Retention and transfer of liquids

Abstract

In a method for retention and transfer of liquid, a fluidic module is rotated about a centre of rotation in order to drive parts of a first liquid out of a first liquid-receiving region into a siphon channel and a connection channel, without the first liquid passing over an apex of the siphon channel into a downstream fluidic structure, and without the first liquid passing from the first liquid-receiving region into a second liquid-receiving region via the connection channel. Parts of a second liquid are driven from a second liquid-receiving region into the connection channel in order to enclose a gas volume between the first liquid and the second liquid in the connection channel and to retain the second liquid in the second liquid-receiving region and the connection channel. By introduction of additional liquid into the first liquid-receiving region, the first liquid can then be emptied into a downstream fluidic structure, as a result of which the counter-pressure in the gas volume is reduced and the second liquid is transferred into the downstream fluidic structure via the connection channel and the siphon channel.

Description

[0001] Holding and transferring liquids

[0002] Description

[0003] The present invention relates to methods, fluidic modules and fluid handling devices for holding and transferring liquids, and in particular for sequentially holding and switching liquids in centrifugal microfluidic systems.

[0004] New applications of microfluidics, such as liquid biopsies or process monitoring, require larger sample volumes than before, with the volume of required reagents generally scaling with the sample volume. Microfluidic platforms are therefore reaching their throughput and capacity limits. For example, centrifugal microfluidic platforms, known, for example, as "LabDisks," can process a maximum of a few hundred pl of sample. For more complex analysis chains, this is less than 100 pl of sample. However, for liquid biopsies, samples of 1 ml or more are desirable. The invention described herein is in this context.

[0005] For example, a combination of robotics for dispensing liquid during analysis or sample preparation and a centrifugal microfluidic chip on which a process chain is carried out can enable the processing of larger sample volumes. Examples of the present invention relate to methods, fluidic modules, and systems that can be based on robotics and a microfluidic platform, in which a combination of switching fluid, which is added to the microfluidic platform, for example, via robotics, and a microfluidic structure in the microfluidic platform is used to switch fluid at a defined time.

[0006] State of the art

[0007] Different approaches to switching liquids are known from the state of the art.

[0008] For example, it is known to use negative pressure to radially pump a fluid inward by transferring a switching fluid. In this regard, Salar Soroori et al., "Design and implementation of fluidic micro-pulleys for flow control on centrifugal microfluidic platforms", Microfluid Nanofluid (2014), Springer-Verlag Berlin Heidelberg 2013, pages 1117 to 1129, use a switching fluid that is forced radially outward under increased centrifugal forces caused by faster rotation. The negative pressure created in the closed fluidic system draws a target fluid radially inward through a siphon channel into a target chamber. Switching is triggered here by increasing the rotation frequency.

[0009] Furthermore, it is known to use negative pressure by transferring a switching fluid for siphon switching. For example, Robert Gorkin et al., "Suction-enhanced siphon valves for centrifugal microfluidic platforms," ​​Microfluid Nanofluid (2012), Springer-Verlag 2011, pages 345 to 354, use a negative pressure created by a transfer fluid flowing past a T-junction to switch a siphon.

[0010] It is also known to use the addition of liquid to close a vent, enabling the switching of a siphon using negative pressure. In this regard, Peter Jülg et al., “Automated serial dilutions for high-dynamic-range assays enabled by fill-level-coupled valving in centrifugal microfluidics”, Lab Chip, 2019, 19, pages 2205 to 2209, describe a microfluidic structure that enables switching / pumping into another chamber depending on the fill level in one chamber. The transfer is made possible by a channel, known as the fill-level-coupled siphon, becoming partially filled with liquid at a specific time and thus no longer being accessible to air. As a result, the liquid is pumped further via another channel, known as the transfer siphon, by creating a negative pressure by cooling a volume of air, which draws the liquid over the siphon.

[0011] US Pat. No. 9,625,916 B2 describes a device and method in centrifugal microfluidics in which two liquid-filled chambers are separated by a siphon with an air pocket. At a low rotational frequency, one of the chambers can be emptied into a connected collection structure. The second chamber only empties at a higher frequency.

[0012] Description of the invention The object of the present invention is to provide a method, a fluidics module and a fluid handling device that enable fluids to be switched on at a defined time.

[0013] This object is achieved by a method according to claim 1, fluidic modules according to claims 5 and 6 and a fluid handling device according to claim 10.

[0014] Examples of the invention provide a method for holding and transferring liquid using a fluidic module having a first liquid receiving area, a second liquid receiving area, a downstream fluidic structure, a siphon channel with an apex, and a connecting channel, wherein a radially outer portion of the first liquid receiving area with respect to a center of rotation is connected to the downstream fluidic structure via the siphon channel, and the radially outer portion of the first liquid receiving area is fluidically connected to an outlet of the second liquid receiving area via the connecting channel, the method comprising the following features: a) rotating the fluidic module about the center of rotation in order to drive portions of a first liquid introduced into the first liquid receiving area from the first liquid receiving area into the siphon channel and the connecting channel,to cause liquid menisci of the first liquid in the first liquid receiving area, the siphon channel and the connecting channel, without the first liquid passing through an apex of the siphon channel into the downstream fluidic structure and without the first liquid passing from the first liquid receiving area into the second liquid receiving area via the connecting channel, b) introducing a second liquid into the second liquid receiving area and rotating the fluidic module to drive parts of the second liquid from the second liquid receiving area into the connecting channel, thereby enclosing a gas volume between the first liquid and the second liquid in the connecting channel and generating a counterpressure in the gas volume, by means of which the second liquid is held in the second liquid receiving area and the connecting channel,and c) introducing additional liquid into the first liquid receiving region to move the liquid meniscus of the first liquid over the apex of the siphon channel, thereby emptying the first liquid from the first liquid receiving region via the siphon channel into the downstream fluidic structure, thereby reducing the backpressure in the gas volume and transferring the second liquid from the second liquid receiving region via the connecting channel and the siphon channel into the downstream fluidic structure.

[0015] The first liquid receiving area, the siphon channel, and the connecting channel constitute a switching structure that is partially filled with the first liquid, which constitutes a switching liquid, whereupon a second liquid, which constitutes an incubation liquid, is introduced into the second liquid receiving area, which constitutes an incubation structure. In order to retain the second liquid in the second liquid receiving area, the hydrostatic pressure of the second liquid induced by the rotation in the second liquid receiving area is balanced by a hydrostatic counterpressure of the first liquid, with which the switching structure is partially filled.The back pressure results from a fill level difference between the two channels connected to the first fluid intake area, the siphon channel and the connecting channel, which occurs when the second fluid is added to the second fluid intake area. There is trapped air between the second fluid and the first fluid in the connecting channel, which connects the second fluid intake area to the first fluid intake area. The second fluid is switched from the second fluid intake area by adding additional switching fluid to the first fluid intake area so that the siphon peak is exceeded and the switching fluid is completely transferred to the downstream fluidic structure. This eliminates the hydrostatic back pressure and clears the path for the second fluid to be transferred through the siphon channel into the downstream fluidic structure.

[0016] Examples of the present invention thus provide a novel way to initially hold liquid in a centrifugal microfluidic system and then transfer or switch it to a downstream fluidic structure. Examples of the invention also enable the holding and switching of larger volumes of liquid through appropriate design.

[0017] In some examples, the introduction of the first liquid into the first liquid receiving area and / or the introduction of the additional liquid into the first liquid receiving area and / or the introduction of the second liquid into the second liquid receiving area can be carried out manually or using a transfer module. The use of a transfer module, for example as part of a robotic system, can result in a high degree of automation of the process. In contrast, manual addition can reduce the complexity of the required hardware. In some examples, the fluidics module has a further liquid receiving area, a further downstream fluidics structure, a further siphon channel, and a further connecting channel.wherein a radially outer portion of the further liquid receiving region with respect to a center of rotation is connected to the further downstream fluidic structure via the further siphon channel, and the radially outer portion of the further liquid receiving region is fluidically connected to the first outlet or a further outlet of the second liquid receiving region via the further connecting channel. In such examples, the method may comprise the following features: after or during a), rotating the fluidic module about the center of rotation to drive portions of a third liquid introduced into the further liquid receiving region from the further liquid receiving region into the further siphon channel and the further connecting channel, in order to cause liquid menisci of the third liquid in the further liquid receiving region, the further siphon channel, and the further connecting channel,without the third liquid passing via an apex of the further siphon channel into the further downstream fluidic structure and without the third liquid passing from the further liquid receiving area via the further connecting channel into the second liquid receiving area, after c), introducing a fourth liquid into the first liquid receiving area and rotating the fluidic module to drive parts of the fourth liquid from the first liquid receiving area into the siphon channel and the connecting channel in order to cause liquid menisci of the fourth liquid in the first liquid receiving area, the siphon channel and the connecting channel, without the fourth liquid passing via an apex of the siphon channel into the downstream fluidic structure and without the fourth liquid passing from the first liquid receiving area via the connecting channel into the second liquid receiving area,

[0018] Introducing a fifth liquid into the second liquid receiving area and rotating the fluidic module to drive parts of the fifth liquid from the second liquid receiving area into the connecting channel and the further connecting channel, thereby enclosing a gas volume between the third liquid and the fifth liquid in the further connecting channel and between the fourth liquid and the fifth liquid in the connecting channel and generating a further counterpressure by which the fifth liquid is held in the second liquid receiving area and the further connecting channel, and

[0019] Introducing additional liquid into the further liquid receiving area to move the liquid meniscus of the third liquid over the apex of the further siphon channel, thereby emptying the third liquid from the further liquid receiving area via the further siphon channel into the further downstream fluidic structure, whereby the further back pressure is reduced and the fifth liquid is transferred from the second liquid receiving area via the further connecting channel and the further siphon channel into the further downstream fluidic structure.

[0020] In examples, the method is thus repeatable, ie in addition to the transfer of a first switching liquid and a first incubation liquid, at least one further switching liquid (third liquid) and one further incubation liquid (fifth liquid) can be added and further holding and switching steps can be carried out.

[0021] In examples, transferring the second and / or fifth liquid to the downstream fluidic structure may cause the second and / or fifth liquid to be contacted with a reagent. Examples thus suitably enable the second and / or fifth liquid to be retained in a suitable fluidic structure before transferring the second and / or fifth liquid to a downstream fluidic structure comprising a reagent.

[0022] Examples of the invention provide a fluidics module for carrying out methods as described herein, which has the first liquid receiving region, the second liquid receiving region, the siphon channel and the connecting channel, wherein the first liquid receiving region is vented, the second liquid receiving region is vented, the connecting channel has a first end which is fluidically connected to the first liquid receiving region and a second end which opens into a radially outer section of the second liquid receiving region, wherein the first end of the connecting channel is radially further outward than the second end of the connecting channel, and an outlet end of the siphon channel is arranged radially further outward than a radially outer end of the first liquid receiving region and than a radially outer end of the second liquid receiving region.

[0023] Such a fluidic module is designed to carry out the inventive methods described herein in that the siphon channel and the connecting channel each have radially rising sections to enable the first fluid to be held in the first fluid receiving area, the siphon channel and the connecting channel and to enable the hydrostatic pressure of the second fluid induced by the rotation to be balanced by the hydrostatic counterpressure of the switching fluid to hold both fluids before the fluids are switched into the subsequent fluidic structure.

[0024] Examples of the present invention provide a fluidics module for carrying out a method as described above, in which a third and fifth liquid are further held and transferred, which comprises the first liquid receiving region, the second liquid receiving region, the siphon channel, the connecting channel, the further liquid receiving region, the further downstream fluidic structure, the further siphon channel and the further connecting channel, wherein the first liquid receiving region is vented, the second liquid receiving region is vented, the further liquid receiving region is vented, the connecting channel has a first end that is fluidically connected to the first liquid receiving region and a second end that opens into a radially outer portion of the second liquid receiving region, wherein the first end of the connecting channel is radially further outward than the second end of the connecting channel,an outlet end of the siphon channel is arranged radially further outward than a radially outer end of the first liquid receiving region and than a radially outer end of the second liquid receiving region, the further connecting channel has a first end which is fluidically connected to the further liquid receiving region and a second end which opens into a radially outer portion of the second liquid receiving region, wherein the first end of the further connecting channel is radially further outward than the second end of the further connecting channel, an outlet end of the further siphon channel is arranged radially further outward than a radially outer end of the further liquid receiving region and than a radially outer end of the second liquid receiving region.

[0025] In such examples, the connecting channel, the further connecting channel, the siphon channel, and the further siphon channel each have radially rising sections that enable the described functionality. Such examples thus enable the holding and transfer of further liquids. The first and the third liquid represent switching liquids, and the first and the further liquid receiving region represent switching liquid receiving regions. In examples, further switching liquid regions can be provided, which correspondingly enable the holding and switching of at least one further incubation liquid from the second liquid holding region. In examples, the first liquid receiving region is arranged on one side of the second liquid receiving region, and the further liquid receiving region is arranged on an opposite side of the second liquid receiving region in the azimuthal direction.

[0026] In examples, the connecting channel has a channel portion extending radially inward and disposed in the azimuthal direction on one side of the first liquid receiving region, and the siphon channel has a channel portion extending radially inward and disposed in the azimuthal direction on an opposite side of the first liquid receiving region. Such examples enable a space-saving arrangement in the fluidics module.

[0027] In examples, the first liquid receiving region is a fluid chamber, wherein the connecting channel and the siphon channel open into the fluid chamber on opposite azimuthal sides.

[0028] Examples of the invention provide a fluid handling device with a fluidics module as described herein and a drive device configured to rotate the fluidics module to perform a method according to the invention. In examples, the fluid handling device further comprises at least one transfer module configured to introduce the first liquid into the first liquid receiving area, and / or introduce the additional liquid into the first liquid receiving area, and / or introduce the second liquid into the second liquid receiving area. Examples thus enable at least partially automated performance of the methods as described herein.

[0029] Short description of the drawings

[0030] Examples of the present invention are explained in more detail below with reference to the accompanying drawings. They show:

[0031] Fig. 1 is a schematic plan view of fluidic structures of an example of a fluidic module according to the invention for holding and switching a first and second fluid; Figs. 2a to 2d are schematic representations of the fluidic module of Fig. 1 for explaining an embodiment of a method according to the invention;

[0032] Fig. 3a to 3d are schematic plan views of fluidic structures of a further example of a fluidic module according to the invention for explaining a further embodiment of a method according to the invention for holding and switching a first, second, third and fifth liquid; and

[0033] Figs. 4A and 4B are schematic representations of examples of fluid handling devices according to the invention.

[0034] Detailed description

[0035] Examples of the present disclosure are described in detail below and with use of the accompanying drawings. It should be noted that like elements or elements having the same functionality are provided with the same or similar reference numerals, and repeated description of elements provided with the same or similar reference numerals is typically omitted. In particular, like or similar elements may each be provided with reference numerals having the same number with a different or no lowercase letter. Descriptions of elements having the same or similar reference numerals may be interchangeable. In the following description, many details are described to provide a more thorough explanation of examples of the disclosure.However, it will be apparent to those skilled in the art that other examples may be implemented without these specific details. Features of the various described examples may be combined with each other, unless features of a corresponding combination are mutually exclusive or such a combination is expressly excluded.

[0036] Before further explaining examples of the present disclosure, definitions of some terms used herein are provided.

[0037] Fluidics module

[0038] A fluidics module is understood herein to be a module that has fluidic structures designed to enable liquid handling as described herein. The fluidic structures have the fluid receiving areas and channels described herein. In examples, the fluidic structures are microfluidic structures designed to process liquids in the picoliter to milliliter range and have suitable dimensions in the micrometer range for handling corresponding liquid volumes. In examples, the fluidic module is a centrifugal microfluidic chip.

[0039] A device for performing fluidic and / or biochemical processes while rotating around a center of rotation. The centrifugal microfluidic chip contains microfluidic structures such as channels and chambers in which fluids are moved. This fluid movement is triggered, driven, and controlled by the rotation of the chip by a rotation unit. Fluidic modules as described herein can be formed by centrifugal microfluidic chips.

[0040] Transfer module

[0041] A device for the precise and time-controlled dispensing of liquids or other substances and mixtures (e.g., dispenser, pipette, gripper, etc.). It transfers samples, reagents, and switching fluids into the centrifugal microfluidic chip and, if necessary, products out of the centrifugal microfluidic chip. A transfer module can be implemented, for example, using robotics.

[0042] liquid

[0043] As will be apparent to those skilled in the art, the term liquid as used herein includes, in particular, liquids containing solid components, such as suspensions, biological samples and reagents.

[0044] sample

[0045] In this context, a sample is a mixture of substances (e.g. blood sample, water sample, process sample, skin sample, insects, etc.) which is completely or partially analyzed within a fluidic module (centrifugal microfluidic chip) and associated drive device (rotation unit) or is prepared in this for a subsequent analysis (e.g. DNA extraction).

[0046] Reagents

[0047] In this context, reagents are all substances and mixtures of substances that are required for the analysis or preparation of the sample within the centrifugal microfluidic chip and associated drive device (rotation unit) (e.g. washing buffers, acids, dilutions, nanoparticles, etc.).

[0048] switching fluid

[0049] The function of switching fluids is to implement a switching process. Switching fluids are used to switch other fluids. Switching fluids can also be used for interaction, for example, to dilute or mix with the sample, for example, in a downstream fluidic structure.

[0050] Incubation fluid is understood here to mean a fluid that is subject to processing and / or examination and can interact with other substances or is incubated with other substances for this purpose.

[0051] A microfluidic channel or part of a microfluidic channel located in a fluidics module (centrifugal microfluidic chip) in which channel sections upstream and downstream of an intermediate channel section are at a greater distance from the center of rotation than an intermediate channel section (inverse siphon). A siphon apex is the region of the siphon channel with the minimum distance from the center of rotation.

[0052] Hydrostatic pressure

[0053] The hydrostatic pressure pHydrostatic on a liquid column in a channel in the centrifugal gravitational field can be calculated using the following formula:

[0054] Where p is the density of the liquid, w is the angular velocity with which the channel rotates around the center of rotation, r a for the outer radius of the liquid column and n for the inner radius of the liquid column.

[0055] Fluid channel / fluid chamber

[0056] When reference is made here to a fluid channel, this means a structure whose length 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. Thus, a fluid channel has a flow resistance for flow through it from the fluid inlet to the fluid outlet. In contrast, a fluid chamber here is a chamber with dimensions such that, when flowing through the chamber, a flow resistance that is negligible compared to connected channels occurs, which can be, for example, 1 / 100 or 1 / 1000 of the flow resistance of the channel structure connected to the chamber with the smallest flow resistance.

[0057] Radial

[0058] When the term radial is used herein, it means radial with respect to the center of rotation around which the fluidic module or the rotating body is rotatable. In the centrifugal field, a radial direction away from the center of rotation is radially decreasing, and a radial direction towards the center of rotation is radially increasing. A fluid channel whose beginning is closer to the center of rotation than its end is thus radially decreasing, while a fluid channel whose beginning is further from the center of rotation than its end is radially increasing. A channel with a radially increasing section therefore has directional components that increase radially or run radially inwards. It is clear that such a channel does not have to run exactly along a radial line, but can run at an angle to the radial line or be curved.Radially further out means further away from the center of rotation and radially further in means closer to the center of rotation.

[0059] Unless otherwise stated herein, room temperature (20°C) shall be assumed with regard to temperature-dependent quantities.

[0060] Examples of the present invention are directed to methods and devices for holding liquids and for selectively switching liquids at a desired time, particularly in a centrifugal microfluidic chip. Corresponding devices can be monolithically integrated into the centrifugal microfluidic chip or can be easily manufactured. In some examples, the structured microfluidic chip does not have any additional components, such as wax valves, that require melting. In some examples, the method according to the invention can be largely independent of time, temperature, and frequency protocols and is adaptable to a wide range of volumes.Holding the incubation liquid (second and fifth liquids in the claims), which may be samples and / or reagents, while rotating in a structure, which is also referred to below as an incubation chamber, can be achieved by a compensating counterpressure from a structure partially filled with switching fluid (first and third liquids in the claims) and connected via a channel, which is also referred to below as a switching structure. The switching structure can consist of a switching chamber and two connected channels, the siphon channel and the connecting channel. In this process, the switching structure can first be partially filled with switching fluid. Subsequently, the incubation structure is filled with incubation fluid.To keep the incubation fluid within the incubation structure, the hydrostatic pressure of the incubation fluid induced by the rotation is balanced by a hydrostatic counterpressure of the switching fluid. This counterpressure results from the fill level difference between the two channels connected to the switching chamber (siphon channel and connecting channel), which occurs when the incubation fluid is added to the incubation structure. Between the incubation fluid and the switching fluid, there is trapped air in the connecting channel that connects the incubation structure to the switching structure.

[0061] The incubation fluid is switched from the incubation structure by adding additional switching fluid to the switching structure, which is already partially filled with switching fluid. The switching structure is connected to a downstream microfluidic system via the siphon channel, which contains an inverse siphon. This additional addition of switching fluid causes the siphon apex to be exceeded, and the switching fluid is completely switched into the downstream structure (downstream fluidic structure). This eliminates the hydrostatic counterpressure and clears the way for the transfer of the incubation fluid, which in turn can be switched into the downstream microfluidic structure. The introduction or addition of the switching fluid and / or the incubation fluid can be done either manually, for example, using a pipette, or via a transfer module. The process is repeatable, i.e.After transferring a first switching and incubation liquid, at least a second switching and incubation liquid could be added and further holding and switching steps could be carried out.

[0062] In contrast to the prior art methods by Sorooir and Gorkin described above, according to the invention the switching is triggered by the addition of liquid, which makes it largely frequency-independent. In the prior art by Jülg mentioned above, the addition of liquid closes a vent, making it possible to draw liquid through the siphon using negative pressure. According to the invention the addition of switching fluid causes the switching fluid to overflow the siphon, the switching fluid is switched into the subsequent structure, and the path is thus clear for the transfer of the incubation fluid (sample / reagents) so that it can be switched on to the subsequent structure. In contrast to the prior art described in US 9,625,916 B2, according to the invention the switching is triggered by the addition of liquid, so that it is largely frequency-independent.Also, in examples of the invention, no siphon is required between the incubation chamber and the switching chamber, but a siphon channel connects both the switching chamber and the incubation chamber with the subsequent microfluidics.

[0063] Fig. 1 shows an example of a fluidic module 10 according to the invention, which has fluidic structures for carrying out embodiments of the methods described herein. The fluidic structures have a first liquid receiving region 12, a second liquid receiving region 14, downstream fluidic structures 16, a siphon channel 18, and a connecting channel 20. In the embodiment shown, the first liquid receiving region 12 is formed by a switching chamber, and the second liquid receiving region 14 is formed by an incubation chamber. In the following, reference is therefore made to the switching chamber 12 and the incubation chamber 14. However, it does not require a separate explanation that the liquid receiving regions can also each be formed by multiple chambers or chamber-like fluidic structures designed to receive liquid in order to carry out the methods described herein.The downstream fluidic structure 16 can also be formed by a fluid chamber in which, for example, reagents are stored. However, it goes without saying that the downstream fluidic structure 16 can be formed by any subsequent microfluidic device into which the liquids are transferred from the siphon channel 18, which is downstream because it is located downstream of the siphon channel 18.

[0064] The switching chamber 12, the incubation chamber 14, and the downstream fluidic structure 16 are each vented, as indicated by vents e in Fig. 1, such that when liquids are introduced into or emptied from them during the performance of the processes, no overpressure or underpressure that could affect the processes is generated in the switching chamber 12, the incubation chamber 14, and the downstream fluidic structure 16. A radially outer section of the switching chamber 12 is connected to the downstream fluidic structure 16 via the siphon channel 18. The radially outer section of the switching chamber 12 is connected to an outlet of the incubation chamber 14 via the connecting channel 20. In the example shown in Fig. 1, the siphon channel 18 opens into the radially outer end of the switching chamber 12, which enables complete emptying of the switching chamber 12 via the siphon channel 18.In other examples, the siphon channel 18 and / or the connecting channel 20 could open into the switching chamber 12 at a distance from the radially outer end. The connecting channel 20 has a first end that is fluidically connected to the switching chamber 12 and a second end that opens into a radially outer portion, for example a radially outer end, of the incubation chamber 14. The first end of the connecting channel 20 is arranged radially further outward than the second end of the connecting channel 20. Thus, the connecting channel rises radially from the switching chamber 12 to the incubation chamber 14 or has at least one radially rising portion. The siphon channel has a radially rising portion up to a radially inner siphon apex thereof.An outlet end of the siphon channel 18, which opens into the downstream fluidic structure 16, is arranged radially further outward than a radially outer end of the switching chamber 12 and than a radially outer end of the incubation chamber 14. Thus, it is possible to completely empty the switching chamber 12 and the incubation chamber 14 via the siphon channel 18, or at least up to the respective radial position at which the siphon channel 18 or the connecting channel 20 open into them.

[0065] In the example shown, the siphon channel 18 and the connecting channel 20 open into the switching chamber 12 on azimuthally opposite sides. Thus, the switching chamber 12 and a channel formed by the siphon channel 18 and the connecting channel 20 form a T-junction. In alternative embodiments, the connecting channel 20 does not open into the switching chamber 12, but rather opens into the siphon channel 18, specifically in a region thereof that lies between the inverse siphon of the latter and the opening of the siphon channel into the switching chamber 12.

[0066] As shown in Fig. 1, the switching chamber 12 and the incubation chamber 14 can have respective inlets 22 and 24, via which liquids can be introduced into the switching chamber 12 and the incubation chamber 14. In examples, the fluidics module thus has an incubation chamber that is vented and is provided with a possibility for introducing incubation liquid into the incubation chamber, wherein the incubation chamber is connected to a radially further outer switching chamber via a connecting channel. The switching chamber is also connected to a siphon channel, the course of which includes an inverse siphon and connects the device according to the invention to a downstream microfluidic system of any desired type. The switching chamber, connecting channel, and siphon channel can be referred to as a switching structure that is vented and is provided with a possibility for introducing switching liquid into the switching structure.

[0067] As shown in Fig. 1, the connecting channel has a channel section that extends radially inward and is arranged in the azimuthal direction on one side of the switching chamber 12, and the siphon channel 18 has a channel section that extends radially inward and is arranged in the azimuthal direction on an opposite side of the switching chamber 12. This enables a space-saving arrangement of the fluidic structures in the fluidic module 10. Alternatively, the radially inwardly extending sections could also be arranged on the same side of the switching chamber 12. In examples, the connecting channel does not have an inverse siphon.

[0068] In the example shown in Fig. 1, the connecting channel 20 has a first channel section extending radially outward from the incubation chamber 14, a second channel section extending at least partially in the azimuthal direction from the first channel section, and a third channel section extending radially outward from the second channel section. In other examples, the connecting channel can have a different course, for example, a straight or curved channel that connects the radially outer section of the switching chamber 12 to the radially outer section of the incubation chamber 14 and is correspondingly small to enable a stable air inclusion.

[0069] In the following, an embodiment of a method for holding and transferring liquid is described with reference to the fluidic module 10 shown in Fig. 1 and with reference to Figures 2a to 2d.

[0070] In a first step, which can be referred to as switching, the switching structure formed by the switching chamber 12, the siphon channel 18, and the connecting channel 20 is partially filled with switching fluid 30, for example via the inlet 22, such that a vertex of the inverse siphon located in the siphon channel 18 is not exceeded during rotation. Filling can be done, for example, manually using a pipette or via a transfer module. If a transfer module is used, this can also be done during rotation. As indicated by an arrow 32 in Fig.As shown in Figure 2a, the fluidic module is rotated about the rotation center R to drive portions of the switching fluid introduced into the switching chamber 12 from the switching chamber 12 into the siphon channel 18 and the connecting channel 20, in order to cause fluid menisci of the switching fluid in the switching chamber 12, the siphon channel 18, and the connecting channel 20, without the switching fluid 30 passing via the apex of the siphon channel 18 into the downstream fluidic structure 16 and without the switching fluid from the switching chamber 12 passing via the connecting channel 20 into the incubation chamber 14. The switching fluid can be introduced into the switching structure before the rotation of the fluidic module is started, while the rotation of the fluidic module is started, or after the rotation of the fluidic module has been started. Due to the rotation, the switching fluid is arranged radially outward in the switching structure.The liquid menisci in the siphon channel 18, the switching chamber 12 and the connecting channel 20 are located at a radial height r, as shown in Fig. 2a.

[0071] In a second step, which may be referred to as holding, incubation liquid 34 is introduced into the incubation chamber 14, for example, via the inlet 24. This can be done, for example, using a transfer module under rotation. Under rotation, the incubation liquid 34 arranges itself radially outward in the incubation chamber 14 and a portion of the incubation liquid 34 penetrates into the connecting channel 20, which leads to an air inclusion between the incubation liquid 34 and the switching fluid 30 in the connecting channel 20. As a result of the penetration, the air in the connecting channel 20 is compressed and the pressure causes the fluid menisci in the siphon channel 18 and the switching chamber 12 to shift radially inward, see r3 in Fig. 2b, and the fluid meniscus in the connecting channel to shift radially outward, see r4 in Fig. 2b.The liquid meniscus of the incubation liquid 34 in the connecting channel 20 is located at r2. Due to the different heights of the liquid menisci in the switching structure, a hydrostatic pressure Ap2 develops. This pressure Ap2 represents a counterpressure to the hydrostatic pressure Api of the incubation liquid 34 in the incubation chamber 14 and the connecting channel 20. If the pressures are equal, an equilibrium state occurs in which the incubation liquid 34 cannot penetrate further into the connecting channel 20 and is retained in the incubation chamber 14.In other words, a second liquid, the incubation liquid 34, is introduced into a second liquid receiving area, the incubation chamber 14, and the fluidic module is rotated to drive portions of the incubation liquid 34 from the incubation chamber 14 into the connecting channel 20, thereby enclosing a gas volume between the switching liquid 30 and the incubation liquid 34 in the connecting channel 20 and generating a counterpressure in the gas volume, by means of which the incubation liquid 34 is held in the incubation chamber 34 and the connecting channel 20.

[0072] In a third step, which can be referred to as switching and emptying, additional switching fluid is added to the switching structure. This can be done, for example, using a rotating transfer module. The addition of the additional switching fluid causes the fluid menisci in the switching chamber 12 and the siphon channel 18 to increase in parallel, since a pressure gradient between the fluid menisci in the switching chamber 12 and the siphon channel 18 is not stable until the apex of the inverse siphon in the siphon channel 18 is exceeded. As soon as this occurs, the switching fluid 30 empties into the downstream microfluidic system 16, as shown in Fig. 2c. Since there is no longer any counterpressure to keep the incubation fluid 34 in the incubation chamber 14, this is also transferred into the downstream microfluidic system 16. The resulting state is shown in Fig. 2d.In other words, additional liquid is introduced into the switching chamber 12, which represents a first liquid receiving area, in order to move the liquid meniscus of the switching liquid 30 over the apex of the siphon channel 18, thereby emptying the first liquid 30 from the switching chamber 12 via the siphon channel 18 into the downstream fluidic structure 16, whereby the back pressure in the gas volume is reduced and the incubation liquid 34 is transferred from the incubation chamber 14 via the connecting channel 20 and the siphon channel 18 into the downstream fluidic structure 16.

[0073] In Figs. 2a to 2d, each rotation is represented by an arrow 32. The rotation speed can remain constant during the process.

[0074] The method described with reference to Figs. 2a to 2d serves to transfer an incubation liquid 34 into a downstream fluidic structure 16 by means of a switching liquid 30. Referring to Figs. 3a to 3d, a fluidic module and a method are described below which are suitable for transferring a first incubation liquid into a first downstream fluidic structure and a second incubation liquid into a second downstream fluidic structure by means of respective switching liquids.

[0075] First, with reference to Fig. 3a, the fluidic structures of a corresponding fluidic module 10' are described. Elements corresponding to those in Fig. 1 are designated by the same reference numerals, and reference is made to the above explanations for their description. In addition to the switching chamber 12, the incubation chamber 14, the downstream fluidic structure 16, the siphon channel 18, and the connecting channel 20, the fluidic structures have a further liquid receiving area 42, a further downstream fluidic structure 46, a further siphon channel 48, and a further connecting channel 50. The further liquid receiving area 42 is in turn formed by a fluid chamber, which represents a switching chamber. The switching chamber 42 has an inlet 62.Furthermore, the above statements regarding the switching chamber 12, the downstream fluidic structure 16, the siphon channel 18, and the connecting channel 20 apply accordingly to the further switching chamber 42, the downstream fluidic structure 46, the siphon channel 48, and the connecting channel 50. This means that the further switching chamber 42 is also vented, that the further connecting channel 50 has a first end that is fluidically connected to the further switching chamber and a second end that opens into a radially outer section of the incubation chamber, wherein the first end of the further connecting channel 50 is radially further outward than the second end of the further connecting channel 50, and that an outlet end of the further siphon channel 48 is arranged radially further outward than a radially outer end of the further switching chamber and than a radially outer end of the incubation chamber.The switching chamber 12 and the further switching chamber 42 are arranged azimuthally on opposite sides of the incubation chamber 14. The second connecting channel 50 can open into another outlet of the incubation chamber 14, as shown in Fig. 3a. In other examples, the two connecting channels can also open into a common outlet of the incubation chamber, for example, via a T-connection.

[0076] The fluidic module 10' shown in Fig. 3a thus has fluidic structures in which the switching structure is duplicated to enable switching of two incubation liquids into downstream fluidic structures 16, 46. The additional switching chamber 42, the siphon channel 48, and the connecting channel 50 represent an additional switching structure. Embodiments can thus include multiple switching structures on the same incubation chamber, each connected to its own downstream microfluidic system. Incubation liquids can thus be switched sequentially into various downstream microfluidic structures. The order and direction of the incubation liquids are determined according to the actuation of the various switching structures according to the method described above.

[0077] Fig. 3a shows a state after a process phase that corresponds to the state shown in Fig. 2b. In addition to the introduction of a first switching fluid 30 into the first switching structure, a further switching fluid 70 was introduced into the further switching structure. The further switching fluid 70 can, for example, have been introduced via the inlet 62. The introduction of the switching fluid 70 can take place together with the introduction of the switching fluid 30, or before or after it. Furthermore, with regard to the creation of the arrangement of the further switching fluid 70 shown in Fig. 3a in the further switching structure, the above explanations regarding the switching fluid 30 in the first switching structure apply in the same way.More specifically, before, after, or during the rotation of the fluidic module 10' in order to introduce the additional switching fluid 70 into the additional switching chamber 42, the fluidic module is rotated about the center of rotation R in order to drive parts of the additional switching fluid 70 (third fluid) introduced into the additional switching chamber 42 from the switching chamber 42 into the additional siphon channel 48 and the additional connecting channel 50 in order to cause fluid menisci of the additional switching fluid 70 in the additional switching chamber 42, the additional siphon channel 48, and the additional connecting channel 50, without the additional switching fluid 70 passing via an apex of the additional siphon channel 48 into the additional downstream fluidic structure 46 and without the additional switching fluid 70 passing from the additional switching chamber 42 via the additional connecting channel 50 into the incubation chamber 14.

[0078] Furthermore, in the state shown in Fig. 3a, the incubation liquid 34 has already been introduced into the incubation chamber 14 while rotating in order to drive portions of the incubation liquid 34 from the incubation chamber 14 into the connecting channel 20 and the further connecting channel 50, in order to thereby enclose a gas volume between the switching liquid 30 and the incubation liquid 34 and between the further switching liquid 70 and the incubation liquid 34, and to generate a counterpressure in the gas volume, by which the incubation liquid 34 is held in the incubation chamber and the connecting channels 20 and 50. The introduction of the incubation liquid 34 takes place after the switching liquids 30 and 70 have been introduced into the switching structures.

[0079] Starting from the state shown in Fig. 3a, additional switching fluid is then first introduced into the first switching chamber 12, so that, according to the above description of Figs. 2c and 2d, the switching fluid 30 is emptied from the switching chamber 12 and then the incubation fluid 34 is emptied from the incubation chamber 14 into the first downstream fluidic structure 16. The resulting state is shown in Fig. 3b.

[0080] Starting from this state, a further switching fluid 74 (fourth fluid) is first introduced into the first switching chamber 12 under rotation in order to drive parts of the further switching fluid 74 from the first switching chamber 12 into the siphon channel 18 and the connecting channel 20 in order to cause fluid menisci of the fourth fluid in the switching chamber 12, the siphon channel 18 and the connecting channel 20, without the further switching fluid 74 passing via the apex of the siphon channel 18 into the downstream fluidic structure 16 and without the further switching fluid 74 passing from the switching chamber 12 via the connecting channel 20 into the incubation chamber 14.Subsequently, with further rotation, a further incubation liquid 76 (fifth liquid) is introduced into the incubation chamber 14 in order to drive portions of the further incubation liquid 76 from the incubation chamber 14 into the connecting channel 20 and the further connecting channel 50, in order to enclose a gas volume between the switching liquid 70 and the incubation liquid 76 in the further connecting channel 50, and in order to enclose a gas volume between the further switching liquid 74 and the further incubation liquid 76 in the connecting channel 20. As described above, these gas volumes generate a counterpressure, which creates different menisci in the switching structures.

[0081] Starting from the state shown in Fig. 3c, additional switching fluid is then introduced into the further switching chamber 42 in order to cause the meniscus of the switching fluid 70 in the further switching structure to exceed the apex of the siphon channel 48 and the switching chamber 42 to empty into the further downstream fluidic structure 46. As a result, the backpressure between the switching fluid 70 and the incubation fluid 76 is reduced and the incubation fluid 76 also empties via the siphon channel 48 into the further fluidic structure 46. This achieves the state shown in Fig. 3d. Thus, in the method described with reference to Figs. 3a to 3d, first a first incubation fluid 34 is switched into the downstream fluidic structure 16 and then a further incubation fluid 76 is switched into the downstream fluidic structure 46.

[0082] The different liquids are numbered herein, for example, in the appended claims. The numbering serves merely to distinguish the liquids and does not necessarily specify any order. The first liquid, the third liquid, and the fourth liquid each represent switching liquids, while the second liquid and the fifth liquid represent incubation liquids. The switching liquids may each be the same or different liquids. The incubation liquids may also be the same or different liquids. The switching liquids and the incubation liquids may also be the same.

[0083] Examples of the present invention provide a fluid handling device with fluidic modules as described herein and a drive device, for example a rotation unit, which is designed to rotate the fluidic module to carry out the methods as described herein or to achieve the functionalities described herein. The fluid handling device can further comprise a transfer module designed to introduce the respective liquids into the respective fluid receiving areas, for example the first liquid into the first liquid receiving area, the additional liquid into the first liquid receiving area, the second liquid into the second liquid receiving area, the third liquid into the further liquid receiving area, the fourth liquid into the first liquid receiving area and / or the fifth liquid into the second liquid receiving area.

[0084] Referring now to Figures 4a and 4b, examples of fluid handling devices in the form of centrifugal microfluidic systems according to examples of the invention will be described, which utilize or comprise a fluidic module as described herein. In other words, the fluidic module in the systems in Figures 4a and 4b can be any of the fluidic modules described herein.

[0085] Fig. 4a shows a fluid handling device with a fluidics module in the form of a rotating body 110, which has a substrate 112 and a cover 114. The substrate 112 and the cover 114 can be circular in plan view, with a central opening through which the rotating body 110 can be attached to a rotating part 118 of a drive device 120 via a conventional fastening device 116. The rotating part 118 is rotatably mounted on a stationary part 122 of the drive device 120. The drive device 120 can be, for example, a conventional centrifuge, which can have an adjustable rotational speed, or a CD or DVD drive. A control device 124 can be provided, which is designed to control the drive device 120 in order to subject the rotating body 110 to a rotation or to rotations at different rotational frequencies.The control device 124 can, as will be apparent to those skilled in the art, be implemented, for example, by an appropriately programmed computing device or a user-specific integrated circuit. The control device 124 can further be configured to control the drive device 120 in response to manual inputs from a user in order to effect the required rotations of the rotating body. In any case, the control device 124 can be configured to control the drive device 120 in order to impart the required rotation to the rotating body in order to implement examples of the invention as described herein. A conventional centrifuge with only one direction of rotation can be used as the drive device 120. The fluid handling device further comprises a transfer module 140 configured to introduce respective liquids into the liquid receiving areas.The control device 124 can be configured to synchronize the rotation of the fluidics module and actuation of the transfer module 140 to introduce liquid into the respective inlets of the liquid receiving areas to implement the methods described herein. The inlets can be configured to support such introduction and can, for example, be formed as annular structures in the fluidics module.

[0086] The rotating body 110 includes the fluidic structures that form the fluidic modules as described herein. The fluidic structures can be formed by cavities and channels in the cover 114, the substrate 112, or in the substrate 112 and the cover 114. In examples, for example, fluidic structures can be depicted in the substrate 112, while fill openings and vent openings are formed in the cover 114. In examples, the structured substrate (including fill openings and vent openings) is arranged on top and the cover is arranged on the bottom.

[0087] In an alternative example shown in Fig. 4b, fluidic modules 132 are inserted into a rotor 130 and, together with the rotor 130, form the rotating body 110. The fluidic modules 132 can each have a substrate and a cover, in which corresponding fluidic structures can be formed. The rotating body 110 formed by the rotor 130 and the fluidic modules 132 can, in turn, be subjected to rotation by the drive device 120, which is controlled by the control device 124.

[0088] In Figures 4a and 4b, the center of rotation around which the fluidic module or the rotating body can rotate is again denoted by R.

[0089] The described devices and methods make it possible to simultaneously meet multiple requirements for holding and subsequently switching a liquid in the field of centrifugal microfluidics. For example, it is possible to initiate the switching process by adding liquid and thereby overcoming a siphon channel. Furthermore, it offers the possibility of sequentially repeating the holding and switching processes. Embodiments also enable robust holding and switching of liquids that is largely independent of the frequency and acceleration of rotation, time, liquid properties, the volume of the liquid to be switched, the temperature or thermopneumatics, and the humidity.

[0090] In embodiments, essentially only the hydrostatic heads play a role in holding and switching the incubation fluid, so that very large amounts of incubation fluid can be held with very small amounts of switching fluid, for example, via a very wide and deep incubation chamber, since the switching structure can be implemented very flat and narrow. If necessary, a medium with a significantly higher density than the incubation fluid could also be used as the switching fluid, with the aim of generating a higher hydrostatic backpressure, since the backpressure is essentially determined by two factors: the density and the hydrostatic heads in the siphon channel and the connecting channel.

[0091] In summary, embodiments thus provide a method for holding and transferring liquid, in which a fluidics module is rotated about a center of rotation to drive portions of a first liquid from a first liquid receiving region into a siphon channel and a connecting channel, without the first liquid passing via an apex of the siphon channel into a downstream fluidic structure and without the first liquid passing from the first liquid receiving region via the connecting channel into a second liquid receiving region. Portions of a second liquid are driven from a second liquid receiving region into the connecting channel to enclose a gas volume between the first liquid and the second liquid in the connecting channel and to hold the second liquid in the second liquid receiving region and the connecting channel.By introducing additional liquid into the first liquid receiving area, the first liquid can then be emptied into a downstream fluidic structure, whereby the back pressure in the gas volume is reduced and the second liquid is transferred via the connecting channel and the siphon channel into the downstream fluidic structure.

[0092] According to the invention, a liquid volume in an incubation chamber is thus maintained by a hydrostatic counterpressure of a switching fluid located in a switching structure. Since the radial positions are proportional to the square of the hydrostatic pressure, switching structures located further outward in the radial direction with smaller hydrostatic height differences can maintain larger height differences in an incubation chamber. The air inclusion stabilizes both fill levels and thus equalizes pressure. Switching occurs by adding fluid to exceed the inverse apex of the siphon in the siphon channel and initiate the flow of the switching fluid.

[0093] In other words, examples of the present invention provide a fluid handling device for operation in a centrifugal microfluidic device and / or a centrifuge, comprising: a vented incubation chamber configured to receive incubation liquid; a vented switching structure comprising a switching chamber and the connected siphon channel and connecting channel configured to receive switching liquid; wherein the connecting channel is connected to the incubation chamber at a radially outward location of the incubation chamber; wherein the siphon channel includes an inverse siphon and is connected to any downstream microfluidic structure; wherein the switching structure is partially filled with switching liquid; wherein the incubation structure is partially or completely filled with incubation liquid;wherein an air inclusion is formed in the connecting channel between the incubation fluid and the switching fluid; wherein a hydrostatic counterpressure is formed in the switching structure, with which the incubation fluid is held in the incubation chamber, and wherein the addition of additional switching fluid leads to the transfer of the switching fluid and the incubation fluid into any downstream microfluidic structure.

[0094] Although features of the invention have been described in each case with reference to device features or method features, it is obvious to those skilled in the art that corresponding features can also be part of a method or device. Thus, the device can be configured to perform corresponding method steps, and the respective functionality of the device can represent corresponding method steps.

[0095] In the foregoing Detailed Description, various features have been grouped together in examples in order to streamline the disclosure. This manner of disclosure should not be interpreted as intending that the claimed examples include more features than are expressly recited in each claim. Rather, as the following claims reflect, the subject matter may lie in fewer than all of the features of a single disclosed example. Accordingly, the following claims are hereby incorporated into the Detailed Description, with each claim being capable of standing as its own separate example.While each claim may stand as its own separate example, it should be noted that although dependent claims in the claims refer to a specific combination with one or more other claims, other examples also include a combination of dependent claims with the subject matter of any other dependent claim or a combination of any feature with other dependent or independent claims. Such combinations are intended to be encompassed unless it is stated that a specific combination is not intended. Furthermore, it is intended to encompass a combination of features of a claim with any other independent claim, even if that claim is not directly dependent on the independent claim.

[0096] The examples described above are merely illustrative of the principles of the present disclosure. It is understood that modifications and variations of the arrangements and details described will be apparent to those skilled in the art. Therefore, it is intended that the disclosure be limited only by the appended claims and not by the specific details set forth for the purpose of describing and explaining the examples.

Claims

Claims 1. A method for holding and transferring liquid using a fluidic module having a first liquid receiving area, a second liquid receiving area, a downstream fluidic structure, a siphon channel with an apex, and a connecting channel, wherein a radially outer portion of the first liquid receiving area with respect to a center of rotation is connected to the downstream fluidic structure via the siphon channel, and the radially outer portion of the first liquid receiving area is fluidically connected to an outlet of the second liquid receiving area via the connecting channel, the method comprising the following features: a) rotating the fluidic module about the center of rotation in order to drive portions of a first liquid introduced into the first liquid receiving area from the first liquid receiving area into the siphon channel and the connecting channel,to cause liquid menisci of the first liquid in the first liquid receiving area, the siphon channel and the connecting channel, without the first liquid passing through an apex of the siphon channel into the downstream fluidic structure and without the first liquid passing from the first liquid receiving area into the second liquid receiving area via the connecting channel, b) introducing a second liquid into the second liquid receiving area and rotating the fluidic module to drive parts of the second liquid from the second liquid receiving area into the connecting channel, thereby enclosing a gas volume between the first liquid and the second liquid in the connecting channel and generating a counterpressure in the gas volume, by means of which the second liquid is held in the second liquid receiving area and the connecting channel,and c) introducing additional liquid into the first liquid receiving region to move the liquid meniscus of the first liquid over the apex of the siphon channel, thereby emptying the first liquid from the first liquid receiving region via the siphon channel into the downstream fluidic structure, thereby reducing the backpressure in the gas volume and transferring the second liquid from the second liquid receiving region via the connecting channel and the siphon channel into the downstream fluidic structure.

2. Method according to claim 1, wherein introducing the first liquid into the first liquid receiving area, introducing the additional liquid into the first liquid receiving area and / or introducing the second liquid into the second liquid intake area is done manually or using a transfer module.

3. The method according to claim 1 or 2, wherein the fluidic module has a further liquid receiving area, a further downstream fluidic structure, a further siphon channel, and a further connecting channel, wherein a radially outer section of the further liquid receiving area with respect to the center of rotation is connected to the further downstream fluidic structure via the further siphon channel, and the radially outer section of the further liquid receiving area is fluidically connected to the first outlet or a further outlet of the second liquid receiving area via the further connecting channel, wherein the method has the following features: after or during a), rotating the fluidic module about the center of rotation in order to drive parts of a third liquid introduced into the further liquid receiving area from the further liquid receiving area into the further siphon channel and the further connecting channel,to cause liquid menisci of the third liquid in the further liquid receiving area, the further siphon channel and the further connecting channel, without the third liquid passing via an apex of the further siphon channel into the further downstream fluidic structure and without the third liquid from the further liquid receiving area passing via the further connecting channel into the second liquid receiving area, after c), introducing a fourth liquid into the first liquid receiving area and rotating the fluidic module to drive parts of the fourth liquid from the first liquid receiving area into the siphon channel and the connecting channel, in order to cause liquid menisci of the fourth liquid in the first liquid receiving area, the siphon channel and the connecting channel,without the fourth liquid passing through a vertex of the siphon channel into the downstream fluidic structure and without the fourth liquid passing from the first liquid receiving area into the second liquid receiving area via the connecting channel, Introducing a fifth liquid into the second liquid receiving area and rotating the fluidic module to drive parts of the fifth liquid from the second liquid receiving area into the connecting channel and the further connecting channel, thereby enclosing a gas volume between the third liquid and the fifth liquid in the further connecting channel and between the fourth liquid and the fifth liquid in the connecting channel and generating a further counterpressure by which the fifth liquid is held in the second liquid receiving area and the further connecting channel, and Introducing additional liquid into the further liquid receiving area to move the liquid meniscus of the third liquid over the apex of the further siphon channel, thereby emptying the third liquid from the further liquid receiving area via the further siphon channel into the further downstream fluidic structure, whereby the further back pressure is reduced and the fifth liquid is transferred from the second liquid receiving area via the further connecting channel and the further siphon channel into the further downstream fluidic structure.

4. The method according to any one of claims 1 to 3, wherein transferring the second liquid into the downstream fluidic structure causes the second liquid to be brought into contact with a reagent.

5. A fluidics module for carrying out a method according to any one of claims 1 to 4, comprising the first liquid receiving region, the second liquid receiving region, the siphon channel and the connecting channel, wherein the first liquid receiving region is vented, the second liquid receiving region is vented, the connecting channel has a first end fluidically connected to the first liquid receiving region and a second end opening into a radially outer portion of the second liquid receiving region, wherein the first end of the connecting channel is radially further outward than the second end of the connecting channel, and an outlet end of the siphon channel is arranged radially further outward than a radially outer end of the first liquid receiving region and than a radially outer end of the second liquid receiving region.

6. A fluidic module for carrying out a method according to claim 3, comprising the first liquid receiving region, the second liquid receiving region, the siphon channel, the connecting channel, the further liquid receiving region, the further downstream fluidic structure, the further siphon channel, and the further connecting channel, wherein the first liquid receiving region is vented, the second liquid receiving region is vented, the further liquid receiving region is vented, the connecting channel has a first end fluidically connected to the first liquid receiving region and a second end opening into a radially outer portion of the second liquid receiving region, wherein the first end of the connecting channel is radially further outward than the second end of the connecting channel, an outlet end of the siphon channel is arranged radially further outwards than a radially outer end of the first liquid receiving region and than a radially outer end of the second liquid receiving region, the further connecting channel has a first end which is fluidically connected to the further liquid receiving region and a second end which opens into a radially outer section of the second liquid receiving region, wherein the first end of the further connecting channel is radially further outwards than the second end of the further connecting channel, an outlet end of the further siphon channel is arranged radially further outwards than a radially outer end of the further liquid receiving region and than a radially outer end of the second liquid receiving region.

7. Fluidic module according to claim 6, wherein, in the azimuthal direction, the first liquid receiving region is arranged on one side of the second liquid receiving region and the further liquid receiving region is arranged on an opposite side of the second liquid receiving region.

8. Fluidic module according to one of claims 5 to 7, wherein the connecting channel has a channel section which extends radially inward and is arranged in the azimuthal direction on one side of the first liquid receiving region, and the siphon channel has a channel section which extends radially inward and is arranged in the azimuthal direction on an opposite side of the first liquid receiving region.

9. Fluidic module according to one of claims 5 to 8, wherein the first liquid receiving region is a fluid chamber, wherein the connecting channel and the siphon channel open into the fluid chamber on opposite azimuthal sides.

10. A fluid handling device comprising: a fluidic module according to any one of claims 5 to 9, and a drive device configured to rotate the fluidic module to perform a method according to any one of claims 1 to 4.

11. The fluid handling device of claim 10, further comprising at least one transfer module configured to introduce the first liquid into the first liquid receiving area, introduce the additional liquid into the first liquid receiving area, and / or introduce the second liquid into the second liquid receiving area.

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