EP3592463A1 - Actionnement centrifuge-pneumatique de liquides - Google Patents

Actionnement centrifuge-pneumatique de liquides

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Publication number
EP3592463A1
EP3592463A1 EP18708690.5A EP18708690A EP3592463A1 EP 3592463 A1 EP3592463 A1 EP 3592463A1 EP 18708690 A EP18708690 A EP 18708690A EP 3592463 A1 EP3592463 A1 EP 3592463A1
Authority
EP
European Patent Office
Prior art keywords
fluid
liquid
chamber
downstream
fluidic
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP18708690.5A
Other languages
German (de)
English (en)
Other versions
EP3592463B1 (fr
Inventor
Ingmar Schwarz
Nils Paust
Steffen ZEHNLE
Mark Keller
Tobias HUTZENLAUB
Frank Schwemmer
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Hann-Schickard-Gesellschaft fuer Angewandte Forschung eV
Original Assignee
Hann-Schickard-Gesellschaft fuer Angewandte Forschung eV
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Priority to PL18708690T priority Critical patent/PL3592463T3/pl
Publication of EP3592463A1 publication Critical patent/EP3592463A1/fr
Application granted granted Critical
Publication of EP3592463B1 publication Critical patent/EP3592463B1/fr
Active legal-status Critical Current
Anticipated expiration legal-status Critical

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/50273—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • 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
    • B01L2200/0684—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
    • B01L2300/0806—Standardised forms, e.g. compact disc [CD] format
    • 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
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0877—Flow chambers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/14—Means for pressure control
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—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
    • B01L2400/0487—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
    • B01L2400/04—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
    • B01L2400/049—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics vacuum

Definitions

  • the present invention is directed to apparatus and methods for centrifugally-pneumatically switching liquids from a liquid holding area to subsequent fluidic structures utilizing a ratio of centrifugal pressure to pneumatic pressure.
  • Centrifugal microfluidics deals with the handling of liquids in the picoliter to milliliter range in rotating systems.
  • Such systems are mostly polymer disposable cartridges used in or in place of centrifuge rotors with the intention of automating laboratory processes.
  • Standard laboratory processes such as pipetting, centrifuging, mixing or aliquoting can be implemented in a microfluidic cartridge.
  • the cartridges contain channels for the fluid guidance, as well as chambers for the collection of liquids.
  • such structures designed to handle fluids may be referred to as fluidic structures.
  • such cartridges may be referred to as fluidic modules.
  • the cartridges are subjected to a predefined sequence of rotational frequencies, the frequency protocol, so that the fluids in the cartridges can be moved by the centrifugal force.
  • Centrifugal microfluidics is mainly used in laboratory analysis and mobile diagnostics. The most common type of cartridge to date is a centrifugal microfluidic disk used in special processing equipment known as "Lab-on-a-disk", “LabDisk”, “Lab-on-CD”, etc.
  • Other formats, such as microfluidic centrifuge tubes, known as "LabTube” can be used in rotors of existing standard laboratory equipment.
  • An example is the measurement of liquid volumes for the production of aliquots, in which after a measuring step, the liquids are switched to subsequent process steps. Further examples are incubation and mixing processes in which the incubation time or the completion of the mixing process must be achieved before switching on.
  • centrifugal microfluidic platform is used to centrifugally pump liquid from a first, non-vented chamber in a first vacuum valve so that gas in the first chamber expands and creates a negative pressure in the first chamber Since a siphon, whose end is vented, is also branched off from the outlet channel, part of the liquid is also driven into the siphon Fill levels, so that the level in the second Chamber is equal to the level in the siphon.
  • valve circuit in which liquid is driven centrifugally from a first chamber through an outlet channel into a second chamber and at the same time into a branching siphon. Since in this further valve circuit, the first chamber is vented and the second chamber is not vented, a volume of gas is trapped in the second chamber and compressed when driving the liquid into the second chamber. This volume of gas expands as the speed decreases, driving fluid into the siphon. With high rate of deceleration of the speed and corresponding dimensioning of the flow resistances, sufficient liquid is forced into the siphon to completely fill it so that the liquid from the first and second chambers can be forced through the siphon and collected in a third chamber.
  • This valve function is also described in EP 2 817 519 B1.
  • valve circuit which is referred to above as a further valve circuit, can optionally be provided with a second siphon to the liquid, depending on the deceleration rate of the rotational speed by one or to pass through both siphons.
  • valve circuits described in the aforementioned document by S. Zehnle have in common that the end of the siphon through which the fluid is driven is vented.
  • the third chamber which serves only as a collecting chamber, vented and not coupled to another fluidic element. It has the function as a collecting chamber beyond any other fluidic functions and can not influence the valve functions described by any type of sizing.
  • the principle of operation of the centrifugal-pneumatic valves described consists of two complementary effects.
  • the first effect is that the liquid closes the connecting channel between the measuring channel and subsequent non-ventilated target chamber during filling of the respective measuring channel and thereby causes the centrifugally induced transfer of liquid from the measuring finger into the target chamber to a compression of the gas present therein.
  • the resulting pneumatic overpressure in the target chamber counteracts further flow of the liquid into the target chamber.
  • the second effect is that the connecting channel between the measuring channel and the target chamber at the opening to the target chamber is a capillary valve, which counteracts the advancement of the liquid in the target chamber.
  • centrifugal pneumatic valves only allow the compression of a small gas volume through the connecting channel between the measuring channel and the target structure before liquid enters the target chamber.
  • the switching frequency is structurally limited to low frequencies.
  • the capillary valve effect which plays a role for the centrifugal-pneumatic valve, depends on the surface tension and the contact angles between the liquid and the cartridge material.
  • the requirement of a sharp-edged transition of the connecting channel to the target chamber arises from the described capillary valve portion of the centrifugal pneumatic valve, which is accompanied by additional expenditure for the production.
  • F. Schwemmer et.al. "Centrifugo-pneumatic multi-liquid aliquoting - parallel aliquoting and combination of multiple liquids in centrifugal microfluidics", Royal Society of Chemistry 2015, Lab Chip, 2015, 15, pages 3250 - 3258, describe structures that consist of a high fluid resistance inlet channel, a measuring chamber, a pressure chamber connected to the measuring chamber via a connecting channel, and a low-fluid resistance outlet channel connected to the measuring chamber , The structures allow the metering and subsequent switching of liquid volumes.
  • the sequence of the measuring and switching process is as follows: First, the liquid to be metered is passed at high rotational frequency through the inlet channel into the measuring chamber until it is completely filled.
  • the radially inwardly connected connecting channel fills to the pressure chamber and excess liquid is fed into the pressure chamber, which represents a trap for them, so that the liquid can not leave the pressure chamber.
  • the from the time of entry of the liquid into the measuring chamber to displaced gas volume in the measuring chamber and the pressure chamber leads to a pneumatic pressure increase in the pressure chamber.
  • the liquid is switched by reducing the rotational frequency in subsequent fluidic structures. This is achieved because the centrifugal pressure in the outlet channel falls below the pneumatic overpressure in the pressure chamber and therefore the liquid is transferred from the pneumatic overpressure and other pressures occurring substantially into the outlet channel.
  • the selected fluidic resistances ensure that the transfer takes place essentially in the outlet channel and not back into the inlet channel.
  • the structures may have a siphon, which ensures during a measuring step that the liquid is not yet switched into a collection chamber. In structures in which the collection chamber is located radially further inward than the measuring chamber, the siphon can be omitted. A corresponding aliquoting is also described in WO 2015/049112 A1.
  • centrifugal-pneumatic aliquoting is suitable only for process chains in which can be switched by reducing the rotational frequency or should.
  • a minimum rate of deceleration must be achieved to transfer the fluid to a target volume, thereby limiting the usable processing equipment.
  • centrifugal-pneumatic aliquoting can likewise not be used.
  • centrifugal-pneumatic aliquoting requires additional space for the pressure chamber, which may be lost for the introduction of structures for other operations on the cartridge.
  • the need for strong differences in the fluidic resistance between inlet and outlet channels leads to additional requirements for the production, since high fluidic resistances are achieved by small channel cross-sections, which thereby make high demands on the manufacturing tolerances.
  • Wisam Al-Faqheri et. al. "Development of a Passive Liquid Valve (PLV) Utilizing a Pressure Equilibrium Phenomenon on the Centrifugal Microfluidic Platform," Sensors 2015, 15, pp. 4658-4676, describe switching fluid as a function of fluid acting on a fluid in an inlet chamber Centrifugal pressure, acting on the liquid in the inlet chamber capillary pressure and acting on a liquid in a venting chamber centrifugal pressure. Air is trapped between the fluids in the inlet chamber and the venting chamber. By increasing the rotational speed, a negative pressure generated in the inlet chamber or an overpressure generated in the deaeration chamber is overcome, thereby to convey liquid from the inlet chamber through a fluid channel into a target chamber.
  • the object of the invention is to provide a fluidic module for switching fluids which can be monolithically integrated and easily manufactured, largely fluid and material properties independent and adaptable to a wide range of processing conditions, as well as devices with such a fluidic module and method comprising such a fluidic module use, create.
  • Embodiments of the present invention relate to fluidic modules, devices, and methods for retaining and selectively switching fluids in centrifugal microfluidic cartridges.
  • Exemplary embodiments provide a fluidic module for switching liquid from a liquid holding region into downstream fluidic structures, comprising: a liquid holding region, into which a liquid can be introduced, at least two fluid paths, which fluidly connect the liquid holding region to downstream fluidic structures, wherein at least a first fluid path of the two fluid paths has a siphon channel, wherein a siphon apex of the siphon channel is radially within a radially outermost position of the liquid holding region, wherein the downstream fluidic structures are not vented or vented only via a venting delay resistor when the Liquid is introduced into the liquid holding area, so that in the downstream fluidic an enclosed gas volume or vented only via a vent delay resistance gas volume is formed when the liquid is introduced into the liquid-holding area, and by a ratio of one by a rotation of the Fluidic module caused centrifugal pressure and prevailing in the gas volume pneumatic pressure is at least temporarily prevented that the liquid passes through the fluid paths in the downstream fluidic structures, wherein a change in the ratio of the centr
  • Embodiments of the invention are based on the recognition that it is possible on a centrifugally microfluidic platform, using appropriate fluidic structures, to fill a liquid holding region that may be centrifugally induced, a pneumatic differential pressure to ambient pressure in downstream (subsequent) fluidic structures. and the connecting fluid paths between liquid holding region and subsequent fluidic structures, by which the liquid can be maintained in the liquid holding region under suitable processing conditions, until, induced by a suitable change in the processing conditions, the liquid can be further transferred into the subsequent fluidic structures. During this liquid transfer into the downstream fluidic structures through one of the fluid paths, a venting of the downstream fluidic structures can take place through the other of the fluid paths.
  • Embodiments continue to be based on the finding that during a, for example, centrifugally induced filling operation of the liquid holding region, gas can be displaced into the downstream fluidic structures through the connecting fluid paths between the liquid holding region and the downstream fluidic structures, and further that the displaced gas volume is merely through the liquid volume is limited, can be chosen arbitrarily by suitable design of the connecting fluid paths, whereby the processing conditions under which the liquid is held in the liquid holding region, as well as the processing conditions under which the liquid is switched into the downstream fluidic structures, in a wide range and largely irrespective of liquid properties or cartridge material properties.
  • the liquid can be introduced by a centrifugal pressure caused by a rotation of the fluidic module via a radially sloping inlet channel into a fluid chamber of the liquid-holding region.
  • the rotation used during introduction of the liquid into the liquid holding region can achieve the ratio between centrifugal pressure and pneumatic pressure, which prevents liquid from entering the downstream fluidic structures.
  • the inlet channel may be further connected to an upstream fluid chamber.
  • a second fluid path of the two fluid paths is a vent channel for the downstream fluidic structures, which is closed by the liquid when the liquid is introduced into the liquid holding area.
  • the first fluid path opens in a radially outer region or at a radially outer end into the liquid-holding region, so that the liquid-holding region at least up to the region in which the first fluid path opens into the liquid-holding region via the first Fluid path is emptied. This makes it possible to empty a large part of the liquid or the entire liquid from the liquid holding area.
  • the liquid holding region has a first fluid chamber, wherein the first fluid path opens into the first fluid chamber in a radially outer region of the first fluid chamber or at a radially outer end of the first fluid chamber.
  • the first fluid chamber may be deflated or vented only via a venting delay resistor when the fluid is introduced into the fluid retaining region, such that a volume of gas trapped in the first fluid chamber and the downstream fluidic structures is merely vented gas volume created by a venting delay resistor occurs when the liquid is introduced into the liquid holding region.
  • the liquid-holding region has a first fluid chamber and a second fluid chamber into which a liquid can be introduced by a centrifugal pressure caused by rotation of the fluidic module, wherein the first fluid path opens into the first fluid chamber and the second fluid path opens into the second fluid chamber, and wherein the second fluid path is closable by a liquid introduced into the second fluid chamber.
  • the first fluid chamber and the second fluid chamber may be fluidly interconnected via a connection channel having its mouth radially inward of the first fluid chamber than a radially outer end of the first fluid chamber such that fluid from the first fluid chamber overflows into the second fluid chamber when the level of liquid in the first fluid chamber reaches the mouth, and closes the second fluid path opening into the second fluid chamber.
  • Such embodiments may allow first liquid is held in the first fluid chamber and only in the downstream Fluidik Modellen is switched by the addition of further liquid, which may be a different liquid from the first liquid.
  • the second fluid path has a siphon channel. This allows increased flexibility with regard to the opening of the second fluid path into the liquid holding region and increased flexibility with regard to the processing conditions, as this can prevent liquid from entering the downstream fluidic structures via the second fluid path.
  • the second fluid path may open into the liquid holding region in a radially outer region of the liquid holding region.
  • a vertex of the siphon channel of the second fluid path may be located radially further inward than a vertex of the siphon channel of the first fluid path.
  • the second fluid path has a siphon channel and a fluid intermediate chamber is disposed in the second fluid path between the apex of the siphon channel of the second fluid path and the mouth of the second fluid path in the liquid holding area, wherein the intermediate fluid chamber is at least partially filled with the liquid when the liquid is introduced into the liquid holding area.
  • the intermediate fluid chamber may have a smaller volume than a first fluid chamber of the liquid holding portion.
  • a radially outer end of the intermediate fluid chamber is located radially outward of the siphon apex of the first fluid path. The first intermediate fluid chamber allows a greater amount of fluid to enter the second fluid path before its meniscus reaches the apex of the siphon channel of the second fluid path.
  • the downstream fluidic structures have at least one downstream fluid chamber into which the first fluid path and the second fluid path open.
  • the first and the second fluid path may also lead into different chambers of the downstream fluidic structures, as long as it is ensured that a pressure equalization between the mouths of the first and the second fluid path into the downstream fluidic structures during the fluid holding phase.
  • the first fluid path can open radially further out into the downstream fluid chamber than the second fluid path. This allows the mouth of the second fluid path to remain in the downstream fluid chamber for venting as the fluid passes into the downstream fluidic structures.
  • the downstream fluid chamber may be a first downstream fluid chamber, the downstream fluidic structures may have a second downstream fluid chamber, which is fluidly connected via at least one third fluid path with the first downstream fluid chamber.
  • the downstream fluidic structures may include a first downstream fluid chamber and a second downstream fluid chamber, the first downstream fluid chamber being fluidly connected to the second downstream fluid chamber via a third fluid path and a fourth fluid path, wherein at least the third fluid path includes a siphon channel third fluid path and the fourth fluid path are closed by the liquid when the liquid by changing the ratio of the centrifugal pressure to the pneumatic Pressure passes through the first fluid path in the first downstream fluid chamber of the downstream fluidic, whereby in the second downstream fluid chamber an enclosed gas volume or vented only via a vent delay resistance gas volume is formed and by a ratio of the centrifugal pressure and in the gas volume in the second downstream Fluid chamber prevailing pneumatic pressure is at least temporarily prevented that the liquid passes through the fluid paths (in particular the third and fourth fluid path) in the second downstream fluid chamber, and wherein caused by a change in the ratio of the centrifugal pressure to the pneumatic duck in the second downstream fluid chamber can that the liquid passes through the third fluid path in the second downstream fluidic chamber and the gas volume from the second downstream
  • Embodiments provide an apparatus for switching fluid from a fluid holding area to downstream fluidic structures having a fluidic module as described herein, driving means configured to impart rotation to the fluidic module, and actuator configured. to effect the change of the ratio of the centrifugal pressure to the pneumatic duck.
  • the actuator is configured to increase or decrease the rotational speed of the fluidic module to effect the change in the ratio of the centrifugal pressure to the pneumatic duck.
  • the actuator is designed to reduce the pneumatic pressure in the downstream fluidic structures by reducing the temperature in the downstream fluidic structures and / or by increasing the volume of the downstream fluidic structures and / or reducing the amount of gas in the downstream fluidic structures.
  • Embodiments provide a method of switching fluid from a fluid holding area to downstream fluidic structures using a fluidic module as described herein, having the following features:
  • holding the liquid in the liquid holding region comprises generating a pneumatic overpressure in the downstream fluidic structures prior to the initiation of the transfer.
  • changing the ratio of the centrifugal pressure to the pneumatic duck includes increasing the rotational speed of the fluidic module, increasing the hydrostatic head of the fluid, and / or decreasing the pneumatic pressure.
  • holding the liquid in the liquid holding region includes creating a negative pressure in the downstream fluidic structures to adjust and hold menisci in the liquid holding region and the first and second fluid paths without passing the liquid through the first fluid path into the downstream one Fluidic structures to transfer, wherein changing the ratio of the centrifugal pressure to the pneumatic pressure, a reduction in the rotational speed of the fluidic module and / or reducing the pneumatic pressure in the downstream fluidic structures and / or increasing the hydrostatic height of the liquid in the liquid holding area.
  • changing the ratio includes decreasing the pneumatic pressure by decreasing the temperature in the downstream fluidic structures, increasing the volume of the downstream fluidic structures, and / or reducing the amount of gas in the downstream fluidic structures.
  • the second fluid path is not completely filled with liquid.
  • the molar amount of the gas in the downstream fluidic structures is not changed while the liquid is held in the liquid holding area.
  • 3A to 3D are schematic representations of fluidic structures according to an embodiment in which the downstream fluidic structures have a fluid receiving chamber and a further chamber;
  • FIGS. 4A to 4D are schematic representations of fluidic structures according to an embodiment, in which a fluid intermediate chamber is arranged in a fluid path between the liquid Haite Scheme and downstream Fluidik Modellen;
  • 5A to 5D are schematic representations of fluidic structures according to an embodiment with changed connection positions of the fluid paths;
  • FIG. 6 is a schematic representation of fluidic structures according to an exemplary embodiment with cascaded structures
  • 8A to 8E are schematic representations of fluidic structures according to an embodiment for the vacuum-based switching
  • FIG. 9 is a schematic representation of fluidic structures according to an embodiment with a liquid-Haite Scheme having two fluid chambers.
  • 10A to 10D are schematic diagrams for explaining the operation of the
  • Embodiment of Fig. 9; 11A to 1E are schematic diagrams for explaining the operation of the embodiment of Figure 9 when using two liquids ..;
  • 12A and 12B are schematic side views for explaining embodiments of devices for switching liquids.
  • FIGS 13A and 13B are schematic plan views of embodiments of Fluidikmo- modules.
  • Embodiments of the invention relate to microfluidic structures for centrifuge-pneumatic switching and to methods for centrifugal-pneumatic switching, in particular for the centrifugo-pneumatic switching of liquids from a liquid-holding region, which may have a first chamber, into subsequent or downstream fluidic structures.
  • Subsequent or subsequent (these terms are used interchangeably herein) fluidic structures herein are referred to as fluidic structures, such as e.g. Channels or chambers, understood to enter the fluid during handling thereof from upstream or upstream (these terms being used interchangeably herein) fluidic structures.
  • the microfluidic structures may have a first chamber, which is connected to the following fluidic structures via at least two fluid paths, wherein at least the fluid path through which the fluid is transferred when switching into the subsequent fluidic structures is configured in the shape of a siphon.
  • the structures and the method may be designed such that the relevant pressures in the direction or opposite to the filling of the path for the liquid transfer by centrifugal pressures or pneumatic pressures are given. Switching in which centrifugal pressures and pneumatic pressures dominate other pressures can be referred to as centrifugal-pneumatic switching.
  • pneumatic overpressures and / or negative pressures may be used.
  • the centrifugal pressure can be increased above the switching pressure, whereby the siphon is wetted and the transfer of the liquid into the subsequent fluidic structures is initiated.
  • the hydrostatic height of the fluid may also be increased to initiate fluid transfer, for example by adding additional fluid into the fluid holding region via upstream fluidic structures.
  • the subsequent fluidic structures can first be heated, so that a gas contained in them expands and part of this gas can escape.
  • the liquid in the fluid communication paths may be at approximately the same radial height as in the liquid holding region.
  • a negative pressure results which acts in the direction of the subsequent fluidic structures.
  • the connection paths are siphon-shaped, this increases the hydrostatic height in the connection paths, so that the centrifugal force in this case counteracts further filling of the connection paths. This is the (quasistatic) equilibrium state under negative pressure conditions.
  • Embodiments illustrate methods of retaining liquids and initiating the switching process by other changes in processing conditions along with the structures associated therewith.
  • the second fluid interconnect between liquid holding area and downstream fluidics structures may be utilized Allow gas from the downstream fluidic in the liquid holding area or a fluid chamber of the liquid-holding area to escape or flow, which can reduce the pneumatic pressure difference to the downstream fluidic structures.
  • hydrostatic head is meant the radial distance between two points in a centrifugal cartridge, if at both points there is liquid of a continuous quantity of liquid.
  • Hydrostatic pressure is the centrifugal force-induced pressure difference between two points due to the hydrostatic head between them.
  • the effective fluidic resistance of a microfluidic structure is the quotient of the pressure that drives a fluid through a microfluidic structure and the resulting fluid flow through the microfluidic structure. Aliquoting is the division of a liquid volume into several separate individual volumes, so-called aliquots.
  • Switching frequency is understood to be the rotational frequency of a microfluidic cartridge, beyond which a transfer process of a liquid from a first structure to a second structure begins.
  • a siphon channel is to be understood as a microfluidic channel or a section of a microfluidic channel in a centrifugally microfluidic cartridge in which the inlet and outlet of the channel are located at a greater distance from the center of rotation than an intermediate region of the channel.
  • a siphon apex is understood to mean the area of a siphon channel in a microfluidic cartridge with a minimum distance from the center of rotation.
  • a venting delay resistance is meant the fluidic resistance through which a fluidic structure in which a pneumatic differential pressure to the ambient pressure prevails, is vented.
  • the fluidic resistance is at least so high that the reduction of the differential pressure to half of it, taking into account only the venting by the fluidic resistance takes at least 0.5 s. This applies at any time during the venting.
  • the time profile of the pressure drop in these fluidic structures can be determined, for example, by filling the liquid holding area at a constant temperature with liquid under centrifugation and the hydrostatic height between an upstream chamber and a fluid Chamber in which the liquid is held in the liquid-retaining structures, in quasi-stationary equilibrium by a suitable camera system (eg with stroboscopic exposure) is recorded.
  • a suitable camera system eg with stroboscopic exposure
  • the rotational frequency and the hydrostatic head result in the pneumatic overpressure existing in the following structures. Therefore, the degradation rate of the overpressure can also be determined from this image information, resulting in the size of the venting delay resistance.
  • the method can be analogously used by liquid is filled at a certain frequency and start temperature and then a defined rapid cooling is generated.
  • a defined rapid cooling is generated.
  • a fluid guide path is to be understood as meaning a fluidic structure through which fluid flows from the fluid-holding region into one or more subsequent fluidic structures during the execution of the method according to the invention.
  • a gas guidance path is to be understood as meaning an IV fluidic structure through which gas exchange takes place between the subsequent fluidic structures and the fluid holding area during the execution of the method according to the invention.
  • a fluid receiving volume is understood to mean a fluidic fluid structure which provides a volume into which fluid is transferred after initiation of the switching process according to the invention.
  • microfluidic cartridge By a microfluidic cartridge is meant herein an apparatus, such as a fluidic module, having microfluidic structures that facilitate liquid handling as described herein.
  • a centrifugal microfluidic cartridge means a corresponding cartridge which is subjected to rotation. can, for example in the form of an insertable into a body of revolution fluidic or a body of revolution.
  • 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 herein is a chamber which has dimensions such that, as it flows through the chamber, there is a negligible flow resistance compared to connected channels, which may be, for example, 1/100 or 1/1000 of the flow resistance of the channel structure with the smallest flow resistance connected to the chamber ,
  • radial is meant to be radial with respect to the center of rotation about which the fluidic module or body 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.
  • FIG. 12A shows a device with a fluidic module in the form of a rotary body 10, which has a substrate 12 and a cover 14.
  • 13A shows schematically a plan view of the rotary body 10.
  • the substrate 12 and the cover 14 may be circular in plan view, with a central opening 15, in which a center of rotation R is arranged and via which the rotary body 10 via a conventional fastening means 16 at a rotating part 18 of a drive device 20 may be attached.
  • 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.
  • the controller 24 may be configured to execute a frequency protocol to achieve the functionalities described herein.
  • the controller 24 may be implemented by, for example, a suitably programmed computing device, a microprocessor, or a 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 fluidic module to implement embodiments of the invention as described herein.
  • the rotary body 10 has the fluidic structures described herein. Corresponding fluidic structures are indicated purely schematically in FIG. 13A by trapezoidal regions 28a to 28d. For example, a plurality of fluidic structures may be juxtaposed in the azimuthal direction, as shown in FIG. 13A, to facilitate parallel handling of multiple fluids.
  • the 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. In embodiments, for example, fluidic structures can be formed in the substrate 12, while filling openings and venting can be formed. openings are formed in the lid 14. In embodiments, 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 together with the rotor 30 form the rotary body 10.
  • FIG. 13B schematically shows a plan view of a corresponding fluidic module.
  • the fluidic modules 32 may each have a substrate and a lid, in which corresponding fluidic structures may again be formed.
  • 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.
  • a center of rotation about which the fluidic module or the rotational body is rotatable is 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 (polymethylmethacrylate), PC (polycarbonate), PVC (polyvinylchloride), or PDMS (polydimethylsiloxane), glass or the like.
  • a plastic such as PMMA (polymethylmethacrylate), PC (polycarbonate), PVC (polyvinylchloride), or PDMS (polydimethylsiloxane), glass or the like.
  • the rotary body 10 may be considered as a centrifugal microfluidic platform.
  • the control means 24 is an actuator which can adjust the rotational speed of the drive means to initiate fluid transfer, ie to cause the ratio of the centrifugal pressure to the pneumatic pressure to cause switching of the fluid becomes.
  • the actuator may additionally include one or more heaters and / or coolers to control the temperature of the fluidic structures to initiate fluid transfer.
  • one or more temperature control elements 40 heating element and / or cooling element
  • one or more external temperature control elements 42 can be provided, via which the temperature of the fluidic structures can be adjusted.
  • the external temperature control elements can be designed, for example, to the temperature of the environment and thus also to control the fluidic module.
  • the controller may be configured to control the temperature control elements 40, 42 so that in such embodiments, the actuator may include the controller 24 and the temperature controls.
  • fluidic modules microfluidic cartridges
  • fluidic structures formed therein will now be described.
  • the fluidic module 50 is rotatable about a center of rotation R.
  • the fluidic structures have a liquid holding region, which has a first chamber 52.
  • the first chamber 52 is connected to preceding fluidic structures which have an upstream chamber 54, which is connected to the first chamber 52 via a radially sloping connection channel 56.
  • the connecting channel 56 opens in a radially outer region 57, for example, the radially outer end, in the first chamber 52.
  • the first chamber is centrifugally filled. It should be noted at this point that the first chamber may also be filled in a manner other than centrifugal, wherein only after the filling, the fluidic module is subjected to a rotation in order to achieve the equilibrium between centrifugal pressure and pneumatic pressure.
  • the fluidic module 50 further includes subsequent fluidic structures having a fluid chamber 58 as the fluid receiving volume and two fluid paths 60, 62 fluidly connecting the first chamber 52 to the fluid chamber 58.
  • the fluid path 62 has a siphon channel whose siphon apex 64 lies radially within the radially outermost position of the first chamber 52.
  • the subsequent fluidic structures in the form of the fluid chamber 58 are either not vented or may be vented via a venting delay resistor 66 which satisfies the above definition.
  • a venting delay resistor 66 may optionally be provided in all of the embodiments described herein without each requiring separate mention.
  • the first fluid path 60 between the first chamber 52 and the subsequent fluidic structure 58 consists of a channel extending from a radially inner region of the first chamber 52, for example, from the radially innermost point 68 of the first chamber 52, to a radially inner region the subsequent fluid chamber mer 58, for example, to the radially innermost point 70 of the subsequent fluid chamber 58 leads.
  • the second fluid path 62 between the first chamber 52 and the subsequent fluid chamber 58 is connected to the first chamber 52 in a radially outer region, for example at the radially outermost point 72 and leads via the siphon vertex 64 to a radially outer region, for example radially outermost point 74, the subsequent fluid chamber 58.
  • Embodiments of a method according to the invention include introducing at least one liquid into a first chamber of the liquid-holding region. This introduction can be effected by a centrifugally induced transfer of a liquid into the first chamber 52. Subsequently, a centrifugally-pneumatically induced retention of the liquid in the liquid-holding region, for example, the first chamber 52, take place. Subsequently, a switching of the liquid in the subsequent fluidic structures, for example, the subsequent fluid chamber 58, take place.
  • At least a portion of the liquid is transferred from the liquid holding region (e.g., first chamber 52) into the subsequent fluidic structures (e.g., fluid chamber 58) through at least one fluid path (e.g., fluid path 62).
  • Fluid paths through which liquid is transferred during the switching process are referred to below as fluid guide paths.
  • gas usually air
  • gas routing paths By means of at least one further fluid path (eg fluid path 62) between the fluid holding region (eg first chamber 52) and the subsequent fluid structures (eg fluid chamber 58), gas (usually air) can be withdrawn from the subsequent fluid structures back into the fluid during the switching process. Holding area to be transferred. Fluid paths that permit this are referred to below as gas routing paths.
  • FIGS. 2A to 2E show fluid operating states of the embodiment shown in FIG. 1 during the execution of the method.
  • the respective reference symbols of the fluidic structures are omitted in FIGS. 2A to 2E.
  • a first state shown in Fig. 2A, liquid 80 is in the first chamber 52 upstream chamber 54 and in the connecting channel 56 between the upstream chamber 54 and the first chamber 52.
  • a part of the upstream chamber 54 is radially closer to the center of rotation R than the siphon vertex 64 of the fluid guide channel.
  • the liquid can be introduced, for example, via an inlet opening or via further upstream fluidic structures into the upstream chamber 54 and the connecting channel 56.
  • the introduced liquid 80 encloses in the first chamber 52, the fluid paths 60 and 62 and the downstream fluid chamber 58 an air volume that is not vented (or vented only via a venting delay resistor).
  • the fluid path 60 which constitutes a venting channel, is also closed to the atmosphere by the liquid 80 in the liquid holding region.
  • the liquid 80 is centrifugally induced to transfer from the upstream chamber 54 into the first chamber 52, compressing the gas in the first chamber 52, the subsequent fluid structures 58, and the communication paths 60, 62 the first chamber 52 is not vented in this operating state or vented only via a venting delay resistor.
  • the upstream chamber 54 may be vented, so that in the same atmospheric pressure p 0 can prevail.
  • Gas is preferably transferred via the gas guide path 60 into the subsequent fluid structures 58.
  • the fluid paths 60, 62 between the first chamber 52 and subsequent fluidic structures are connected to one another via the subsequent fluidic structures, so that it is ensured that the same pneumatic overpressure prevails in the fluid paths. Simultaneously with the filling of the first chamber 52 and the liquid guide path 62 can be filled with liquid, but not up to the siphon vertex 64th
  • the resulting pneumatic overpressure ⁇ in the first chamber 52 and the subsequent fluid structures 58 counteracts the further centrifugally induced filling of the first chamber 52 and the filling of the fluid guide channel 62, so that the Siphonscheitei 64 is not wetted in the fluid guide channel 62 and the liquid is in the first chamber 52 and in the first chamber 52 upstream chamber 54 is retained.
  • these fluidic structures constitute a liquid holding area.
  • the retention of the liquid in the liquid holding area is achieved by 1) the liquid transfer into the first chamber 52 reduces the hydrostatic height between the upstream chamber 54 and the first chamber 52, which reduces the centrifugal pressure acting in the direction of filling the first chamber 52, and
  • centrifugal pressure and pneumatic overpressure over other pressure sources such as capillary pressure, taking into account any fluid properties and cartridge material properties.
  • capillary pressure taking into account any fluid properties and cartridge material properties.
  • these other pressure sources are not able to cause a switching-triggering deviation from the Be Stirllschreib the liquid guide path, which results in the sole consideration of the balance of pneumatic pressure and centrifugal pressure.
  • This equilibrium is also realized in accordance with the invention if, by slight targeted variations of the processing conditions, the pressures involved are varied continuously, leaving the qualitative state of retention of the liquid in the liquid holding region (e.g., the first chamber). In other words, while maintaining the liquid in a quasi-steady state equilibrium, a slight variation of the processing conditions may occur without initiating the switching operation.
  • the switching operation can be achieved by increasing the centrifugal pressure on the switching frequency or the centrifugal switching pressure. This can e.g. be achieved by
  • the switching operation can be achieved by reducing the pneumatic overpressure in the subsequent fluidic structures, so that liquid is induced pneumatically induced from the upstream chamber 54 into the first chamber 52 and the siphon apex 64 of the liquid guide path 62 is filled at a constant rotational frequency.
  • the reduction of the pneumatic overpressure may e.g. by reducing the temperature in the subsequent fluidic structures, by increasing the volume of the subsequent fluidic structures, or by reducing the amount of gas in the subsequent fluidic structures.
  • the latter can be done via a venting delay resistor, for example the venting delay resistor 66 shown in FIG.
  • the radially outwardly extending portion of the siphoned channel 64 fills in the liquid guide path 62, thereby increasing the hydrostatic head in that channel.
  • the centrifugal pressure resulting from the hydrostatic head between the first chamber 52 and subsequent fluidic structures results in fluid transfer from the first chamber 52 to the subsequent fluidic structures, as shown in Figures 2C through 2E.
  • gas from the subsequent fluidic structures is transferred via the at least one gas guide path 60 into the first chamber 52, which counteracts the build-up of an additional pneumatic overpressure in the sequence of fluid transfer into the subsequent fluidic structures, see FIG. 2D.
  • a complete transfer of the liquid from the first chamber 52 into the subsequent fluidic structures at a fixed rotational frequency above the switching frequency can be achieved, as shown in Fig. 2E.
  • the fluidic structures may be at atmospheric pressure po.
  • the switching pressure and the associated rotation frequency of the cartridge can be selected by a suitable choice of the positions and geometries of the chambers and the fluid guide paths in a wide range.
  • FIG. 3A schematically shows an exemplary embodiment of fluidic structures of a fluidic module 50 in which the complete first fluid chamber 52 is filled with fluid 80 in the quasi-stationary equilibrium state, which is shown in FIG. 3B.
  • both the liquid guide path 62 and the gas guide path 60 have a siphon-shaped channel.
  • an upstream chamber 54 via a connecting channel 56 which opens into a radially outer end 90 of the upstream chamber 54, fluidly connected to the first chamber 52.
  • the liquid guide path 62 and the gas guide path 60 may open into the first chamber 52 and the downstream chamber 58 as in the embodiment described with reference to FIG.
  • the siphon apex 64 of the liquid guide path 62 is disposed radially within the radially innermost point of the first chamber, and a siphon apex 92 of the siphon channel of the gas guide path 60 may preferably be radially inwardly of the siphon apex 64 of the liquid guide path 62.
  • the following fluidic structures in this embodiment in addition to the downstream fluid chamber 58, which is a fluid receiving volume and a fluid receiving chamber, another, separate volume 94 on.
  • the point of connection of the gas guide path 60 to the liquid receiving volume 58 (in the embodiment shown, the radially innermost Preferably, the point of fluid receiving volume 58) may be closer to the center of rotation R of the cartridge than the radially outermost point of the fluid receiving volume 58, thereby wetting the port 70 of the gas routing path 60 with the fluid 80 transferred during the shift under the influence of the transfer during the transfer Prevent centrifugal force.
  • the optional volume 94 which is separate from the liquid receiving volume 52, specifically increases the volume of the subsequent fluidic structures, as a result of which the pneumatic overpressure in the subsequent fluidic structures can be reduced when carrying out the method according to the invention.
  • the additional volume 94 is coupled to the gas routing path 60 via a fluid path 96.
  • the fluid path 96 opens at an orifice 98 into the gas guide path 60 and at an orifice 100 into the additional volume 94.
  • the foregoing fluidic structures comprise the chamber 54, the volume of which preferably comprises a fraction of the volume of the first chamber 52, and which is connected to the first chamber 52 through the fluid path 56, its connection point 90 to the upstream chamber 54 closer to the center of rotation R of the cartridge than the apex of the siphon 64 in the liquid guide path 62.
  • the volume of the chamber 54 may be greater than the volume of the first chamber 52.
  • the chamber 54 may in turn be vented and at atmospheric pressure.
  • the connection point 57 of the fluid connection path 56 between the preceding chamber 54 and the first chamber 52 can lie at any desired point of the first chamber 52 and need not be arranged in a radially outer region thereof.
  • FIGS. 3A to 3D The embodiment of a pneumatic counter-pressure siphon valve shown in FIGS. 3A to 3D is designed to compress the full volume of the first chamber.
  • 3B shows an operating state in which there is a balance between pneumatic overpressure in the subsequent fluidic structures and the pressures in the direction of the filling of the subsequent fluidic structures.
  • 3C shows an operating state in which the liquid is transferred from the first chamber into the subsequent fluidic structures, and
  • FIG. 3D shows an operating state after completion of the liquid transfer.
  • liquid 80 is introduced into the first fluid chamber 52 via the upstream fluidic structures.
  • the fluidic structures are designed such that the first te fluid chamber 52 is completely filled with the liquid 80.
  • the introduced liquid encloses a gas volume in the downstream fluidic structures.
  • Fig. 3B the corresponding state is shown, in which the liquid 80 is retained in the first chamber 52.
  • the cartridge or the fluidic module can be in rotation with a rotational frequency ⁇ .
  • the location of the liquid menisci 102, 104 in the fluid communication paths 60, 62 makes it possible to utilize the described structure to measure the amount of fluid in the first chamber 52 and fluid communication paths, with high accuracy of the metered volume.
  • the siphon apex 64 of the liquid guide path 62 can be filled.
  • the liquid may then be sequentially transferred from the first chamber 52 into the liquid receiving volume 58 by the acting centrifugal force, as shown in Fig. 3C.
  • the gas is transferred from the liquid receiving chamber 58 via the gas guide path 60 into the first chamber 52, whereby an increase in the pneumatic overpressure in the liquid receiving chamber 58 is counteracted.
  • FIG. 4A shows fluidic structures formed in a fluidic module 50, which have an inlet channel 110, a first fluid chamber 52, a liquid guide path 62, a gas guide path 60, a downstream fluid chamber 58 and a volume chamber 112 arranged in the gas guide path 60.
  • the inlet channel 110 may in turn be fluidly coupled to an upstream chamber (not shown in FIG. 4A).
  • a fluidic connection to previous fluidic structures may be provided through the channel 110 having its point of attachment to the first fluid chamber 52 radially inward of the siphon apex 64 of the fluid guide path 62.
  • Downstream Fluidik Designen are in turn formed by the downstream fluid chamber 58, which is a fluid receiving chamber.
  • the liquid receiving chamber 58 is connected to the gas guide path 60 at a mouth point.
  • the orifice point is preferably not at the radially outermost position of the fluid receiving chamber 58, for example, in a radially inner portion thereof or at the radially innermost position 70.
  • the fluid receiving chamber 58 is also fluidically connected to the fluid guide path 62, preferably radially outward of the port position 72 between the fluid guide path 62 and the first fluid chamber 52.
  • the fluid guide path 62 may open at a radially outer position, for example at the radially outermost position 74, into the fluid receiving chamber 58.
  • the liquid receiving path 62 opens into the first fluid chamber 52 in a radially outer region, such as the radially outermost position 72, and the gas guide path 60 also opens at a radially outer position, such as the radially outermost position 116 of FIG In FIG. 4A, the left-hand area of the first fluid chamber 52, into the first fluid chamber 52.
  • the gas-guidance path 60 has a siphon channel, the siphon apex 92 of which lies radially inside the siphon apex 64 of the liquid guide path 62.
  • the volume chamber 112, too may be referred to as a partial compression chamber is disposed in the radially rising portion of the siphon channel of the gas guide path 60, wherein the gas guide path 60 opens into the partial compression chamber 112 at mouth points 118 and 120.
  • the partial compression chamber 112 is preferably located at a greater radial distance from the center of rotation than the siphon vertex 64 of the liquid guide path 62.
  • the partial compression chamber 112 may be connected to the first fluid chamber 52 through a portion of the gas routing path 60, the junction at which that portion of the gas routing path is in the sub-compression chamber 112 opens, preferably radially further away from the center of rotation than the siphon vertex 64 of the fluid routing path 62.
  • the orifice point 120 can then be connected to the downstream fluidic structures via the siphon channel of the gas routing path 60 having the siphon apex 92.
  • fluid from pre-switched fluidic structures (not shown) centrifugally induced may be transferred into the first fluid chamber 52 via the inlet channel 110.
  • the liquid 80 fills the first chamber from the radially outer side toward the radially inner side.
  • the fluid paths 60 and 62 connecting the first fluid chamber 52 to the subsequent fluidic structures, such as the downstream fluid chamber 58, are filled and gas (typically air) trapped by the fluid 80 in the downstream fluidic structures and fluid communication paths 60 and 62 .
  • gas typically air
  • the increase in the hydrostatic head between the liquid meniscus 122 in the first fluid chamber 52 and the menisci 102, 104 in the fluid communication paths 60 and 62 transfers liquid into the subcompression chamber 112 under the influence of centrifugal force, thereby injecting the gas present therein into the subsequent fluidic structures is displaced.
  • a pneumatic overpressure ⁇ is generated in the latter, which counteracts further filling of the fluid connection paths 60 and 62.
  • a balance is formed between the pressures toward and against the filling of the fluid paths 60 and 62 in which the siphon apex 64 of the liquid guide path 62 is not wetted and the meniscus 122 of the liquid in the first fluid chamber 52 radially within the siphon apex 64 of the liquid guide path 62 is located.
  • This operating state is shown in FIG. 4B.
  • the liquid 80 encloses a gas volume in the fluid paths 60, 62 and the downstream fluidic structures 58, in which the pneumatic overpressure ⁇ is generated. Because the first Fluid chamber 52 is vented, the area of the first fluid chamber 52 above the liquid meniscus 122 is at atmospheric pressure po.
  • the pneumatic overpressure ⁇ which prevails in equilibrium in the following fluidic structures can be selected largely freely.
  • the centrifugal pressure in the direction of filling the liquid guide path 62 can be increased, whereby the siphon vertex 64 of the liquid guide path 62 fills and a centrifugally induced transfer of the liquid into the subsequent fluidic structures 58 is set in motion.
  • the partial compression chamber 112 has a smaller volume of fluid than the first fluid chamber 52. Due to the fluid transfer from the first fluid chamber 52 into the downstream fluidic structures via the fluid guide path 62, an additional pneumatic overpressure is built up in the trapped volume of the subsequent fluid structures, resulting in transfer of fluid Liquid from the partial compression chamber 112 into the first fluid chamber 52 leads.
  • FIG. 5A demonstrate a possible range of possible variations in the choice of port locations between the first fluid chamber 52 and the fluid communication paths 60 and 62, as well as the design of the gas routing path 60 and the ports between the fluid communication paths 60 and 62 and FIG downstream fluidic structures 58.
  • the port position 130 between the preceding fluidic structures (eg, the inlet port 110 and the upstream fluid chamber 54) and the first fluid chamber 52 may be at a freely selectable position of the first fluid chamber 52.
  • the connection points 132 and 118 of the connections between the first fluid chamber 52 and the partial compression chamber 112 and the connection points 120, 136 between the partial compression chamber 112 and the subsequent fluidic structures 58 can also be freely selected.
  • the mouth point 136 of the gas guide path 60 is in the downstream fluid chamber 58, that is, the liquid target volume, not at the radially outermost position of the liquid target volume.
  • the connection position 138 of the diesstechniks Operations- path 62 can be freely selected in the downstream fluid chamber 58.
  • the connection position 134 is preferably located in a radially outer region of the first fluid chamber 52, since the first fluid chamber 52 can be emptied only up to this connection position above the liquid guide path 62.
  • liquid from the upstream fluidic structures such as upstream chamber 54
  • first fluid chamber 52 and associated fluid communication paths 60 and 62 the level of the first fluid chamber 52 increases continuously in the radial direction from the radially outermost point of the same to radially further inward positions.
  • the gas in the first fluid chamber 52 is displaced by the inflowing fluid 80, thereby transferring gas into the non-fluid wetted ports of the fluid communication paths 60, 62 between the first fluid chamber 52 and the downstream fluidic structures. This results during the filling of the first fluid chamber 52, a pressure equalization between the first fluid chamber 52 and the subsequent fluidic structures, as long as the level in the first fluid chamber 52 is radially outside the radially innermost connection point.
  • the terminal position 134 of the liquid guide path 62 to the first fluid chamber 52 may be closer to the rotation center R than the terminal position 132 of the gas guide path 60. Further, more fluid may be transferred into the first fluid chamber 52 than through the first fluid chamber 52 and the fluid connection paths 60, 62 to the radial position of the radially inner connection point (of the connection point 134 in the embodiment shown in FIG. 5A). Example) can be included.
  • the first fluid chamber 52 can be designed without further vents, so that in the gas volume trapped by the liquid 80, with continued transfer of liquid from the upstream fluidic structures into the first fluid chamber 52, a pneumatic overpressure ⁇ can be established is not identical to the pneumatic overpressure ⁇ in the subsequent fluidic structures.
  • the partial compression chamber 112 in the gas guide path 60 can be filled with liquid, whereby gas is transferred into the subsequent fluidic structures.
  • connection point 120 of the fluid path 60 between the sub-compression chamber 112 and the downstream fluidic structures 58 at a position radially outwardly of the innermost point of the sub-compression chamber 112 compression of gas in the sub-compression chamber may be analogous to the described processes in the first fluid chamber 112 occur as soon as the liquid level in the sub-compression chamber 112 is radially within the radially innermost connection point to the sub-compression chamber 112.
  • a state of equilibrium can be achieved, in which the meniscus 104 of the liquid is in the radially inwardly extending portion of the siphon-shaped portion of the liquid guide path 62, and the pressures acting in the direction of wetting of the siphon vertex 64 (centrifugal pressure and possibly other pressures, such as the overpressure ⁇ ) are in equilibrium with the pressures acting against the wetting (the pneumatic overpressure in the subsequent fluidic structures and possibly other pressures).
  • This operating state is shown in Fig. 5B.
  • the transfer may stop as soon as the fluid meniscus 122 in the first fluid chamber 52 reaches the radial position of the connection point 134. This may result in the retention of fluid in the first fluid chamber 52, as shown in FIG. 5D, resulting in the possibility of mixing them in the first fluid chamber 52 by multiple use of the same fluidic structures with different fluids.
  • This may also be used to create dilution series if, in a first step, a volume of liquid to be diluted defined by the fluidic structure remains in the first fluid chamber after the transfer step, and in subsequent steps the dilution liquid through the preceding fluidic structures into the first fluid chamber transferred and mixed with the liquid to be diluted.
  • the downstream fluidic structures can be given for this purpose by a cascading of the structures described, that is, by radially outwardly offset instances of the structure described.
  • FIG. 6 shows an exemplary embodiment of cascaded fluidic structures in a fluidic module 50.
  • the cascaded fluidic structures essentially represent a combination of the embodiments described with reference to FIGS. 3A to 3D and FIGS. 4A to 4D.
  • the first fluid chamber 52, the gas guide path 60, the diesstechniksat- tion path 62 and the downstream fluid chamber 58 corresponds to the above-described reference to FIGS. 3A to 3D described structure of the corresponding structures.
  • These elements form a first switching structure in the cascaded fluidic structures shown in FIG.
  • a gas guide path 160, a liquid guide path 162 and a further downstream fluid chamber 158 form a second switching structure.
  • a venting delay resistor 66 may optionally be provided.
  • an intermediate compression chamber 112 is arranged in the gas guide path 160.
  • the structure of the gas guide path 160, the intermediate compression chamber 1 12 and the liquid guide path 162 may be substantially the structure of the gas guide path 60, the intermediate compression chamber 112 and the gas guide path 62 described above with reference to FIG. 4A. As shown in FIG.
  • the liquid guide path 162 can open into the downstream fluid chamber 58 in a radially outer region, for example the radially outermost position, and can open into the downstream fluid chamber 158 in a radially outer region, for example the radially outermost position
  • the gas guide path 160 may open into the downstream fluid chamber 58 in a radially outer region, for example the radially outermost position, and may open into the downstream fluid chamber 158 in a radially inner region, for example the radially innermost position.
  • the fluid paths 160 and 162 have a total of a radial gradient, that is, the mouth of the same in the fluid chamber 158 is located radially further outward than the mouth thereof in the fluid chamber 58th
  • FIG. 6 thus represent two cascaded switching structures, wherein the fluid chamber 58 for the first switching structure represents a downstream fluidic structure and represents a liquid holding area for the second switching structure.
  • FIGS. 7A to 7E show an illustration of the fluidic processes during the process of cascading fluid switching using the venting delay resistor 66.
  • FIG. 7A shows fluid 80 in the first fluid chamber 52 of the first switching structure.
  • FIG. 7B shows a fluid transfer into the liquid-targeting chamber 58 of the first switching structure, which at the same time represents the first fluid chamber of the second switching structure.
  • FIG. 7C shows the final state of the first switching operation, which simultaneously represents the equilibrium state before the initiation of the second switching operation.
  • Fig. 7D shows the transfer of the liquid into the liquid-targeting chamber 158 of the second switching structure.
  • Fig. 7E shows the final state after completion of the second liquid transfer.
  • a second switching operation may be implemented due to the presence of a development delay resistor.
  • liquid is centrifugally induced induced in the first fluid chamber 52 and the fluid connection paths 60, 62 analogously to the method described above, and the gas present in these is displaced into the subsequent fluidic structures, whereby in this a pneumatic overpressure arises, which counteracts the further filling and thus the wetting of the siphon vertex 64 in the liquid guide channel 62.
  • the downstream fluidic structures have the downstream fluid chamber 58, the fluid paths 160, 162 and the downstream fluid chamber 158.
  • the first fluid chamber of the second switching structure that is, the fluid chamber 58 and the partial compression chamber 112 of the second gas guide path 160 are filled with liquid and the above Gas contained therein displaced in the downstream fluidic 158.
  • the resulting pneumatic overpressure ⁇ leads to the quasi-static state shown in FIG. 7C, in which the pressures opposing the wetting of the siphon vertex 164 of the liquid guide path 162 are in quasi-static equilibrium with those in the direction of wetting.
  • liquid transfer is effected by changing the ratio of the centrifugal pressure to the pneumatic pressure.
  • the change of this ratio can be done in different ways.
  • the ratio can be changed by increasing a rotational speed of the fluidic module.
  • a drive device by means of which the fluidic module is set in rotation, can be correspondingly controlled by means of a corresponding control device.
  • a venting delay resistor may be provided, which may be considered as an actuator designed to reduce the pneumatic pressure.
  • the pneumatic pressure may be reduced by controlling, in particular reducing, the temperature of the trapped gas volume.
  • thermocontrol elements may be provided.
  • a reduction of the pneumatic pressure can be achieved by increasing the volume of the downstream fluidic structures.
  • the downstream fluidic structures may have one or more fluid chambers whose volume is adjustable.
  • a negative pressure is used in the downstream fluidic structures, that is, an embodiment of the present invention will be described below.
  • a reduction of the pressure in the downstream fluidic structures below the ambient pressure may occur using temperature and / or centrifugal pressure changes.
  • a temperature-controlled reduction of the pressure in the subsequent fluidic structures which serves to initiate the transfer of liquid from the first fluid chamber into the liquid target volume, can be achieved by a reduction of the temperature of the gas in the subsequent fluidic structures.
  • the fluidic structures formed in a fluidic module 50 have an inlet channel 200 connecting a first fluid chamber 202 to preceding fluidic structures (not shown).
  • the first fluid chamber 202 may be vented via a fluid path 204.
  • the first fluid chamber 202 is connected via a first fluid path 206 and a second fluid path 208 to downstream fluidic structures 210, which have a fluid receiving chamber.
  • the first fluid path 206 has a siphon channel with a siphon vertex 212.
  • the second fluid path 208 also has a siphon channel in the embodiment shown, the siphon apex 214 of which is located radially further inward than the siphon apex 212 of the first fluid path 206.
  • the first fluid path 206 represents a liquid guide path
  • the second fluid path 214 provides a gas guide path
  • the fluid communication paths 206 and 208 need not include any further chambers.
  • the liquid guide path 212 is connected to the first fluid chamber in a radially outer region, preferably at the radially outermost position.
  • the gas guide path 208 is connected in a region of the first fluid chamber 202 with the latter, which is wetted with liquid when filling the first fluid chamber 202. Such a filling of the first fluid chamber can be effected centrifugally induced via the inlet channel 200. Possible positions for the orifices of the fluid paths 206 and 208 in the first fluid chamber 202 result from the chamber geometry and the amounts of liquid used in the process.
  • the siphon apex 212 of the liquid guide path 206 is preferably radially within the position reached during operation by the meniscus of the liquid in the first fluid chamber, particularly during a first processing step during which liquid in the first fluid chamber 202 representing a liquid holding region. is held.
  • the gas guidance path 208 can open into the downstream fluidic structures 210 in a radially inner region
  • the liquid guidance path 206 can open into the downstream fluidic structures 210 in a radially outer region.
  • fluidic structures shown in Figure 8A illustrate fluidic structures for vacuum-based centrifugal-pneumatic vent-siphon valve switching, as will become apparent from the following description of an embodiment of a method according to the invention using the fluidic structures shown in Figure 8A.
  • liquid is transferred from upstream fluidic structures (not shown) centrifugally induced through the inlet channel 200 into the first fluid chamber 202.
  • liquid is also transferred into the radially inwardly extending regions of the siphon-shaped connection paths 206, 208 between the first fluid chamber 202 and the subsequent fluidic structures 210.
  • the further liquid flowing into the connection paths displaces the gas contained in the connection paths into the downstream fluidic structures, resulting in overpressure at constant temperature in the subsequent fluidic structures, as shown in FIG. 8B is shown.
  • This excess pressure as the difference to the atmospheric pressure may be a small fraction of the atmospheric pressure, so that there is a negligible overpressure during the introduction.
  • cooling of the subsequent fluidic structures 210 can be achieved at a preferably constant rotational speed, for example by a reduction in the ambient temperature or by cooling elements in contact with the cartridge, whereby a negative pressure results in the subsequent fluidic structures, as indicated in Fig. 8C.
  • wetting of the siphon apex 212 of the liquid guide path 206 can be achieved in a subsequent step by reducing the centrifugal pressure, for example by reducing the rotational frequency or by further reducing the pressure in the subsequent fluidic structures, for example by further reducing the temperature
  • liquid may be added to the fluid chamber 202 to wet the siphon apex, whereby the fill level may be raised above the siphon apex.
  • the transferred liquid can lead to a compression of the gas present in the subsequent fluidic structures 210, so that an overpressure can arise therein, which leads to a transfer of gas from the downstream fluidic structures via the gas guide path 208 into the first fluid chamber 202 as shown in Fig. 8D.
  • the first fluid chamber 202 completely empties via the liquid guide path 206 into the downstream fluidic structures, as shown in FIG. 8E.
  • the liquid-holding region has a first fluid chamber.
  • the fluid retaining region may include a plurality of fluid chambers, which may or may not be connected via one or more fluid channels.
  • liquid holding portion has a plurality of fluid chambers and in which switching can be effected by temperature-controlled pressure reduction will be explained below with reference to FIG. 9.
  • the fluidic structures have upstream fluidic structures, a liquid holding region and downstream fluidic structures.
  • the liquid holding region has a first fluid chamber 300 and a second fluid chamber 302.
  • the first fluid chamber 300 and the second fluid chamber 302 are fluidly connected via a radially sloping connection channel 304.
  • the upstream fluidic structures have an upstream fluid chamber 306 which may have in a radially outer region of the same chamber segments 306a and 306b with respect to a center of rotation R, which allow a measurement of liquid volumes.
  • the chamber segment 306 a is fluidically connected to the first fluid chamber 300 via a fluid channel 308, and the chamber segment 306 b is fluidically connected to the second fluid chamber 302 via a fluid channel 310.
  • Another inlet channel 312 may be fluidly connected to the first fluid chamber 300.
  • Another inlet channel / vent channel 314 may be fluidly connected to the second fluid chamber 302.
  • a vent 316 is shown schematically in FIG. Further, another fill / vent passage 318 may be provided.
  • upstream fluidic structures in the embodiment shown in Fig. 9 could also consist of only one inlet channel, which is fluidly connected to the first fluid chamber 300 and which allows filling of the first fluid chamber 300, for example, a centrifugally induced filling from an inlet chamber fluidly connected to the corresponding inlet channel.
  • the first fluid chamber 300 is connected via a fluid guidance path 320 to downstream fluidic structures 322 in the form of a downstream fluid chamber.
  • the second fluid chamber 302 is connected to the downstream fluidic structure 322 via a gas guide path 324.
  • the liquid guide path 320 has a siphon channel with a siphon vertex 326.
  • the gas routing path 324 also has a siphon channel with a siphon vertex 328.
  • the achievable hydrostatic head difference between the meniscus in chamber 302 and the siphon apex 328 is preferably higher than the hydrostatic head difference between the meniscus in chamber 300 and the siphon apex 326 to overcome.
  • the liquid guide path 320 opens into the first fluid chamber 300 in a radially outer region, preferably at a radially outer end.
  • the gas guide path 328 opens into the second fluid chamber 302 in a radially outer region, preferably at a radially outer end may be configured such that when filling the same with a first volume of liquid, the downstream fluidic structures 322 remains vented via the gas guide path 324 to the second fluid chamber 302.
  • This operating state in which a first liquid volume is introduced into the first fluid chamber 300, 380 is shown in Fig. 10A. Changes in the temperature and / or rotational frequency can be further carried out without the liquid being switched into the downstream fluidic structures 322. In the event that capillary forces are negligible, the liquid is stored in this state, so to speak, in the fluid chamber 300.
  • both fluid paths 320 and 324 are now hermetically sealed to the downstream fluidic structures, after the liquid guide path 320 has already been hermetically sealed when introducing the liquid volume 380 into the first fluid chamber 300. This operating state is shown in FIG. 10B.
  • a negative pressure can be generated in the downstream fluidic structures 322, as shown in FIG. 10C.
  • the liquid can be caused to be transferred via the liquid guide path 320 into the downstream fluidic structures 322, as shown in Fig. 10D.
  • the siphon channel of the liquid guide path 320 is configured such that, for example, when reducing the temperature and thereby reducing the pressure induced only this siphon, so that preferably only the liquid from the first fluid chamber 300 and not the liquid from the second fluid chamber 302 transfers becomes.
  • a potential overpressure in the downstream fluidic structures 322 due to the transfer of the liquid from the first fluid chamber 300 forces the liquid from the gas guide channel 324 back into the second fluid chamber 302, wherein air through the second fluid chamber 302 in the form of rising through the liquid bubbles can give way.
  • all of the liquid from the first fluid chamber 300 can be transferred to the downstream fluidic structures 322.
  • the siphon channels of both the liquid guide path 320 and the gas guide path 324 can also be filled with liquid.
  • both the fluid in the first fluid chamber 300 and the fluid in the second fluid chamber 302 would then be at least partially transferred.
  • the negative pressure in the chamber 322 can be at least partially compensated.
  • an overpressure can be generated in addition to the compensation of the negative pressure, which leads to a reversal of the flow direction of the liquid within one of the siphon channels, in the embodiment shown in the gas guide channel 324, and then to a phase change to gas, whereby gas from the subsequent fluidic structures 322 is vented into the chamber 302.
  • One embodiment, as described with reference to FIGS. 9 to 10D, may be useful for metering a fluid prior to switching to a predefined volume. Liquid volumes below the target volume are not switched.
  • the fluidic structures described with reference to FIG. 9 may also be used to add a second liquid, as will be explained below with reference to FIGS. 11A to 11E.
  • FIG. 11A corresponds to the operating state from FIG. 10A, in which a first liquid volume 380 is introduced into the first fluid chamber 300 and is quasi stored in the first fluid chamber 300. If a second liquid then flows through the inlet channel 310 into the second fluid chamber 302, the following fluidic structures 302 are hermetically sealed. For this purpose, the second liquid can flow either exclusively into the second fluid chamber 302 via the channel 310, or divided into the first fluid chamber 300 and the second fluid chamber 302 via the channels 308 and 310. The corresponding volumes supplied for this purpose in the chamber segments 306a and 306b of the upstream fluid chamber 306 are measured, as shown in Fig. 1 B is shown.
  • the first and second fluids in the first fluid chamber 300 may be mixed.
  • the liquid may be transferred from the first fluid chamber 300 to the downstream fluidic structures 322 as described above with reference to FIGS. 8A-8E and 10A-10D.
  • the liquid can be transferred by reducing the temperature and corresponding reduction of the pressure in the downstream fluidic structures.
  • Fluidic structures may be particularly useful for storing a first fluid in a first fluid chamber of a fluid holding region while a second fluid is undergoing further independent process steps. These process steps can use largely freely required rotational frequencies and temperatures, without the liquid in the first fluid chamber 300 being switched via the liquid guide path 320.
  • the second liquid may be added to the first fluid chamber 300 and the second fluid chamber 302. The resulting liquid mixture can then be switched by reducing the temperature.
  • the fluid chamber of the fluid holding area may also be divided into three or more chambers.
  • the various chambers of the liquid holding area need not be connected via channels, except for the connection via the downstream fluidic structures and the connection channels connecting the fluid chamber to the downstream fluidic structures.
  • the fluid guide path opens at a position into a fluid receiving chamber of the subsequent fluidic structures, which is radially outward of a position at which the fluid guide path opens into a fluid chamber of the fluid retaining region.
  • the liquid guide path has an overall radial gradient.
  • the downstream fluidic structures may include at least one fluid receiving chamber into which the fluid is transferred.
  • the liquid-holding region can have at least one fluid chamber from which the liquid is transferred into the downstream fluidic structures.
  • the fluidic structures are designed such that centrifugal pressures and pneumatic pressures play a major role, while capillary forces can be negligible.
  • the respective fluid paths may be formed as fluid channels, wherein in the fluid paths chambers, for example, partial compression chambers may be arranged.
  • Embodiments thus provide fluidic modules, devices and methods in which two fluid communication paths are provided between a chamber in which a liquid is retained prior to switching and a target structure for the liquid after the switching operation. This allows a largely liquid-property-independent monolithic realization of a structure for switching a liquid in the event of selectively exceeding or dropping below a high rotational frequency of the cartridge.
  • Embodiments provide a centrifugal pneumatic venting siphon valve having fluidic structures on a centrifugal test carrier.
  • the fluidic structures may include a first number of chambers, subsequent fluidic structures, and at least two fluid paths connecting the first number of chambers to the subsequent fluidic structures.
  • At least one of the fluid paths between the first plurality of chambers and the subsequent fluidic structures includes a siphon channel, the connection being arranged via the fluid paths from the first plurality of chambers to the subsequent fluidic structures such that when the first plurality of chambers are filled with fluid a state can be produced in which in the subsequent fluidic structures, a gas volume trapped by the liquid is formed or a quasi-enclosed gas volume is produced, in which the following structures have a vent with a venting delay resistance.
  • a siphon channel is provided in at least one of the fluid communication paths between the first plurality of chambers and the subsequent fluidic structures, the siphon apex being located radially within the radially outermost position of a first chamber into which the siphon channel terminates.
  • the subsequent fluidic structures are not vented.
  • the number of chambers may include one chamber or more than one chamber.
  • Embodiments provide a method for retaining and switching liquids using a corresponding centrifugal pneumatic venting siphon valve, wherein one or more liquids in a liquid holding region (a first number of chambers) in a quasi-static manner dominated by centrifugal pressures and pneumatic pressures Balance is retained / so that a subsequent initiation of a transfer of at least one liquid from the liquid-holding region in the subsequent fluidic structures is possible only by changing the acting centrifugal and / or pneumatic pressures.
  • gas is transferred from the subsequent fluidic structures in the direction of the liquid holding region via at least one fluid path.
  • At least one fluid connection path between the liquid-holding region and the subsequent fluidic structures is not completely filled with liquid.
  • the molar amount of gas in the subsequent fluidic structures is not changed by a fluid path associated with the environment while retaining liquid in the liquid holding area.
  • liquid in the liquid holding region is retained in the subsequent fluidic structures due to a pneumatic negative pressure prior to the initiation of the transfer.
  • liquid in the liquid holding area is retained due to a pneumatic overpressure in the subsequent fluidic structures prior to the initiation of the transfer.
  • Embodiments may include and are not limited to any modifications and combinations of the illustrated schematic embodiments.
  • Embodiments of the invention thus provide methods and apparatus for switching fluid using a centrifugal pneumatic venting siphon valve having fluidic structures as described herein.
  • embodiments of the described structure in conjunction with the described method in the field of centrifugal microfluidics, can simultaneously meet several requirements for the unit operations of retention and later targeted switching of a liquid. Exemplary embodiments enable a monolithic realization of the associated fluidic structures in a centrifugally microfluidic cartridge.
  • Embodiments offer the possibility of designing the structure, so that the functional principle is largely independent of liquid and cartridge material properties. This includes in particular the contact angle between the liquid and the cartridge material, as well as the viscosity and surface tension of the liquid.
  • Embodiments offer the possibility of further adaptations of the fluidic structures in order to determine the necessary process conditions for triggering a switching process in a wide range.
  • the adaptation possibilities can relate in particular to the possibility of freely selecting the gas volume transferred into the subsequent fluidic structures and the pneumatic overpressure achieved thereby.
  • Embodiments provide the opportunity to initiate the switching process using various changes in the processing conditions. This includes in particular rotational frequencies, temperatures and waiting times (when using a venting delay resistor) during processing.
  • Embodiments offer the possibility, under recourse to temperature changes as a function of the process control, of switching a liquid above a threshold frequency or below a threshold frequency when the rotational frequency is reduced.
  • Embodiments offer the possibility of producing the microfluidic structures without sharp edges, that is, with low demands on manufacturing processes, such.
  • B. injection molding and injection-compression molding Embodiments of the invention make it possible to avoid strongly increasing pneumatic pressures in the fluidic target volume during the fluid transfer after the switching operation.
  • Embodiments offer the possibility of cascading the fluidic structures.
  • Embodiments provide the opportunity for multiple use of the fluidic structures to sequentially retain and selectively switch multiple fluids.
  • Embodiments of the invention are configured to change the ratio of the centrifugal pressure to the pneumatic pressure to exceed a threshold at which a siphon apex of the siphon channel in the first fluid path is overcome, such that transfer of the liquid from the liquid holding region takes place in the downstream fluidic structures.
  • Embodiments of the invention describe variants of the fluidic structures and associated methods, which show various possibilities for influencing the equilibrium of the pressures which act in the direction or contrary to the initiation of the switching process according to the invention.
  • Embodiments of the invention are further based on the recognition that the described switching principle can easily be combined with other operations on the same centrifugal microfluidic platform, for example by passing a liquid after previous fluidic operations in a structure according to the invention or by cascading the described switching structure.

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Abstract

Module fluidique pour l'actionnement d'un liquide à partir d'une zone de retenue de liquide, dans laquelle un liquide peut être introduit, vers des structures fluidiques en aval, comprenant au moins deux trajets de fluide qui connectent de manière fluidique la zone de retenue de liquide avec les structures fluidiques en aval. Un des deux trajets de fluide comprend un canal-siphon. Les structures fluidiques en aval ne sont pas purgées ou purgées uniquement au moyen d'une résistance de retard de purge, de telle sorte que, lorsque le liquide est introduit dans la zone de retenue de liquides, un volume de gaz emprisonné se forme dans les structures fluidiques en aval. Le réglage du rapport entre une pression centrifuge engendrée par une rotation du module fluidique et une pression pneumatique régnant dans le volume de gaz permet le maintien du liquide dans la zone de retenue de liquides ou son transfert à travers le canal-siphon dans les structures fluidiques en aval, la purge étant réalisée dans le deuxième trajet de fluide.
EP18708690.5A 2017-03-10 2018-03-05 Procédé de commutation centrifugo-pneumatique de liquide Active EP3592463B1 (fr)

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PL18708690T PL3592463T3 (pl) 2017-03-10 2018-03-05 Sposób odśrodkowo pneumatycznego przełączania cieczy

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DE102017204002.5A DE102017204002B4 (de) 2017-03-10 2017-03-10 Zentrifugo-pneumatisches schalten von flüssigkeit
PCT/EP2018/055344 WO2018162413A1 (fr) 2017-03-10 2018-03-05 Actionnement centrifuge-pneumatique de liquides

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DE102019007512A1 (de) * 2019-10-29 2021-04-29 Lilian Labs GmbH Mikrofluidische Vorrichtung zur Aufnahme von Flüssigkeiten und zugehöriges Verfahren
CN113546699B (zh) * 2020-04-24 2023-07-07 康怡科技有限公司 用于分配流体的流体设备、装置和方法
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DE102022203875B3 (de) 2022-04-20 2023-06-15 Hahn-Schickard-Gesellschaft für angewandte Forschung e.V. Handhabung zweier flüssigkeitsvolumina

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CN110650801A (zh) 2020-01-03
PL3592463T3 (pl) 2021-09-13
WO2018162413A1 (fr) 2018-09-13
ES2864739T3 (es) 2021-10-14
US20190388886A1 (en) 2019-12-26
CN110650801B (zh) 2021-11-02
DE102017204002B4 (de) 2019-05-23
US11141728B2 (en) 2021-10-12
DE102017204002A1 (de) 2018-09-13
EP3592463B1 (fr) 2021-01-27

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