Fluidic module, fluidic-treatment device and process involving temporary pressure equalization in a pneumatic chamber

Abstract

A fluidic module has a mixing chamber (2) and a pneumatic chamber (4). A first fluid path connects the mixing chamber (2) fluidically to the pneumatic chamber (4) in order to allow liquid to be transferred centrifugally from the mixing chamber (2) into the pneumatic chamber (4). A second fluid path connects the pneumatic chamber (4) fluidically to the fluid outlet (6). A pressure-equalizing channel (12) connects the pneumatic chamber (4) fluidically to the surroundings, the mixing chamber (2) and / or the fluid outlet (6), in order to allow a pressure equalization, and enters the pneumatic chamber (4) at a pressure-equalizing port. The pressure-equalizing port is arranged at such a position that it is closed by liquid transferred into the pneumatic chamber (4) via the first fluid path (8) after a defined volume of the liquid has been transferred into the pneumatic chamber (4) in order, after closing, to compress a gas enclosed in the pneumatic chamber (4) when there is a further centrifugal transfer of liquid from the mixing chamber (2) into the pneumatic chamber (4). An expansion of the compressed gas in the pneumatic chamber (4) at a first expansion rate has the effect that liquid is transferred from the pneumatic chamber (4) into the mixing chamber (2) via the first fluid path (8). An expansion of the compressed gas in the pneumatic chamber (4) at a second expansion rate, which is greater than the first expansion rate, has the effect that liquid is transferred from the pneumatic chamber (4) to the fluid outlet (6) via the second fluid path (10).

Description

[0001] Fluidics module, fluid handling device and method with temporary pressure equalization in a pneumatic chamber

[0002] Description

[0003] The present invention relates to fluidic modules, fluid handling devices, and methods that enable switching of fluid through a first fluid path and a second fluid path using a pneumatic chamber. Whether the fluid is transferred from the pneumatic chamber via the first fluid path or the second fluid path depends on the expansion rate of a compressed gas in the pneumatic chamber. In particular, the invention relates to such devices and methods suitable for handling fluids in a centrifugal microfluidic system.

[0004] Many processes implemented on centrifugal fluidic modules, which can also be referred to as centrifugal microfluidic cartridges, involve mixing processes. These include, for example, mixing liquids, dissolving lyophilized pellets, or mixing particles. The components to be mixed often have density differences, for example, when mixing blood plasma with buffers or dissolving lyophilized pellets.

[0005] To enable a controlled mixing process, a valve is required that keeps the liquid in the mixing chamber during mixing and then enables controlled further transfer. For example, capillary valves, siphon structures, or pneumatic valves can be used for this purpose in isothermal playback devices. Breakthrough frequencies of capillary valves are too low to allow a robust and flexible design. Siphon structures can only be used for highly hydrophilic or highly hydrophobic liquids. Therefore, only pneumatic valves are suitable for slightly hydrophobic or hydrophilic liquids.

[0006] Various mixing approaches are known. Reciprocal mixing or shake-mode mixing are possible mixing operations on isothermal devices (players). Reciprocal mixing takes a long time and is described, for example, in WO 2005 / 061084 A1 or in Z. Noroozi et al., "Reciprocating flow-based centrifugal microfluidics mixer," Review of Scientific Instruments, Volume 80, June 2009. In reciprocal mixing, liquids are pumped back and forth between two chambers on a rotating system, thereby mixing them.

[0007] Shake-mode mixing allows components with different densities to be efficiently mixed at frequency zero crossings. Shake-mode mixing, also known as batch-mode mixing, aims to mix substances in a rotating system. An alternating frequency protocol generates inertial forces during acceleration phases, which, in conjunction with the geometry of the mixing chamber, generate vortices to mix the substances. One such process is described, for example, in M. Grumann et al., "Batch-mode mixing on centrifugal microfluidic platforms," ​​Review of Scientific Instruments, pages 560-565, March 16, 2005.

[0008] A pneumatic valve is understood herein to be a microfluidic valve in which centrifugal forces generate pneumatic pressure in a pneumatic chamber, which can be used to specifically direct fluids radially inward or via a siphon. An example of such a pneumatic valve is described in I. Schwarz et al., "System-level network simulation for robust centrifugalmicrofluidic lab-on-a-chip systems", Lab on a Chip, Volume 16, pages 1873-1885, March 29, 2016. This describes fluidic structures that form a pneumatic valve and are used for mixing. The fluidic structures have a mixing chamber and a pneumatic chamber. A fluid channel branches at a T-junction into a first fluid channel that opens into the mixing chamber and a second fluid channel that has a siphon valve. Fluid is first driven from an inlet chamber into the pneumatic chamber under rotation.Mixing then occurs, with the rotation rate being repeatedly changed at such acceleration / deceleration rates that the siphon valve does not switch. After mixing is complete, deceleration occurs at such a high deceleration rate that the siphon valve switches, and the liquid is transferred through the second fluid channel.

[0009] DE 10 2013 203 293 A1 describes a structure for pneumatic switching in which a fluid can be guided radially outward through various channels using a pneumatic valve. Which of the channels is used can be determined by the frequencies and accelerations. The structure has a compression chamber, wherein an inlet channel, a first outlet channel, and a second outlet channel are fluidically coupled to the compression chamber. The first outlet channel and the second outlet channel are designed such that when a gas compressed in the compression chamber expands at a first expansion rate, the fluid is guided via the first outlet channel, and when the compressed gas expands at an expansion rate that is lower than the first expansion rate, the fluid is guided via the second outlet channel.

[0010] Methods for pumping liquids inward in centrifugal microfluidic systems against centrifugal forces are described, for example, in DE 10 2012 202 775 A1. Centrifugal forces force a liquid into a closed chamber, compressing a compressible medium present there, such as air. Upon significant deceleration, the liquid is pumped radially inward through an outlet channel with low fluidic resistance.

[0011] WO 2014 / 198703 A1 discloses the use of a diffusion barrier, which can be used to reduce the vapor pressure in the chamber of a pneumatic valve. The chamber is divided into two sections and connected by a channel. The goal is to ensure that the liquid only reaches the first section. The channel delays the saturation of the air in the second section, and the vapor pressure builds up slowly.

[0012] Description of the invention

[0013] The present invention is based on a conventional pneumatic valve consisting of a mixing chamber, a pneumatic chamber, and an outlet chamber. The mixing chamber is located radially further inward than the pneumatic chamber. A siphon channel with low fluid resistance connects the pneumatic chamber and the outlet chamber. A resistance channel with high fluid resistance leads from the mixing chamber via a T-junction into the siphon channel, thus connecting the mixing and pneumatic chambers. Fluid is introduced into the mixing chamber and, due to centrifugal forces, enters the pneumatic chamber. Pneumatic pressure is built up in the pneumatic chamber, which can be used to switch the siphon to transfer the fluid further radially inward or outward.

[0014] As fluid enters the pneumatic chamber, the air becomes saturated, creating vapor pressure. At low frequencies, vapor pressure can completely displace the fluid from the chamber. This can lead to two problems. First, the T-junction can be emptied, resulting in bubble formation that prevents the siphon from switching. Second, the fluid can rise in the siphon and prematurely switch it. Thus, the classic pneumatic valve cannot be robustly designed for shake-mode mixing with frequency zero crossings.

[0015] The vapor pressure increases the lower the initial air saturation and the higher the temperature. Fluid cartridges are often stored in dry conditions, for example, because moisture-sensitive reagents are stored upstream. This increases the risk of malfunction, as do the high or monotonically rising temperatures required for many assays.

[0016] Without a reduction in vapor pressure, there is currently no efficient and robust mixing process for mixing and switching slightly hydrophilic and slightly hydrophobic liquids with density differences for devices with constant or increasing temperatures. Furthermore, the design of a conventional pneumatic valve can be very complex, and robust operation cannot be guaranteed for some other applications (e.g., where space is limited).

[0017] It is the object of the invention to provide a fluidics module, a fluid handling device and a method that enable mixing of liquids and / or mixing of liquid and solids in a robust manner.

[0018] This object is achieved by a fluidic module according to claim 1, a fluid handling device according to claim 12 and a method according to claim 13.

[0019] Examples of the invention provide a fluidics module with a mixing chamber, a pneumatic chamber, a fluid outlet, a first fluid path, a second fluid path, and a pressure equalization channel. The first fluid path fluidically connects the mixing chamber to the pneumatic chamber to enable liquid to be centrifugally transferred from the mixing chamber to the pneumatic chamber. The second fluid path fluidly connects the pneumatic chamber to the fluid outlet. The pressure equalization channel fluidly connects the pneumatic chamber to the environment, the mixing chamber, and / or the fluid outlet to enable pressure equalization.The pressure equalization channel opens into the pneumatic chamber at a pressure equalization orifice, wherein this pressure equalization orifice is arranged in such a position that it is closed by liquid transferred into the pneumatic chamber via the first fluid path after a defined volume of the liquid has been transferred into the pneumatic chamber in order to compress a gas trapped in the pneumatic chamber after closing during a further centrifugal transfer of liquid from the mixing chamber into the pneumatic chamber.Expansion of the compressed gas in the pneumatic chamber at a first expansion rate causes liquid to be transferred from the pneumatic chamber to the mixing chamber via the first fluid path, and expansion of the compressed gas in the pneumatic chamber at a second expansion rate greater than the first expansion rate causes liquid to be transferred from the pneumatic chamber to the fluid outlet via the second fluid path.

[0020] The mixing chamber, the pneumatic chamber, the first fluid path, the second fluid path, and the fluid outlet, which can be connected to an outlet chamber, form a pneumatic valve for switching fluid, wherein vapor pressure in the pneumatic chamber can be at least partially reduced through the pressure equalization channel. The pressure equalization channel enables flexible design and robust operation of the pneumatic valve and thus robust mixing using the pneumatic valve. As soon as fluid enters the pneumatic chamber via the first fluid path, the gas saturates, and the resulting vapor pressure can escape via the pressure equalization channel. The pressure equalization channel is closed when a defined volume of fluid has entered the pneumatic chamber.If further liquid enters, pneumatic pressure is then built up, which can be used at high deceleration rates to transfer liquid through the second fluid path, for example, to switch a siphon channel of the second fluid path. At low deceleration rates, the liquid is pumped back into the mixing chamber. If the vapor pressure has been completely reduced, at low deceleration rates the pneumatic chamber only empties to the radial position of the opening of the pressure equalization channel into the pneumatic chamber. This allows strong shake modes with frequency zero crossings to be realized without transferring liquid through the second fluid path. Without the pressure equalization channel, this is not reliably possible.

[0021] In examples, the second fluid path for fluid flow from the pneumatic chamber to the fluid outlet has a lower fluid resistance than the first fluid path for fluid flow from the pneumatic chamber into the mixing chamber, and the second fluid path has a channel portion that extends radially further inward than a radially innermost portion of the first fluid path. Thus, it is possible to appropriately transfer the fluid either through the first fluid path or through the second fluid path, depending on the expansion rate of the gas (which is a compressible medium).

[0022] In examples, the second fluid path comprises a siphon channel whose apex is arranged radially further inward than a radially innermost section of the first fluid path. The radially innermost section of the first fluid path can be the mouth of the first fluid path into the mixing chamber or an apex of a siphon channel of the first fluid path. Thus, it is possible to transfer the liquid via the siphon channel of the second fluid path to the fluid outlet, which is arranged radially further outward than the mouth of the second fluid path into the pneumatic chamber. Furthermore, stable mixing can be reliably implemented by subjecting the fluidic module to rotation at a rotational frequency protocol in which priming of the siphon channel of the second fluid path is prevented during mixing.

[0023] In examples, the fluid outlet is arranged radially further inward than a radial position at which the second fluid path opens into the pneumatic chamber. Thus, examples enable pumping of fluid radially inward after, for example, shake-mode mixing with frequency zero crossings has been performed. In examples, the fluid outlet is arranged radially further inward than a radial position at which the first fluid path opens into the mixing chamber or than an apex of a siphon of the first fluid path, if the first fluid path has a siphon.

[0024] In some examples, an end of the pressure equalization channel remote from the pressure equalization opening opens into the environment or into a vented area of ​​the fluidic structures of the fluidic module, for example, the mixing chamber or an outlet chamber into which the second fluid path opens. In such examples, the pressure equalization channel can also be referred to as a vent channel, and the resulting vapor pressure can be reliably dissipated until the fluid penetrating the pneumatic chamber closes the pressure equalization opening.

[0025] In some examples, the position of the pressure equalization port is located radially further inward than the position where the first fluid path opens into the pneumatic chamber. This makes it possible to maintain a defined fluid volume in the pneumatic chamber even during shake-mode mixing with frequency zero crossings, thus preventing the first fluid path from running idle during shake-mode mixing.

[0026] In examples, the first fluid path and the second fluid path have a common channel section that opens into the pneumatic chamber, wherein the common channel section divides at a junction into a channel section of the first fluid path that opens into the mixing chamber and a channel section of the second fluid path that leads to the fluid outlet. The first fluid path and the second fluid path can form a T-junction, as in conventional pneumatic valves. This makes it possible to draw on existing knowledge regarding the design of the first and second fluid paths to achieve the functionalities described herein.

[0027] In examples, the first fluid path opens into the mixing chamber in a radially outer region of the mixing chamber. The mixing chamber can thus be emptied by centrifugal force via the first fluid path up to the position at which the first fluid path opens into it. In examples, the first fluid path opens into the mixing chamber at the radially outer end of the mixing chamber, which enables corresponding complete emptying. In examples, the first and second fluid paths open into the pneumatic chamber in a radially outer region of the pneumatic chamber. In examples, a common channel section of the first and second fluid paths opens into the pneumatic chamber.

[0028] In examples, the fluidics module further comprises one or more inlet chambers fluidically coupled to the mixing chamber for centrifugally transferring liquid from the one or more inlet chambers into the mixing chamber. Examples thus enable automated introduction of liquid into the mixing chamber on a centrifugal platform using the inlet chamber(s). In examples, the fluidics module further comprises an outlet chamber into which an end of the second fluid path remote from the pneumatic chamber opens and which is configured to receive liquid transferred via the second fluid path to the fluid outlet. Examples thus enable the transfer of the liquid after mixing to an outlet chamber, which may be configured for processing and / or evaluating the mixed liquid.

[0029] In some examples, the first fluid path includes a siphon channel configured to switch when a liquid level in the mixing chamber exceeds a predetermined level. This makes it possible to enable bubble-free filling of the downstream fluidic structures.

[0030] Examples provide a fluid handling device comprising a fluidic module as described herein and a drive device. The drive device is configured to: in a first phase, rotate the fluidic module at a rotational frequency to transfer liquid from the mixing chamber into the pneumatic chamber and compress gas trapped in the pneumatic chamber; in a second phase, reduce the rotational frequency at a deceleration rate at which the compressed gas expands at an expansion rate that causes liquid to be transferred from the pneumatic chamber via the first fluid path into the mixing chamber; in a third phase, control the rotational frequency to switch multiple times between rotations in different directions or to switch multiple times between different rotational frequencies in one rotational direction to effect mixing of the liquid in the mixing chamber.in a fourth phase, to increase the rotational frequency to transfer the liquid from the mixing chamber to the pneumatic chamber and to compress gas trapped in the pneumatic chamber, and in a fifth phase, to reduce the rotational frequency at a deceleration rate at which the compressed gas expands at an expansion rate that causes liquid to be transferred from the pneumatic chamber via the second fluid path to the fluid outlet.

[0031] In examples, the drive device is configured to apply a rotation according to a specific frequency protocol to the fluidic module in order to effect the functionalities described herein, for example, to effect rotations with corresponding rotational frequencies and deceleration rates in the first to fifth phases.

[0032] Examples provide a method for mixing one or more liquids using a fluidics module as described herein, having the following features:

[0033] Introducing one or more liquids into the mixing chamber,

[0034] Rotating the fluidic module at a rotational frequency to transfer liquid from the mixing chamber to the pneumatic chamber and to compress gas trapped in the pneumatic chamber,

[0035] Reducing the rotation frequency at a deceleration rate at which the compressed gas expands at an expansion rate that causes fluid to be transferred from the pneumatic chamber via the first fluid path into the mixing chamber,

[0036] Controlling the rotation frequency to switch several times between rotations in different directions or to switch several times between different rotation frequencies in one direction of rotation in order to cause mixing of the liquid in the mixing chamber and / or to cause mixing of the liquid in the mixing chamber with solids upstream in the mixing chamber,

[0037] Increasing the rotation frequency to transfer the liquid from the mixing chamber to the pneumatic chamber and to compress gas trapped in the pneumatic chamber, and

[0038] Reducing the rotational frequency at a deceleration rate at which the compressed gas expands at an expansion rate that causes fluid to be transferred from the pneumatic chamber to the fluid outlet via the second fluid path.

[0039] Examples thus provide fluid handling devices and methods suitable for robust mixing under changes in rotational frequency and / or rotational direction. When reducing the rotational frequency at a deceleration rate at which the compressed gas expands at a rate that causes liquid to be transferred from the pneumatic chamber into the mixing chamber via the first fluid path, the pneumatic chamber does not empty completely, but only to the radial position where the pressure equalization channel opens into it. Thus, the first fluid path can be reliably prevented from being completely emptied during the mixing process, even during frequency zero crossings of the mixing process.In some examples, the introduction of one or more liquids into the mixing chamber occurs while the fluidics module rotates to centrifugally transfer the one or more liquids from one or more inlet chambers into the mixing chamber. This enables further automation on a centrifugal platform.

[0040] In some examples, an overpressure created by gas saturation in the pneumatic chamber when the liquid is transferred from the mixing chamber to the pneumatic chamber is at least partially relieved via the pressure equalization channel. This makes it possible to at least partially or completely relieve the vapor pressure and / or the escape of gases from the liquid, for example, after a pellet has been released, before the pressure equalization opening is closed by the liquid.

[0041] Short description of the drawings

[0042] Examples of the present invention are explained in more detail below with reference to the accompanying drawings. They show:

[0043] Fig. 1 is a schematic representation of an example of a fluidic module according to the invention;

[0044] Fig. 2 is a schematic representation of an example of a fluidic module according to the invention with inlet chambers and outlet chamber;

[0045] Fig. 3 is a schematic representation of an example of a fluidic module according to the invention with a siphon in the first fluid path;

[0046] Fig. 4 schematic representations of the example shown in Fig. 3 in different operating phases A to F;

[0047] Fig. 5 is a schematic representation of a rotation frequency protocol for

[0048] Carrying out an example of a method according to the invention;

[0049] Fig. 6 is a schematic representation of an example of a fluidic module according to the invention with a radially inwardly arranged outlet chamber; Fig. 7A is a schematic representation of an example of a fluidic module according to the invention with closed fluidics;

[0050] Fig. 7B and 7C are schematic representations of examples of fluidic modules according to the invention in which the pressure equalization channel is connected to an outlet chamber or inlet chambers; and

[0051] Figs. 8A and 8B are schematic representations of examples of fluid handling devices according to the invention.

[0052] Detailed description

[0053] Examples of the present disclosure are described in detail below with the 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 in order 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.

[0054] Before further explaining examples of the present disclosure, definitions of some terms used herein are provided.

[0055] The term liquid, as used herein, includes, as will be obvious to those skilled in the art, in particular liquids containing solid components, such as suspensions, biological samples, and reagents. A siphon or siphon channel is understood herein to be a microfluidic channel or section of a microfluidic channel in a fluidic module (a centrifugal microfluidic cartridge), in which the inlet and outlet of the channel (when used in a centrifugal microfluidic system or a centrifugal microfluidic platform) are at a greater distance from the center of rotation than an intermediate region of the channel. A siphon apex is understood to be the region of a siphon channel in a fluidic module with the minimal distance from the center of rotation.Since the apex of such a siphon in the centrifugal field is inverted compared to the arrangement of a typical siphon in the Earth's gravitational field, such a siphon in the centrifugal field could also be called an inverted siphon.

[0056] A fluidic module is understood here to be a module, for example a cartridge, that has microfluidic structures designed to enable liquid handling as described herein. A centrifugal microfluidic fluidic module (cartridge) is understood to be a corresponding module that can be subjected to rotation, for example in the form of a fluidic module that can be inserted into a rotating body or a rotating body. In examples of the present invention, the fluidic module is a centrifugal microfluidic fluidic module.

[0057] A pneumatic chamber is understood here to be a fluid chamber in which pneumatic pressure can be built up by compressing a compressible medium contained therein.

[0058] 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, for example, be 1 / 100 or 1 / 1000 of the flow resistance of the channel structure connected to the chamber with the smallest flow resistance. Examples of the invention can find particular application in the field of centrifugal microfluidics, which involves the processing of liquids in the picoliter to milliliter range.Accordingly, the fluidic structures can have suitable dimensions in the micrometer range for handling corresponding liquid volumes.

[0059] 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.

[0060] Unless otherwise stated herein, room temperature (20°C) shall be assumed with regard to temperature-dependent quantities.

[0061] Examples of the present disclosure provide microfluidic structures and methods in a centrifugal microfluidic system for centrifugo-pneumatic switching of liquids, and in particular, such structures and methods that enable mixing of liquids and / or liquids and solids. In particular, the invention is intended to be applicable to simple isothermal devices or even centrifuges, although this is not necessarily the case.

[0062] An example of a fluidic module M according to the invention is shown in Fig. 1. The fluidic module M has a mixing chamber 2, a pneumatic chamber 4, a fluid outlet 6, a first fluid path 8, a second fluid path 10, and a pressure equalization channel 12. The fluidic module M is rotatable about a center of rotation R, which is shown schematically in Fig. 1. The first fluid path 8 fluidically connects the mixing chamber 2 to the pneumatic chamber 4. The first fluid path 8 opens into the mixing chamber 2 in a radially outer region of the mixing chamber 2, preferably at a radially outer end, in order to enable complete emptying of the mixing chamber through the first fluid path 8. The first fluid path 8 slopes radially overall between the mixing chamber 2 and the pneumatic chamber 4, so that when the fluidic module M rotates, liquid can be centrifugally transferred from the mixing chamber 2 via the first fluid path 8 into the pneumatic chamber 4.The first fluid path 8 can open into the pneumatic chamber 4 in a radially outer region. In some examples, the first fluid path 8 opens into the pneumatic chamber 4 at the radially outer end of the pneumatic chamber 4. The second fluid path 10 fluidically connects the pneumatic chamber 4 to the fluid outlet 6. The second fluid path 10 opens into the pneumatic chamber 4 in a radially outer region thereof. In some examples, the second fluid path 10 opens into the pneumatic chamber 4 at the radially outer end of the pneumatic chamber 4 to enable complete emptying of the pneumatic chamber 4 via the second fluid path. The pressure equalization channel 12 opens into the pneumatic chamber 4 at an opening 14.

[0063] The orifice 14 is arranged at such a radial position that it is closed by fluid transferred into the pneumatic chamber 4 via the first fluid path 8, after a defined volume of fluid has been transferred into the pneumatic chamber 4. In examples, the orifice 14 can be arranged at a position that is radially further inward than the position at which the first fluid path 8 opens into the pneumatic chamber 4. The defined volume can then be given by the cross-sectional area of ​​the pneumatic chamber 4 viewed in the radial direction and the radial difference between the positions of the orifices of the pressure equalization channel 12 and the first fluid path 8.

[0064] In the example shown, the first fluid path 8 and the second fluid path 10 have a common channel section 20 that opens into the pneumatic chamber 4 and branches into a channel section 8a that is fluidically connected to the mixing chamber 2, and a channel section 10a that is fluidically connected to the fluid outlet 6. The branching can be implemented by a T-junction 22. The branching can be implemented by any intersection with three channels. In examples, the channel section 8a runs radially downwards and opens into a channel formed by the common channel section 20 and the channel section 10a. The first fluid path 8 is thus formed by the common channel section 20 and the channel section 8a, and the second fluid path is thus formed by the common channel section 20 and the channel section 10a.In alternative examples, the fluid paths 8 and 10 can also open into the pneumatic chamber separately from one another, for example at azimuthally spaced positions, in which case reference can be made to the corresponding teaching of DE 10 2012 202 775 A1.

[0065] As soon as the mouth 14 is closed by the liquid, a compressible medium (gas), such as air, enclosed therein can be compressed by a further centrifugal transfer of liquid into the pneumatic chamber 4. Before the pressure equalization channel is closed, an excess pressure that arises due to saturation of the gas in the pneumatic chamber 4 when the liquid is transferred from the mixing chamber 2 into the pneumatic chamber 4 can be at least partially dissipated via the pressure equalization channel. The cause of such an excess pressure can be the vapor pressure or the escape of gases from the liquid, for example if a pellet has been dissolved in the mixing chamber 2. In the example shown, the pressure equalization channel is fluidically coupled to the environment 16 and thus represents a venting channel.In other examples, the pressure equalization channel may be fluidly connected to the mixing chamber 2 or the fluid outlet 6 to enable pressure equalization with the mixing chamber 2 or the fluid outlet 6.

[0066] The mixing chamber 2, the pneumatic chamber 4, and the fluid paths 8 and 10 act as a pneumatic valve, in which centrifugal forces generate pneumatic pressure in the pneumatic chamber 4, which can be used to specifically direct liquids radially inward via the second fluid path or via a siphon. The first and second fluid paths 8 and 10 are designed such that when the compressed gas in the pneumatic chamber 4 expands at a first expansion rate, liquid is transferred from the pneumatic chamber 4 via the first fluid path 8 into the mixing chamber 2, and that when the compressed gas in the pneumatic chamber 4 expands at a second expansion rate that is greater than the first expansion rate, liquid is transferred from the pneumatic chamber 4 via the second fluid path 10 to the fluid outlet 6.The different expansion rates can be generated by different braking rates (deceleration rates) with which the fluidic module M is decelerated from a higher rotational speed.

[0067] The first fluid path 8 represents a resistance channel that presents a higher fluid resistance (flow resistance) for fluid flow from the pneumatic chamber 4 to the mixing chamber 2 than the second fluid path 10 presents for fluid flow from the pneumatic chamber to the flow outlet 6. When comparing fluid resistances, this applies to identical fluids at the same temperature, typically room temperature (20°C). The second fluid path 10 has a section that extends radially further inward than the radially innermost section of the first fluid path 8.Thus, starting from a state in which a compressible medium is compressed in the pneumatic chamber, it is possible to transfer fluid through the first fluid path 8 back into the mixing chamber 2 by decelerating the fluidic module M at a first deceleration rate, and to transfer fluid through the second fluid path 10 to the fluid outlet by decelerating the fluidic module at a second deceleration rate that is higher than the first deceleration rate. The radially innermost section can be the radial position at which the first fluid path 8 opens into the mixing chamber 2, or can be an apex of a siphon if the first fluid path 8 has a siphon. The section of the second fluid path 10 that extends radially further inward than the radially innermost section of the first fluid path 8 can be the fluid outlet 6, e.g.if the second fluid path 10 is fluidically coupled to an outlet chamber at the fluid outlet 6, or may be the apex of a siphon if the second fluid path 8 has a siphon.

[0068] With regard to the functionality of transferring the liquid through the first fluid path or the second fluid path and the design of the first fluid path and the second fluid path to achieve this functionality, reference may be made to the relevant teachings of DE 10 2012 202 775 A1 and DE 10 2013 203 293 A1, which are hereby incorporated by reference.

[0069] In contrast to known pneumatic microfluidic valves, the invention provides a pressure equalization channel 12 through which pressure equalization takes place, allowing vapor pressure to be at least partially reduced before the opening of the pressure equalization channel 12 is closed by liquid flowing in via the first fluid path 8. Thus, the invention enables robust shake-mode mixing, even with frequency zero crossings.

[0070] The above statements regarding the example shown in Fig. 1 also apply to the other examples described herein. Fig. 2 shows an example of a fluidic module M according to the invention in the form of a centrifugo-pneumatic fluidic module for mixing and switching liquids. In addition to the mixing chamber 2, the pneumatic chamber 4, the fluid outlet 6, the first fluid path 8, the second fluid path 10, and the pressure equalization channel 12, the fluidic module shown in Fig. 2 has a plurality of inlet chambers 24a, 24b and an outlet chamber 26, wherein the opening of the second fluid path 10 into the outlet chamber 26 represents the fluid outlet 6. The second fluid path 10 has a siphon 28, the apex 28S of which lies radially further inward than the opening of the first fluid path 8 into the mixing chamber 6.The fluid outlet 6 is located radially further outward than the opening of the second fluid path 10 into the pneumatic chamber 4, so that the fluid from the pneumatic chamber 4 can be emptied into the outlet chamber 26 after the siphon 28 has been fully primed. The first fluid path 8, and in particular the channel section 8a from the T-junction 22 to the mixing chamber 2, has a high fluidic resistance, which is higher than the fluidic resistance of the channel section 10a from the T-junction 22 to the fluid outlet 6. To enable switching of the siphon 28, design parameters are selected such that, during deceleration to transfer fluid into the outlet chamber 26, sufficient fluid enters the siphon channel 28 so that the meniscus in the siphon channel 28 is radially further outward than the meniscus in channel 8 or in the mixing chamber 2.Important design parameters are the rotation frequencies, the deceleration rate, the volumes of the pneumatic chamber 4 and the fluidic paths 8 and 28, the fluidic resistances of the fluidic paths 8 and 28, the radial position of the chambers, their orifices, the radial position of the siphon apex 28S, and the geometries of the pneumatic chamber 4 and the mixing chamber 2. These are the most important parameters, although other parameters may also play a role. In examples, the first fluid path 8, and in particular the channel section 8a from the T-junction 22 to the mixing chamber 2, may have a high fluidic resistance that is higher than the fluidic resistance of the channel section 10a from the T-junction 22 to the fluid outlet 6. This can simplify selecting the design parameters to enable switching of the siphon 28.

[0071] The mixing chamber 2, the inlet chambers 24a and 24b, and the outlet chamber 26 are vented, as schematically shown in Fig. 2 by vents 30. The pressure equalization channel 12 vents the pneumatic chamber 4 into the environment 16. Alternatively, as indicated in Fig. 2 by a channel 32, the pressure equalization channel 12 can be fluidically connected to a vented area of ​​the mixing chamber 2. The opening 14 of the pressure equalization channel 12 into the pneumatic chamber 4 is located radially further inward than the opening of the siphon channel 28 into the outlet chamber 26, i.e., than the fluid outlet 6. The opening of the common channel section 20 into the pneumatic chamber 4 is located radially further inward than the fluid outlet 6.

[0072] As indicated in Fig. 2, a radially outer region of the pneumatic chamber may have a smaller cross-sectional area in the radial direction than the rest of the pneumatic chamber 4 in order to define a defined volume VT, which is indicated by a dashed line in Fig. 2. When this defined volume of fluid has been transferred into the pneumatic chamber 4, the pressure equalization channel 12 is closed by this fluid.

[0073] The outlet chamber can be configured for processing the liquid, for example, by storing reagents upstream or by having structures that allow the liquid to be divided into multiple subvolumes. The outlet chamber can be configured for analysis by making at least parts of the structures forming the outlet chamber transparent to enable optical detection. The outlet chamber can be fluidically coupled to downstream fluidic structures, for example, an aliquoting structure.

[0074] Liquids to be mixed are guided from the inlet chambers 24a and 24b into the mixing chamber 2 under rotation by centrifugal forces. Alternatively, only one inlet chamber could be provided, through which a liquid to be mixed or to be mixed with solids in the mixing chamber is introduced into the mixing chamber. Alternatively, different liquids can be introduced into the mixing chamber one after the other via the same inlet chamber. Already during the filling of the mixing chamber 2, the liquid is conveyed by rotation via the first fluid path 8, which has the resistance channel 8a, into the pneumatic chamber 4. As soon as the liquid reaches the pneumatic chamber 4, the gas in the pneumatic chamber 4 becomes saturated, and a vapor pressure develops in the gas volume. As long as the fill level in the pneumatic chamber 4 lies radially further out than the opening (orifice) 14 of the pressure equalization channel 12, the vapor pressure escapes via the pressure equalization channel 12.If the fill level continues to rise, pneumatic pressure builds up in the pneumatic chamber 4 until an equilibrium between centrifugal and pneumatic pressure is reached. To carry out a shake-mode mixing process, the liquids to be mixed are transferred into the mixing chamber 2. For this purpose, a slow deceleration takes place, i.e., the rotational frequency is reduced at such a low rate that liquid is pumped back into the mixing chamber 2 via the first fluid path 8 by the pneumatic pressure in the pneumatic chamber 4. Due to the low deceleration rate, the expansion of the compressed gas in the pneumatic chamber 4 takes place sufficiently slowly to prevent switching (priming) of the siphon 28. If the deceleration took place too quickly, the siphon 28 would be switched.Because the vapor pressure has been reduced, the fill level in the pneumatic chamber 4 only drops to the opening 14 of the pressure equalization channel 12 during slow deceleration. A shake mode with frequency zero crossings (or without frequency zero crossings) can be carried out and maintained for any length of time.

[0075] Without the pressure equalization channel, at low frequencies, all the fluid could be forced out of the pneumatic chamber 4. On the one hand, this could lead to the T-junction being emptied and air bubbles forming in the common channel section 20 and the siphon channel 28, preventing further flow through the siphon 28. On the other hand, this could lead to the siphon 28 being activated too early. Both errors can be avoided by the pressure equalization channel 12.

[0076] After shake-mode mixing, the mixed fluid can be transferred from the mixing chamber 2 back into the pneumatic chamber 4 by increasing the rotational frequency, so that pneumatic pressure is built up in the pneumatic chamber 4. A subsequent rapid deceleration switches the siphon 28 through the pneumatic pressure, and the fluid can be transferred further radially outward through the second fluid path 10 into the outlet chamber 26.

[0077] The volume VT, which is located radially further outward in the pneumatic chamber 4 than the opening 14 of the pressure equalization channel, can be referred to as the dead volume, since this volume is not mixed in the mixing chamber 2. Due to the small chamber volumes in microfluidic cartridges, the air saturates very quickly, so that with a sufficiently large dead volume or sufficiently slow filling, the entire vapor pressure can be reduced. A suitable volume V Tcan be adjusted by the radial difference between the openings of the first fluid path and the pressure equalization channel as well as a corresponding cross-sectional area of ​​the area of ​​the pneumatic chamber there.

[0078] As explained above, the pressure equalization channel 12 can serve as a venting channel to reduce the vapor pressure in the pneumatic chamber 4 compared to the ambient pressure. If the mixing chamber 2 is vented from the environment, the pressure equalization channel 12 can also be led from the pneumatic chamber 4 into the mixing chamber 2, as shown schematically in Fig. 2 by a dashed line 32 representing a fluid channel. The direct connection of the pressure equalization channel 12 to the environment 16 can then be omitted. The pressure equalization channel 32 must be led radially further inward into the mixing chamber 2 than the maximum fill level in the mixing chamber 2. Depending on the design of the pneumatic valve, it may happen that fluid is pumped from the pneumatic chamber 4 through the pressure equalization channel 32 into the mixing chamber 2. This is not a problem since the fluids are the same.

[0079] During the transfer of liquids into the mixing chamber 2, air bubbles may form in the first fluid path 8, which represents a resistance channel, at the outlet of the mixing chamber 2. This can happen if the inflow velocity into the mixing chamber 2 is lower than the outflow velocity through the first fluid path 8. Fig. 3 shows an example of a fluidic module M in which such bubble formation is prevented. In the following, only differences between the fluidic module shown in Fig. 3 and the fluidic module shown in Fig. 2 are described, whereby the above description also applies to the fluidic module M shown in Fig. 3. In the example shown in Fig. 3, the first fluid path 8 and in particular the channel section 8a thereof has a siphon channel 38 which forms a volume siphon in the resistance channel.The siphon channel 38 is designed to only switch when there is enough fluid in the mixing chamber 2 to fill the downstream structures without bubbles. The siphon channel 38 thus prevents the fluid from immediately switching to the pneumatic chamber 4, so that the inflow from 24a and 24b can be less than the outflow through the siphon channel 38 without air bubbles forming. An apex 38S of the siphon channel 38 is arranged radially further outward than the apex 28S of the siphon channel 28 of the second fluid path 10.

[0080] A method for shake-mode mixing using a fluidic module as shown in Fig. 3 is explained below with reference to Figs. 4 and 5. Fig. 4 shows the fluidic module during various operating phases or process steps A to F of the method. As shown in Fig. 4, the pressure equalization channel 32 in this example opens into a vented part of the mixing chamber 2, but could alternatively also be directly connected to the environment 16. Fig. 5 shows an example of a possible associated rotation frequency protocol, whereby the rotation frequencies shown are purely exemplary.

[0081] In an operating phase A, two liquids are transferred from the inlet chambers 24a and 24b into the mixing chamber 2 under rotation. In this example, the liquid from the inlet chamber 24b has a higher density and sediments in the mixing chamber 2. As soon as there is sufficient liquid in the mixing chamber 2, the siphon channel 28 is switched and the liquid passes through the T-junction 22 into the pneumatic chamber 4, as shown schematically in operating phase B in Fig. 4. The gas in the pneumatic chamber 4 saturates and a vapor pressure develops, which is dissipated via the pressure equalization channel 32. If the liquid transfer into the pneumatic chamber 4 is sufficiently slow, the vapor pressure can dissipate completely.After a defined liquid volume (VT) has been transferred into the pneumatic chamber 4, the overpressure channel 32 is closed and the remaining gas volume is compressed during the further liquid transfer, see operating phase C in Fig. 4.

[0082] After the inlet chambers 24A and 24b have been emptied, a slow deceleration takes place to reduce the excess pressure in the pneumatic chamber 4 without switching the siphon channel 28. The slow deceleration 40 (Fig. 5) takes place at a deceleration rate that is below a limit deceleration rate at which a liquid transfer via the second fluid path 10 would be effected, i.e., for example, the siphon channel 28 would be switched. As a result, the gas expands at such an expansion rate that the liquid is transferred from the pneumatic chamber 4 back into the mixing chamber 2. A certain liquid volume, corresponding to the dead volume VT, remains in the pneumatic chamber 4. On the one hand, this liquid volume cannot be mixed using a shake mode in the mixing chamber 2, and on the other hand, this guarantees that the T-junction 22 never runs dry and no air bubbles form there.

[0083] After the liquid is transferred into the mixing chamber 2, shake-mode mixing takes place in operating phase D. Shake-mode mixing can be performed with frequency zero crossings because the pneumatic pressure in the pneumatic chamber 4 is insufficient to switch the siphon channel 28. As shown in Fig. 5, the rotation frequency can be switched several times between different directions, while remaining lower than a rotation frequency that could be sufficient to switch the siphon channel 28. The strong shake-mode process allows even liquids with density differences to be mixed efficiently. In alternative examples, mixing could also be achieved by repeatedly changing the rotation frequency without reversing the direction, for example, by switching between rotation frequencies of 5 Hz and 15 Hz. Mixing with a change in the rotation direction is more effective.

[0084] After the mixing process, the rotation frequency is increased to transfer the mixed liquids into the pneumatic chamber 4 and thereby build up pneumatic pressure in the pneumatic chamber 4 at high frequencies, operating phase E. This is followed by a rapid deceleration 42, which switches the siphon channel 28. The rapid deceleration 42 takes place at a deceleration rate that is above the limit deceleration rate, so that the gas in the pneumatic chamber 4 expands at such an expansion rate that a liquid transfer is transferred via the second fluid path 10 into the outlet chamber 26. After the transfer to the outlet chamber, poorly mixed fractions of the liquid can optionally be separated, for example by increasing the rotation frequency, if the outlet chamber is designed accordingly, see operating phase F. For example, as shown in Fig.4, the outlet chamber may have a partition wall through which such a separation can take place in the event of changes in rotational frequency.

[0085] The rotational frequency during operating phases A, B, and C may be in a range that is higher than the rotational frequencies during mixing in operating phase D and lower than the rotational frequency in operating phase E, from which fluid transfer through the second fluid path takes place. The rotational frequency during operating phases A, B, and C may be in a range of 20 to 30 Hz, for example, 25 Hz. Mixing may be achieved by switching between rotational frequencies below 15 Hz, for example, switching between rotational frequencies of 10 Hz and -10 Hz. The rotational frequency in operating phase E may be increased to a frequency above 50 Hz, for example, 80 Hz.

[0086] In examples, the fluidic module is designed for inward pumping of the liquid. Fig. 6 shows an example of a fluidic module M, wherein differences from the example shown in Fig. 2 are again described and reference is made to the above description. In the example shown in Fig. 6, the second fluid path 10 and in particular the channel section 10a do not have a siphon channel, but extend radially inward to the fluid outlet 6. At the fluid outlet 6, the second fluid path opens into the outlet chamber 26. The fluid outlet 6, i.e. the opening of the second fluid path 10 into the outlet chamber 26, is located radially further inward than the opening of the fluid path 10 into the pneumatic chamber 4, so that when the liquid is transferred from the pneumatic chamber 4 via the second fluid path 10 into the outlet chamber 26, an inward pumping of the liquid takes place.The pressure reduction via the pressure equalization channel 12 prevents premature inward pumping or bubble formation in the T-junction. The channel section 10a of the second fluid path 10, which connects the T-junction 22 to the fluid outlet 6, has a lower fluidic resistance than the channel section 8a of the first fluid path 8, which connects the T-junction point 22 to the mixing chamber 2.

[0087] In the above examples, the mixing chamber is vented and, if present, the inlet chambers and the outlet chamber are vented. In alternative examples, the fluidics module can implement closed fluidics. As shown in Fig. 7A, it is also possible for the pressure equalization channel to be formed in a closed structure. The pressure equalization channel 12 fluidically connects the pneumatic chamber 4 to the other fluidic structures; there is no fluidic connection to the environment. More precisely, the pressure equalization channel 12 connects the pneumatic chamber 4 to the inlet chambers 24a, 24b, the mixing chamber 2, and the outlet chamber 26. In this case, pressure equalization takes place throughout the entire fluidic structure. There is no premature switching of the siphon channel 28 because the pneumatic chamber 4 does not have any overpressure relative to the outlet chamber 26.

[0088] Fig. 7B shows an example in which the pressure equalization channel 12 fluidically connects the pneumatic chamber 4 with the outlet chamber 26 and thus with the fluid outlet 6. The mixing chamber 2 is vented to the environment. Here, too, after closing the pressure equalization channel 12, it is possible to return to low rotational frequencies without prematurely switching the siphon channel 28.

[0089] Fig. 7C shows an example in which the pressure equalization channel 12 fluidically connects the pneumatic chamber 4 with the mixing chamber 2 and the inlet chambers 24a and 24b. However, this example is complicated to implement because, after the pressure equalization channel 12 is closed, further transfer from the mixing chamber 2 creates a negative pressure in the mixing chamber 2. In the examples shown in Figures 7A to 7C, the pressure equalization channel differs from the example shown in Fig. 2. Furthermore, the above statements also apply to the examples shown in Figures 7A to 7C.

[0090] Examples of the present invention provide a fluid handling device comprising a fluidic module M as described herein and a drive device for rotating the fluidic module to achieve the functionalities described herein.

[0091] Referring now to Figures 8A and 8B, examples of fluid handling devices in the form of centrifugal microfluidic systems according to examples of the invention will be described, respectively, which utilize or comprise a fluidic module as described herein. In other words, the fluidic module in the systems in Figures 8A and 8B can be any of the fluidic modules described herein.

[0092] Fig. 8A 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 rotation speed, or a CD or DVD drive. A control device 124 may be provided which is designed to control the drive device 120 in order to subject the rotating body 110 to a rotation or 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.

[0093] The rotating body 110 has 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.

[0094] In an alternative example shown in Fig. 8B, 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.

[0095] In Figures 8A and 8B, the center of rotation around which the fluidic module or the rotation body can rotate is again denoted by R.

[0096] In examples of the invention, the fluidic module or the rotating body comprising 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 110 can be considered a centrifugal microfluidic platform. In preferred examples, the fluidic module or the rotating body can be formed from a thermoplastic such as PP (polypropylene), PC, COP (cyclic olefin polymer), COC (cyclo olefin copolymer) or PS (polystyrene).

[0097] In examples, the drive device 120 and any of the fluidic modules described herein form an example of a fluid handling device according to the invention. In examples, the drive device 120 is configured, for example, controlled by the controller 124, to rotate the fluidic module M at a rotational frequency in a first phase to transfer liquid from the mixing chamber 2 into the pneumatic chamber 4 and to compress gas trapped in the pneumatic chamber 4, in a second phase to reduce the rotational frequency at a deceleration rate at which the compressed gas expands at an expansion rate that causes liquid to be transferred from the pneumatic chamber 4 via the first fluid path 8 into the mixing chamber 2, in a third phase to control the rotational frequency,to switch several times between rotations in different directions or to switch several times between different rotation frequencies in one rotation direction to cause mixing of the liquid in the mixing chamber 2, in a fourth phase to increase the rotation frequency to transfer the liquid from the mixing chamber 2 into the pneumatic chamber 4 and to compress gas trapped in the pneumatic chamber 2, and in a fifth phase to reduce the rotation frequency at a deceleration rate at which the compressed gas expands at an expansion rate that causes liquid to be transferred from the pneumatic chamber 4 via the second fluid path 10 to the fluid outlet 6.

[0098] In examples, the drive device is designed to perform a method as described above with reference to Figures 4 and 5. It goes without saying that a method as described above with reference to the example shown in Figure 3 can also be performed in the other described examples in a correspondingly adapted manner.

[0099] Examples of the present invention provide corresponding methods for effective mixing. Such methods can be carried out using fluidic modules and fluid handling devices as described herein. During mixing, a liquid can be thoroughly mixed, several liquids can be mixed with one another, particles can be mixed, solids stored upstream in the mixing chamber can be dissolved, or one or more liquids can be mixed with solids stored upstream in the mixing chamber, e.g., lyophilized pellets. In examples, the fluidic module has solids stored upstream in the mixing chamber, e.g., lyophilized pellets, which are to be mixed with liquid(s). In particular, components to be mixed with density differences can be mixed, for example, when mixing blood plasma with buffers or when dissolving lyophilized pellets.

[0100] Examples of the invention relate to the extension of a pneumatic valve by adding a pressure equalization channel to the pneumatic chamber. When the pneumatic chamber is filled with fluid, the pressure equalization channel (vent channel) is closed once a defined fluid volume has been reached. When the pneumatic chamber is filled, vapor pressure is generated, which can escape until the pressure equalization channel is closed. This allows the pneumatic valve to operate even at low frequencies without the siphon being activated.

[0101] The invention thus enables shake-mode mixing using shake-mode protocols with frequency zero crossings for pneumatic valves. This enables rapid mixing of liquids with density differences. In comparison, reciprocal mixing with a pneumatic valve is slow, as the deceleration must be slow to prevent premature switching via the siphon channel. Furthermore, liquids with density differences are poorly mixed during reciprocal mixing due to constant sedimentation.

[0102] Conventional pneumatic valves without a pressure equalization channel require a lot of space to operate at low frequencies, and their design is complex. If the vapor pressure is not reduced, robustness is low. This is critical because fluctuations in manufacturing, volume and properties of liquids, temperature, humidity, rotational frequency, and acceleration occur. In contrast, examples of the invention enable a more flexible and simpler design of pneumatic valves and increase their robustness against such tolerances.

[0103] Although features of the invention have been described in terms of device features or method features, it will be apparent to those skilled in the art that corresponding features may also be part of a method or device. For example, the device may be configured to perform corresponding method steps, and the respective functionality of the device may represent corresponding method steps. In the foregoing detailed description, various features have sometimes 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 contain more features than are expressly recited in each claim. Rather, as the following claims reflect, the subject matter may lie in fewer than all features of a individually disclosed example.Accordingly, the following claims are hereby incorporated into the Detailed Description, where each claim may stand 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.

[0104] 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 fluidic module having the following features: a mixing chamber, a pneumatic chamber, a fluid outlet, a first fluid path fluidically connecting the mixing chamber to the pneumatic chamber to enable centrifugal transfer of fluid from the mixing chamber into the pneumatic chamber, a second fluid path fluidically connecting the pneumatic chamber to the fluid outlet, a pressure equalization channel fluidically connecting the pneumatic chamber to the environment, the mixing chamber, and / or the fluid outlet to enable pressure equalization and opening into the pneumatic chamber at a pressure equalization opening, said pressure equalization opening being arranged in such a position that it is closed by fluid transferred into the pneumatic chamber via the first fluid path after a defined volume of fluid has been transferred into the pneumatic chamber,to compress a gas enclosed in the pneumatic chamber after closure during a further centrifugal transfer of liquid from the mixing chamber into the pneumatic chamber, wherein an expansion of the compressed gas in the pneumatic chamber at a first expansion rate causes liquid to be transferred from the pneumatic chamber to the mixing chamber via the first fluid path, and wherein an expansion of the compressed gas in the pneumatic chamber at a second expansion rate, which is greater than the first expansion rate, causes liquid to be transferred from the pneumatic chamber to the fluid outlet via the second fluid path.

2. Fluidic module according to claim 1, wherein the second fluid path has a siphon channel whose apex is arranged radially further inward than a radially innermost portion of the first fluid path.

3. Fluidic module according to claim 1, wherein the second fluid path for a fluid flow from the pneumatic chamber to the fluid outlet has a lower fluidic resistance than the first fluid path for a fluid flow from the pneumatic chamber into the mixing chamber, and wherein the second fluid path has a channel section which extends radially further inward than a radially innermost section of the first fluid path.

4. Fluidic module according to claim 1, wherein the fluid outlet is arranged radially further inward than a radial position at which the second fluid path opens into the pneumatic chamber.

5. Fluidic module according to one of claims 1 to 4, wherein an end of the pressure equalization channel remote from the pressure equalization opening opens into the environment or into a vented area of ​​the mixing chamber.

6. Fluidic module according to one of claims 1 to 5, wherein the position of the pressure equalization opening is radially further inward than a position at which the first fluid path opens into the pneumatic chamber.

7. Fluidic module according to one of claims 1 to 6, wherein the first fluid path and the second fluid path have a common channel section which opens into the pneumatic chamber, wherein the common channel section divides at a branch into a section of the first fluid path which opens into the mixing chamber and a section of the second fluid path which leads to the fluid outlet.

8. Fluidic module according to one of claims 1 to 7, wherein the first fluid path opens into the mixing chamber in a radially outer region of the mixing chamber and / or wherein the first and the second fluid path open into the pneumatic chamber in a radially outer region of the pneumatic chamber.

9. The fluidic module of any one of claims 1 to 8, further comprising one or more inlet chambers fluidly coupled to the mixing chamber for centrifugally transferring liquid from the one or more inlet chambers into the mixing chamber.

10. Fluidics module according to one of claims 1 to 9, further comprising an outlet chamber into which an end of the second fluid path remote from the pneumatic chamber opens, and which is designed to receive liquid transferred via the second fluid path to the fluid outlet. 1 1. Fluidic module according to one of claims 1 to 10, wherein the first fluid path comprises a siphon channel which is designed to switch when a Liquid level in the mixing chamber exceeds a predetermined level, wherein an apex of the siphon channel of the first fluid path represents one or the radially innermost portion of the first fluid path.

12. A fluid handling device having the following features: a fluidics module according to one of claims 1 to 11, and a drive device configured to rotate the fluidics module, wherein the drive device is configured to: in a first phase, rotate the fluidics module at a rotational frequency to transfer liquid from the mixing chamber into the pneumatic chamber and compress gas trapped in the pneumatic chamber; in a second phase, reduce the rotational frequency at a deceleration rate at which the compressed gas expands at an expansion rate that causes liquid to be transferred from the pneumatic chamber into the mixing chamber via the first fluid path; in a third phase, control the rotational frequency to switch multiple times between rotations in different directions or to switch multiple times between different rotational frequencies in one rotational direction,to cause mixing of the liquid in the mixing chamber, in a fourth phase, to increase the rotational frequency to transfer the liquid from the mixing chamber into the pneumatic chamber and to compress gas trapped in the pneumatic chamber, and in a fifth phase, to reduce the rotational frequency at a deceleration rate at which the compressed gas expands at an expansion rate that causes liquid to be transferred from the pneumatic chamber via the second fluid path to the fluid outlet.

13. A method for mixing one or more liquids using a fluidic module according to one of claims 1 to 11, having the following features: Introducing one or more liquids into the mixing chamber, Rotating the fluidic module at a rotational frequency to transfer liquid from the mixing chamber to the pneumatic chamber and to compress gas trapped in the pneumatic chamber, Reducing the rotation frequency at a deceleration rate at which the compressed gas expands at an expansion rate that causes fluid to be transferred from the pneumatic chamber via the first fluid path into the mixing chamber, Controlling the rotation frequency to switch several times between rotations in different directions or to switch several times between different rotation frequencies in one direction of rotation in order to cause mixing of the liquid in the mixing chamber and / or to cause mixing of the liquid in the mixing chamber with solids upstream in the mixing chamber, Increasing the rotation frequency to transfer the liquid from the mixing chamber to the pneumatic chamber and to compress gas trapped in the pneumatic chamber, and Reducing the rotational frequency at a deceleration rate at which the compressed gas expands at an expansion rate that causes fluid to be transferred from the pneumatic chamber to the fluid outlet via the second fluid path.

14. The method of claim 13, wherein the introduction of one or more liquids into the mixing chamber occurs while rotating the fluidic module to centrifugally transfer the one or more liquids from one or more inlet chambers into the mixing chamber.

15. The method according to claim 13 or 14, wherein an overpressure which arises due to saturation of the gas in the pneumatic chamber when the liquid is transferred from the mixing chamber into the pneumatic chamber is at least partially reduced via the pressure equalization channel.

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