP 3154692B1
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EP
European Patent Office
Prior art keywords
compression chamber
fluid
channel
liquid
fluid channel
Prior art date
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EP15731267.9A
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German (de)
English (en)
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EP3154692A1 (fr
Inventor
Frank Schwemmer
Steffen ZEHNLE
Nils Paust
Daniel Mark
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Hahn-Schickard-Gesellschaft fur Angewandte Forsch
Original Assignee
Hann-Schickard-Gesellschaft fuer Angewandte Forschung eV
Albert Ludwigs Universitaet Freiburg
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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
    • B01L3/502746—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
    • B01L2200/0621—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
    • 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
    • B01L2300/087—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
    • B01L2400/08—Regulating or influencing the flow resistance
    • B01L2400/084—Passive control of flow resistance

Definitions

  • the present invention relates to a fluidic module, apparatus and method for handling liquid which are particularly suitable for handling such as retaining and releasing or pumping liquid in a centrifugal microfluidic system.
  • Centrifugal microfluidics deals with the handling of liquids in the pl to ml range in rotating systems.
  • Such systems are mostly disposable polymer cartridges used in or in place of centrifuge rotors, with the intention of enabling completely novel processes that can not be imaged by manual processes or pipetting robots due to the required precision or volume, or to automate laboratory processes.
  • Standard laboratory processes such as pipetting, centrifuging, mixing or aliquoting can be implemented in a microfluidic cartridge.
  • the cartridges contain channels for fluid guidance, as well as chambers for collecting liquids.
  • the cartridges are subjected to a predefined sequence of rotational frequencies, the frequency protocol, so that the fluids in the cartridges can be guided by inertial forces into corresponding chambers.
  • Centrifugal microfluidics is mainly used in laboratory analysis and mobile diagnostics.
  • centrifugal microfluidic disks known, for example, under the names “Lab-on-a-disk”, “Lab-Disk”, and “Lab-on-CD", which fall into special Processing devices are used.
  • Other formats such as a microfluidic centrifuge tube, known as “LabTube”, can be used in rotors of existing standard laboratory equipment.
  • a certain threshold of the rotational frequency (threshold frequency) must be exceeded in order to retain the fluid in the first fluid chamber.
  • the same threshold frequency must subsequently be exceeded in order to return the liquid via the siphon vertex and to start the fluid transfer from the first fluid chamber into the second fluid chamber.
  • the threshold frequency should be as high as possible.
  • the threshold frequency in pneumatic pumping should be as high as possible in order to minimize the influence of capillary forces.
  • the siphon is usually filled even at high rotational frequencies (even if the deceleration rate is several 10 Hz / s).
  • the inventors have realized that this entails disadvantages.
  • the inclusion of air bubbles and thus the malfunction of the siphon can be the result.
  • This effect could be minimized in a siphon with a small cross-sectional area, but this would increase the dependence on capillary forces, as well as the fluidic resistance and thus the time required for the fluid transfer.
  • the object of the present invention is to provide a fluidic module, a device and a method for handling, in particular pumping, a liquid, which allow a time-controlled and decoupled from the centrifuge dynamics pumping over a certain radial distance.
  • Embodiments of the invention provide an apparatus for handling, in particular pumping, fluid with a fluidic module as described herein and a drive apparatus configured to apply rotations to the fluidic module at different rotational frequencies.
  • the drive device is configured to, in a first phase, pressurize the fluidic module with rotation at a rotational frequency at or above a first rotational frequency at which fluid is centrifugally driven through the first fluid channel into the first compression chamber, at which first compression chamber is filled with the liquid and is driven at the liquid from the first compression chamber into the second fluid passage, thereby to enclose and compress the compressible medium in the second compression chamber.
  • the drive device is further configured to lower the rotational frequency in a second phase after the first phase below a second rotational frequency at which the force exerted on the fluid by the compressed medium in the second compression chamber outweighs the centrifugal force exerted by the fluid, so that expands the compressible medium and thereby fluid is driven from the second fluid channel into the first compression chamber, from the first compression chamber into the outlet channel and through the outlet channel.
  • Embodiments of the invention provide a method of handling fluid with a fluidic module as described herein.
  • the fluidic module is rotated with rotation at a rotational frequency at or above a first rotational frequency to centrifugally drive liquid through the first fluid channel into the first compression chamber to fill the first compression chamber with the fluid and to remove fluid from the first compression chamber driving the first compression chamber into the second fluid channel to thereby enclose and compress the compressible medium in the second compression chamber.
  • the rotational frequency is lowered below a second rotational frequency at which the force exerted on the fluid by the compressed medium in the second compression chamber outweighs the centrifugal force exerted by the fluid so that the compressible medium expands and thereby Fluid is driven from the second fluid channel into the first compression chamber, from the first compression chamber into the outlet channel and through the outlet channel.
  • Embodiments of the invention thus relate to fluidic modules, devices and methods suitable for controlled release and controlled passage of liquid through a channel, and more particularly to such fluidic modules, devices and methods suitable for timed pumping of a liquid in centrifuge rotors.
  • Embodiments of the invention are based on the realization that it is possible by providing a first compression chamber, a second compression chamber and a second fluid channel, which fluidly connects the first and the second compression chamber, and a corresponding design of the course and the dimensions of the second fluid channel.
  • the dynamics of the pumping action through the exhaust passage during and after the reduction of the rotational frequency passive, that is to control without further change of the rotational frequency.
  • the second fluid channel may have a higher flow resistance than the outlet channel.
  • the cross section of the second fluid channel may be small enough to represent a flow resistance for the liquid that is higher than the flow resistance of the outlet channel.
  • the viscosity of the liquid e.g., water
  • the viscosity of the compressible medium e.g., air
  • the pumping process takes place through the outlet channel at a much higher flow rate, which is not limited by the flow resistance in the second fluid channel. Due to the delay of the pumping process, the conduction of the liquid through the outlet channel thus at any rotational frequency, especially at standstill, take place.
  • the end of the second fluid channel may be located radially further out than the beginning of the second fluid channel, such that expansion of the compressible medium in the second compression chamber and the second fluid channel causes the centrifugal back pressure to be applied to the second fluid channel during emptying expansible compressible medium significantly decreases due to this course of the second fluid channel.
  • this drop in the centrifugal counter-pressure is brought about by only a smaller change in the volume of the compressible medium, which means that the almost constant overpressure of the compressible medium is offset by a significant change in the centrifugal counter-pressure. This pressure change is compensated by the high pressure in the first compression chamber Flow rate is pumped into the outlet channel.
  • embodiments of the invention provide high dynamics in draining the liquid from the first compression chamber. Due to the strong change in the centrifugal back pressure during emptying, but also during the filling of the second fluid channel not only the dynamics of the emptying of the first compression chamber, or the dynamics of the filling of the second compression chamber is affected, but also the rotational frequency, in which - the liquid levels are in equilibrium - the emptying of the first compression chamber takes place. Thus, embodiments of the invention allow adjustment of the switching frequencies due to the different radial positions of the fluid outlet of the first compression chamber and the fluid inlet of the second compression chamber.
  • the outlet channel may be at least partially formed by the first fluid channel.
  • the first channel is the outlet channel.
  • the outlet channel includes a portion of the first fluid channel and a third fluid channel branching from the first fluid channel.
  • the outlet channel is a fluid channel separate from the first fluid channel, which opens at a radially outer portion or the radially outer end thereof into the first compression chamber.
  • the outlet channel has a lower flow resistance than the first fluid channel.
  • the outlet channel has a siphon, wherein an outlet end of the siphon with respect to the rotation center is arranged radially further out than the position at which the outlet channel opens into the first compression chamber.
  • Embodiments of the invention are centrifugal-pneumatic delay switches.
  • there is first a delay of emptying a first compression chamber whereupon dynamic emptying can take place without further change of the rotational frequency.
  • radial is meant to be radial with respect to the center of rotation about which the fluidic module or rotor is rotatable.
  • a radial direction is radially sloping away from the center of rotation and a radial direction toward the center of rotation is radially increasing.
  • a fluid channel, the beginning of which is closer to the center of rotation than the end is thus radially sloping, while a fluid channel, the beginning of which is farther from the center of rotation than its end, is radially increasing.
  • a channel which has a radially rising section thus has directional components which rise radially or extend radially inwards. It is clear that such a channel does not have to run exactly along a radial line, but can run at an angle to the radial line or bent.
  • compression chamber is meant herein a chamber that allows the compression of a compressible medium.
  • this may be a non-vented chamber.
  • it may be a chamber, which indeed has a vent, the vent but for the compressible medium has such a high flow resistance, that still occurs by an inflowing liquid compressing the compressible medium and that by a by such a vent occurring pressure reduction in the compression chamber (in the relevant period) is negligible.
  • the first and second compression chambers described herein could also be considered as a compression chamber having two regions connected via the second fluid channel.
  • the compression chambers, with the exception of the inlets and outlets described no further fluid openings.
  • the compression chamber may be coupled to additional compression volume via one or more optional additional channels.
  • one or more compression chambers may include a closable vent.
  • a fluid channel means a structure whose length dimension is greater from a fluid inlet to a fluid outlet, for example more than 5 times or more than 10 times greater than the dimension defining the flow area or define.
  • a fluid channel has a flow resistance for flowing through it from the fluid inlet to the fluid outlet.
  • a fluid chamber is a chamber having dimensions such that a relevant flow resistance does not occur in the same.
  • Fig. 6 shows a device with a fluidic module 10 in the form of a body of revolution, which has a substrate 12 and a lid 14.
  • the substrate 12 and the cover 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 20.
  • the rotating part 18 is rotatably supported on a stationary part 22 of the drive device 20.
  • the drive device 20 may be, for example, a conventional adjustable-speed centrifuge or a CD or DVD drive.
  • a control device 24 may be provided, which is designed to control the drive device 20 in order to act on the rotation body 10 with rotations with different rotational frequencies.
  • controller 24 may be implemented by, for example, a suitably programmed computing device or custom integrated circuit.
  • the controller 24 may further be 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 may be configured to control the drive device 20 to apply the required rotational frequencies to the rotating body
  • Embodiments of the invention as described herein are to be implemented.
  • 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.
  • the patterned substrate (including fill openings and vents) is located at the top and the lid is located at the bottom.
  • fluidic modules 32 are inserted into a rotor 30 and form together with the rotor 30, the rotary body 10.
  • the fluidic modules 32 may each have a substrate and a lid, in which corresponding fluidic structures may be formed again.
  • the rotational body 10 formed by the rotor 30 and the fluidic modules 32 in turn can be acted upon by a drive device 20, which is controlled by the control device 24, with a rotation.
  • FIGS. 6 and 7 is a rotation center about which the fluidic module or the rotation body is rotatable, denoted by R.
  • the fluidic module or body having the fluidic structures may be formed of any suitable material, for example a plastic such as PMMA (polymethyl methacrylate), PC (polycarbonate), PVC (polyvinylchloride) or PDMS (Polydimethylsiloxane), glass or the like.
  • a plastic such as PMMA (polymethyl methacrylate), PC (polycarbonate), PVC (polyvinylchloride) or PDMS (Polydimethylsiloxane), glass or the like.
  • the rotary body 10 may be considered as a centrifugal microfluidic platform.
  • FIGS Fig. 1A to 1D an embodiment of a fluidic module described with corresponding fluidic structures, wherein in the Fig. 1A to 1D the fluidic structures formed in a respective fluidic module are shown during different phases of operation.
  • the fluidic structures have a first fluid channel 2, which constitutes an inlet channel, a first compression chamber 3 and a second compression chamber 5, which are connected to one another via a second fluid channel 4, and a third fluid channel 1, which forms part of an outlet channel. More precisely, branches in the in the Fig. 1A to 1D As shown, the third fluid channel 1 at a branch 50 from the first fluid channel 2, so that a part of the first fluid channel between the first compression chamber 3 and the branch 50 and the third fluid channel represent the outlet channel.
  • the third fluid channel 1 can have a lower flow resistance (that is, for example, a larger flow cross section) than the first fluid channel 2, so that a discharge of the first compression chamber 3 takes place to a greater extent through the third fluid channel 1.
  • the fluid inlet 8 of the second compression chamber 5 is located radially further outward than the fluid outlet 7 of the first compression chamber 3.
  • a portion of the second fluid channel extends between the radially innermost portion 4a and the radially outermost portion 4b of the second fluid channel with respect to the center of rotation in Fig. 1A is denoted by R, radially outward.
  • the first compression chamber 3 and the third channel (fluid outlet channel) 1 are partially filled via the first channel (fluid inlet channel) 2.
  • a radially inner end of the first fluid inlet channel may be fluidly coupled to an inlet chamber (not shown) for this purpose.
  • a compressible medium is enclosed, which is compressed by the fluid flowing into the first compression chamber, Fig. 1A ,
  • an overpressure builds up in the compressible medium, which is compensated by the centrifugal pressure of the liquid in the fluid inlet channel 2 and in the fluid outlet channel 1.
  • Phase 2a Discharge process with dynamics due to hysteresis behavior
  • the second compression chamber 5 is completely emptied only when the rotational frequency f 2 is reached , where f 2 ⁇ f 1 .
  • the connecting channel 4 is also emptied, as a result of which the System again is located outside the equilibrium of centrifugal pressure and pneumatic (in the case of gas as a compressible medium) back pressure of the compressible medium. This imbalance is according to Fig. 2 balanced by fast ('dynamic') emptying of the first compression chamber 3 until the equilibrium state is reached again.
  • the fluid in the third fluid channel 1 can reach radially inner positions that are not attainable in the equilibrium state.
  • the second fluid channel 3 increases the dynamics of the emptying process, whereby in the first and third fluid channels 2 and 1 higher filling levels are achieved than in the equilibrium state.
  • the third fluid channel may be configured as a siphon, the outlet end of which is arranged radially further outward than the fluid inlet of the first compression chamber 3 in order to allow the entire liquid to drain off.
  • the liquid volumes in the fluid chambers 3 and 5 are subject to a hysteresis behavior with respect to the rotational frequency.
  • the rotational frequency which increases in FIG Fig. 2 is marked by + arrows, a dynamic "sudden” filling of the fluid chamber 5 as soon as the rotational frequency f 1 is exceeded.
  • the in Fig. 2 is marked by arrows with -, there is a dynamic "sudden” emptying of the fluid chamber 3 as soon as the rotational frequency f 2 is exceeded.
  • Phase 2b Discharge process with dynamics due to high flow resistance
  • Fig. 3 shows an alternative embodiment of the invention, in which the fluid inlet 8 of the second compression chamber 5 is not disposed radially further out than the fluid outlet of the first compression chamber. Rather, the in Fig. 3 1, the fluid inlet 8 of the second compression chamber 5 is radially further inward than the fluid outlet 7 of the first compression chamber 3.
  • the rotational center in the figures is above the fluidic structure, as in FIG Fig. 3 in turn indicated by that designated by the reference numeral R rotation center.
  • the rotational frequency is subsequently reduced, the return flow of the fluid is limited by the high flow resistance in the second fluid channel 4.
  • the flow rate of the liquid during the backflow is so low even when the centrifuge rotor is at a standstill that the liquid fill levels in the fluid channels 1 and 2 change only slightly.
  • the rotational frequency can be significantly below the critical value f 1 or even zero. If the rotational frequency f 1 falls short enough, then first the second compression chamber 5 is emptied, followed by the second fluid channel 4.
  • the flow resistance in the second fluid channel 4 decreases (due to the lower viscosity of the compressible medium), so that the flow rate of the liquid increases during the backflow.
  • the flow rate during and after the emptying of the second fluid channel 4 may increase strong enough to reach in the third fluid channel (Fluidauslasskanal) 1, a radially inner position in the equilibrium state is unreachable.
  • the high flow resistance and the hysteresis behavior can be combined.
  • the dynamics of the evacuation process can be increased or maximized be designed by both a connecting channel with a higher flow resistance than the outlet channel and the fluid inlet of the second compression chamber is arranged radially further outward than the fluid outlet of the first compression chamber.
  • Fig. 4 shows a further embodiment of the invention, in which the fluid inlet channel 2 also represents the fluid outlet channel.
  • the effects described above can also be achieved in an analogous manner if the fluid inlet channel 2 is also operated as a fluid outlet channel.
  • Fig. 5 shows a further embodiment in which the fluid outlet channel 1 is designed as a siphon 60, so that at least one area, for example an outlet end 62 of the fluid outlet channel 1 radially outward than the fluid inlet 6 of the first compression chamber. This makes it possible to empty all the fluid from the fluidic structure having the described fluid channels and compression chambers.
  • the second compression chamber may be divided into a plurality of compression chambers, which are connected in series via respective fluid channels. It is thus possible that the second compression chamber is again subdivided into a plurality of chambers. This makes it possible that certain chambers are filled exclusively with the compressible medium, while other chambers are filled with both the compressible medium and with the liquid.
  • a plurality of fluids supplied sequentially via the first fluid conduit may be used for the described operation, wherein one or more of the fluids may also be compressible.
  • several of the described fluidic structures may be connected in parallel.
  • a sequential switching of the fluids can then be predefined Times are reached. This is useful for automating a wide variety of bio-chemical processes.
  • the outlet channel need not open into the first compression chamber together with the inlet channel.
  • the outlet channel can also open separately in a radially outer portion, for example, the radially outer end, in the first compression chamber, as long as the design ensures that the compressible medium can be compressed in the compression chamber.
  • the separate outlet channel can be designed to be closed by the liquid during the filling of the first compression chamber through the first fluid channel.
  • connection channel 4 may have a diameter of 20 ⁇ m to 200 ⁇ m.
  • the volume of the compression chamber 3 may be between 25 and 75 .mu.l, for example, 50 .mu.l, and the volume of the compression chamber 4 may be at 150 ul to 360 ul.
  • the volume of the first compression chamber is smaller, for example by a factor of 2 to 6, than the volume of the second compression chamber.
  • Typical fluid volumes of the processed liquid can be 100 .mu.l, with volumes of 100 nl to 5 ml are conceivable with appropriate design of the chambers.
  • the outlet channel may have a fluidic resistance (flow resistance) that is at least a factor of 2 or at least a factor of 10 smaller than the fluidic resistance of the connection channel. As has been described, this is not required in every embodiment.
  • the viscosity of the processed liquid eg water
  • the fluidic structures need not have the shapes shown.
  • the chambers need not be rectangular, but may take any shape and may typically have rounded corners.
  • the maximum volume of the connection channel may be limited to about 0.3 ⁇ l to 0.5 ⁇ l.
  • the minimum volume of the first compression chamber should be approximately 5 ⁇ l in this case.
  • the connecting channel can also be designed with a large length, in which case also higher channel volumes would be conceivable. However, this would be associated with technical disadvantages, for example, a higher dead volume and a greater manufacturing effort.
  • a dynamic filling and emptying of a compression chamber takes place.
  • Such dynamic filling and emptying can be achieved by the first and second compression chambers connected via the connecting channel.
  • filling and emptying can be achieved, which differs from dynamic filling and emptying in compression chambers, as known in the art.
  • the equilibrium level as a function of the rotational frequency is steady, i. with a very small change in the frequency of rotation (e.g., 0.1 Hz), there is always a very small change in the level of the compression chamber (e.g., ⁇ 1%).
  • the equilibrium level is defined as the level that sets at an infinitely long lasting constant rotation frequency.
  • a dynamic filling or a dynamic emptying with a hysteresis behavior can be achieved.
  • a rotational frequency range due to the geometric arrangement of a chamber system (consisting of at least two compression chambers or pneumatic chambers) no rotational frequency in the equilibrium state, ie at infinite length of centrifugation, a defined liquid level can be assigned.
  • a first or a second equilibrium level can be set. If this rotation frequency range is left, a new equilibrium level can be reached be sought, which deviates greatly from the current level. This large deviation can be compensated by accelerating the filling or emptying process, driven by centrifugal force or pneumatic force.
  • a dynamic filling or a dynamic emptying can be achieved by using high flow resistance.
  • the time course of the filling or emptying process can be significantly determined by channel cross sections.
  • flow rates not equal to zero can be achieved due to viscous forces even at a constant rotational frequency.
  • the replacement of different media in narrow channels and the associated changes in viscosity can lead to high flow rate changes, which can accelerate the filling and emptying even at a constant rotational frequency.
  • Embodiments of the present invention provide a fluidic module rotatable about a center of rotation, comprising: a first fluid channel; a first compression chamber fluidly coupled to the first fluid channel; a second compression chamber fluidly coupled to the first compression chamber via a second fluid channel; and a third fluid channel fluidly coupled to the first compression chamber.
  • a liquid is centrifugally drivable through the first fluid channel into the first compression chamber.
  • a compressible medium in the second compression chamber is trappable and compressible by a liquid forced by the centrifugal force through the first fluid channel into the first compression chamber, the second fluid channel, and the second compression chamber.
  • Liquid is drivable by lowering the rotational frequency and thereby conditionally expanding the compressible medium from the second compression chamber and from the second fluid channel through the third fluid channel.
  • Embodiments of the invention provide a centrifugal microfluidic structure having a compression chamber divided into a first part and a second part by a fluid channel, wherein both parts can be reversibly at least partially filled with liquid and emptied.
  • embodiments of the present invention include the generation of high dynamic fluidic switching operations that do not require rapid changes in rotational frequency.
  • embodiments of the present invention have in operation the generation of highly dynamic fluidic switching operations, in which neither rapid changes of the rotational frequency, nor high fluidic resistances are required.
  • embodiments of the invention show the maintenance of the compression of a compressible medium in a centrifuge rotor over a certain minimum period of time with any variation of the rotational frequency.
  • Embodiments of the present invention allow liquids to be held in fluid chambers while any rotational frequency protocol can be used for a certain time. This allows parallel processes to be carried out while maintaining the liquid and thus automating more complex processes than are known in the prior art.
  • embodiments of the present invention also enable liquids to be maintained above a defined rotational frequency that may be well below the rotational frequency used to activate compliance with the fluid.
  • Embodiments of the present invention enable a highly dynamic release of fluid from fluid chambers even if only very low acceleration rates are available. This is especially useful for operation in standard laboratory centrifuges. Furthermore, they enable fluid transfer via a fluid outlet channel, in particular via a siphon, at low rotational frequencies. Thus, the aforementioned disadvantages of emptying can be avoided at high rotational frequencies.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
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  • Reciprocating Pumps (AREA)

Claims (14)

  1. Module fluidique (10, 32) pouvant tourner autour d'un centre de rotation (R), aux caractéristiques suivantes:
    une première chambre (3) avec une entrée de fluide (6) et une sortie de fluide (7);
    une deuxième chambre de compression (5) avec une entrée de fluide (8);
    un premier canal de fluide (2) qui est relié à travers l'entrée de fluide (6) de la première chambre (3) à la première chambre (3); et
    un deuxième canal de fluide (4) qui relie la sortie de fluide (7) de la première chambre (3) à l'entrée de fluide (8) de la deuxième chambre de compression (5),
    dans lequel, par une rotation du module fluidique (10, 32), un liquide peut être entraîné par centrifugation à travers le premier canal de fluide (2) vers la première chambre (3), vers le deuxième canal de fluide (4) et vers la deuxième chambre de compression (5) et un milieu compressible peut ainsi être renfermé et comprimé dans la deuxième chambre de compression (5),
    dans lequel au moins l'une des caractéristiques suivantes est remplie:
    le deuxième canal de fluide (4) présente une résistance à l'écoulement du liquide supérieure à celle du canal de sortie (1, 2), et
    l'entrée de fluide (8) de la deuxième chambre de compression (5) est disposée, par rapport au centre de rotation (R), radialement plus à l'extérieur que la sortie de fluide (7) de la première chambre (3),
    caractérisé par le fait que
    la première chambre (3) est une première chambre de compression (3), et
    par réduction de la fréquence de rotation et l'expansion du milieu compressible qui en résulte, du liquide peut être entraîné de la deuxième chambre de compression (5) et du deuxième canal de fluide (4) vers la première chambre de compression (3), de la première chambre de compression (3) vers un canal de sortie (1, 2) et à travers le canal de sortie (1, 2).
  2. Module fluidique (10, 32) selon la revendication 1, dans lequel le premier canal de fluide (2) est le canal de sortie (2).
  3. Module fluidique (10, 32) selon la revendication 1, dans lequel le canal de sortie (1, 2) présente une partie du premier canal de fluide (2) et au moins un troisième canal de fluide (1) qui est dérivé du premier canal de fluide (2).
  4. Module fluidique (10, 32) selon la revendication 3, dans lequel l'au moins un troisième canal de fluide (1) présente une résistance à l'écoulement de liquide plus faible que le premier canal de fluide (2).
  5. Module fluidique (10, 32) selon la revendication 1 à 4, dans lequel le canal de sortie (1, 2) présente un siphon (60), dans lequel une extrémité de sortie (60) du siphon (60) est disposée, par rapport au centre de rotation (R), radialement plus à l'extérieur que la position à laquelle le canal de sortie (1, 2) débouche dans la première chambre de compression (3).
  6. Module fluidique (10, 32) selon la revendication 1, dans lequel le canal de sortie est un canal de fluide, séparé du premier canal de fluide (2), qui débouche dans la première chambre de compression (3) à un segment radialement extérieur ou à l'extrémité radialement extérieure de cette dernière.
  7. Module fluidique (10, 32) selon l'une des revendications 1 à 6, dans lequel la sortie de fluide (7) de la première chambre de compression (3) est disposée à un segment radialement intérieur ou une extrémité radialement intérieure, par rapport au centre de rotation (R), de la première chambre de compression (3).
  8. Module fluidique (10, 32) selon l'une des revendications 1 à 7, dans lequel l'entrée de fluide (8) de la deuxième chambre de compression (5) est disposée à un segment radialement extérieur ou une extrémité radialement extérieure, par rapport au centre de rotation (R), de la deuxième chambre de compression (5).
  9. Module fluidique (10, 32) selon l'une des revendications 1 à 8, dans lequel le deuxième canal de fluide (4) présente, dans la direction d'écoulement de la deuxième chambre de compression (5) vers la première chambre de compression (4) par rapport au centre de rotation (R), un segment dont le début est plus éloigné du centre de rotation (R) que sa fin.
  10. Dispositif de manipulation de liquide, aux caractéristiques suivantes:
    un module fluidique (10, 32) selon l'une des revendications 1 à 9; et
    un dispositif d'entraînement (20) qui est conçu pour soumettre le module fluidique (10, 32) à des rotations à différentes fréquences de rotation,
    dans lequel le dispositif d'entraînement (20) est conçu pour soumettre le module fluidique (10, 32), dans une première phase, à une rotation à une fréquence de rotation égale ou supérieure à une première fréquence de rotation à laquelle le liquide est entraîné par centrifugation à travers le premier canal de fluide (2) vers la première chambre de compression (3), à laquelle la première chambre de compression (3) est remplie par le liquide et à laquelle le liquide est entraîné de la première chambre de compression (3) vers le deuxième canal de fluide (4) et la deuxième chambre de compression (5), pour ainsi renfermer et comprimer le milieu compressible dans la deuxième chambre de compression (5),
    dans lequel le dispositif d'entraînement (20) est conçu pour faire descendre, dans une deuxième phase après la première phase, la fréquence de rotation au-dessous d'une deuxième fréquence de rotation à laquelle la force exercée sur le liquide par le milieu comprimé dans la deuxième chambre de compression (5) prédomine sur la force centrifuge exercée par le fluide, de sorte que le milieu compressible se dilate et que, de ce fait, du liquide soit entraîné de la deuxième chambre de compression (5) et du deuxième canal de fluide (4) vers la première chambre de compression (3), de la première chambre de compression (3) vers le canal de sortie (1, 2) et à travers le canal de sortie (1, 2).
  11. Dispositif selon la revendication 10, dans lequel l'entrée de fluide (8) de la deuxième chambre de compression (5) est disposée, par rapport au centre de rotation (R), radialement plus à l'extérieur que la sortie de fluide (7) de la première chambre de compression (3), dans lequel la deuxième fréquence de rotation est inférieure à la première fréquence de rotation et dans lequel le dispositif d'entraînement est conçu pour soumettre, dans une phase intermédiaire entre la première phase et la deuxième phase, le module fluidique (10, 32) à une fréquence de rotation qui se situe entre la première fréquence de rotation et la deuxième fréquence de rotation, sans que du liquide ne soit entraîné du deuxième canal de fluide (4) vers la première chambre de compression (3).
  12. Procédé de manipulation de fluide par un module fluidique (10, 32) selon l'une des revendications 1 à 9, aux caractéristiques suivantes consistant à:
    dans une première phase, faire tourner le module fluidique (10, 32) selon une rotation à une fréquence de rotation égale ou supérieure à une première fréquence de rotation pour entraîner du liquide par centrifugation à travers le premier canal de fluide (2) vers la première chambre de compression (3) et la deuxième chambre de compression (5), pour remplir la première chambre de compression (3) par le liquide, et pour entraîner du liquide de la première chambre de compression (3) vers le deuxième canal de fluide (4), pour renfermer et comprimer ainsi le milieu compressible dans la deuxième chambre de compression (5),
    dans une deuxième phase après la première phase, faire descendre la fréquence de rotation au-dessous d'une deuxième fréquence de rotation à laquelle la force exercée sur le liquide par le milieu comprimé dans la deuxième chambre de compression (5) prédomine sur la force centrifuge exercée par le liquide, de sorte que le milieu compressible se dilate et que, de ce fait, du liquide soit entraîné de la deuxième chambre de compression (5) et du deuxième canal de fluide (4) vers la première chambre de compression (3), de la première chambre de compression (3) vers le canal de sortie (1, 2) et à travers le canal de sortie (1, 2).
  13. Procédé selon la revendication 12, dans lequel l'entrée de fluide (8) de la deuxième chambre de compression (5) est disposée, par rapport au centre de rotation (R), radialement plus à l'extérieur que la sortie de fluide (7) de la première chambre de compression (3), dans lequel la deuxième fréquence de rotation est inférieure à la première fréquence de rotation, et qui présente, dans une phase intermédiaire entre la première phase et la deuxième phase, une rotation du module fluidique à une fréquence de rotation qui se situe entre la première fréquence de rotation et la deuxième fréquence de rotation, sans que du fluide ne soit entraîné du deuxième canal de fluide (4) vers la première chambre de compression (3).
  14. Procédé selon la revendication 12 ou 13, qui présente une utilisation d'un module fluidique dont l'entrée de fluide (8) est disposée, par rapport au centre de rotation (R), radialement plus à l'extérieur que la sortie de fluide (7) de la première chambre de compression (3), dans lequel, dans la première phase commence, à une fréquence de rotation croissante, un remplissage dynamique de la deuxième chambre de compression (5) dès qu'une première fréquence de rotation f1 est excédée, et dans lequel, dans la deuxième phase commence, à une fréquence de rotation décroissante, un vidage dynamique de la première chambre de compression (3) dès qu'il est descendu au-dessous d'une deuxième fréquence de rotation f2 , où f2 < f1.
EP15731267.9A 2014-06-11 2015-06-10 Module fluidique, dispositif et procédé de manipulation de fluide Active EP3154692B1 (fr)

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DE102014211121.8A DE102014211121A1 (de) 2014-06-11 2014-06-11 Fluidikmodul, vorrichtung und verfahren zum handhaben von flüssigkeit
PCT/EP2015/062956 WO2015189280A1 (fr) 2014-06-11 2015-06-10 Module fluidique, dispositif et procédé de manipulation de fluide

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DE102012202775B4 (de) * 2012-02-23 2016-08-25 Hahn-Schickard-Gesellschaft für angewandte Forschung e.V. Fluidikmodul, vorrichtung und verfahren zum pumpen einer 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
CN114026252A (zh) 2019-03-19 2022-02-08 欧罗克隆纳利蒂基金会 准确评估克隆免疫球蛋白(ig)/t细胞受体(tr)基因重組的手段和方法
CN109932523A (zh) * 2019-04-11 2019-06-25 石家庄禾柏生物技术股份有限公司 一种基于离心力的液体定量转移装置
DE102019007512A1 (de) * 2019-10-29 2021-04-29 Lilian Labs GmbH Mikrofluidische Vorrichtung zur Aufnahme von Flüssigkeiten und zugehöriges Verfahren
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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PL3154692T3 (pl) 2019-06-28
US20170216837A1 (en) 2017-08-03
EP3154692A1 (fr) 2017-04-19
US10350598B2 (en) 2019-07-16
ES2711088T3 (es) 2019-04-30
DE102014211121A1 (de) 2015-12-17
TR201901927T4 (tr) 2019-03-21
WO2015189280A1 (fr) 2015-12-17
DK3154692T3 (en) 2019-03-04

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