EP3592463B1 - Method for centrifugo-pneumatic switching of liquid - Google Patents

Description

The present invention is concerned with methods for centrifugo-pneumatic switching of liquids from a liquid holding area into downstream fluidic structures using a ratio of centrifugal pressure to pneumatic pressure.

introduction

Centrifugal microfluidics deals with the handling of liquids in the picoliter to milliliter range in rotating systems. Such systems are mostly single-use polymer cartridges that are 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. For this purpose, the cartridges contain channels for guiding the fluid, as well as chambers for collecting liquids. In general, such structures that are designed to handle fluids can be referred to as fluidic structures. Such cartridges can generally be referred to as fluidics modules.

The cartridges are subjected to a predefined sequence of rotational frequencies, the frequency protocol, so that the liquids in the cartridges can be moved by the centrifugal force. Centrifugal microfluidics are mainly used in laboratory analysis and mobile diagnostics. The most common design of cartridges to date has been a centrifugal microfluidic disk that is used in special processing devices and is known under the names "Lab-on-a-disk", "LabDisk", "Lab-on-CD", etc. Other formats, such as microfluidic centrifuge tubes known as "LabTube", can be used in the rotors of existing standard laboratory equipment.

For the use of fluidic basic operations in a possible product, the robustness and simplicity of the handling of the process is of the utmost importance. It is also advantageous if the basic operation is implemented monolithically, so that no additional components or materials that are caused by material costs or additional construction and connection technology (assembly) would significantly increase the cost of the cartridge.

In particular, the switching of liquids is required as a fundamental operation for the execution of process chains in order to separate successive fluidic processing steps from one another. Switching processes are therefore indispensable for the automation of laboratory processes in a centrifugal microfluidic rotor.

One example is the measuring of liquid volumes for the generation of aliquots, in which the liquids are switched to subsequent process steps after a measuring step. Further examples are incubation and mixing processes in which the incubation time or the completion of the mixing process must be reached before switching on.

A major challenge during the development of cartridges for centrifugal microfluidic fluid handling is the adaptation of the structures involved to the properties of the fluids to be processed as well as to the interactions of the fluids with the cartridge materials used. This results in a need in particular for structures and methods for switching fluids that are largely independent of the properties of the fluids and their interaction with the cartridge material. This includes in particular the following properties of the fluids and cartridge materials: the surface tension of the fluids, their contact angle with the cartridge materials used, the viscosities of the fluids and the chemical composition of the fluids.

Another challenge for the development of microfluidic cartridges lies in the manufacturing requirements. Structures that place high demands on manufacturing tolerances lead to higher manufacturing costs and a greater risk of cartridge failure during processing. This results in a need for structures and methods for switching fluids, in particular liquids, which are robust with regard to their function against production-related deviations. Furthermore, there is a need for structures that can be easily manufactured using established manufacturing processes - which allow high manufacturing precision. In particular for the manufacturing processes of injection molding and injection compression molding, there is a need for structures and processes for switching fluids which, in contrast to so-called capillary valves, for example, manage without sharp-edged geometrical transitions.

In the field of centrifugal microfluidics, a processing protocol generally acts simultaneously on all fluidic structures of a cartridge. As a result of the increasing integration of processing steps running one after the other or in parallel, there are generally increasing restrictions for the permissible processing protocols. In order to still be able to integrate various fluidic operations on a centrifugal microfluidic cartridge, there is a need for structures and methods for switching fluids for which the exact conditions for the switching operation to occur can be set within a wide range by suitable design.

State of the art

Different ways of switching liquids on centrifugal microfluidic platforms are known from the prior art. An overview of active and passive, as well as monolithic and non-monolithic structures and methods for switching liquids is at O. Strohmeier et al., "Centrifugal microfluidic platforms: Advanced unit operations and applications", Royal Society of Chemistry 2015, Chem. Soc. Rev. , to find. In the following, further prior art is presented, which relates to passive monolithic structures and associated methods, the switching principle of which is based, among other things, on an interplay between centrifugally induced pressures and pneumatic pressures.

S. Zehnle et. al. "Pneumatic siphon valving and switching in centrifugal microfluidics controlled by rotational frequency or rotational acceleration", Springer Verlag, Microfluid Nanofluid (2015) 19, pages 1259-1269 , describe several structures and associated methods for switching liquids on a centrifugal microfluidic platform. In this case, liquid is centrifugally driven out of a first, non-vented chamber in a first vacuum valve, so that gas in the first chamber expands and a vacuum is created in the first chamber. The liquid is forced into the second chamber through an outlet channel which opens at a radially outer end into a second, vented chamber. Since a siphon branches off from the outlet channel, the end of which is vented, part of the liquid is also driven into the siphon. At a constant rotational frequency, the filling levels are in equilibrium, so that the filling level in the second chamber equals the filling level in the siphon. Both levels rise with increasing rotational frequency. If the fill level in the siphon exceeds the top of the siphon, in this way the liquid from the first and the second chamber is driven through the siphon and can be collected in a third, vented chamber. In a second configuration of the vacuum valve described, it is shown that with appropriate dimensioning of the flow resistances between the respective chambers, the siphon apex can be reached by high rotational acceleration, but not with low rotational acceleration. Corresponding valve functions are also in the DE 10 2013 215 002 B3 described.

In the cited paper by S. Zehnle et.al. a further valve circuit is also described 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 the first chamber is vented and the second chamber is not vented in this further valve circuit, a volume of gas is enclosed and compressed in the second chamber when the liquid is driven into the second chamber. This volume of gas expands when the speed is reduced and drives liquid into the siphon. With a high rate of deceleration of the speed and a corresponding dimensioning of the flow resistances, enough liquid is driven into the siphon to fill it completely, so that the liquid can be driven out of the first and second chambers through the siphon and collected in a third chamber. This valve function is also in the EP 2 817 519 B1 described.

From the DE 10 2013 203 293 B4 it is also known that such a valve circuit, which is referred to above as a further valve circuit, can optionally also be provided with a second siphon in order to guide the liquid, depending on the rate of deceleration of the speed, through one or both siphons.

All the valve circuits described in the cited document by S. Zehnle have in common that the end of the siphon through which the liquid is driven is vented. The third chamber, which only serves as a collecting chamber, is thus also vented and not coupled to a further fluidic element. In addition to its function as a collecting chamber, it has no other fluidic functions and cannot influence the valve functions described by any type of dimensioning.

In D. Mark et.al., "Aliquoting on the centrifugal microfluidic platform based on centrifugal-pneumatic valves", Springer Verlag, Microfluid Nanofluid (2011) 10, pages 1279-1288 , describes a structure for aliquoting liquids in which liquid flows sequentially through a feed channel into a series of measuring channels in which the liquid is held during an aliquoting process by so-called centrifugal-pneumatic valves. After completion of the aliquoting process, the centrifugal-pneumatic valves are switched between the measuring channels and radially further outward chambers connected to the measuring channels by increasing the rotation frequency, and the liquids are transferred to the radially further outward chambers. The functional principle of the centrifugal-pneumatic valves described consists of two complementary effects. The first effect is that when the respective measuring channel is filled, the liquid closes the connecting channel between the measuring channel and the subsequent non-ventilated target chamber and the centrifugally induced transfer of liquid from the measuring finger into the target chamber leads to a compression of the gas therein. The resulting pneumatic overpressure in the target chamber counteracts any 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 that counteracts the switching of the liquid into the target chamber. The sum of the two effects results in the functional principle of the centrifugo-pneumatic valve. By increasing the rotation frequency, both effects can be overcome, so that the liquid is transferred into the target chamber. Corresponding centrifugal-pneumatic valves are in the DE 10 2008 003 979 B3 just like D. Mark, "Centrifugo-pneumatic valve for metering of highly wetting liquids on centrifugal microfluidic patforms", Lab Chip, 2009, 9, pp. 3599-3603 described.

Such centrifugal-pneumatic valves only allow the compression of a small volume of gas given by the connecting channel between the measuring channel and the target structure before liquid reaches the target chamber. As a result, the switching frequency is restricted to low frequencies due to the structure. At the same time, the switching frequency is dependent on the liquid properties, since the capillary valve effect, which plays a role for the centrifugo-pneumatic valve, depends on the surface tension and the contact angles between the liquid and the cartridge material. Furthermore, the described capillary valve portion of the centrifugal-pneumatic valve may result in the requirement for a sharp-edged transition from the connecting channel to the target chamber, which is associated with additional manufacturing costs.

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 an inlet channel with high fluidic resistance, a measuring chamber, a pressure chamber connected to the measuring chamber via a connecting channel, and an outlet channel with low fluidic resistance connected to the measuring chamber. The structures allow the measurement and subsequent indexing of liquid volumes. The sequence of the measuring and switching process is as follows: First, the liquid to be measured is fed through the inlet channel into the measuring chamber at a high rotational frequency until it is completely filled. Thereafter, the connection channel to the pressure chamber, which is connected radially on the inside, is filled and excess liquid is passed into the pressure chamber, which represents a trap for this, so that the liquid can no longer leave the pressure chamber. The gas volume displaced in the measuring chamber and the pressure chamber from the moment the liquid enters the measuring chamber leads to a pneumatic pressure increase in the pressure chamber. After the filling of the structure through the inlet channel has been completed, in a second step the liquid is switched to subsequent fluidic structures by reducing the rotation frequency. This is achieved because the centrifugal pressure in the outlet channel falls below the pneumatic overpressure in the pressure chamber and therefore the liquid from the pneumatic overpressure and other pressures that occur is essentially transferred into the outlet channel. The selected fluidic resistances ensure that the transfer essentially takes place in the outlet channel and not back into the inlet channel. The structures can have a siphon, which ensures that the liquid is not yet switched into a collecting chamber during a measuring step. The siphon can be omitted for structures in which the collecting chamber is located radially further inward than the measuring chamber. A corresponding aliquoting is also in the WO 2015/049112 A1 described.

Due to the switching principle, such centrifugal-pneumatic aliquoting is only suitable for process chains in which switching can or should be done by reducing the rotation frequency. In addition, a minimum deceleration rate has to be achieved in order to transfer the liquid into a target volume, which results in restrictions in the processing devices that can be used. If switching is to be carried out by increasing the rotation frequency, since processes must run at a low rotation frequency before switching, centrifugal-pneumatic aliquoting cannot be used either. Furthermore, for the centrifugal-pneumatic aliquoting, additional space is required for the pressure chamber, which may be lost for the introduction of structures for other operations on the cartridge. The The need for strong differences in the fluidic resistances between inlet and outlet channels leads to additional demands on production, since high fluidic resistances are achieved through small channel cross-sections, which therefore place high demands on the manufacturing tolerances.

Wisam AI-Faqheri et. al., "Development of a Passive Liquid Valve (PLV) Utilizing a Pressure Equilibrium Phenomenon on the Centrifugal Microfluidic Platform", Sensors 2015, 15, pages 4658-4676 , describe a switching of liquid depending on a centrifugal pressure acting on a liquid in an inlet chamber, a capillary pressure acting on the liquid in the inlet chamber and a centrifugal pressure acting on a liquid in a venting chamber. Air is trapped between the liquids in the inlet chamber and the vent chamber. By increasing the speed of rotation, a negative pressure generated in the inlet chamber or an overpressure generated in the venting chamber is overcome, in order thereby to convey liquid from the inlet chamber through a fluid channel into a target chamber. The US2012 / 295781 A1 also belongs to the state of the art.

Description of the invention

The invention is defined by the present claims. A fluidics module for switching liquids is described, which can be monolithically integrated and easily manufactured, largely independent of fluid and material properties and can be adapted to a wide range of processing conditions, as well as devices with such a fluidics module and methods that use such a fluidics module.

Exemplary embodiments relate to fluidic modules, devices and methods for retaining and selectively switching liquids in centrifugal microfluidic cartridges.

• einem Flüssigkeits-Haltebereich, in den eine Flüssigkeit einbringbar ist,
• mindestens zwei Fluidpfaden, die den Flüssigkeits-Haltebereich mit nachgeschalteten Fluidikstrukturen fluidisch verbinden,
• wobei mindestens ein erster Fluidpfad der beiden Fluidpfade einen Siphonkanal aufweist, wobei ein Siphonscheitel des Siphonkanals radial innerhalb einer radial äußersten Position des Flüssigkeits-Haltebereichs liegt,
• wobei die nachgeschalteten Fluidikstrukturen nicht entlüftet sind oder nur über einen Entlüftungs-Verzögerungswiderstand entlüftet sind, wenn die Flüssigkeit in den Flüssigkeits-Haltebereich eingebracht ist, so dass in den nachgeschalteten Fluidikstrukturen ein eingeschlossenes Gasvolumen oder ein lediglich über einen Entlüftungs-Verzögerungswiderstand entlüftetes Gasvolumen entsteht, wenn die Flüssigkeit in den Flüssigkeits-Haltebereich eingebracht wird, und durch ein Verhältnis eines durch eine Rotation des Fluidikmoduls bewirkten Zentrifugaldrucks und eines in dem Gasvolumen herrschenden pneumatischen Drucks zumindest temporär verhindert wird, dass die Flüssigkeit durch die Fluidpfade in die nachgeschalteten Fluidikstrukturen gelangt,
• wobei durch eine Änderung des Verhältnisses des Zentrifugaldrucks zu dem pneumatischen Duck bewirkt werden kann, dass die Flüssigkeit zumindest teilweise durch den ersten Fluidpfad in die nachgeschalteten Fluidikstrukturen gelangt und das Gasvolumen durch den zweiten Fluidpfad der beiden Fluidpfade zumindest teilweise in den Flüssigkeits-Haltebereich entlüftet wird.

Embodiments create a fluidic module for switching liquid from a liquid holding area into downstream fluidic structures, with the following features:

• a liquid holding area into which a liquid can be introduced,
• at least two fluid paths that fluidically connect the liquid holding area with downstream fluidic structures,
• wherein at least one first fluid path of the two fluid paths has a siphon channel, a siphon apex of the siphon channel lying radially inside a radially outermost position of the liquid holding area,
• The downstream fluidic structures are not vented or are only vented via a venting delay resistor when the liquid is introduced into the liquid holding area, so that an enclosed gas volume or a gas volume that is only vented via a venting delay resistor is created in the downstream fluidic structures if the liquid is introduced into the liquid holding area, and a ratio of a centrifugal pressure caused by a rotation of the fluidics module and a pneumatic pressure prevailing in the gas volume prevents the liquid from reaching the downstream fluidic structures through the fluid paths,
• whereby a change in the ratio of the centrifugal pressure to the pneumatic pressure can cause the liquid to at least partially pass through the first fluid path into the downstream fluidic structures and the gas volume is at least partially vented through the second fluid path of the two fluid paths into the liquid holding area.

Embodiments are based on the knowledge that it is possible on a centrifugal microfluidic platform, using appropriate fluidic structures to fill a liquid holding area, which can be centrifugally induced, a pneumatic differential pressure to the ambient pressure in downstream fluidic structures, as well as the To generate connecting fluid paths between the liquid holding area and subsequent fluidic structures, through which the liquid can be held in the liquid holding area under suitable processing conditions until the liquid can be further transferred into the subsequent fluidic structures induced by a suitable change in the processing conditions. During this liquid transfer into the downstream fluidic structures through one of the fluid paths, the downstream fluidic structures can be vented through the other of the fluid paths. The ratio between pneumatic pressure and centrifugal pressure can be set or changed by appropriate processing conditions, for example rotation speed and / or temperature, in order to achieve the functionalities described.

Embodiments are also based on the knowledge that during a, for example, centrifugally induced filling process of the liquid holding area, gas can be displaced through the connecting fluid paths between the liquid holding area and the downstream fluidic structures into the downstream fluidic structures, and that the displaced gas volume continues only by the liquid volume limited, can be selected arbitrarily by suitable configuration of the connecting fluid paths, whereby the processing conditions under which the liquid is kept in the liquid holding area, as well as the processing conditions under which the liquid is switched on into the downstream fluidic structures, are broadly and largely independent of Have fluid properties or cartridge material properties determined.

In embodiments, the liquid can be introduced into a fluid chamber of the liquid holding area via a radially sloping inlet channel by a centrifugal pressure brought about by a rotation of the fluidics module. As a result, the rotation used when introducing the liquid into the liquid holding area can achieve the ratio between centrifugal pressure and pneumatic pressure, which prevents liquid from reaching the downstream fluidic structures. In embodiments, the inlet channel can also be connected to an upstream fluid chamber.

In embodiments, a second fluid path of the two fluid paths is a ventilation channel for the downstream fluidic structures, which is closed by the liquid when the liquid is introduced into the liquid holding area. It is thus possible, at the same time as the introduction of a volume of liquid into the liquid holding area, to close a ventilation channel for the downstream fluidic structures, so that no separate means are required for this.

In embodiments, the first fluid path opens into the liquid holding area in a radially outer area or at a radially outer end, so that the liquid holding area at least up to the area in which the first fluid path opens into the liquid holding area, via the first Fluid path is drainable. This makes it possible to empty a large part of the liquid or all of the liquid from the liquid holding area.

In exemplary embodiments, the liquid holding area has a first fluid chamber, the first fluid path opening into the first fluid chamber in a radially outer area of the first fluid chamber or at a radially outer end of the first fluid chamber. In such exemplary embodiments, the first fluid chamber can not be vented or can only be vented via a venting delay resistor when the liquid is (is) introduced into the liquid holding area, so that a gas volume enclosed in the first fluid chamber and the downstream fluidic structures or only a The volume of gas vented via a venting delay resistor arises when the liquid is (is) introduced into the liquid holding area.

In exemplary embodiments, the liquid holding area has a first fluid chamber and a second fluid chamber into which a liquid can be introduced by a centrifugal pressure caused by a rotation of the fluidics module, the first fluid path opening into the first fluid chamber and the second fluid path opening into the second fluid chamber, and wherein the second fluid path can be closed by a liquid introduced into the second fluid chamber. In such embodiments, the first fluid chamber and the second fluid chamber can be fluidically connected to one another via a connecting channel, the opening of which into the first fluid chamber lies radially further inward than a radially outer end of the first fluid chamber, so that liquid overflows from the first fluid chamber into the second fluid chamber when the fill level of the liquid in the first fluid chamber reaches the mouth and closes the second fluid path opening into the second fluid chamber. Such exemplary embodiments can make it possible that liquid is initially held in the first fluid chamber and is only switched into the downstream fluidic structures by adding further liquid, which can be a liquid different from the first liquid.

In embodiments, the second fluid path has a siphon channel. This enables increased flexibility with regard to the opening of the second fluid path into the liquid holding area and increased flexibility with regard to the processing conditions, since it can prevent liquid from reaching the downstream fluidic structures via the second fluid path. For example, in such exemplary embodiments, the second fluid path can open into the liquid holding area in a radially outer area of the liquid holding area. In such exemplary embodiments, an apex of the siphon channel of the second fluid path can lie radially further inward than an apex of the siphon channel of the first fluid path.

In embodiments, the second fluid path has a siphon channel and an intermediate fluid chamber is arranged 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 fluid intermediate chamber is at least partially filled with the liquid when the liquid is introduced into the liquid holding area. The intermediate fluid chamber can have a smaller volume than a first fluid chamber of the liquid holding area. In embodiments, a radially outer end of the intermediate fluid chamber is located radially outside of the siphon apex of the first fluid path. The first intermediate fluid chamber enables a larger amount of liquid to enter the second fluid path before its meniscus reaches the apex of the siphon channel of the second fluid path.

In exemplary embodiments, the downstream fluidic structures have at least one downstream fluid chamber into which the first fluid path and the second fluid path open. Alternatively, the first and second fluid paths can also open into different chambers of the downstream fluidic structures, as long as it is ensured that there is pressure equalization between the mouths of the first and second fluid paths into the downstream fluidic structures during the fluid holding phase. It is thus possible to collect the switched liquid in the downstream fluidic structures. The first fluid path can open into the downstream fluid chamber radially further outward than the second fluid path. This enables the opening of the second fluid path into the downstream fluid chamber to remain free for venting when the liquid reaches or is transferred into the downstream fluidic structures. The downstream fluid chamber can be a first downstream fluid chamber, wherein the downstream fluidic structures can have a second downstream fluid chamber which is fluidically connected to the first downstream fluid chamber via at least one third fluid path. It is thus possible to implement fluidic structures that enable cascaded switching.

In exemplary embodiments, the downstream fluidic structures can have a first downstream fluid chamber and a second downstream fluid chamber, the first downstream fluid chamber being fluidically connected to the second downstream fluid chamber via a third fluid path and a fourth fluid path, with at least the third fluid path having a siphon channel, the The third fluid path and the fourth fluid path are closed by the liquid when the liquid is caused by a change in the ratio of the centrifugal pressure to the pneumatic pressure Pressure passes through the first fluid path into the first downstream fluid chamber of the downstream fluidic structures, whereby in the second downstream fluid chamber an enclosed gas volume or a gas volume that is only vented via a venting delay resistor is created and through a ratio of the centrifugal pressure and that in the gas volume downstream in the second The pneumatic pressure prevailing in the fluid chamber prevents the liquid from passing through the fluid paths (in particular the third and fourth fluid paths) into the second downstream fluid chamber, and a change in the ratio of the centrifugal pressure to the pneumatic pressure in the second downstream fluid chamber is effected can that the liquid passes through the third fluid path into the second downstream fluidic chamber and the gas volume from the second downstream fluid chamber through the fourth fluid path at least partially wisely vented into the fluid holding area. It is thus possible to implement fluidic structures that enable cascaded switching.

Embodiments provide a device for switching liquid from a liquid holding area into downstream fluidic structures with a fluidic module as described herein, which has a drive device that is designed to subject the fluidic module to rotation, and an actuating device that is designed to to effect the change in the ratio of the centrifugal pressure to the pneumatic pressure. In exemplary embodiments, the actuating device is designed to increase or decrease the rotational speed of the fluidics module in order to bring about the change in the ratio of the centrifugal pressure to the pneumatic pressure. In embodiments, the actuating device 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 create a method for switching liquid from a liquid holding area into downstream fluidic structures using a fluidic module as described herein, having the following features:
Introducing at least one liquid into the liquid holding area and holding the liquid in the liquid holding area by rotating the fluidics module, so that the liquid is dominated by the centrifugal pressure and the pneumatic pressure quasi-steady-state equilibrium is maintained in the liquid holding area; and
Changing the ratio of the centrifugal pressure to the pneumatic pressure in order to transfer the liquid at least partially through the first fluid path into the downstream fluidic structures and to vent the gas volume through the second fluid path of the two fluid paths at least partially into the liquid holding area.

In exemplary embodiments, holding the liquid in the liquid holding area includes generating a pneumatic overpressure in the downstream fluidic structures before the transfer is initiated. In exemplary embodiments, changing the ratio of the centrifugal pressure to the pneumatic pressure includes an increase in the rotational speed of the fluidics module, an increase in the hydrostatic height of the liquid and / or a decrease in the pneumatic pressure. In exemplary embodiments, the holding of the liquid in the liquid holding area comprises generating a negative pressure in the downstream fluidic structures in order to set and hold menisci in the liquid holding area and the first and second fluid paths without the liquid through the first fluid path into the downstream ones To transfer fluidic structures, wherein the changing of the ratio of the centrifugal pressure to the pneumatic pressure comprises a decrease in the rotational speed of the fluidic module and / or a decrease in the pneumatic pressure in the downstream fluidic structures and / or an increase in the hydrostatic height of the liquid in the liquid holding area.

In embodiments, changing the ratio includes reducing the pneumatic pressure by reducing 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. In exemplary embodiments, the second fluid path is not completely filled with liquid during the transfer of the liquid through the first fluid path. In embodiments, the amount of substance of the gas in the downstream fluidic structures is not changed while the liquid is held in the liquid holding area.

Fig. 1

eine schematische Darstellung von Fluidikstrukturen gemäß einem Ausführungsbeispiel zum überdruckbasierten Schalten;

Fig. 2A bis 2E

schematische Darstellungen zur Erläuterung der Funktionsweise des Ausführungsbeispiels von Fig. 1;

Fig. 3A bis 3D

schematische Darstellungen von Fluidikstrukturen gemäß einem Ausführungsbeispiel, bei dem die nachgeschalteten Fluidikstrukturen eine Flüssigkeitsaufnahmekammer und eine weitere Kammer aufweisen;

Fig. 4A bis 4D

schematische Darstellungen von Fluidikstrukturen gemäß einem Ausführungsbeispiel, bei dem eine Fluidzwischenkammer in einem Fluidpfad zwischen Flüssigkeits-Haltebereich und nachgeschalteten Fluidikstrukturen angeordnet ist;

Fig. 5A bis 5D

schematische Darstellungen von Fluidikstrukturen gemäß einem Ausführungsbeispiel mit geänderten Anschlusspositionen der Fluidpfade;

Fig. 6

eine schematische Darstellung von Fluidikstrukturen gemäß einem Ausführungsbeispiel mit kaskadierten Strukturen;

Fig. 7A bis 7E

schematische Darstellungen zur Erläuterung der Funktionsweise des Ausführungsbeispiels von Fig. 6;

Fig. 8A bis 8E

schematische Darstellungen von Fluidikstrukturen gemäß einem Ausführungsbeispiel zum unterdruckbasierten Schalten;

Fig. 9

eine schematische Darstellung von Fluidikstrukturen gemäß einem Ausführungsbeispiel mit eine Flüssigkeits-Haltebereich, der zwei Fluidkammern aufweist;

Fig. 10A bis 10D

schematische Darstellungen zur Erläuterung der Funktionsweise des Ausführungsbeispiels von Fig. 9;

Fig. 11A bis 11E

schematische Darstellungen zur Erläuterung der Funktionsweise des Ausführungsbeispiels von Fig. 9 bei Verwendung von zwei Flüssigkeiten;

Fig. 12A und 12B

schematische Seitenansichten zur Erläuterung von Ausführungsbeispielen von Vorrichtungen zum Schalten von Flüssigkeiten; und

Fig. 13A und 13B

schematische Draufsichten von Ausführungsbeispielen von Fluidikmodulen.

Exemplary embodiments are explained in more detail below with reference to the accompanying drawings. Show it:

Fig. 1

a schematic representation of fluidic structures according to an embodiment for overpressure-based switching;

Figures 2A through 2E

schematic representations to explain the mode of operation of the exemplary embodiment from FIG Fig. 1 ;

Figures 3A to 3D

schematic representations of fluidic structures according to an exemplary embodiment in which the downstream fluidic structures have a liquid receiving chamber and a further chamber;

Figures 4A to 4D

schematic representations of fluidic structures according to an exemplary embodiment, in which an intermediate fluid chamber is arranged in a fluid path between the liquid holding area and downstream fluidic structures;

Figures 5A to 5D

schematic representations of fluidic structures according to an exemplary embodiment with changed connection positions of the fluid paths;

Fig. 6

a schematic representation of fluidic structures according to an embodiment with cascaded structures;

Figures 7A through 7E

schematic representations to explain the mode of operation of the exemplary embodiment from FIG Fig. 6 ;

Figures 8A through 8E

schematic representations of fluidic structures according to an embodiment for vacuum-based switching;

Fig. 9

a schematic representation of fluidic structures according to an embodiment with a liquid holding area that has two fluid chambers;

Figures 10A to 10D

schematic representations to explain the mode of operation of the exemplary embodiment from FIG Fig. 9 ;

Figures 11A to 11E

schematic representations to explain the mode of operation of the exemplary embodiment from FIG Fig. 9 when using two liquids;

Figures 12A and 12B

schematic side views to explain exemplary embodiments of devices for switching liquids; and

Figures 13A and 13B

schematic top views of exemplary embodiments of fluidics modules.

Embodiments relate to microfluidic structures for centrifugal-pneumatic switching and methods for centrifugal-pneumatic switching, in particular for centrifugal-pneumatic switching of liquids from a liquid holding area, which can have a first chamber, into subsequent or downstream fluidic structures. Subsequent or subsequent (these terms are used interchangeably herein) fluidic structures are understood here to mean fluidic structures, such as channels or chambers, into which the liquid during handling of the same from preceding or upstream (these terms are used interchangeably herein) fluidic structures got. The microfluidic structures can have a first chamber that is connected to the subsequent fluidic structures via at least two fluid paths, at least the fluid path through which the liquid is transferred when switching into the subsequent fluidic structures is designed in the shape of a siphon. The structures and the method can be designed in such a way that the relevant pressures are given in the direction of or against the filling of the path for the liquid transfer by centrifugal pressures or pneumatic pressures. Switching in which centrifugal pressures and pneumatic pressures dominate other pressures can be referred to as centrifugo-pneumatic switching.

In exemplary embodiments, pneumatic positive pressures and / or negative pressures can be used.

If excess pressures are used, when the first chamber is filled with a liquid, gas is displaced into the subsequent fluidic structures, as a result of which a pneumatic excess pressure is created in them. This pneumatic overpressure can be selected over a wide range by suitable design and, with otherwise unchanged processing conditions, it is decisive for the switching of the liquid necessary rotation frequency (switching frequency). In this case, before the switching process, the centrifugally induced pressure in the first chamber is lower than the pressure necessary to wet the apex of the siphon-shaped channel against the pneumatic overpressure in the subsequent fluidic structures, through which the liquid is transferred into the subsequent fluidic structures during the switching process . This represents a (quasi-static) state of equilibrium. By increasing the rotation frequency of the cartridge above the switching frequency, the centrifugal pressure can be increased via the switching pressure, whereby the siphon is wetted and the transfer of the liquid into the subsequent fluidic structures is initiated. Alternatively or in combination, the hydrostatic height of the liquid can also be increased in order to initiate the liquid transfer, for example by adding additional liquid to the liquid holding area via upstream fluidic structures.

In the case of the use of negative pressure for the switching principle, the following fluidic structures can first be heated in exemplary embodiments, so that a gas contained in them expands and a part of this gas can escape. If, as a result, liquid is transferred into the liquid holding area and the frequency of rotation is increased, the liquid in the fluid connection paths can be at approximately the same radial height as in the liquid holding area. When the temperature is reduced in the subsequent fluidic structures, a negative pressure results which acts in the direction of the subsequent fluidic structures. Since the connecting paths are designed in the shape of a siphon, this increases the hydrostatic height in the connecting paths, so that in this case the centrifugal force counteracts any further filling of the connecting paths. This is the (quasi-static) state of equilibrium under negative pressure conditions. A switching process can then be initiated by further increasing the negative pressure and / or by reducing the centrifugal pressure.

Embodiments represent methods for holding back liquids and triggering the switching process through other changes in the processing conditions together with the associated structures. All structures and methods have in common that during the transfer the second fluid connection between the liquid holding area and downstream fluidic structures can be used to To allow gas to escape from the downstream fluidic structures into the liquid holding area or a fluid chamber of the liquid holding area or to allow it to flow in, whereby the pneumatic pressure difference to the downstream fluidic structures can be reduced.

Some definitions of terms used herein are given below.

The hydrostatic height is to be understood as the radial distance between two points in a centrifugal cartridge if there is a coherent amount of liquid at both points. Under hydrostatic pressure is to be understood the pressure difference induced by centrifugal force between two points due to the hydrostatic height between them. The effective fluidic resistance of a microfluidic structure is to be understood as the quotient of the pressure that drives a fluid through a microfluidic structure and the resulting liquid flow through the microfluidic structure. Aliquoting means dividing a volume of liquid into several separate individual volumes, so-called aliquots.

Metering is the measurement of a defined volume of liquid from a larger volume of liquid. Switching frequency is to be understood as the rotation frequency of a microfluidic cartridge which, when exceeded, starts a transfer process of a liquid from a first structure to a second structure. A siphon channel is understood to mean a microfluidic channel or a section of a microfluidic channel in a centrifugal microfluidic cartridge, in which the inlet and outlet of the channel are at a greater distance from the center of rotation than an intermediate region of the channel. A siphon apex is to be understood as the area of a siphon channel in a microfluidic cartridge with a minimal distance from the center of rotation.

A venting delay resistor is to be understood as the fluidic resistance through which a fluidic structure in which there is a pneumatic differential pressure to the ambient pressure is vented. The fluidic resistance is at least so high that the reduction in the differential pressure by half, taking into account the ventilation through the fluidic resistance, takes at least 0.5 s. This applies at any point during the venting.

If, in exemplary embodiments, a venting delay resistor is provided for the downstream fluidic structures, the time profile of the pressure drop in these fluidic structures can be determined, for example, by filling the liquid holding area with liquid at a constant temperature under centrifugation and the hydrostatic height between an upstream chamber and a fluid chamber, in which the liquid is held in the liquid-holding structures, is recorded in quasi-stationary equilibrium by a suitable camera system (eg with stroboscopic exposure). The pneumatic overpressure in the following structures results from the rotation frequency and the hydrostatic height. The rate of reduction of the overpressure can therefore also be determined from this image information, from which the size of the venting delay resistor results. In other exemplary embodiments, such as switching at negative pressure, the method can be used analogously, in that liquid is filled in at a specific frequency and starting temperature and then a defined rapid cooling is generated. The size of the venting delay resistance results from the developing hydrostatic height in the connecting paths and their degradation rate.

All liquids that are in a quasi-static fluid state change their position within the cartridge in which they are located, as a direct function of the processing conditions. This means that all fluid transport processes between fluidic structures that take place under constant processing conditions are completed. Furthermore, liquid transport processes that are a consequence of changes in processing conditions decrease at any time during the change in processing conditions to their respective half within a maximum of 1s as soon as the change in processing conditions is abruptly stopped.

A liquid guide path is understood to mean a microfluidic structure through which liquid flows from the liquid holding area into one or more subsequent fluidic structures while the method according to the invention is being carried out. A gas routing path is to be understood as a microfluidic structure through which a gas exchange takes place between the subsequent fluidic structures and the liquid holding area while the method according to the invention is being carried out. A liquid absorption volume is to be understood as a microfluidic structure which provides a volume into which liquid is transferred after the switching process according to the invention has been triggered.

A microfluidic cartridge is to be understood here as a device, such as a fluidic module, for example, which has microfluidic structures that enable liquid handling as described herein. A centrifugal microfluidic cartridge is to be understood as meaning a corresponding cartridge that is subjected to rotation can, for example, in the form of a fluidics module that can be inserted into a body of revolution or a body of revolution.

When a fluid channel is referred to herein, a structure is meant whose length dimension from a fluid inlet to a fluid outlet is greater, for example more than 5 times or more than 10 times greater than the dimension or dimensions that define the flow cross section or define. Thus, a fluid channel has a flow resistance for flowing through it from the fluid inlet to the fluid outlet. In contrast, a fluid chamber is a chamber with such dimensions that the flow through the chamber results in a negligible flow resistance compared to connected channels, which can be, for example, 1/100 or 1/1000 of the flow resistance of the channel structure connected to the chamber with the lowest flow resistance .

Before exemplary embodiments of the invention are explained in more detail, it should first be pointed out that examples of the invention can be used in particular in the field of centrifugal microfluidics, which involves the processing of liquids in the picoliter to milliliter range. Correspondingly, the fluidic structures can have suitable dimensions in the micrometer range for handling corresponding liquid volumes. In particular, embodiments of the invention can be used on centrifugal microfluidic systems, such as are known, for example, under the designation “lab-on-a-disk”.

If the term radial is used herein, it is meant in each case radially with respect to the center of rotation about which the fluidics module or the rotating body can be rotated. In the centrifugal field, a radial direction is thus radially sloping away from the center of rotation and a radial direction towards the center of rotation is rising radially. A fluid channel whose start is closer to the center of rotation than its end is therefore radially sloping, while a fluid channel whose start is further away from the center of rotation than its end rises radially. A channel that has a radially rising section thus has directional components that rise radially or run radially inward. It is clear that such a channel does not have to run exactly along a radial line, but can run at an angle to the radial line or in a curved manner.

Referring to the Figures 12A, 12B , 13A and 13B Examples of centrifugal microfluidic systems or fluidic modules are first described, in which the invention can be used.

Figure 12A shows a device with a fluidics module in the form of a rotary body 10, which has a substrate 12 and a cover 14. Figure 13A shows a schematic plan view of the rotary body 10. The substrate 12 and the cover 14 can 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 device 16 on a rotating part 18 of a drive device 20 can be attached. The rotating part 18 is rotatably mounted on a stationary part 22 of the drive device 20. The drive device 20 can be, for example, a conventional centrifuge with an adjustable rotational speed or also a CD or DVD drive. A control device 24 can be provided, which is designed to control the drive device 20 in order to apply rotations at different rotational frequencies to the rotating body 10. The control device 24 can be designed to execute a frequency protocol in order to achieve the functionalities described herein. As is obvious to those skilled in the art, the control device 24 can be implemented, for example, by a suitably programmed computing device, a microprocessor or a user-specific integrated circuit. The control device 24 can also be designed to control the drive device 20 in response to manual input by a user in order to effect the required rotations of the rotating body. In any case, the control device 24 can be configured to control the drive device 20 in order to apply the required rotational frequencies to the fluidics module in order to implement exemplary embodiments of the invention as described herein. A conventional centrifuge with only one direction of rotation can be used as the drive device 20.

The rotational body 10 has the fluidic structures described herein. Corresponding fluidic structures are in Figure 13A indicated purely schematically by trapezoidal areas 28a to 28d. For example, several fluidic structures can be arranged next to one another in the azimuthal direction, as shown in FIG Figure 13A is shown to enable parallel handling of multiple liquids. The fluidic structures can be formed by cavities and channels in the cover 14, the substrate 12 or in the substrate 12 and the cover 14. In exemplary embodiments, fluidic structures can be formed in the substrate 12, for example, while filling openings and ventilation openings are formed in the lid 14. In embodiments, the structured substrate (including filling openings and ventilation openings) is arranged at the top and the cover is arranged at the bottom.

With an alternative in Figure 12B The embodiment shown, fluidic modules 32 are inserted into a rotor 30 and together with the rotor 30 form the rotary body 10. Figure 13B shows schematically a plan view of a corresponding fluidics module. The fluidic modules 32 can each have a substrate and a cover, in which in turn corresponding fluidic structures can be formed. The rotation body 10 formed by the rotor 30 and the fluidics modules 32 can in turn be acted upon by a drive device 20 which is controlled by the control device 24.

In the Figures 12 and 13 is a center of rotation about which the fluidics module or the rotating body can be rotated, denoted by R.

In exemplary embodiments, the fluidic module or the rotary body, which has the fluidic structures, can be formed from any suitable material, for example a plastic such as PMMA (polymethyl methacrylate), PC (polycarbonate), PVC (polyvinyl chloride) or PDMS ( Polydimethylsiloxane), glass or the like. The rotating body 10 can be viewed as a centrifugal microfluidic platform.

As will be explained below, the control device 24 in exemplary embodiments represents an actuating device which can adjust the rotational speed of the drive device in order to initiate the liquid transfer, ie to cause the change in the ratio of the centrifugal pressure to the pneumatic pressure by which the liquid is switched becomes. In exemplary embodiments, the actuating device can additionally have one or more heating devices and / or cooling devices in order to control the temperature of the fluidic structures in order to initiate the liquid transfer. For example, one or more temperature control elements 40 (heating element and / or cooling element) can be integrated into the rotating body, as in FIG Figures 12A and 12B is shown. Alternatively or additionally, 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, for example, be designed to measure the temperature of the environment and thus also to control the fluidics module. The controller can be designed to control the temperature control elements 40, 42, so that in such exemplary embodiments the actuating device can have the controller 24 and the temperature control elements.

Referring to the Figures 1 to 11 In the following, exemplary embodiments of fluidic modules (microfluidic cartridges) and fluidic structures formed therein are described.

Fig. 1 shows schematically fluidic structures formed in a fluidic module 50. The fluidics module 50 is rotatable about a rotation center R. The fluidic structures have a liquid holding area which has a first chamber 52. Upstream fluidic structures are connected to the first chamber 52 and have an upstream chamber 54 which is connected to the first chamber 52 via a radially sloping connecting channel 56. The connecting channel 56 opens into the first chamber 52 in a radially outer region 57, for example the radially outer end. The first chamber can be filled centrifugally via the upstream chamber and the connecting channel 56. It should be noted at this point that the first chamber can also be filled in a different way than centrifugally, the fluidics module only being subjected to rotation after filling in order to achieve equilibrium between centrifugal pressure and pneumatic pressure.

The fluidics module 50 furthermore has downstream fluidics structures which have a fluid chamber 58 as the fluid receiving volume, and two fluid paths 60, 62 which fluidically connect the first chamber 52 to the fluid chamber 58. The fluid path 62 has a siphon channel, the siphon apex 64 of which lies radially inside 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 can be vented via a venting delay resistor 66 which satisfies the above definition. Such a venting delay resistor 66 can optionally be provided in all of the exemplary embodiments described herein, without each having to be mentioned separately.

In the exemplary embodiment shown, the first fluid path 60 between the first chamber 52 and the subsequent fluidic structure 58 consists of a channel that runs 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 58, for example to the radially innermost point 70 of the subsequent fluid chamber 58. 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 area, for example at the radially outermost point 72, and leads via the siphon apex 64 to a radially outer area, for example the radial outermost point 74, the subsequent fluid chamber 58.

There is a radial gradient between the respective opening of the two fluid paths 60 and 62 into the first fluid chamber 52 and the respective opening into 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 area. This introduction can take place by a centrifugally induced transfer of a liquid into the first chamber 52. Subsequently, the fluid can be retained in the fluid holding area, for example the first chamber 52, induced by centrifugal pneumatics. The liquid can then be switched into the downstream fluidic structures, for example the downstream fluid chamber 58. During the switching process, at least one fluid path (e.g. fluid path 62) transfers at least part of the liquid from the liquid holding area (e.g. first chamber 52) into the subsequent fluidic structures (e.g. fluid chamber 58). Fluid paths through which liquid is transferred during the switching process are referred to below as liquid guiding paths. Through at least one further fluid path (e.g. fluid path 62) between the liquid holding area (e.g. first chamber 52) and the subsequent fluid structures (e.g. fluid chamber 58), gas (usually air) from the subsequent fluid structures can be returned to the liquid during the switching process. Holding area can be transferred. Fluid paths that allow this are called gas routing paths below.

An exemplary embodiment of such a method is described below on the basis of the operation of the in Fig. 1 fluidic module 50 shown referring to FIGS Figures 2A to 2E described. The Figures 2A to 2E show fluidic operating states of the in Fig. 1 embodiment shown during the implementation of the method. For the sake of clarity, the respective reference symbols of the fluidic structures are in FIG Figures 2A to 2E omitted.

In a first state, which in Figure 2A As shown, there is liquid 80 in the chamber 54 upstream of the first chamber 52 and in the connecting channel 56 between the upstream chamber 54 and the first chamber 52. Part of the upstream chamber 54 is located radially closer to the center of rotation R than the siphon apex 64 of the fluid guide channel . The liquid can be introduced into the upstream chamber 54 and the connecting channel 56, for example, via an inlet opening or via further upstream fluidic structures. The introduced liquid 80 traps an air volume in the first chamber 52, the fluid paths 60 and 62 and the downstream fluid chamber 58 that is not vented (or is only vented via a venting delay resistor). In other words, the fluid path 60, which represents a ventilation channel, is also closed to the atmosphere by the liquid 80 located in the liquid holding area.

As in Figure 2B is shown, the liquid 80 is subsequently transferred centrifugally induced from the upstream chamber 54 into the first chamber 52, the gas being compressed in the first chamber 52, the subsequent fluid structures 58 and the connecting paths 60, 62, since the first chamber 52 in is not vented in this operating state or is only vented via a venting delay resistor. The upstream chamber 54 can be vented so that atmospheric pressure p ₀ can prevail in the same. In this case, gas is preferably transferred into the subsequent fluid structures 58 via the gas guide path 60. The fluid paths 60, 62 between 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, the liquid guide path 62 can also be filled with liquid, but not up to the siphon apex 64.

The pneumatic overpressure Δp that builds up 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 siphon apex 64 in the fluid guide channel 62 is not wetted and the liquid that is located in the first chamber 52 and in the chamber 54 upstream of the first chamber 52, is retained. Thus, these fluidic structures represent a liquid holding area.

1. 1) der Flüssigkeitstransfer in die erste Kammer 52 die hydrostatischen Höhe zwischen vorgeschalteter Kammer 54 und erster Kammer 52 verringert, wodurch sich der in Richtung der Befüllung der ersten Kammer 52 wirkende Zentrifugaldruck verringert, und
2. 2) gleichzeitig der pneumatische Überdruck in den nachfolgenden Fluidikstrukturen mit fortschreitender Befüllung der ersten Kammer 52 steigt,

so dass sich bei einer geeigneten Rotationsfrequenz der Kartusche ein Gleichgewicht zwischen den in Richtung der Befüllung des Flüssigkeitsführungspfads 62 wirkenden Drücken und den der Befüllung des Flüssigkeitsführungspfads entgegenwirkenden Drücken einstellt. Die entsprechende geeignete Rotationsfrequenz kann ohne weiteres abhängig von den verwendeten Geometrien und Flüssigkeitsmengen ermittelt werden.Holding the liquid in the liquid holding area is achieved by

1. 1) the liquid transfer into the first chamber 52 reduces the hydrostatic height between the upstream chamber 54 and the first chamber 52, as a result of which the centrifugal pressure acting in the direction of filling the first chamber 52 is reduced, and
2. 2) at the same time the pneumatic overpressure in the subsequent fluidic structures increases as the first chamber 52 is filled,

so that at a suitable rotation frequency of the cartridge, an equilibrium is established between the pressures acting in the direction of filling the liquid guiding path 62 and the pressures counteracting the filling of the liquid guiding path. The corresponding suitable rotation frequency can easily be determined as a function of the geometries and amounts of liquid used.

In all the exemplary embodiments described herein, with a suitable choice of the geometries of the chambers and the fluid guide channel, it can be achieved that centrifugal pressure and pneumatic overpressure dominate over other pressure sources such as capillary pressure, taking into account any fluid properties and cartridge material properties. This means that these other pressure sources are not able to cause a switching process-triggering deviation from the filling state of the liquid guide path, which results from the sole consideration of the balance of pneumatic overpressure and centrifugal pressure. This equilibrium is also achieved within the meaning of the invention if the pressures involved are continuously varied by slight, targeted variations in the processing conditions, whereby the qualitative state of retention of the liquid in the liquid holding area (e.g. the first chamber) is not abandoned. In other words, while maintaining the liquid in a quasi-stationary equilibrium, a slight variation in the processing conditions can take place without triggering the switching process.

1. 1) die Rotationsfrequenz erhöht wird oder
2. 2) die hydrostatische Höhe durch Hinzufügen von Flüssigkeit in den vorausgehenden Fluidikstrukturen vergrößert wird.

Based on the in Figure 2B The switching process can be achieved by increasing the centrifugal pressure above the switching frequency or the centrifugal switching pressure. This can be achieved, for example, by

1. 1) the rotation frequency is increased or
2. 2) the hydrostatic head is increased by adding liquid in the preceding fluidic structures.

By increasing the centrifugal pressure, more liquid is transferred from the chamber 54 upstream of the first chamber 52 into the first chamber, so that the fill level in the first chamber 52 and the liquid guide path 62 increases and the siphon apex 64 of the fluid guide channel 62 is filled, as in FIG Figure 2C is shown.

Alternatively, the switching process can be achieved by reducing the pneumatic overpressure in the subsequent fluidic structures, so that while the rotational frequency remains the same, fluid is pneumatically induced from the upstream chamber 54 and transferred to the first chamber 52, thereby filling the siphon apex 64 of the fluid guide path 62. The reduction in the pneumatic overpressure can be achieved, for example, 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 achieved via a venting delay resistor, for example the one in Fig. 1 vent delay resistor 66 shown.

As a result of one of the described switching-triggering process condition changes or a combination thereof, the radially outwardly extending part of the siphon-shaped channel 64 in the liquid guide path 62 is filled, as a result of which the hydrostatic height in this channel increases. The centrifugal pressure resulting from the hydrostatic height between the first chamber 52 and subsequent fluidic structures leads to the transfer of liquid from the first chamber 52 into the subsequent fluidic structures, as in FIG Figures 2C to 2E is shown.

During the liquid transfer, gas is transferred from the subsequent fluidic structures via the at least one gas guide path 60 into the first chamber 52, which counteracts the build-up of additional pneumatic overpressure as a result of the liquid transfer into the subsequent fluidic structures, see Figure 2D . As a result, a complete transfer of the liquid from the first chamber 52 into the subsequent fluidic structures can be achieved at a fixed rotational frequency above the switching frequency, as in FIG Figure 2E is shown. After the complete transfer of the liquid into the downstream fluid chamber, the fluidic structures can be at atmospheric pressure po.

The switching pressure and the associated rotation frequency of the cartridge (switching frequency) can be selected over a wide range by suitable selection of the positions and geometries of the chambers and the fluid guide paths.

Further exemplary embodiments are explained in more detail below. Because of the dependencies between structure and method, the special features and the special features of the method resulting from the features are specified together for the exemplary embodiments. Where parts of the description would be repeated in the description of the various exemplary embodiments, these are partially omitted so that parts of the description can apply across all exemplary embodiments. Although the described exemplary embodiments in each case show only one fluid path between the preceding fluidic structures and the first chamber and only one liquid guide path and one gas guide path between the first chamber and the subsequent fluidic structures, this does not mean any restriction of the number of possible connection paths between the fluidic structures and only serves to simplify the Description of the exemplary embodiments.

Figure 3A shows schematically an embodiment of fluidic structures of a fluidic module 50, in which in the quasi-steady state of equilibrium, the in Figure 3B As shown, the complete first fluid chamber 52 is filled with liquid 80.

The in Figure 3A The embodiment shown, both the liquid guide path 62 and the gas guide path 60 have a siphon-shaped channel. Again, an upstream chamber 54 is fluidically connected to the first chamber 52 via a connecting channel 56 which opens into a radially outer end 90 of the upstream chamber 54. The liquid guide path 62 and the gas guide path 60 can as in the case of reference Fig. 1 The embodiment described open into the first chamber 52 and the downstream chamber 58. The siphon apex 64 of the liquid guide path 62 is arranged radially inside the radially innermost point of the first chamber, and a siphon apex 92 of the siphon channel of the gas guide path 60 can preferably lie radially inside the siphon apex 64 of the liquid guide path 62. In this exemplary embodiment, the following fluidic structures have, in addition to the downstream fluid chamber 58, which represents a liquid holding volume or a liquid holding chamber, a further, separate volume 94. The connection point of the gas guiding path 60 to the liquid receiving volume 58 (in the embodiment shown, the radially innermost The point of the liquid absorption volume 58) can preferably be located closer to the center of rotation R of the cartridge than the radially outermost point of the liquid absorption volume 58, which means that the connection point 70 of the gas guide path 60 is wetted with the liquid 80 transferred during the switching process under the influence of the prevailing during the transfer Can prevent centrifugal force. The optional volume 94 separated from the liquid absorption volume 52 increases the volume of the subsequent fluidic structures in a targeted manner, whereby the pneumatic overpressure in the subsequent fluidic structures can be reduced when the method according to the invention is carried out. In the exemplary embodiment shown, the additional volume 94 is coupled to the gas guide path 60 via a fluid path 96. The fluid path 96 opens into the gas guide path 60 at an opening point 98 and into the additional volume 94 at an opening point 100.

The one in the Figures 3A to 3D In the exemplary embodiment shown, the preceding fluidic structures have 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 by the fluid path 56, the connection point 90 of which to the upstream chamber 54 is closer to the center of rotation R. of the cartridge lies as the apex of the siphon 64 in the liquid guide path 62. In alternative exemplary embodiments, the volume of the chamber 54 can also be greater than the volume of the first chamber 52. Again, the chamber 54 may be vented and at atmospheric pressure. The connection point 57 of the fluid connection path 56 between the preceding chamber 54 and first chamber 52 can be at any point in the first chamber 52 and does not have to be arranged in a radially outer region thereof.

That in the Figures 3A to 3D The embodiment shown of a pneumatic counter-pressure siphon valve is designed for compressing the full volume of the first chamber. Figure 3B shows an operating state in which there is an equilibrium between the pneumatic overpressure in the subsequent fluidic structures and the pressures in the direction of the filling of the subsequent fluidic structures. Figure 3C shows an operating state in which the liquid is transferred from the first chamber into the subsequent fluidic structures, and Figure 3D an operating state after the liquid transfer is complete.

During operation, liquid 80 is introduced into first fluid chamber 52 via the upstream fluidic structures. The fluidic structures are designed in such a way that the first Fluid chamber 52 is completely filled with the liquid 80. The liquid introduced traps a gas volume in the downstream fluidic structures. In Figure 3B the corresponding state is shown in which the liquid 80 is retained in the first chamber 52. The cartridge or the fluidics module can be in rotation with a rotation frequency ω ₁ . There is liquid in the chamber 54 of the preceding fluidic structures, the first fluid chamber 52 and the radially inwardly extending sections of the liquid guide path 62 and the gas guide path 60. Due to the hydrostatic height difference between the liquid meniscus in the preceding fluidic structures and meniscuses 102, 104 in the fluid communication paths 60 and 62, a centrifugal pressure acts in the direction of the filling of the fluid connection paths 60 and 62. The pressures that counteract the filling of the siphon at a greater radial distance from the center of rotation R (i.e. the siphon in the liquid guide path 62) (pneumatic overpressure Δp and possibly others such as pressures , e.g. capillary pressure) are in equilibrium with the pressures which act in the direction of the filling of this siphon (centrifugal pressure and possibly others). As a result, the liquid is in a quasi-stationary equilibrium.

The position of the liquid menisci 102, 104 in the fluid connection paths 60, 62 means that the structure described can be used to measure the amount of liquid in the first chamber 52 and the fluid connection paths, with a high level of accuracy of the measured volume being able to be achieved.

Based on the in Figure 3B The state shown can be filled by increasing the rotation frequency to a value> ω ₁ , which leads to an increase in the centrifugal pressure in the direction of the subsequent fluidic structures, or by reducing the counterpressure in the subsequent fluidic structures, the siphon apex 64 of the liquid guide path 62. The liquid can then be transferred from the first chamber 52 into the liquid holding volume 58 by the acting centrifugal force, as in FIG Figure 3C is shown. During this process, the gas is transferred from the liquid holding chamber 58 via the gas guide path 60 into the first chamber 52, as a result of which an increase in the pneumatic overpressure in the liquid holding chamber 58 is counteracted. During this liquid transfer, the gas volume initially remains enclosed in the downstream fluidic structures and the first chamber, so that a pneumatic overpressure Δp prevails in each of these, as in FIG Figure 3C is indicated. After the liquid transfer is complete, the pneumatic overpressure of the subsequent fluidic structures and is balanced the first chamber with the preceding fluidic structures via the connecting channel 56 instead. After the liquid transfer, the fluidic structures are at atmospheric pressure po, as in Figure 3D is shown.

In the following, reference is made to the Figures 4A to 4D an embodiment is described in which a compression chamber volume is provided in the gas guide path.

Figure 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 can in turn be provided with an upstream chamber (in Figure 4A not shown) be fluidically coupled. Thus, in turn, a fluidic connection to preceding fluidic structures can be provided by the channel 110, the connection point of which to the first fluid chamber 52 lies radially inside the siphon apex 64 of the liquid guiding path 62. Downstream fluidic structures are in turn formed by downstream fluid chamber 58, which represents a liquid receiving chamber.

The liquid receiving chamber 58 is connected to the gas guide path 60 at an opening point. The orifice point is preferably not at the radially outermost position of the liquid receiving chamber 58, for example in a radially inner region thereof or at the radially innermost position 70. The liquid receiving chamber 58 is also fluidly connected to the liquid guide path 62, preferably radially outside the connection position 72 between the liquid guide path 62 and the first fluid chamber 52. The liquid guiding path 62 can open into the liquid receiving chamber 58 at a radially outer position, for example at the radially outermost position 74.

The in Figure 4A The embodiment shown, the liquid intake path 62 opens in a radially outer region, for example the radially outermost position 72, into the first fluid chamber 52, and the gas guide path 60 also opens out in a radially outer position, for example the radially outermost position 116 of FIG Figure 4A left area of the first fluid chamber 52, into the first fluid chamber 52. The gas guide 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 that too can be referred to as a partial compression chamber, is arranged in the radially rising part of the siphon channel of the gas guide path 60, the gas guide path 60 opening into the partial compression chamber 112 at opening 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 apex 64 of the liquid guide path 62. The partial compression chamber 112 can be connected to the first fluid chamber 52 by part of the gas guide path 60, the connection point at which this part of the gas guide path in the partial compression chamber 112 opens, preferably radially further away from the center of rotation than the siphon vertex 64 of the fluid guide path 62. The orifice point 120 can then be connected to the downstream fluidic structures via the siphon channel of the gas guide path 60, which has the siphon vertex 92.

An embodiment of a method according to the invention using fluidic structures as shown in Figure 4A now referring to FIG Figures 4B to 4D described. First, centrifugally induced liquid can be transferred from previously connected fluidic structures (not shown) via the inlet channel 110 into the first fluid chamber 52. Under the influence of the centrifugal force, the liquid 80 fills the first chamber from the radially outer side in the direction of the radially inner side. As a result, the fluid paths 60 and 62, which connect the first fluid chamber 52 with the downstream fluidic structures, for example the downstream fluid chamber 58, are filled and gas (usually air) is enclosed by the liquid 80 in the downstream fluidic structures and the fluid connection paths 60 and 62 . Due to the increase in the hydrostatic height between the liquid meniscus 122 in the first fluid chamber 52 and the meniscuses 102, 104 in the fluid connection paths 60 and 62, liquid is transferred under the influence of the centrifugal force into the partial compression chamber 112, whereby the gas present in this is transferred into the subsequent fluidic structures is displaced. As a result, a pneumatic overpressure Δp is generated in these, which counteracts any further filling of the fluid connection paths 60 and 62. An equilibrium is established between the pressures in the direction of 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 is radially inside the siphon apex 64 of the liquid guide path 62 lies. This operating state is in Figure 4B shown. The liquid 80 encloses a gas volume in the fluid paths 60, 62 and the downstream fluidic structures 58, in which the pneumatic overpressure Δp is generated. Since the first Fluid chamber 52 is vented, the area of the first fluid chamber 52 is located above the liquid meniscus 122 at atmospheric pressure po.

Through a suitable selection of the partial compression volume 112 and the volumes of the downstream fluidic structures, the pneumatic overpressure Δp that prevails in equilibrium in the downstream fluidic structures can be largely freely selected.

By increasing the rotation frequency, starting from the in Figure 4B The operating state shown, the centrifugal pressure can be increased in the direction of filling the liquid guide path 62, whereby the siphon apex 64 of the liquid guide path 62 is filled and a centrifugally induced transfer of the liquid into the subsequent fluidic structures 58 is set in motion. In exemplary embodiments, the partial compression chamber 112 has a smaller liquid volume than the first fluid chamber 52. Due to the liquid transfer from the first fluid chamber 52 into the downstream fluidic structures via the liquid guide path 62, an additional pneumatic overpressure is built up in the enclosed volume of the downstream fluid structures, which leads to a transfer of the Liquid leads from the partial compression chamber 112 into the first fluid chamber 52. As soon as the pneumatic overpressure Δp in the downstream fluidic structures exceeds the hydrostatic pressure that acts on the gas guide path 60 in the first fluid chamber 52, gas is transferred from the subsequent fluidic structures 58 via the gas guide path 60 into the first fluid chamber 52 and through the liquid, this being Operating status in Figure 4C is shown. The operating state after the liquid transfer is complete is in Figure 4D shown.

Referring to the Figures 5A to 5D An embodiment with connection position variations of the fluid paths will now be described. In the Figure 5A The fluidic structures shown demonstrate a possible selection of possible variations in the selection of the connection positions between the first fluid chamber 52 and the fluid connection paths 60 and 62, as well as in the design of the gas guide path 60 and the connections between the fluid connection paths 60 and 62 and the downstream fluidic structures 58.

In exemplary embodiments, the connection position 130 between the preceding fluidic structures (for example the inlet channel 110 and the upstream fluid chamber 54) and the first fluid chamber 52 can be at a freely selectable position of the first fluid chamber 52. The same applies to connection positions 132, 134 of the connection paths 60, 62 between the first fluid chamber 52 and subsequent fluidic structures 58 to the first fluid chamber 52. In the event that a partial compression chamber 112 is present in the gas guide path 60, 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 opening point 136 of the gas guide path 60 into the downstream fluid chamber 58, that is to say the target liquid volume, is preferably not at the radially outermost position of the target liquid volume. Furthermore, the connection position 138 of the liquid guide path 62 into the downstream fluid chamber 58 can be freely selected. The connection position 134 is preferably in a radially outer region of the first fluid chamber 52, since the first fluid chamber 52 can only be emptied up to this connection position above the liquid guide path 62.

Based on Figures 5B to 5D an embodiment of a method according to the invention based on the operation using the in Figure 5A illustrated fluidic structures explained. First, liquid from the upstream fluidic structures, for example the upstream chamber 54, is centrifugally induced and transferred into the first fluid chamber 52 and the fluid connection paths 60 and 62 connected to it. The filling level of the first fluid chamber 52 rises continuously in the radial direction from the radially outermost point of the same to positions lying further radially inward. During the filling process, the gas in the first fluid chamber 52 is displaced by the inflowing liquid 80, as a result of which gas is transferred into the connections of the fluid connection paths 60, 62 between the first fluid chamber 52 and the downstream fluidic structures that are not yet wetted by the liquid. This results in a pressure equalization between the first fluid chamber 52 and the subsequent fluidic structures during the filling process of the first fluid chamber 52, as long as the filling level in the first fluid chamber 52 lies radially outside the radially most inner connection point.

As in Figure 5A is shown, the connection position 134 of the liquid guide path 62 to the first fluid chamber 52 can be closer to the center of rotation R than the connection position 132 of the gas guide path 60. Furthermore, more liquid can 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 connection point located radially further inwards (the connection point 134 in the case of the in Figure 5A shown embodiment) can be included. In this case, the first fluid chamber 52 can also be designed without further vents, so that a pneumatic overpressure Δp _{1 can} build up in the gas volume enclosed by the liquid 80 with the continued transfer of liquid from the upstream fluidic structures into the first fluid chamber 52, which does not is identical to the pneumatic overpressure Δp in the following fluidic structures. During the filling of the first fluid chamber 52, the partial compression chamber 112 in the gas guide path 60 can furthermore be filled with liquid, as a result of which gas is transferred into the subsequent fluidic structures. By choosing the connection point 120 of the fluid path 60 between the partial compression chamber 112 and the downstream fluidic structures 58 at a position that is radially outside the innermost point of the partial compression chamber 112, a compression of gas in the partial compression chamber can be achieved in the first fluid chamber in a manner analogous to the processes described 112 occur as soon as the fill level of the liquid in the partial compression chamber 112 lies radially inside the radially innermost connection point to the partial compression chamber 112.

By appropriately filling the liquid holding area, which has the first chamber 52 and the partial compression chamber 112, a state of equilibrium can be achieved in which the meniscus 104 of the liquid is located in the radially inwardly extending area of the siphon-shaped area of the liquid guide path 62, and the pressures acting in the direction of wetting of the siphon apex 64 (centrifugal pressure and possibly other pressures, such as the overpressure Δp ₁ ) are in equilibrium with the pressures acting against wetting (the pneumatic overpressure in the subsequent fluidic structures and possibly other pressures). This operating state is in Figure 5B shown.

Based on the in Figure 5B analogous to the description above, by increasing the centrifugal pressure or reducing the pneumatic counterpressure, wetting of the siphon apex 64 of the liquid guide path 62 can be achieved, as a result of which a liquid transfer from the first fluid chamber 52 into the liquid target volume 58 of the downstream fluidic structures is initiated. As a result, the level in the first fluid chamber 52 can drop below the connection point 130 of the inlet channel 110 in the first fluid chamber 52, so that the first fluid chamber 52 is vented to atmospheric pressure p ₀ . As referring to that in the above Figures 4A to 4D described embodiment has been set out, as soon as the pneumatic overpressure in the downstream fluidic structures exceeds the hydrostatic Pressure, which acts in the first fluid chamber 52 on the gas guide path 60, gas from the subsequent fluidic structures are transferred via the gas guide path into the first fluid chamber and through the liquid, this operating state in turn in Figure 5C is shown.

After the in the Figures 5A to 5D The embodiment shown, the connection point 134 between the liquid guide path 62 and the first fluid chamber 52 lies radially inside the radially outermost point of the first fluid chamber 52, the transfer can stop as soon as the liquid meniscus 122 in the first fluid chamber 52 reaches the radial position of the connection point 134. As in Figure 5D is shown, lead to liquid remaining in the first fluid chamber 52, which results in the possibility of mixing the same fluidic structures with different liquids in the first fluid chamber 52 by using the same fluidic structures several times. This can also be used to generate dilution series if, in a first step, a volume of a liquid to be diluted, defined by the fluidic structure, remains in the first fluid chamber after the transfer step and, in subsequent steps, the liquid used for dilution is passed through the preceding fluidic structures into the first fluid chamber is transferred and mixed with the liquid to be diluted. For this purpose, the downstream fluidic structures can be provided by cascading the structures described, that is to say by instances of the structure described being offset radially outward.

Fig. 6 FIG. 11 shows an exemplary embodiment of cascaded fluidic structures in a fluidic module 50. The cascaded fluidic structures essentially represent a combination of those referring to FIG Figures 3A to 3D and 4A to 4D The construction of the upstream fluid chamber 54, the connecting channel 56, the first fluid chamber 52, the gas guide path 60, the liquid guide path 62 and the downstream fluid chamber 58 corresponds to that referring to FIG Figures 3A to 3D described structure of the corresponding structures. These elements form the in Fig. 6 cascaded fluidic structures shown a first switching structure. A gas guide path 160, a liquid guide path 162 and a further downstream fluid chamber 158 form a second switching structure. As in Fig. 6 As shown, a vent 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 112 and the liquid guide path 162 can be substantially the same as the structure of the gas guide path 60, the intermediate compression chamber 112, and the gas guide path 62 correspond to those referring to FIG Figure 4A have been described. As in Fig. 6 As shown, the liquid guiding 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 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 inner region, for example the radially innermost position. The fluid paths 160 and 162 overall have a radial gradient, that is to say the opening of the same into the fluid chamber 158 lies radially further outward than the opening of the same into the fluid chamber 58.

In the Fig. 6 The fluidic structures shown thus represent two cascaded switching structures, the fluid chamber 58 representing a downstream fluidic structure for the first switching structure and representing a liquid holding area for the second switching structure. Referring to the Figures 7A to 7E an embodiment of a method according to the invention for cascaded switching of liquids is described below. The Figures 7A through 7E FIG. 10 shows an illustration of the fluidic processes during the method for cascading liquids using the vent delay resistor 66. Figure 7A shows liquid 80 in the first fluid chamber 52 of the first switching structure. Figure 7B shows a liquid transfer into the liquid target chamber 58 of the first switching structure, which at the same time represents the first fluid chamber of the second switching structure. Figure 7C shows the final state of the first switching process, which at the same time represents the equilibrium state before the initiation of the second switching process. Figure 7D Figure 12 shows the transfer of the liquid into the liquid target chamber 158 of the second switching structure. Figure 7E shows the final state after completion of the second liquid transfer.

When referring to the Figures 7A through 7E A second switching operation can be implemented due to the presence of a development delay resistor.

First, in a manner analogous to the method described above, liquid is centrifugally induced and transferred into the first fluid chamber 52 and the fluid connection paths 60, 62 and the gas present in these is displaced into the subsequent fluidic structures, whereby a pneumatic overpressure arises in these, which counteracts the further filling and thus the wetting of the siphon apex 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. After the first fluid chamber 52 has preferably been completely filled with liquid, the in Figure 7A shown quasi-static state reached. The pressures acting in the direction of wetting of the siphon apex 64 of the liquid guiding path 62 are in quasi-static equilibrium with the pressures counteracting this wetting, the pneumatic overpressure in the downstream fluidic structures slowly reducing via the venting delay resistor 66. As a result, the wetting of the siphon apex 64 of the liquid guide path 62 and, associated with this, the initiation of the transfer process into the downstream fluid chamber 58, i.e. the first target liquid volume, can be achieved with a constant or also decreasing rotational frequency due to the reduction in the pneumatic counter pressure. This operating state is in Figure 7B shown. Alternatively or in combination, the other process condition changes that are described herein for initiating the switching process can also be used, for example an increase in the rotation frequency or a reduction in the pneumatic overpressure, for example by reducing the temperature.

During the first transfer process, as above with reference to the Figures 3A to 3D has been described, gas is vented via the gas guide path 60 through the first fluid chamber 52. During this first transfer process, overpressure still present from the first gas displacement process can be partially retained in the subsequent fluidic structures of the second switching structure, since complete venting does not have to occur during the transfer. This is in Figure 7C represented by the pneumatic overpressure Δp remaining in the downstream fluid chamber 158. In the context of the centrifugally induced first transfer process, analogous to the above with reference to the Figures 4A to 4D processes described, the first fluid chamber of the second switching structure, i.e. the fluid chamber 58, and the partial compression chamber 112 of the second gas guide path 160 are filled with liquid and the gas previously contained therein is displaced into the downstream fluidic structures 158. The pneumatic overpressure Δp that builds up leads to the in Figure 7C shown quasi-static state in which the wetting of the siphon apex 164 of the liquid guide path 162 counteracting pressures are in quasi-static equilibrium with the pressures acting in the direction of wetting. Because of the continuous slow venting of the pneumatic overpressure in the subsequent fluidic structures 158 of the second switching structure (due to the venting delay resistor 66), the wetting of the siphon apex 164 of the liquid guide path 162 can in turn be achieved at a constant or decreasing rotational frequency, whereby the second liquid transfer into the downstream fluid chamber 158, that is, the liquid target structure of the second switching structure can be achieved. During this liquid transfer, gas can be vented from the fluid chamber 158 via the gas guide path 160 into the fluid chamber 58. The operating state of the liquid transfer is in Figure 7D shown. The operating state after completion of the second liquid transfer into the liquid chamber 158 is shown in Figure 10E.

Referring to the Figures 6 through 7E an exemplary embodiment for cascaded switching structures has thus been described. There is no need for a separate explanation that other of the exemplary embodiments described herein can also be cascaded, it being possible in each case for all process condition changes described herein to be used to initiate the respective switching process. Although, in the example described, a cascaded structure using a venting delay resistor is described as an actuator, this is not required.

In general, according to the invention, a liquid transfer is effected by changing the ratio of the centrifugal pressure to the pneumatic pressure. This ratio can be changed in different ways. In exemplary embodiments, the ratio can be changed by increasing a rotation speed of the fluidics module. For this purpose, for example, a drive device, by means of which the fluidics module is set in rotation, can be controlled accordingly by means of a corresponding control device. Alternatively or additionally it is possible to reduce the pneumatic pressure in order to change the ratio. To this end, a vent delay resistor can be provided which can be viewed as an actuator designed to reduce the pneumatic pressure. Alternatively or in combination, the pneumatic pressure can be reduced by controlling, in particular reducing, the temperature of the enclosed gas volume. This can be done by appropriately controlling either the temperature of the entire fluidics module or at least parts of the fluidics module in which the gas volume is enclosed. For this purpose, as above reference taking on the Figures 12A and 12B has been described, temperature control elements may be provided. Alternatively or in combination, the pneumatic pressure can be reduced by increasing the volume of the downstream fluidic structures. For example, the downstream fluidic structures can have one or more fluid chambers, the volume of which is adjustable.

Referring to the Figures 8A through 8E an exemplary embodiment is described below in which a negative pressure is used in the downstream fluidic structures, ie a reduction in the pressure in the downstream fluidic structures below the ambient pressure. In such embodiments, switching can take place using temperature and / or centrifugal pressure changes.

As already described, a temperature-controlled reduction in pressure in the subsequent fluidic structures, which is used to initiate the transfer of liquid from the first fluid chamber into the target liquid volume, can be achieved by reducing the temperature of the gas in the subsequent fluidic structures.

As in Figure 8A As shown, the fluidic structures formed in a fluidic module 50 have an inlet channel 200 which connects a first fluid chamber 202 to preceding fluidic structures (not shown). The first fluid chamber 202 can 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 apex 212. In the exemplary embodiment shown, the second fluid path 208 also has a siphon channel, the siphon apex 214 of which is arranged radially further inward than the siphon apex 212 of the first fluid path 206. The first fluid path 206 represents a liquid guide path, and the second fluid path 214 represents 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 area, preferably at the radially outermost position. The gas guide path 208 is connected to the first fluid chamber 202 in a region which is wetted with liquid when the first fluid chamber 202 is filled. Such a filling of the first fluid chamber can be induced centrifugally via the inlet channel 200. Possible positions for the openings of the fluid paths 206 and 208 into the first fluid chamber 202 result from the chamber geometry and the amounts of liquid used in the context of the method. The Siphon vertex 212 of the liquid guide path 206 is preferably located radially inside the position which is reached during operation through the meniscus of the liquid in the first fluid chamber, in particular during a first processing step, while the liquid in the first fluid chamber 202, which represents a liquid holding area, is held. As in Figure 8A As shown, the gas guide path 208 can open into the downstream fluidic structures 210 in a radially inner region, and the liquid guide path 206 can open into the downstream fluidic structures 210 in a radially outer region.

In the Figure 8A The fluidic structures shown represent fluidic structures for vacuum-based centrifugal-pneumatic venting siphon valve switching, as can be seen from the following description of an embodiment of a method according to the invention using the in Figure 8A fluidic structures shown becomes clear.

In a first step, liquid from upstream fluidic structures (not shown) is centrifugally induced and transferred through the inlet channel 200 into the first fluid chamber 202. In the process, liquid is also transferred into the radially inwardly extending regions of the siphon-shaped connecting paths 206, 208 between the first fluid chamber 202 and the subsequent fluidic structures 210. From the point in time at which the connection point of the last of the connection paths 206, 208 is wetted, the further liquid flowing into the connection paths displaces the gas contained in the connection paths into the downstream fluidic structures, which results in an overpressure in the subsequent fluidic structures at a constant temperature, as in Figure 8B is shown. This overpressure as the difference to atmospheric pressure can be a small fraction of the atmospheric pressure, so that a negligible overpressure results during the introduction.

Based on the in Figure 8B With a preferably constant rotation speed, the following fluidic structures 210 can be cooled, for example by reducing the ambient temperature or by cooling elements in contact with the cartridge, which results in a negative pressure in the following fluidic structures, as shown in FIG Figure 8C is indicated. As a result, depending on the processing conditions (e.g. rotation frequency, geometry of the chambers and channels, start and end temperature in the subsequent fluidic structures, etc.), a new hydrostatic height arises between the menisci 102, 104 in the fluid connection paths 206, 208 and the Meniscus 122 of the fluid in the first fluid chamber 202, which leads to a new equilibrium between the pressures in the direction of the filling of the siphon apex 212 of the liquid guide path 206 (in this exemplary embodiment the pneumatic negative pressure in the subsequent fluidic structures and possibly other subordinate pressures) and the pressures against this filling (at In this exemplary embodiment, the centrifugal pressure due to the hydrostatic head and possibly other subordinate pressures) leads, as in Figure 8C is shown. Starting from the operating state present under these process conditions, 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 and thus a transfer of the liquid from the first fluid chamber 202 into the downstream fluidic structures 210. Alternatively or in addition, liquid can also be fed into the fluid chamber 202 in order to wet the top of the siphon, wherein the fill level can be raised above the top of the siphon. As part of the liquid transfer, the transferred liquid can lead to a compression of the gas present in the downstream fluidic structures 210, so that an overpressure can arise in it, 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 in Figure 8D is shown. In the following, the first fluid chamber 202 empties completely into the downstream fluidic structures via the liquid guide path 206, as in FIG Figure 8E is shown.

In the exemplary embodiments described so far, the liquid holding area has a first fluid chamber. In alternative exemplary embodiments, the liquid holding area can have a plurality of fluid chambers, which may or may not be connected via one or more fluid channels.

An exemplary embodiment in which the liquid holding area has a plurality of fluid chambers and in which switching can take place by means of temperature-controlled pressure reduction is described below with reference to FIG Fig. 9 explained.

Corresponding fluidic structures are again formed in a fluidic module 50. The fluidic structures have upstream fluidic structures, a liquid holding area and downstream fluidic structures. The liquid holding area has a first fluid chamber 300 and a second fluid chamber 302. The first fluid chamber 300 and the second fluid chamber 302 are fluidically connected via a radially sloping connection channel 304. The upstream fluidic structures have an upstream fluid chamber 306 which, in a region thereof which is radially outer with respect to a rotation center R, can have chamber segments 306a and 306b which enable liquid volumes to be measured. The chamber segment 306a is fluidically connected to the first fluid chamber 300 via a fluid channel 308 and the chamber segment 306b is fluidically connected to the second fluid chamber 302 via a fluid channel 310. Another inlet channel 312 can be fluidically connected to the first fluid chamber 300. Another inlet channel / vent channel 314 can be fluidically connected to the second fluid chamber 302. A vent 316 is shown schematically in FIG Fig. 9 shown. A further filling / venting channel 318 can also be provided.

At this point it should be noted that the upstream fluidic structures in the in Fig. 9 The embodiment shown could also consist only of an inlet channel which is fluidically connected to the first fluid chamber 300 and which enables the first fluid chamber 300 to be filled, for example centrifugally induced filling from an inlet chamber fluidly connected to the corresponding inlet channel.

As in Fig. 9 is shown, the first fluid chamber 300 is connected via a liquid guide path 320 with 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 apex 326. In the exemplary embodiment shown, the gas routing path 324 likewise has a siphon channel with a siphon apex 328. The achievable hydrostatic height difference between the meniscus in chamber 302 and the siphon apex 328 is preferably higher than the hydrostatic height difference to be overcome between the meniscus in chamber 300 and the siphon apex 326.

The liquid guide path 320 opens into the first fluid chamber 300 in a radially outer area, preferably at a radially outer end. The gas guide path 328 opens into the second fluid chamber 302 in a radially outer area, preferably at a radially outer end. The first fluid chamber 300 can be designed in such a way that when the same is filled with a first volume of liquid, the downstream fluidic structures 322 remain vented via the gas guide path 324 to the second fluid chamber 302. This operating state in which a first volume of liquid 380 is introduced into the first fluid chamber 300 is shown in FIG Figure 10A shown. Changes in the temperature and / or rotational frequency can continue to be carried out without the liquid being switched into the downstream fluidic structures 322. In the event that capillary forces are negligible, the liquid in this state is quasi stored in the fluid chamber 300.

If a further volume of liquid is now introduced into the first fluid chamber 300, for example via the channels 308 and / or 312, the liquid volume in the first fluid chamber 300 increases until the excess volume through the connecting channel 304, which represents an overflow, into the second fluid chamber 302 flows. For this purpose, the opening of the connection channel into the first fluid chamber 300 lies radially further inward than a radially outer end of the first fluid chamber 300. The excess liquid volume 382 overflowing into the second fluid chamber 302 closes the gas guide path 324, which at a radially outer end into the second fluid chamber 302 opens, airtight. Thus, both fluid paths 320 and 324 to the downstream fluidic structures are now closed airtight after the liquid guide path 320 was already closed airtight when the liquid volume 380 was introduced into the first fluid chamber 300. This operating state is in Figure 10B shown.

Starting from this operating state, as above with reference to the Figures 8A through 8E has been described, a negative pressure can be generated in the downstream fluidic structures 322 by reducing the temperature and correspondingly reducing the pressure, as shown in FIG Figure 10C is shown. As also referring to the Figures 8A through 8E has been described, it can subsequently be brought about by reducing the centrifugal pressure and / or by further reducing the pressure in the subsequent fluidic structures that the liquid is transferred via the liquid guide path 320 into the downstream fluidic structures 322, as in FIG Figure 10D is shown. The siphon channel of the liquid guide path 320 is designed in such a way that, for example, when the temperature is reduced and the pressure is reduced as a result, only this siphon switches, so that preferably only the liquid is transferred from the first fluid chamber 300 and not the liquid from the second fluid chamber 302 becomes. A potential overpressure in the downstream fluidic structures 322 due to the transfer of the liquid from the first fluid chamber 300 pushes the liquid from the gas guide channel 324 back into the second fluid chamber 302, with air escaping through the second fluid chamber 302 in the form of air bubbles rising through the liquid can. The entire liquid can thus be transferred from the first fluid chamber 300 into the downstream fluidic structures 322.

In the event of a strong negative pressure, the siphon channels of both the liquid guide path 320 and the gas guide path 324 can also be filled with liquid. As a result, both the liquid in the first fluid chamber 300 and the liquid in the second fluid chamber 302 would then be at least partially transferred. As a result of the subsequent transfer of the liquid through the fluid guide path into the chamber 322, the negative pressure in the chamber 322 can be at least partially compensated for. By transferring sufficiently large amounts of liquid, an overpressure can be generated beyond the equalization of the negative pressure, which leads to a reversal of the flow direction of the liquid and then to a phase change to gas within one of the siphon channels, in the embodiment shown in the gas guide channel 324, whereby gas from the subsequent fluidic structures 322 is vented into the chamber 302.

An embodiment as described with reference to the Figures 9 to 10D can be useful for measuring a liquid before switching to a predefined volume. Liquid volumes below the target volume are not switched.

The referring to Fig. 9 The fluidic structures described can also be used to add a second liquid, as hereinafter referred to in FIG Figures 11A to 11E is explained.

Figure 11A corresponds to the operating state off Figure 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 now flows through the inlet channel 310 into the second fluid chamber 302, the subsequent fluidic structures 302 are hermetically sealed. For this purpose, the second liquid can either flow 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 supplied volumes can for this purpose in the chamber segments 306a and 306b of upstream fluid chamber 306 are measured, as in Figure 11B is shown. When the second liquid flows into the first fluid chamber 300 and the second fluid chamber 302, the first and second liquids can be mixed in the first fluid chamber 300.

As in the Figures 11C through 11E is shown, the liquid can subsequently be transferred from the first fluid chamber 300 into the downstream fluidic structures 322, as described above with reference to FIG Figures 8A through 8E and 10A to 10D has been described. In particular, the liquid can be transferred into the downstream fluidic structures by reducing the temperature and correspondingly reducing the pressure.

Fluidic structures as referring to the Figures 9 through 11E may be particularly useful for storing a first liquid in a first fluid chamber of a fluid holding area while a second liquid is still undergoing further independent process steps. These process steps can largely use freely required rotational frequencies and temperatures without the liquid in the first fluid chamber 300 being switched via the liquid guiding path 320. After its processing, the second liquid can be added to the first fluid chamber 300 and the second fluid chamber 302. The resulting liquid mixture can then be switched on by reducing the temperature.

It is obvious to those skilled in the art that with the described use of negative pressure the fluid chamber of the fluid holding area can also be divided into three or more chambers. In exemplary embodiments, the various chambers of the liquid holding area do not have to be connected via channels, with the exception of the connection via the downstream fluidic structures and the connecting channels that connect the fluid chamber to the downstream fluidic structures.

In general, in exemplary embodiments, the liquid guiding path opens into a liquid receiving chamber of the downstream fluidic structures at a position that lies radially outside a position at which the liquid guiding path opens into a fluid chamber of the liquid holding area. In other words, the liquid guide path has a radial gradient overall. It is thus possible to transfer the liquid from the corresponding chamber of the liquid holding area into the subsequent fluidic structures via the liquid guiding path, which has a siphon channel, via a siphon apex, which is radially inside the mouth of the liquid guiding path into the fluid chamber of the liquid holding area is arranged.

In embodiments, the downstream fluidic structures can have at least one liquid receiving chamber into which the liquid is transferred. In exemplary embodiments the liquid holding area can have at least one fluid chamber from which the liquid is transferred into the downstream fluidic structures.

In exemplary embodiments, the fluidic structures are designed in such a way that centrifugal pressures and pneumatic pressures play a major role, while capillary forces can be negligible. In exemplary embodiments, the respective fluid paths can be designed as fluid channels, with chambers, for example partial compression chambers, being able to be arranged in the fluid paths.

Embodiments thus create fluidic modules, devices and methods in which two fluid connection paths are provided between a chamber in which a liquid is retained before switching and a target structure for the liquid after the switching process. This enables a monolithic implementation of a structure for switching a liquid, which is largely independent of the properties of the liquid, when a high rotational frequency of the cartridge is either exceeded or not reached. Exemplary embodiments create a centrifugal-pneumatic vent siphon valve that has fluidic structures on a centrifugal test carrier. The fluidic structures can have a first number of chambers, subsequent fluidic structures, and at least two fluid paths which connect the first number of chambers to the subsequent fluidic structures. At least one of the fluid paths between the first number of chambers and the subsequent fluidic structures contains a siphon channel, the connection via the fluid paths from the first number of chambers to the subsequent fluidic structures being arranged such that when the first number of chambers is filled with liquid a state can be created in which a gas volume enclosed by the liquid arises in the subsequent fluidic structures or a quasi-enclosed gas volume arises in which the subsequent structures have a vent with a vent delay resistor. In embodiments of such fluidic structures, a siphon channel is provided in at least one of the fluid connection paths between the first number of chambers and the subsequent fluidic structures, the siphon apex lying radially inside the radially outermost position of a first chamber into which the siphon channel opens. In embodiments of such fluidic structures, the following fluidic structures are not vented. In embodiments, the number of chambers can comprise one chamber or more than one chamber.

Embodiments create a method for retaining and switching liquids using a corresponding centrifugo-pneumatic vent siphon valve, in which one or more liquids in a liquid holding area (a first number of chambers) in a quasi-static dominated by centrifugal pressures and pneumatic pressures Equilibrium is / are retained, so that a subsequent initiation of a transfer of at least one liquid from the liquid holding area into the subsequent fluidic structures is only possible by changing the acting centrifugal and / or pneumatic pressures. In embodiments of such a method, in the course of the transfer of liquid from the liquid holding area into the subsequent fluidic structures, gas is transferred from the subsequent fluidic structures in the direction of the liquid holding area via at least one fluid path. In embodiments of such a method, at least one fluid connection path between the liquid holding area and the following fluidic structures is not completely filled with liquid during the transfer of liquid from the liquid holding area into the subsequent fluidic structures. In embodiments of such a method, the amount of substance of the gas in the subsequent fluidic structures is not changed by a fluid path connected to the environment, while liquid is retained in the liquid holding area. In exemplary embodiments of such a method, liquid is retained in the liquid holding area due to a pneumatic negative pressure in the subsequent fluidic structures before the transfer is initiated. In exemplary embodiments of such a method, liquid is retained in the liquid holding area due to a pneumatic overpressure in the subsequent fluidic structures before the transfer is initiated. Exemplary embodiments can have any modifications and combinations of the schematic exemplary embodiments shown and are not restricted by these.

Embodiments of the invention thus provide methods for switching fluid using a centrifugo-pneumatic vent siphon valve having fluidic structures as described herein. In contrast to the known prior art, embodiments of the structure described in connection with the described method in the field of centrifugal microfluidics can simultaneously meet several requirements for the unit operations of holding back and later targeted switching on of a liquid. Embodiments enable a monolithic realization of the associated fluidic structures in a centrifugal microfluidic cartridge. Exemplary embodiments offer the possibility of designing the structure, so that the functional principle is largely independent of the properties of the liquid and cartridge material. 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 processing conditions for the triggering of a switching process in wide areas. The adaptation possibilities can in particular relate to the possibility of free choice of the gas volume transferred into the subsequent fluidic structures and the pneumatic overpressure achieved thereby.

Exemplary embodiments offer the possibility of initiating the switching process using various changes in the processing conditions. This includes, in particular, rotation frequencies, temperatures and waiting times (when using a ventilation delay resistor) during processing. Embodiments offer the possibility of using temperature changes as a function of the process control to switch a liquid when increasing above a threshold frequency or when reducing the rotation frequency below a threshold frequency. Embodiments offer the possibility of producing the microfluidic structures without sharp edges, that is, with low demands on production processes, such as. B. Injection molding and injection compression molding. Embodiments make it possible to avoid strongly increasing pneumatic pressures in the fluid target volume during the fluid transfer after the switching process. Exemplary embodiments offer the possibility of cascading the fluidic structures. Finally, embodiments offer the possibility of multiple use of the fluidic structures in order to hold back several liquids one after the other and to switch them in a targeted manner.

Embodiments are configured to change the ratio of the centrifugal pressure to the pneumatic pressure in order to exceed a threshold at which a siphon apex of the siphon channel in the first fluid path is overcome, so that a transfer of the liquid from the liquid holding area into the downstream fluidic structures takes place.

Exemplary embodiments describe variants of the fluidic structures and associated methods, which show different possibilities for influencing the equilibrium of the pressures that act in the direction of or against the initiation of the switching process according to the invention. Embodiments of the invention are also based on the knowledge that the switching principle described can easily be combined with other operations on the same centrifugal microfluidic platform, for example by directing a liquid into a structure according to the invention after previous fluidic operations or by cascading the switching structure described.

Claims (15)

1. Method for switching liquid from a liquid retaining area (52, 202, 300, 302) into downstream fluidic structures (58, 94, 158, 210, 322) by using a fluidic module (50), comprising:

   a liquid retaining area (52, 202, 300, 302) into which liquid (80) can be introduced,

   at least two fluid paths (60, 62, 206, 208, 320, 324) fluidically connecting the liquid retaining area (52, 202, 300, 302) to downstream fluidic structures (58, 94, 158, 210, 322),

   wherein at least a first fluid path (62, 206, 320) of the two fluid paths comprises a syphon channel, wherein a syphon crest (64, 212, 326) of the syphon channel is located radially inside of a radial outermost position of the liquid retaining area (52, 202, 300, 302), wherein the syphon crest (64, 212, 326) is an area of the syphon channel with minimum distance to the center of rotation,

   wherein the downstream fluidic structures (58, 94, 158, 210, 322) are not vented or only vented via a vent delay resistor (66), the fluidic resistance of which is at least high enough that the reduction of a differential pressure in the downstream fluidic structures to the ambient pressure to its half, taking into account venting through the fluidic resistance alone, takes at least 0,5 s, when the liquid (80) is introduced into the liquid retaining area (52, 202, 300, 302), such that an enclosed gas volume or a gas volume onely vented via the vent delay resistor (66) results in the downstream fluidic structures (58, 94, 158, 210, 322) when the liquid is introduced into the liquid retaining area (52, 202, 300, 302), and a ratio of a centrifugal pressure effected by a rotation of the fluidic module (50) to a pneumatic pressure prevailing in the gas volume at least temporarily prevents the liquid from reaching the downstream fluidic structures (58, 94, 158, 210, 322) through the fluid paths (60, 62, 206, 208, 320, 324),

   wherein it can be effected by changing the ratio of the centrifugal pressure to the pneumatic pressure that the liquid at least partly reaches the downstream fluidic structures (58, 94, 158, 210, 322) through the first fluid path (62, 206, 320) and the gas volume is at least partly vented into the liquid retaining area (52, 202, 300, 302) through the second fluid path (60, 208, 324) of the two fluid paths,

   the method comprising the steps of:

   introducing at least one liquid (80) into the liquid retaining area (52, 202, 300, 302) and retaining the liquid in the liquid retaining area (52, 202, 300, 302) by rotating the fluidic module (50), such that the liquid is retained in the liquid retaining area (52, 202, 300, 302) in a quasi-stationary equilibrium dominated by the centrifugal pressure and the pneumatic pressure; and

   changing the ratio of the centrifugal pressure to the pneumatic pressure in order to transfer the liquid at least partly through the first fluid path (62, 206, 320) into the downstream fluidic structures (58, 94, 158, 210, 322) and to vent the gas volume at least partly into the liquid retaining area (52, 202, 300, 302) through the second fluid path of the two fluid paths,

   wherein

   a) retaining the liquid in the liquid retaining area (52) comprises generating a pneumatic overpressure in the downstream fluidic structures (58, 94, 158) prior to initiating the transfer, and changing the ratio of the centrifugal pressure to the pneumatic pressure comprises increasing the rotational speed of the fluidic module (50), increasing the hydrostatic height of the liquid and/or reducing the pneumatic pressure, or

   b) retaining the liquid in the liquid retaining area comprises generating a negative pressure in the downstream fluidic structures (210, 322) in order to adjust and retain menisci (102, 104, 122) in the liquid retaining area and the first and second fluid paths (206, 208, 320, 324) without transferring the liquid into the downstream fluidic structures (210, 322) through the first fluid path (206, 320), and wherein changing the ratio of the centrifugal pressure to the pneumatic pressure comprises reducing the rotational speed of the fluidic module (50) and/or reducing the pneumatic pressure in the downstream fluidic structures (210, 322).
2. Method according to claim 1, wherein changing the ratio comprises reducing the pneumatic pressure by reducing the temperature in the downstream fluidic structures (210, 322), increasing the volume of the downstream fluidic structures (210, 322) and/or reducing the amount of gas in the downstream fluidic structures (210, 322).
3. Method according to one of claims 1 or 2, wherein the second fluid path (60, 208, 324) is not completely filled with liquid during the transfer of the liquid through the first fluid path (62, 206, 320).
4. Method according to one of claims 1 to 3, wherein the amount of the gas in the downstream fluidic structures (58, 94, 158, 210, 322) is not changed while the liquid is retained in the liquid retaining area (52, 202, 300, 302).
5. Method according to one of claims 1 to 4, wherein the second fluid path (60, 208, 324) of the two fluid paths is a venting channel for the downstream fluidic structures (58, 94, 158, 210, 322) closed by the liquid when the liquid is introduced into the liquid retaining area (52, 202, 300, 302).
6. Method according to one of claims 1 to 5, wherein the first fluid path (62, 206, 320) leads into the liquid retaining area (52, 202, 300, 302) in a radial outer area or at a radial outer end, such that the liquid retaining area (52, 202, 300, 302) can be emptied via the first fluid path (62, 206, 320), at least up to the area where the first fluid path (62, 206, 320) leads into the liquid retaining area.
7. Method according to one of claims 1 to 6, wherein the liquid retaining area comprises a first fluid chamber (52, 202, 300), wherein the first fluid path (62, 206, 320) leads into the first fluid chamber (52, 202, 300) in a radial outer area of the first fluid chamber (52, 202, 300) or at a radial outer end of the first fluid chamber (52, 202, 300).
8. Method according to claim 7, wherein the first fluid chamber (52) is not vented or only vented via a vent delay resistor, the fluidic resistance of which is at least high enough that the reduction of a differential pressure in the first fluid chamber (52) to the ambient pressure to its half, taking into account venting through the fluidic resistance alone, takes at least 0,5 s, when the liquid is introduced into the liquid retaining area, such that a gas volume enclosed in the first fluid chamber (52) and the downstream fluidic structures (58, 94) or a gas volume onely vented via the vent delay resistor results when the liquid is introduced into the liquid retaining area.
9. Method according to claim 7, wherein the liquid retaining area further comprises a second fluid chamber (302) into which liquid can be introduced by a centrifugal pressure effected by a rotation of the fluidic module (50), wherein the first fluid path (320) leads into the first fluid chamber (300) and the second fluid path (324) leads into the second fluid chamber (302), and wherein the second fluid path (324) can be closed by liquid introduced into the second fluid chamber (300).
10. Method according to claim 9, wherein the first fluid chamber (300) and the second fluid chamber (302) are fluidically connected via a connecting channel (304) whose orifice into the first fluid chamber (300) is located radially further inside than a radial outer end of the first fluid chamber (300), such that liquid from the first fluid chamber (300) flows over into the second fluid chamber (302) when the filling level of the liquid in the first fluid chamber (300) reaches the orifice and closes the second fluid path (324) leading into the second fluid chamber (302).
11. Method according to one of claims 1 to 10, wherein the second fluid path (60, 208, 324) comprises a siphon channel, wherein the second fluid path (208, 324) leads into the liquid retaining area (52, 202, 302) in a radial outer area of the liquid retaining area (52, 202, 302), and wherein a crest (92, 214, 328) of the siphon channel of the second fluid path (60, 208, 324) is located radially further inside than a crest (64, 212, 326) of the siphon channel of the first fluid path (62, 206, 320).
12. Method according to claim 11, wherein a fluid intermediate chamber (112) is arranged in the second fluid path (60) between the crest (92) of the siphon channel of the second fluid path (60) and the orifice (116, 132) of the second fluid path (60) into the liquid retaining area (52), wherein the fluid intermediate chamber (112) is at least partly filled with the liquid when the liquid is introduced into the liquid retaining area (52).
13. Method according to one of claims 1 to 12, wherein the downstream fluidic structures comprise at least one downstream fluid chamber (58, 210, 322) into which the first fluid path (62, 206, 320) leads.
14. Method according to claim 13, wherein the first fluid path (62, 206) leads into the downstream fluid chamber (58, 210) radially further outside than the second fluid path (60, 208).
15. Method according to claim 13 or 14, wherein the downstream fluid chamber (58) is a first downstream fluid chamber and the downstream fluidic structures comprise a second downstream fluid chamber (94, 158) fluidically connected to the first downstream fluid chamber (58) via at least a third fluid path (96, 160),
    wherein the first downstream fluid chamber (58) is fluidically connected to the second downstream fluid chamber (158) via a third fluid path (160) and a fourth fluid path (162),
    wherein at least the third fluid path (160) comprises a siphon channel,
    wherein the third fluid path (160) and the fourth fluid path (162) are closed by the liquid when the liquid reaches the first downstream fluid chamber (58) of the downstream fluidic structures through the first fluid path (62) due to a change of the ratio of the centrifugal pressure to the pneumatic pressure, wherein, in the second downstream fluid chamber (158), an enclosed gas volume or a gas volume results which is onely vented via a vent delay resistor, the fluidic resistance of which is at least high enough that the reduction of a differential pressure in the gas volume to the ambient pressure of its half, taking into account venting through the fluidic resistance alone, takes at least 0,5 s, and a ratio of the centrifugal pressure to the pneumatic pressure prevailing in the gas volume in the second downstream fluid chamber (158) at least temporarily prevents the liquid from reaching the second downstream fluid chamber (158) through the fluid paths (160, 162),
    wherein it can be effected by changing the ratio of the centrifugal pressure to the pneumatic pressure in the second downstream fluid chamber (158) that the liquid at least partly reaches the second downstream fluid chamber (158) through the third fluid path (160) and the gas volume is vented from the second downstream fluid chamber (158) at least partly into the liquid retaining area through the fourth fluid path (162).

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