WO2014198703A1

WO2014198703A1 - Fluid handling apparatus and method for processing a liquid using a diffusion barrier

Info

Publication number: WO2014198703A1
Application number: PCT/EP2014/061990
Authority: WO
Inventors: Nils Paust; Simon Wadle; Gregor CZILWIK
Original assignee: Hahn-Schickard-Gesellschaft für angewandte Forschung e.V.; Albert-Ludwigs-Universität Freiburg
Priority date: 2013-06-10
Filing date: 2014-06-10
Publication date: 2014-12-18
Also published as: DE102013210818B3

Abstract

A fluid handling apparatus has a compression chamber with a first compression chamber portion and a second compression chamber portion, wherein the first compression chamber portion has a fluid inlet, by way of which a liquid can be introduced into the compression chamber. A vapour diffusion barrier is provided between the first compression chamber portion and the second compression chamber portion. A heating device is designed to heat at least the first compression chamber portion and the content thereof. The vapour diffusion barrier is designed at least to reduce a rate of evaporation of a liquid arranged in the first compression chamber portion into a gas arranged in the second compression chamber portion during heating of the first compression chamber portion and the content thereof, and thereby to reduce an increase in pressure in the compression chamber.

Description

Fluid handling device and method for processing a fluid using a diffusion barrier

description

The present invention relates to a fluid handling apparatus and method for processing a fluid in which a liquid disposed in a compression chamber is heated to process the same.

Such devices and methods can be used in particular in biochemical methods, such as temperature-controlled, biochemical analysis methods (eg, those known as Sanger Sequencing, Ligase Chain Reaction, DNA Restriction, S nger Sequencing, Enzyme Kinetic Monitoring), and in particular a PCR ( Polymerase chain reaction) can be used.

In many cases it has been necessary in biochemical processes to vent the reaction space with a valve in order to prevent increased overpressure, in particular at maximum process temperatures of up to 99 ° C., and to allow the expanding air-gas mixture to escape. In particular, in DN A-ampli fizierenden method increases in principle the risk of DNA contamination of the environment, since amplified DNA fragments in enormous copy numbers (»1 billion DNA fragments) are present and can escape through valves in the laboratory environment.

By completely closed systems, such an escape per se could be prevented. However, elevated temperatures can lead to an enormous increase in pressure, primarily due to the generation of water vapor. The overpressure caused thereby can lead to a loss of fluidic operation, for example an early switching of a valve, and thus to the complete failure of the entire fluidic system. In extreme cases, however, the overpressure may also lead to material breaks in a reaction chamber or to the delamination of a cover film, or it may be necessary to apply a counterpressure by means of active external elements, such as e.g. Press members. Thus, the risk of DNA contamination in a closed system is also increased due to the generated overpressure.

Zehnle et al. "Centrifugal-dynamic Inward Pumping of Liquids on a Centrifugal Microilucid Platform", Lab Chip, 2012, 1 pp. 5142-5145, describe a partially closed micro fluidic system in which fluid from an inlet chamber is caused by centrifugal force is introduced into a compression chamber, so that in the compression chamber befindliches gas is compressed. Subsequently, the rotational speed is lowered so that the gas expands, whereby liquid from the compression chamber can be pumped radially inwardly via an outlet channel into a collection chamber.

Wang et al "Microfabricated valveless deviees for thermal bioreactions based on diffusion-limited evaporation", Lab on a Chip, 8, pp. 88-97, 2007, and Zhang et al "Decreasing microfluidic evaporation loss using the HMDL method: open Systems for nucleic acid amplification and analysis ", Microfluid Nano fluid, 9, p. 17-30, 2010, describe a diffusion barrier used to minimize fluid losses at elevated temperatures. To minimize liquid loss through evaporation, long narrow diffusion channels are used to achieve diffusion-limited evaporation.

US 812,893 B2 describes the use of an overpressure due to a temperature increase for switching liquids by means of a thermal control. By locally heating air is expanded and thus liquids are transported on.

The object underlying the present invention is to provide a fluid handling device and a method for processing a fluid, which allow pressure reduction in order to realize unitary fluid operations, such as in-pumping, even at elevated temperatures.

This object is achieved by a fluid handling device according to claim 1 and a method according to claim 13.

Embodiments of the invention provide a fluid handling device comprising: a compression chamber having a first compression chamber portion and a second compression chamber portion, the first compression chamber portion having a fluid inlet through which a fluid is insertable into the compression chamber; a vapor diffusion barrier between the first compression chamber portion and the second compression chamber portion; and a heater configured to heat at least the first compression chamber portion and the contents thereof, wherein the steam diffusion barrier is configured to heat an evaporating rate of a liquid disposed in the first compression chamber portion to a temperature at which the first compression chamber portion and its contents heat up At least reduce second compression chamber portion arranged gas and thus to reduce a pressure increase in the compression chamber.

Embodiments of the invention provide a method for processing a liquid having the following features:

Introducing a liquid through a fluid inlet into a first compression chamber portion of a compression chamber having the first compression chamber portion and a second compression chamber portion;

Processing the liquid in the first compression chamber portion, wherein the processing comprises heating at least the liquid disposed in the first compression chamber portion, wherein a vapor diffusion barrier is disposed between the compression chamber portion and the second compression chamber portion, such that when heated, an evaporation rate of the liquid disposed in the first compression chamber portion is at least reduced in the arranged in the second compression chamber section gas and thus a pressure increase in the compression chamber is reduced.

Embodiments of the invention are based on the recognition that by separating a liquid volume from an enclosed gas volume in a compression chamber by a diffusion barrier, the total pressure for the duration of a processing (for example, according to a processing protocol) can be significantly reduced because the total amount of water vapor produced is reduced or reduced can be minimized. The vapor diffusion barrier is one way to reduce or regulate the total pressure in a closed reaction space. By reducing and controlling the total pressure, a completely closed system can be realized whose function is not affected by the elevated temperatures and in which no external elements are necessary to build up a back pressure. In embodiments, the compression chamber is not vented, wherein the fluid is introduced into the compression chamber via the fluid inlet to compress a volume of gas trapped in the compression chamber.

In embodiments, one of the compression chamber sections is provided with a valve which can be selectively opened to allow venting of the compression chamber or closed to prevent venting of the compression chamber. Embodiments may include a controller configured to open the valve during introduction of the liquid to establish pressure equalization in the compression chamber, and after insertion of the liquid or after introduction of the liquid and at least partial heating of the liquid, the valve in order to subsequently reduce, with the valve closed, during periods of elevated temperature, an increase in pressure in the compression chamber caused by evaporation through the diffusion barrier.

In embodiments of the invention, the vapor diffusion barrier has a capillary channel fluidly connecting the first compression chamber portion to the second compression chamber portion. Thus, the total pressure in the closed system, i. the non-vented compression chamber, by the choice of geometric parameters, such as channel cross-section or channel length of the capillary channel, are regulated.

In embodiments of the invention, the capillary channel has a length which is at least 3 times, 5 times or 10 times greater than the hydraulic diameter of the capillary channel and / or in which the volume of the second compression chamber portion at least 5 times 10 times or 20 times larger than the product of cross section and length of the capillary channel. The hydraulic diameter Dh is defined as Dh = 4 * A / U, where A is the cross-sectional area through which flows and U is the circumference of the cross-sectional area through which flows. As a result, a sufficient reduction of the evaporation rate and thus of the pressure increase in the compression chamber can be advantageously implemented.

In alternative embodiments, the vapor diffusion barrier comprises a gas-permeable and liquid-impermeable membrane that separates the first compression chamber portion and the second compression chamber portion. In such embodiments, a capillary channel between two compression chamber sections is not necessary. Alternati can also be a vapor diffusion barrier a combination of a capillary channel and a gas permeable and liquid impermeable membrane may be implemented.

In embodiments of the invention, the fluid handling device further includes a collection chamber fluidly connected to the compression chamber via an outlet fluid channel, the outlet fluid channel having an outlet fluid channel inlet opening into the compression chamber and located radially outward than an outlet fluid channel outlet of the outlet fluid channel flows into the catch chamber, wherein liquid from the first compression chamber portion is drivable by expanding the gas arranged in the compression chamber through the Auslassfluidkanal into the catch chamber. Embodiments of the invention thus allow passive inward pumping, for example by expanding the gas located in the compression chamber, which can be achieved, for example, by lowering a rotational speed or heating the gas.

In embodiments, the fluid inlet is fluidically connected to an inlet chamber, wherein the compression chamber and the inlet chamber are formed in a rotary body or a fluidic module that is insertable into a rotary body, so that by rotation of the rotary body, the liquid by centrifugal force from the inlet chamber into the first compression chamber section can be introduced.

In alternative embodiments, the corresponding fluidic structures may be implemented in a non-centrifugal system, such as a gravitational force-based system or a pressure-driven system.

In such embodiments, a ratio between flow resistance of the outlet fluid channel for fluid flow from the compression chamber to the collection chamber and flow resistance of an inlet fluid channel between the compression chamber and the inlet chamber for fluid flow from the compression chamber to the inlet chamber may be adjusted by a particular ratio between volume flow into the collecting chamber and a volume flow into the inlet chamber. In embodiments, the corresponding flow resistance of the Auslassfluidkanals may be smaller than the corresponding flow resistance of the inlet fluid channel, so that a targeted emptying of the liquid from the compression chamber can be effected in the collecting chamber. In exemplary embodiments, equal or greater flow resistances of the outlet fluid channel can also be selected in order to meter different volumes, for example from a pre-amplification, given a given deceleration In embodiments, the fluid handling device further includes a drive device configured to apply rotation to the fluid handling device. The drive device can be designed in such a way that, in a first phase, the rotational body is subjected to a rotation frequency such that the gas in the compression chamber is compressed by the introduced liquid, and in a second phase, after a temperature treatment of the fluid, to reduce the rotational frequency, in order to drive at least parts of the liquid out of the compression chamber into the collecting chamber via the outlet channel. Thus, a passive inward pumping can be achieved only by changing the rotational frequency,

Embodiments of the present invention will be explained below with reference to the accompanying drawings. Show it:

Figure 1 is a schematic representation of a closed system with a gas-liquid mixture.

FIG. 2 is a schematic plan view of a fluid handling device; FIG.

Fig. 3 is a diagram for explaining the operation of the fluid handling device shown in Fig. 2;

FIG. 4 is a schematic plan view of fluidic structures of an alternative embodiment; FIG. and

5 and 6 are schematic side views for explaining embodiments of inventive devices,

In the context of the present application, a vapor diffusion barrier is understood to mean a device which reduces evaporation of a liquid into a gas compared to a case in which the diffusion barrier is absent, when the liquid and the gas are arranged in a fluidic system, the gas is trapped by the liquid in a non-vented fluidic structure. In other words, the gas is in a space that is closed by mechanical structures and the liquid. The fluidic structures on the side of the liquid away from the gas may be vented. In embodiments, a vapor diffusion barrier may be formed by a geometric structure in the form of a capillary channel. By inward pumping, herein is meant a transport of liquid in a tube. Tor or rotational body of a respect to a rotational axis radially outer position to a radially inner position understood.

Embodiments of the invention may be implemented in lab-on-a-chip systems wherein a vapor diffusion barrier is used to reduce the pressure in closed reaction spaces in which a liquid-gas mixture is located for temperature-controlled biochemical analysis methods. Such methods may, for example, be methods such as Sanger Sequencing, Ligase Chain Reaction, DNA Restriction,, Enzymes Kinetic Monitoring, and in particular a PCR.

As will be shown below, in embodiments of the invention, the fluidic operation of passive radial inward pumping at elevated temperatures is not limited, as a pressure increase in the trapped liquid-gas mixture can be reduced or avoided, which could otherwise lead to fluid loss , For example, by early venting or by delamination of a lidding film.

In embodiments of the invention, the controlled overpressure can be used selectively, for example, to pump an amplificate volume after the thermocycling to a further process module, for example a DNA array.

Embodiments of the present invention thus allow the performance of temperature-regulated, biochemical assays, the processing of elevated temperatures up to 99 ° C are necessary, with such a temperature increase leads to an increased pressure in the trapped volume of a liquid-gas mixture. The invention makes it possible to reduce and regulate the existing pressure at such elevated temperatures in an enclosed volume through a passive diffusion barrier, so that the reaction spaces can be closed, for example, to avoid cross-contamination from the environment or parallel reactions. In this case, an increase in pressure, which can lead to delamination or uncontrolled ventilation in I, ab-on-a-chip systems, can be avoided. Venting the reaction space, in which by using a valve, the pressure could be regulated in principle, but with the risk of DNA contamination, is therefore not necessary.

Embodiments of the invention thus use a Dampfdi ffusionsbarriere to reduce pressure or pressure control. Available systems use diffusion barriers, for example in the form of a capillary, only to reduce fluid losses, but not to reduce and regulate pressure or to switch fluid. Of Furthermore, in known systems, the capillary is not closed, so that there is a risk of leakage of molecules, for example of synthetic molecules.

In embodiments of the invention, no use of diaphragms or phase change valves (integrated or with active external elements) is necessary. Thus, an associated with the use of such means complication of the

Hersteilungsprozesses, which occurs by the fact that different materials or layers of material must be connected, can be avoided. Furthermore, no external pressure sources are required, which either reduce the vapor pressure of the liquid or provide for the switching of phase change valves, so also for this reason the production cost of a lab-on-a-chip cartridge and the complexity of a required accordingly Processing device can be reduced. Also, electrodes for the generation of bubbles are not necessary according to the invention.

Before referring to a specific embodiment of the invention with reference to FIGS. 2, 3 and 4, the background of the invention will first be described with reference to FIG. In a fluidically closed (dense) reaction space with a liquid-gas mixture, an increased pressure results during heating, which is also increasingly influenced by the formation of steam with increasing temperature. According to the invention, the use of a diffusion barrier controls the pressure in a trapped gas volume,

Fig. La shows schematically a closed container 2a, in which a gas-liquid mixture is arranged. Fig. 1b shows schematically a closed container 2b having a first container portion 3a and a second container portion 3b, between which a vapor diffusion barrier 4 is arranged in the form of a capillary channel.

In a closed system, such as formed by containers 2a and 2b, which is filled with liquid and a volume of gas, more vapor will form during a heating process because the equilibrium between vapor formation and liquid formation shifts with increasing temperature. Embodiments of the invention are based, as shown in FIG. 1b, on the spatial separation of the liquid and the gas through the vapor diffusion barrier, wherein the liquid is disposed in the container portion 3a and the gas is disposed in the container portion 3b. The volume of the liquid is thus spatially separated from the volume of trapped gas, but there is a connection of the two volumes across the vapor diffusion barrier. When heating the entire system, and especially the liquid, which is to be subjected to a temperature treatment, initially in the gas layer at the interface from the liquid to the gas will increasingly form steam until the gas layer is saturated with water vapor according to the equilibrium reaction (formation of liquid - vapor formation). The water vapor diffuses along a vapor concentration gradient towards the air volume with lower relative humidity. Due to the diffusive mass transport, the vapor content at the phase interface is reduced, which in turn triggers the formation of further vapor. This process of forming steam will continue until the entire gas volume is saturated with steam.

In the closed system shown in Figure la, this vapor / liquid equilibrium is rapidly reached due to the large liquid / gas interface. In the closed system shown in Fig. 1b, a vapor diffusion barrier in the form of a capillary prevents the propagation of the vapor, so that the equilibrium is reached only after a very long time, depending on the design of the capillary. Through a capillary, which acts as a vapor barrier, the diffusion length can be chosen very far. The formation of steam in this case depends on the slow diffusion rate of the vapor along the capillary or vapor barrier. A convective mass transport along a capillary can be neglected. From this Grand can be controlled by the choice of the cross-sectional area and the length of the capillary, the time course of the increase in the vapor content and thus the pressure increase in the entire volume.

"GGW

In FIGS. 1 a and 1 ^b , the term ^{gas gas designates} the pressure which prevails in the gas when the vapor-liquid equilibrium is reached.

Illustratively, in the following, a water-air mixture is considered, which is located in a closed room. It is heated to 95 ° C. This temperature is used, for example, as Denaturierangstemperatur in a polymerase chain reaction (PCR). Assuming that the vapor pressure of water in the water-air mixture depends only on temperature, the air consists only of oxygen (0 ₂ ) and nitrogen ( ₂ ) and both gases in the mixture can behave as ideal gases the effect of the diffusion barrier can be described as follows:

The total distance in a gas volume results from the sum of the partial pressures. For the water-air mixture the components N2 (80%) and 02 (20%) are considered for the air. This results in the total track approximately to:

Before heating at room temperature (23 ° C), the total crack is about 1000 mbar. The saturation vapor pressure at room temperature at ^ ¹¹ - '^ ^ 2 mbar j ~) _ement _ speaking are the Parti aldrücke for nitrogen and oxygen at about _Pm _(SSD 23 ° C) = mmbar ^ ^ _Po2 {2 C) = I94mbar _{the & dcn Dnnnaturation} step of the PCR necessary temperature of about 95 ° C, the saturation vapor pressure is about Ρ> ^! ι ° ^^ ^ ~ _^ ^ j ^ j ^ _SSR _of nitrogen and oxygen in accordance with rise of the ideal gas equation to ca.

= lilmbar _{] m} equilibrium, that is to say that everywhere in the closed system the gas volume is saturated with steam, then the total distance increases to about: p ^ gas (95 ° C) = 205QmBar

In the case of an ideal diffusion barrier, no water evaporates and the total crack is approximately: p ' ^d ff (9 s ° C) = l200 mbar

With the help of the present invention, the time course of the pressure increase of

"Id-Diff GGW

g ^as controlled by ^gas . For this is approximately the 1st Fick'sche

Law considered:

dx

where J is the material flow, A is the cross-sectional area of the capillary, D is the diffusion coefficient

cients and ^"x represents the concentration gradient. This shows that the material flow and thereby the rate of evaporation and, consequently, the time course of the mean

Vapor pressure in the gas volume over the cross-sectional area A and the length L of the capillary

re is adjustable. The length L is included in the estimation via the concentration gradient ^χ .

Thus, in embodiments of the invention, a vapor diffusion barrier may be used to reduce an evaporation rate in a closed system and thereby to reduce a pressure increase in a compression chamber upon heating of an air-liquid mixture disposed in the chamber.

FIG. 2 shows a schematic plan view of fluidic structures of a fluid handling device. FIG. Before these fluidic structures are explained in more detail with reference to FIG. 2, features of exemplary embodiments of devices according to the invention will first be described with reference to FIGS. 5 and 6.

FIG. 5 shows a device with a fluidic module 10 in the form of a rotational body, which has a substrate 12 and a cover 14. The substrate 12 and the lid 14 may be circular in plan view, with a central opening through which the rotary body 10 may be attached via a conventional fastening means 16 to a rotating part 18 of a drive device. The rotating part 18 is rotatably supported on a stationary part 22 of the drive device 20. The drive device may be, for example, a conventional centrifuge with adjustable rotational speed or a CD or DVD drive. A controller 24 may be provided which is configured to control the drive unit 20 to apply rotation to the rotary body 10 at different rotational frequencies. As will be appreciated by those skilled in the art, controller 24 may be implemented by, for example, a suitably programmed computing device or custom integrated circuit. The controller 24 may be further configured to control the drive device 20 upon manual inputs by a user to effect the required rotations of the rotating body. In either case, the controller 24 is configured to control the drive device 20 to apply the rotational body at the required rotational frequencies to implement the invention as described herein. As drive device 20, a conventional centrifuge with only one direction of rotation can be used.

The rotary body 10 has the required fluidic structures. The required fluidic structures may be formed by cavities and channels in the lid 14, the substrate 12 or in the substrate 12 and the lid 14. For example, in embodiments, fluidic structures may be imaged in the substrate 12 while fill openings and vents are formed in the lid 14.

In an alternative embodiment shown in FIG. 6, fluidic modules 32 are inserted into a rotor 30 and together with the rotor 30 form the rotary body 10. The fluidic modules 32 can each have a substrate and a lid, in which corresponding fluidic structures can be formed , The through the rotor 30th and the fluid body module 32 formed rotational body 10 is in turn by a drive device 20 which is controlled by the control device 24, acted upon by a rotation.

In embodiments of the invention, the fluidic module or body having the fluidic structures may be formed of any suitable material, for example, a plastic such as PMMA (polymethylmethacrylate, polycarbonate, PVC, polyvinyl chloride) or PDMS (polydimethylsiloxane ) Glass or the like. The rotary body 10 may be considered as a centrifugal microfluidic platform.

Furthermore, in FIGS. 5 and 6, purely schematically, a heating device 40 is shown, which is designed to heat at least portions of the rotational body 10 in FIG. 5 or the fluidic module 32 in FIG. 6, such that at least one first compression chamber portion and whose contents are heated. In this case, the heating device 40 can be designed as an external heating device, for example jet heating, or can be integrated into the fluidic module or the drive device.

2 shows a plan view of a rotary body 50 having a rotation axis 52. If the term "radial" is used herein, the rotational axis is in each case radial with respect to the center of rotation about which the fluidic module or the rotor is rotatable, that is to say in FIG Thus, in the centrifugal field, a radial direction is radially sloping away from the center of rotation, and a radial direction toward the center of rotation is radially increasing, and a fluid channel whose beginning is closer to the center of rotation than its end is thus radially sloping while a fluid channel whose beginning is farther from the center of rotation than the end of which is radially increasing.

Embodiments of the present invention may find particular application in the field of centrifugal micro-scrolling, which involves the processing of liquids in the nanoliter to milliliter range. Correspondingly, the fluidic structures can have suitable dimensions in the micrometer range for the corresponding liquid volumes.

As shown in FIG. 2, the fluidic structures formed in a rotary body 50 have an inlet chamber 54, which can be vented via a vent opening 56. The inlet chamber 54 is fluidly connected to a compression chamber 60 via an inlet channel 58. The compression chamber 60 has a first compression chamber section 62, a second compression chamber section 64 and an intermediate compression chamber section 64. see Dampfdi ff usions Barriere 66 in the form of a capillary channel arranged on the first compression chamber section 62 and the second compression chamber section 64. The structures 62, 64, and 66 form a compression chamber because a volume of gas trapped therein can be trapped and compressed by a liquid introduced into the first compression chamber portion 62 via the inlet chamber 54 and the inlet channel 58.

The first compression chamber section 62 is fluidically connected via a discharge channel 68 to a collecting chamber 70. The collecting chamber 70 has a vent 72.

The inlet passage 58 is fluidly coupled to a valve outlet of the first compression chamber section 62. In the embodiment shown, the outlet channel 68 is also fluidly coupled to the fluid inlet of the first compression chamber section 62, wherein the inlet channel 58 and the outlet channel 68 have a common channel section. In alternative embodiments, the first compression chamber portion may include a separate fluid outlet to which the outlet channel is fluidically coupled.

The compression chamber is a non-vented chamber in embodiments to facilitate compression of the compressible medium. In embodiments, the compression chamber, with the exception of the fluid inlet or a plurality of fluid inlets, which are connected to inlet chambers and / or collecting chambers, no fluid openings. In embodiments, the compression chamber may have additional fluid openings, but with respect to the gas in the compression chamber have such a high flow resistance that compression of the gas is possible and thus no venting of the compression chamber takes place in the sense of pressure equalization. In Ausiührungsbeispielen the compression chamber may have at least one additional fluid opening, which can be optionally closed, for example by a valve that can be actively actuated, so that in the closed state of the additional fluid opening, a gas in the compression chamber can be compressed.

In embodiments of the invention, the diffusion barrier is in the form of a capillary channel having a length that is at least 3, 5 or 10 times greater than the hydraulic diameter of the capillary channel. In alternative embodiments, the capillary channel may have a length which is at least 20 times greater than the hydraulic diameter of the capillary channel. In embodiments of the invention, alternatively or additionally, the volume of the second compression chamber portion 64 may be at least 5 times, 10 times or at least 20 times greater than the product of a cross-section and length of the capillary channel.

As shown in FIG. 2, the collection chamber 70 is located radially further inward than the first compression chamber portion 62 so that liquid from the first compression chamber portion 62 can be pumped radially inward into the collection chamber 70 via a pumping height 80. The capillary channel 66 may, for example, have a cross section of ΙΟΟμηι x 1 ΟΟμιτι and separates a disposed in the second compression chamber section 64 gas volume of a arranged in the first compression chamber section 62 liquid volume. The volume of liquid disposed in the second compression chamber portion is thereby heated by means of the heater, which is also shown schematically in phantom in Fig. 2, to effect, for example, a biochemical reaction (e.g., a PCR reaction) in the liquid phase. The second compression chamber portion 62 may therefore also be referred to as a reaction chamber.

The fluidics shown in FIG. 2 provide a pneumatic pumping structure that allows radial inward pumping in combination with a diffusion pressure barrier.

With reference to Fig. 3, the operation and, accordingly, a method of processing a liquid will be described below with reference to the shown example of a pneumatic siphon structure for PCR amplification. First, liquid is introduced into the engagement chamber 54, which can be done for example via the vent opening 56. This can be done at room temperature. By increasing the rotational frequency of the rotor, the sample liquid at room temperature of, for example, 25 ° C is forced by centrifugal force from the inlet chamber 54 through the inlet channel 58 into the compression chamber 60, in particular the first compression chamber portion 62, and the outlet channel. In this case, gas arranged in the second compression chamber section 64, for example air, which represents a compressible medium, is compressed. As a result, an overpressure p is generated in the gas, as shown in phase 1 in FIG. The increase in the rotational frequency can take place, for example, with an acceleration of 10 Hz / s.

Subsequently, in phase 2, the rotational frequency is kept constant, with the liquid levels in the inlet channel 58, the compression chamber 60 and the outlet channel 68 assuming an equilibrium position, while the gas in the second compression Chamber section 64 is still compressed. For example, the constant rotational frequency can be 35 Hz.

During Phase 2, the temperatures are cycled using the heater, for example between 50 ° C and max. 99 ° C, as shown in Fig. 3. During this temperature treatment, the excess pressure between the compression chamber 60 and the ambient pressure, in this case the atmospheric pressure, is reduced by an overall low formation of steam, so that the fluidic functionality can be ensured. The low vapor formation is achieved by the vapor diffusion barrier 66, wherein in phase 2 schematically diffusing vapor molecules in an enlarged portion of the interface between liquid in the first compression chamber portion 62 and gas in the diffusion barrier 60 are shown.

After the temperature treatment in phase 2, a rapid reduction of the rotational frequency occurs, for example with a deceleration rate of 20 Hz / s. Thereby, the pressure in the compression chamber 60 is reduced, wherein the compressed gas expands and a majority of the sample liquid escapes through the path of least resistance. In this case, the outlet channel 68 and the inlet channel 58 are designed such that the flow resistance of the outlet channel 68 for a liquid flow from the compression chamber 60 to the collection chamber 70 is less than a flow resistance of the inlet channel 58 for a liquid flow from the compression chamber 60 to the inlet chamber 54 The liquid escapes from the second compression chamber section 62 through the outlet channel 68 into the catch chamber 70, as shown by phase 3 in FIG.

In the example shown, the rotation frequency is lowered to 10 Hz. In alternative embodiments, the lower rotational frequency may also become zero or assume negative values (reverse rotational direction). The temperature of discharging the liquid into the catching chamber, which is 70 ° in the example shown, may be selected in a range from room temperature to 99 ° C. In addition, temperatures below room temperature are possible, because then the pressure is reduced.

For example, the implementation outlined in these embodiments may be implemented monolithically. It has been shown that, under the conditions described above, after a PCR thermocycling of a 40 μΙ sample, more than 90% can be pumped radially inwards over a pump height of 30 mm within one second.

FIG. 4 shows fluidic structures of an alternative embodiment which includes a compression chamber 60 'having a first compression chamber portion 62' and a second compression chamber portion 62 ' Compression chamber section 64% have an inlet channel 58 'and a diffusion barrier 66' in the form of a fluid channel. The first compression chamber portion 62 'has a valve 90 which may be open during a case of zero action to achieve pressure equalization and then closed. Optionally, the inlet (inlet channel 58 ') of the reaction chamber (compression chamber 60') can also have a valve 92 which is open during filling and can subsequently be closed. Thus, one of the compression chamber sections has a valve which can be selectively opened during the Befiilvorgangs or even during heating to produce a pressure equalization. In the further course, the valve can be closed. During the elevated temperature phases, a pressure increase due to evaporation across the vapor diffusion barrier is reduced.

The heater may be configured in embodiments of the invention to locally heat the first compression chamber portion and the liquid disposed therein. However, in alternative embodiments of the invention, the insulating means may also be configured to globally heat the entire rotary body or the entire fluidic module. Thus, exemplary embodiments of the invention allow a simple construction, since no specific etching device is required for heating only a part of the rotary body or of the fluidic module. For example, the heater may be a global heater configured to heat the entire rotary body by heating the rotary part of the drive device to which the rotary body is attached.

Embodiments of the present invention thus provide a passive method of reducing and regulating a pressure increase through vapor formation in an enclosed volume of gas. Embodiments of the invention can be used for completely closed systems and also for partially ventilated systems in which fluid structures associated with the liquid, but not with the enclosed gas, are vented.

In embodiments of the invention, a vapor diffusion barrier is used for the first time to reduce or minimize the total pressure in a completely or partially closed system with gas-liquid mixture by reducing the formation of steam at elevated temperatures up to 99 ° C. By choosing the geometric parameters of the vapor diffusion barrier, ie the cross section and the length of the capillary, the pressure can be regulated. The use of vapor diffusion barriers to reduce the pressure in closed systems is not known in the prior art. In other words, embodiments of the invention provide geometric structures and methods that reduce the overall pressure globally in a closed or locally partially closed system liquid-gas mixture by using a vapor diffusion barrier. Embodiments provide geometric structures and methods in which the pressure can be regulated by selecting the geometric parameters of the diffusion barrier.

Although specific rotational rates and temperatures have been described with reference to FIG. 3, it will be apparent to those skilled in the art that other rotational rates and temperatures may be used in other embodiments. The present invention can be used everywhere, where a gas / liquid mixture is exposed during a temperature treatment to a pressure and an additional pressure due to evaporation of the liquid is to be reduced in the gas.

Claims

claims

A fluid handling apparatus comprising: a compression chamber (60) having a first compression chamber portion (62) and a second compression chamber portion (64), the first compression chamber portion (62) having a fluid inlet through which a fluid enters the compression chamber (60) can be introduced; a vapor diffusion barrier (66) between the first compression chamber portion (62) and the second compression chamber portion (64); and a heater (40) configured to heat at least the first compression chamber portion (62) and its contents, wherein the vapor diffusion barrier (66) is configured to provide a vaporization rate of a first compression chamber portion (62) and its contents to at least reduce liquid disposed in the first compression chamber portion (62) into a gas disposed in the second compression chamber portion (64), and thus to reduce a pressure increase in the compression chamber (60).

2, fluid handling device according to claim 1, wherein the compression chamber is not vented and wherein the liquid is introduced via the FMdeinlass in the compression chamber to compress a trapped in the compression chamber (60) gas volume.

3, fluid handling device according to claim 1, wherein one of the compression chamber sections is provided with a valve which can be selectively opened to allow venting of the compression chamber, or can be closed to prevent venting of the compression chamber.

4. A fluid handling apparatus according to claim 3, comprising a controller adapted to open the valve during liquid introduction to establish pressure equalization in the compression chamber and after introduction of the liquid or after introduction of the liquid and the at least one partial heating of the liquid to close the valve to subsequently, when the valve is closed during periods of elevated temperature, to reduce a pressure increase in the compression chamber (60) due to evaporation through the diffusion barrier,

Fluid handling device according to one of claims 1 to 4, wherein the

Vapor diffusion barrier (66) has a capillary channel fluidly connecting the first compression chamber portion (62) to the second compression chamber portion (64).

The fluid handling device of claim 5 wherein the capillary channel has a length at least 3, 5 or 10 times greater than the capillary channel hydraulic diameter and / or at least the volume of the second compression chamber section (64) 5 times, 10 times or 20 times larger than the product of cross section and length of the capillary channel is.

The fluid handling device of any one of claims 1 to 6, wherein the vapor diffusion barrier (66) comprises a gas permeable and liquid impermeable membrane separating the first compression chamber portion (62) and the second compression chamber portion (64).

Fluid handling device according to one of claims 1 to 7, wherein the fluid inlet is fluidically connected to an inlet chamber (54), wherein the compression chamber (60) and the inlet chamber (54) in a rotary body (10; 50) or a fluidic module (32 ), which is insertable into a rotary body (10) are formed, so that by rotation of the rotary body (10), the liquid by centrifugal force from the inlet chamber (54) in the first compression chamber section (62) can be introduced.

The fluid handling device of claim 8, further comprising a collection chamber (70) fluidly coupled to the compression chamber (60) via an outlet fluid channel (68), the outlet fluid channel (68) having an outlet fluid channel inlet opening into the compression chamber (60) and disposed radially farther out than an outlet fluid passage outlet of the discharge fluid passageway opening into the collection chamber (70), wherein liquid from the first compression chamber section (62) is expanded by expanding the gas disposed in the compression chamber (60) through the outlet fluid passageway (68) Drift chamber (70) is drivable.

10. The fluid handling apparatus of claim 9, wherein a ratio of flow resistance of the outlet fluid channel for fluid flow from the compression chamber to the collection chamber and a flow resistance of a return fluid channel between the compression chamber and the inlet chamber for fluid flow from the compression chamber (60) is set to the inlet chamber to set a certain ratio between a volume flow into the catch chamber and a volume flow into the inlet chamber.

1 1. Fluid handling device according to claim 9 or 10, further comprising a drive device (20) which is designed to apply in a first phase, the rotary body (10; 50) with a rotational frequency such that the gas in the compression chamber (60 ) is compressed by the introduced liquid, and in a second phase, after a temperature treatment of the liquid, to reduce the rotational frequency to drive at least parts of the liquid through the Auslassfluidkanal (68) from the compression chamber (60) in the collecting chamber (70) ,

The fluid handling apparatus according to any one of claims 8 to 1 1, wherein the heater (40) is a global heater configured to heat the entire rotary body.

13. A process for processing a liquid having the following features:

Introducing a liquid through a fluid inlet into a first compression chamber section (62) of a compression chamber (60) containing the first compression chamber section (62) and a second compression chamber section

(64);

Processing the liquid in the first compression chamber portion (62), wherein the processing comprises heating at least the liquid disposed in the first compression chamber portion (62), wherein a vapor diffusion barrier (66) is disposed between the first compression chamber portion (62) and the second compression chamber portion (64) is such that upon heating, an evaporation rate of the liquid arranged in the first compression chamber section (62) into that in the second chamber Pression chamber section (64) arranged at least reduced gas and thus a pressure increase in the compression chamber (60) is reduced.

The method of claim 13, wherein the compression chamber (60) is a non-vented compression chamber, wherein the introduction of the fluid comprises compressing a volume of gas trapped in the compression chamber (60).

15. The method of claim 13, wherein one of the compression chamber portions (62, 64) is provided with a valve which can be selectively opened to allow venting of the compression chamber (60) or can be closed to vent the compression chamber (60), the method comprising opening the valve during introduction of the liquid to make pressure equalization in the compression chamber, and closing the valve after introduction of the liquid or after introduction of the liquid and at least partial heating of the liquid in order subsequently to reduce an increase in pressure in the compression chamber (60) caused by evaporation by the diffusion barrier when the valve is closed during periods of elevated temperature.

The method of any one of claims 13 to 15, further comprising rotating a body of revolution to introduce the liquid from an inlet chamber (54) by centrifugal force into the first compression chamber portion (62) and to compress the volume of gas.

7. The method of claim 16, further comprising rotating the rotating body to reduce the rotational frequency of the rotational frequency to cause the trapped gas volume to expand and at least portions of the fluid to escape from the compression chamber via an outlet fluid passage (68). 60) are driven into a collecting chamber (70).