Handling of two volumes of liquid

Abstract

A fluidic module for use in a centrifugal microfluidic system comprises a fluid chamber having a first chamber region and a second chamber region, separated from each other by a dividing wall which extends radially inward with regard to a rotation centre. A first outlet channel feeds into the first chamber region and constitutes, for a flow of liquid from the first chamber region, an outflow barrier in the form of a channel section rising radially inward, which extends up to a first radial position. A second outlet channel feeds into the second chamber region and constitutes, for a flow of liquid from the second chamber region, an outflow barrier in the form of a channel section rising radially inward, which extends up to a second radial position. The first radial position lies further radially inward than the second radial position, wherein the fluidic module is designed such that, preceding from a rotation in which hydrostatic pressure acting on the first and second liquid volumes prevents the liquid volumes from flowing through the first and second outlet channel out of the fluid chamber, a positive pressure in the total air volume which is required in order to transfer the first liquid volume out of the fluid chamber through the first outlet channel against the hydrostatic pressure acting on the first liquid volume, is greater than a positive pressure in the total air volume which is required in order to transfer the second liquid volume out of the fluid chamber through the second outlet channel against the hydrostatic pressure acting on the second liquid volume.

Description

[0001] Handling two liquid volumes

[0002] Area

[0003] The present invention relates to fluidic modules, devices and methods for handling two liquid volumes and in particular to fluidic modules, devices and methods suitable for receiving two liquid volumes in a fluid chamber and transferring them from the fluid chamber via separate outlet channels.

[0004] Introduction

[0005] Microfluidics deals with the handling of liquids in the femtoliter to milliliter range. In centrifugal microfluidics, microfluidic systems are operated in rotating systems to automate laboratory processes. All standard laboratory processes can be implemented in the system, which features a fluidic module, usually in the form of a disposable polymer cartridge. Thus, standard laboratory processes such as pipetting, centrifuging, mixing, or aliquoting can be implemented in a microfluidic cartridge, allowing entire laboratory processes to be automated. For this purpose, the fluidic modules or cartridges contain channels for fluid flow and chambers for collecting liquids. Through a predefined sequence of rotation frequencies, the liquids can be moved through the cartridge in a targeted manner using centrifugal force.Microfluidics is used in laboratory analysis and mobile diagnostics, among other areas.

[0006] For many potential applications, such as the extraction and purification of DNA (deoxyribonucleic acid), a variety of liquid reagents are required, such as lysis buffer, binding buffer, wash buffer, and elution buffer. These reagents are typically stored in tubular bags, so-called stick packs, on the microfluidic cartridge. The stick packs can be opened during processing using a combination of centrifugal force and temperature. A disadvantage of this approach is the relatively large space requirement, as each stick pack is typically stored in its own chamber if the liquid is to be pumped radially inward after the stick pack is opened. State of the art

[0007] Methods for liquid transport in centrifugal microfluidic systems and cartridges are known. For example, Zehnle, S., et al., "Pneumatic Siphon Valving and Switching in Centrifugal Microfluidics Controlled by Rotational Frequency or Rotational Acceleration," Microfluidics and Nanofluidics, 19.6 (2015), pages 1259-1269, disclose that a liquid can be distributed between two chambers via two different siphons. Liquid is centrifugally driven from an inlet chamber into a compression chamber. The compression chamber is connected to a first collection chamber via a first fluid channel with a first inverse siphon and to a second collection chamber via a second fluid channel with a second inverse siphon. The apex of the first inverse siphon is located radially further outward than the apex of the second inverse siphon, and the flow resistance of the first fluid channel is much greater than the flow resistance of the second fluid channel.Initially, rotation occurs at a speed at which air is compressed in the compression chamber. If, starting from this state, a slow deceleration occurs, the first siphon fills, and fluid is driven from the compression chamber through the first fluid channel into the first collection chamber. If, starting from this state, a rapid deceleration occurs, the majority is driven through the second siphon into the second collection chamber. The fluid is transported exclusively by centrifugal forces into the subsequent chambers, with pneumatic pressure being generated in the compression chamber, which is used for switching. A corresponding procedure is described in DE 10 2013 203 293 A1.

[0008] overview

[0009] The object underlying the present invention is to provide a fluidics module, a fluid handling device and a method which make it possible to transfer two fluid volumes from a fluid chamber through different outlet channels.

[0010] This object is achieved by a fluidic module according to claim 1, a fluid handling device according to claim 8, and a method according to claim 15. Examples of the present disclosure provide a fluidic module for use in a centrifugal microfluidic system, comprising: a fluid chamber having a first chamber region and a second chamber region, which are separated from one another by a partition wall extending radially inward with respect to a center of rotation, wherein a first liquid volume in the first chamber region can be stored separately from a second liquid volume in the second chamber region, while a common air volume is arranged radially within the first and second liquid volumes; a first outlet structure having at least one first outlet channel,which opens into the first chamber region and has an outflow barrier in the form of a radially inwardly rising channel section for a liquid flow out of the first chamber region, which extends to a first radial position; and a second outlet structure which has at least one second outlet channel which opens into the second chamber region and has an outflow barrier in the form of a radially inwardly rising channel section for a liquid flow out of the second chamber region, which outflow barrier extends to a second radial position, wherein the first radial position is radially further inward than the second radial position, so that, starting from a rotation in which a hydrostatic pressure acting on the first and second liquid volumes prevents the liquid volumes from flowing out of the fluid chamber through the first and second outlet structure, an overpressure in the common air volume which is requiredin order to transfer the first liquid volume from the fluid chamber through the first outlet structure against the hydrostatic pressure acting on the first liquid volume, is greater than an overpressure in the common air volume required to transfer the second liquid volume from the fluid chamber through the second outlet structure against the hydrostatic pressure acting on the second liquid volume.

[0011] Examples of the present disclosure thus relate to a fluidic module having fluidic structures with which liquids can be transported from a chamber to different areas of the fluidic module, for example, a centrifugal microfluidic cartridge. The common chamber is designed as a compression chamber to enable the generation of overpressure in the chamber, for example, by heating the common air volume in the chamber. Two spatially separated liquid volumes are present in the common chamber, with the chamber simultaneously serving to generate pressure and thus enabling the transport of the two liquids independently of one another.To make this possible, an overpressure required to transfer the first liquid volume from the fluid chamber through the first outlet structure against the hydrostatic pressure acting on the first liquid volume is greater than an overpressure in the common air volume required to transfer the second liquid volume from the fluid chamber through the second outlet structure against the hydrostatic pressure acting on the second liquid volume.

[0012] By generating an overpressure sufficient to transfer the second liquid volume out of the fluid chamber through the second outlet structure, but insufficient to transfer the first liquid volume out of the fluid chamber through the first outlet structure, it is thus possible to transfer the second liquid volume out of the fluid chamber independently of the first liquid volume. Subsequently, the first liquid volume can be transferred out of the fluid chamber by creating a ratio of hydrostatic pressure acting on the first liquid volume and overpressure in the fluid chamber at which the first liquid volume is transferred out of the fluid chamber through the first outlet structure.

[0013] In examples, the fluidic resistance of the second outlet structure for a fluid flow out of the fluid chamber is greater than the fluidic resistance of the first outlet structure for a fluid flow out of the fluid chamber. In examples, the fluidic resistance of the second outlet structure for venting from the fluid chamber is greater than the fluidic resistance of the first outlet structure for a liquid flow of the first liquid volume out of the fluid chamber. This makes it possible to generate a sufficient overpressure in the fluid chamber for the duration of the transport of the first liquid volume via the first outlet structure, wherein the fluid chamber is not prematurely vented via the second outlet structure once the transport via the second outlet structure is completed.To achieve this, the first outlet channel and the second outlet channel may be designed such that the fluidic resistance of the second channel is greater than that of the first channel.

[0014] In examples, the second outlet structure has a plurality of second outlet channels that open into the second chamber region, wherein the total fluidic resistance of the plurality of second outlet channels for a fluid flow out of the fluid chamber is greater than the fluidic resistance of the first outlet channel for a fluid flow out of the fluid chamber. Such examples make it possible to transfer portions of the second liquid volume via different outlet channels into different, redesigned fluidic structures. In examples, the second chamber region is separated into a plurality of chamber region sections by at least one radially inwardly extending region partition wall, wherein one of the plurality of second outlet channels opens into each of the chamber region sections. Thus, it is possible to transfer mutually separated portions of the second liquid volume to different downstream fluidic structures.

[0015] The term "outlet structure," as used herein, refers to one or more outlet channels. The term "fluidic resistance of an outlet structure" thus refers to the fluidic resistance of the outlet channel if the outlet structure has one outlet channel, or to the total fluidic resistance of multiple outlet channels if the outlet structure has multiple outlet channels.

[0016] In examples, a ratio of the fluidic resistance of the second outlet structure to the fluidic resistance of the first outlet structure when filled with the same fluid is at least a factor of 30, preferably a factor of at least 50. In examples, the second outlet structure can thus have such a fluidic resistance for venting the fluid chamber that the overpressure in the air volume in the fluid chamber, which is required to transfer the first liquid volume through the first outlet structure out of the fluid chamber against the hydrostatic pressure acting on the first liquid volume, at a given rotational frequency and at a given hydrostatic height of the apex of the first outlet channel, can be generated in the fluid chamber.It has been shown that a factor of 30 may be sufficient here, with a factor of at least 50 being preferred in order to enable a safe transfer of the first liquid volume from the first outlet structure.

[0017] In embodiments, fluidic structures of the fluidic module are designed to allow the second outlet structure to remain at least partially filled with liquid or to be refilled with liquid following the transfer of the second liquid volume through the second outlet structure. As a result, the fluidic resistance of the second outlet structure during a liquid transfer through the first outlet structure can be determined by the viscosity of the liquid in the second outlet structure, thus better supporting pressure buildup in the fluid chamber than if the second outlet structure were filled with gas.

[0018] In examples, the fluidic structures comprise a radially inwardly extending projection in an outer chamber wall of the second chamber region, which projection is designed to retain a portion of the liquid of the second liquid volume in the second chamber region during the transfer of the liquid of the second liquid volume through the second outlet structure and to subsequently be flushed by changing the rotational frequency so that liquid enters the second outlet structure.

[0019] In examples, the fluidic structures comprise an intermediate chamber arranged in the second outlet structure or fluidically coupled thereto and configured to be filled with liquid of the second liquid volume upon transfer of liquid of the second liquid volume through the second outlet structure, and to at least partially fill the second outlet channel(s) with the liquid after the transfer. The intermediate chamber can be configured not to empty completely upon transfer of the liquid of the second liquid volume through the second outlet structure, so that liquid can remain in the second outlet channel(s) after the transfer, and thus the fluidic resistance of the outlet structure depends on the viscosity of the liquid, which is many times higher than that of a gas, such as air.

[0020] In examples, the fluidic structures comprise an opening of the second outlet channel(s) into a downstream fluid chamber configured to retain or return a portion of the liquid of the second liquid volume to the second outlet channel(s) after transfer through the second outlet structure.

[0021] In examples, the fluidic structures have chamber walls of the fluid chamber which are designed such that liquid of the first liquid volume which evaporates by heating and condenses on the chamber walls is guided at least partially into the second chamber region by centrifugation and there at least partially fills the second outlet channel(s).

[0022] Appropriate fluidic structures can thus ensure that the second outlet structure, i.e., the outlet channel(s) thereof, can be at least partially filled with liquid from the second or first liquid volume after the transfer of the second liquid volume, or at least a large portion thereof. Thus, during the liquid transfer through the first outlet structure, the fluidic resistance of the second outlet structure can be determined by the viscosity of the liquid and not by the gas, such as air. This can promote a pressure buildup to generate the overpressure required for liquid transfer through the first outlet structure.

[0023] In examples, the first outlet channel comprises a first inverse siphon channel, wherein the apex of the first inverse siphon channel extends to the first radial position. In examples, the second outlet channel comprises a second inverse siphon channel, wherein the apex of the second inverse siphon channel extends to the second radial position. In such examples, the hydrostatic pressure acting on the respective liquid volume, in particular the respective liquid volume in the radially inwardly extending portion of the outlet channel, is easily adjustable by the radial position of the apex of the respective siphon channel.

[0024] The fluid chamber represents a compression chamber configured to enable the generation of overpressure therein. In some examples, the fluid chamber is not vented when the first and second liquid volumes are located upstream in the first and second chamber regions. In some examples, a vent channel may further be provided that connects the fluid chamber to further fluidic structures of the fluidic module or the outside world. The vent channel includes a vent resistance that allows the generation of overpressure in the fluid chamber sufficient to transfer the second liquid volume out of the fluid chamber through the second outlet structure.In other words, in examples, the fluid chamber may be vented, but the venting provides sufficient venting resistance to generate sufficient positive pressure in the fluid chamber despite the venting to enable transfer of the first and second fluid volumes from the fluid chamber as described herein.

[0025] Examples of the present disclosure provide a fluid handling device comprising such a fluidic module, a drive device configured to impart rotation to the fluidic module, a pressure generating device for generating an overpressure in the common air volume, and a control device. The control device is configured to control the drive device to impart rotation to the fluidic module, during which the first and second liquid volumes are held in the fluid chamber by the acting hydrostatic pressure, and to control the pressure generating device to generate, based on this rotation, an overpressure in the common air volume sufficient to transfer the second liquid volume out of the fluid chamber through the second outlet structure against the hydrostatic pressure.

[0026] Examples thus provide a fluid handling device with a fluidics module as disclosed herein, wherein the pressure generating device is configured to generate an overpressure in the common air volume sufficient to transfer the second liquid volume out of the fluid chamber through the second outlet structure. The pressure generating device can be configured to generate the overpressure sufficient to transfer the second liquid volume out of the fluid chamber through the second outlet structure, but not to transfer the first liquid volume out of the fluid chamber through the first outlet structure. Thus, it is possible to transfer the liquid volumes independently of one another through the respective outlet structure.For this purpose, the pressure generating device can be designed to transfer such an overpressure in the fluid chamber after transferring the second liquid volume that the first liquid volume is transferred out of the fluid chamber through the first outlet structure. In some examples, the pressure generating device can comprise a heating device designed to heat the common air volume in the fluid chamber to generate the overpressure. Thus, the required overpressure can be generated in the fluid chamber in a simple manner. In other examples, the pressure generating device can comprise substances in the fluid chamber designed to generate the overpressure through a chemical reaction.

[0027] In examples, the control device can be configured to reduce a rotational speed of the fluidic module to at least assist in transferring the first liquid volume through the first outlet structure from the fluid chamber. In such examples, by reducing the rotational speed, the hydrostatic pressure that opposes a transfer of the first liquid volume through the first outlet structure can be reduced such that the excess pressure generated and / or remaining in the fluid chamber outweighs the hydrostatic pressure that opposes the flow of the first liquid volume through the first outlet structure.

[0028] In embodiments, the control device may be designed to control the pressure generating device after transferring the second liquid volume through the second outlet structure and after reducing the overpressure in the air volume in the fluid chamber to generate an overpressure in the air volume in the fluid chamber that is sufficient to transfer the first liquid volume against the hydrostatic pressure through the first outlet structure out of the fluid chamber.

[0029] The fluid handling device may thus be designed to effect a transfer of the first volume of liquid through the first outlet structure by either increasing the overpressure in the pressure chamber to overcome the opposing hydrostatic pressure or by reducing the hydrostatic pressure by reducing the rotational speed so that the overpressure in the fluid chamber prevails.

[0030] In examples, the pressure generating device comprises a heating device, wherein the control device is configured to switch off the heating device after the second liquid volume has been transferred through the second outlet structure, thereby cooling the air volume in the fluid chamber, and to control the heating device, after the air volume in the fluid chamber has cooled and a resulting negative pressure in the air volume in the fluid chamber has been reduced, to heat the air volume in the fluid chamber in order to generate an overpressure in the air volume in the fluid chamber that is sufficient to transfer the first liquid volume against the hydrostatic pressure through the first outlet structure out of the fluid chamber. Examples thus enable a mutually independent transfer of the first and second liquid volumes in a flexible manner.

[0031] Examples of the present disclosure provide methods for transferring a first liquid volume from a first chamber region of a fluid chamber through a first outlet structure having a first outlet channel, and a second liquid volume from a second chamber region of the fluid chamber through a second outlet structure having a second outlet channel, wherein the first chamber region and the second chamber region are separated from one another by a partition wall extending radially inward with respect to a center of rotation, wherein a common air volume is arranged radially inside the first and second liquid volumes, wherein the first outlet channel opens into the first chamber region and has an outflow barrier for liquid flow from the first chamber region in the form of a radially inwardly rising channel section extending to a first radial position,wherein the second outlet channel opens into the second chamber region and has an outflow barrier for a liquid flow out of the second chamber region in the form of a radially inwardly rising channel section which extends to a second radial position, wherein the first radial position is radially further inward than the second radial position, so that, starting from a rotation in which a hydrostatic pressure acting on the first and second liquid volumes prevents the liquid volumes from flowing out of the fluid chamber through the first and second outlet structures, an overpressure in the common air volume which is required to transfer the first liquid volume against the hydrostatic pressure acting on the first liquid volume through the first outlet structure out of the fluid chamber is greater than an overpressure in the common air volume which is required,to transfer the second liquid volume out of the fluid chamber through the second outlet structure against the hydrostatic pressure acting on the second liquid volume. The method comprises subjecting the fluidic module to a rotation in which the first and second liquid volumes are held in the fluid chamber by the acting hydrostatic pressure, and, based on this rotation, generating an overpressure in the common air volume sufficient to transfer the second liquid volume out of the fluid chamber against the hydrostatic pressure, and subsequently transferring the first liquid volume out of the fluid chamber through the first outlet structure.

[0032] In examples, two stick packs are disposed upstream in the fluid chamber, with the radially outer end of one stick pack located in the first chamber region and the radially outer end of the other stick pack located in the second chamber region. In examples, the method includes opening the stick packs to allow the liquids to exit the stick packs. In examples, opening the stick packs during processing can be achieved by a combination of centrifugal force and temperature.

[0033] In examples, the method for transferring the first liquid volume from the fluid chamber comprises increasing the overpressure, for example by heating the common air volume, and / or reducing the hydrostatic pressure, for example by reducing the rotation speed.

[0034] In examples of the method, the positive pressure generated to transfer the second volume of liquid from the fluid chamber is insufficient to transfer the first volume of liquid from the fluid chamber against the hydrostatic pressure. In examples of the method, generating the positive pressure comprises heating the common air volume or causing a chemical reaction in the fluid chamber. Examples of the method comprise reducing a rotational speed of the fluidic module to assist and / or effect transfer of the first volume of liquid from the fluid chamber through the first outlet structure.In such examples, the method may include, after transferring the second liquid volume through the second outlet structure, reducing the rotational speed of the fluidic module to reduce the hydrostatic pressure acting on the first liquid volume such that the overpressure in the air volume in the fluid chamber is sufficient to transfer the first liquid volume out of the fluid chamber through the first outlet structure against the hydrostatic pressure. In examples of the method, after transferring the second liquid volume through the second outlet structure, the overpressure in the air volume in the fluid chamber is relieved. The relief of the overpressure may, for example, take place through the second outlet structure and / or an additional venting channel.After the overpressure has been relieved, in some examples, an overpressure is generated in the air volume in the fluid chamber, which overpressure is sufficient to transfer the first liquid volume against the hydrostatic pressure through the first outlet structure out of the fluid chamber. In such examples, after the second liquid volume has been transferred through the second outlet structure, a heating device used to generate the overpressure can be switched off in order to cool the air volume in the second fluid chamber. After a negative pressure in the air volume caused by the cooling has been relieved, the air volume in the fluid chamber can then be heated in order to generate an overpressure in the air volume, which is sufficient to transfer the first liquid volume against the hydrostatic pressure through the first outlet structure out of the fluid chamber.

[0035] In examples of the method, following the transfer of the second liquid volume through the second outlet structure, the second outlet structure remains or is at least partially filled with liquid, such that the fluidic resistance of the second outlet structure during the transfer of the first liquid volume through the first outlet structure is determined by the viscosity of the liquid in the second outlet structure.

[0036] When reference is made here to a volume of liquid being transferred, this may mean that the entire volume of liquid is being transferred, or at least a large portion of the volume of liquid is being transferred. In some examples, a portion of the transferred volume of liquid may thus remain in the original structure or the transfer structure.

[0037] Examples of the present invention thus enable a space-saving concept through the multiple use of a fluid chamber as a pumping structure. In examples, the fluid chamber can be used to pump multiple liquids or liquid volumes through different outlet channels. Examples of the present invention thus create a microfluidic structure with which two spatially separated liquids, which are present within a single chamber, can be specifically pumped into areas of a microfluidic cartridge. The transport of the liquid can be achieved simply by generating excess pressure, for example, by increasing the temperature. No additional pneumatic chambers are required, thus enabling a compact design.

[0038] Short description of the drawings

[0039] Embodiments of the invention are explained in more detail below with reference to the accompanying drawings. They show:

[0040] Fig. 1 schematically shows a fluidic module according to an example;

[0041] Fig. 2A to 2D are schematic representations of an example of a fluidic module during different operating phases;

[0042] Fig. 3A to 3D are schematic views of an example of a fluidic module during different operating phases;

[0043] Fig. 4 schematically shows another example of a fluidic module;

[0044] Fig. 5 to 7 schematically show examples of fluidic modules in which

[0045] Fluidic structures are designed to support pressure generation in the fluid chamber for transfer of the first liquid; and

[0046] Fig. 9A and 9B are schematic representations of examples of

[0047] Fluid handling devices.

[0048] Detailed description

[0049] 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 descriptions of elements provided with the same or similar reference numerals may typically be 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.

[0050] Before further explaining examples of the present disclosure, definitions of some terms used herein are provided.

[0051] The fluidic resistance of a channel can be defined as the quotient of the pressure drop Ap in a channel and the flow rate q: R = p / q. Depending on the channel's cross-sectional geometry, the pressure drop can be derived analytically or approximated. The fluidic resistance of a channel can be determined, for example, by measuring the pressure drop and the flow rate. Unless otherwise stated, it is assumed that fluidic resistances are being compared for identical fluids at identical temperatures.

[0052] The rotation caused by centrifugation exerts a hydrostatic pressure. The hydrostatic pressure pHydrostatic acting on a column of liquid in a channel in the centrifugal gravitational field can be calculated using the following formula:

[0053] Where p is the density of the liquid, w is the angular velocity with which the channel rotates around the center of rotation, r afor the outer radius of the liquid column and n for the inner radius of the liquid column.

[0054] The total pressure generated in a fluid chamber partially filled with a liquid and partially with a gas, such as air, consists of two components: a pressure generated by the ideal gas law and a vapor pressure resulting from the evaporation of the liquids. The total pressure of the system, p, can be described by the following formula:

[0055] Here describe p Gas the pressure generated by the ideal gas law, and P is the pressure generated by the evaporated liquid. The formula for the vapor pressure component is usually based on empirically determined correlations, which are determined individually for each liquid and depend on temperature. <j>Describes the relative humidity of the air. At 100%, the air is completely saturated with a liquid. In microfluidic structures, the air is usually completely saturated.

[0056] Examples of fluidic structures, such as microfluidic structures, are fluid channels and fluid chambers. Fluidic structures can define an overflow structure that can be used to measure fluid volumes. The basic principle is that the fluid first fills a chamber with a defined volume, and the remaining fluid is then transported to another chamber. Compression chambers are chambers that either have no venting or only one vent with high fluidic resistance. This allows a pressure pcesamt to build up in these chambers, which is described by the formula defined above.

[0057] Unless otherwise stated, an overpressure can be understood as the pressure difference between the ambient pressure (usually atmospheric pressure: patm -1013 hPa) and a generated higher pressure (> patm), while a negative pressure can be understood as the pressure difference between the ambient pressure and a generated lower pressure (< patm).

[0058] The term liquid, as used herein, includes, as will be obvious to those skilled in the art, in particular liquids that contain solid components, such as suspensions, biological samples and reagents. In particular, this includes buffer solutions such as lysis buffers, binding buffers, washing buffers and elution buffers, as used in laboratory analysis and mobile diagnostics. An inverted siphon channel is understood here to be a microfluidic channel or section of a microfluidic channel in a fluidics module (a centrifugal microfluidic cartridge) in which the inlet and outlet of the channel are at a greater distance from the center of rotation than an intermediate region of the channel. A siphon apex is understood to be the region of an inverted siphon channel in a fluidics module with the minimal distance from the center of rotation.

[0059] 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.

[0060] 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 or fluidic 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.

[0061] Examples of the invention can be applied in particular 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.

[0062] 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.

[0063] Unless otherwise stated herein, room temperature (20°C) shall be assumed with regard to temperature-dependent quantities.

[0064] Examples of the present disclosure relate to microfluidic structures on a centrifugal microfluidic cartridge, by means of which liquids can be transported via channels from one chamber to different areas on the cartridge. At least two liquid volumes are located in spatially separated chamber areas, which can be referred to as compartments, within a chamber. The air volume in the chamber makes it possible to exert pressure, for example, pneumatically or thermally induced, on different liquids. The liquids can be pumped out of this chamber through channels that open into the respective chamber areas. At least one of these channels can have such a high fluidic resistance that, in the event of a complete liquid transfer through this channel, a sudden pressure drop in the shared chamber is not possible.In other words, the fluidic resistance of this channel can be so high that, even if this channel acts as a vent channel, an overpressure can be generated in the shared chamber sufficient to transfer the fluid from the other chamber area through the other channel. The described structures thus enable the delayed or simultaneous pumping of different fluids from a single chamber into different areas of a microfluidic cartridge, thus increasing the integration density of the microfluidics.

[0065] Examples of the present disclosure provide a fluidic module with microfluidic structures that enable the transfer of different liquids from the same fluid chamber. Fig. 1 shows an example of a fluidic module 10 having fluidic structures that include a fluid chamber 12, a first outlet channel 14, and a second outlet channel 16. The fluid chamber 12 has a first chamber region 24 and a second chamber region 26. The fluidic module 10 is rotatable about a center of rotation R and can be designed as a rotating body or as a module that can be inserted into a rotating body. The first chamber region 24 and the second chamber region 26 are separated from one another by a partition wall 28 that extends radially inward with respect to the center of rotation R.The partition wall 28 has a radial height such that the two liquid volumes are separated from each other when they are centrifugally driven into radially outer sections of the chamber regions 24, 26. Thus, a first liquid volume 30 in the first chamber region 24 can be pre-stored separately from a second liquid volume 32 in the second chamber region 26. Corresponding liquid volumes 30 and 32 are shown in Fig. 1. The liquid volumes can be pre-stored in the respective chamber regions, for example, by inserting two stick packs into the chamber 12, which overlap in the radially inward part and whose ends are each located in one of the two chamber regions 24, 26. If the stick packs are opened and ejected, the two contained liquid volumes are each located in the first chamber region 24 and the second chamber region 26, respectively.These two fluid volumes can be the same fluid or different fluids. Rotation of the fluidic module 10 around the center of rotation R creates a centrifugal gravitational field that prevents mixing of the two fluids due to the geometric design of the chamber with the radially inwardly projecting partition wall 28.

[0066] In examples, the chamber regions 24 and 26, viewed from above the fluidics module, may each have an elongated shape extending in different radial directions, with the inner ends of the chamber regions overlapping and thus defining a common fluid chamber region. This makes it possible to insert two stick packs into a common chamber in a space-saving manner, with the fluids contained therein being pre-stored in spatially separate chamber regions.

[0067] A microfluidic channel is connected to each of the two chamber regions, usually, but not necessarily, at the radially outermost point of the chamber region. Thus, the first outlet channel 14 is fluidically coupled to a radially outer portion of the first chamber region 24, and the second outlet channel 16 is fluidically coupled to a radially outer portion of the second chamber region 26. The first outlet channel thus opens into the first chamber region 24 and has an outflow barrier for liquid flow out of the first chamber region 24 in the form of a radially rising channel portion 14a that extends to a first radial position P1. The second outlet channel 16 opens into the second chamber region 26 and has an outflow barrier for liquid flow out of the second chamber region 26 in the form of a radially inwardly rising channel portion 16a that extends to a second radial position P2.The first radial position Pi is located radially further inward than the second radial position P2. In examples, one or both of the outlet channels 14 and 16 may open into a fluid chamber at the radial position Pi, P2. In examples, the first outlet channel 14 and / or the second outlet channel 16 may comprise an inverse siphon channel whose apex is located at the first radial position Pi or second radial position P2, respectively.

[0068] The fluidic module 10 can be subjected to a rotation during which a hydrostatic pressure acting on the first and second liquid volumes prevents the liquid volumes from flowing out of the fluid chamber 12 through the first and second outlet channels 14, 16. A common air volume is arranged in the fluid chamber 12 above the liquid volumes 30 and 32. Based on such a rotation, an overpressure in the common air volume required to transfer the first liquid volume 30 through the first outlet channel 14 out of the fluid chamber 12 against the hydrostatic pressure acting on the first liquid volume 30 is greater than an overpressure in the common air volume required to transfer the second liquid volume 32 through the second outlet channel 16 out of the fluid chamber 12 against the hydrostatic pressure acting on the second liquid volume 32.To achieve this, the two channels can have different radial siphon heights and / or different fluidic resistances.

[0069] The fluid chamber 12 can be designed as a compression chamber which, apart from the first and second outlet channels, is fluid-tight, i.e., has no vent openings. As shown in Fig. 1, a vent channel 34 can optionally be provided, which fluidically connects the fluid chamber 12 to other fluidic structures of the fluidic module 10 or to the outside world. Fig. 2A schematically shows fluidic structures of the fluidic module 10, in which the first outlet channel 14 has a first inverse siphon S1 and the second outlet channel 16 has a second inverse siphon S2. An apex of the first inverse siphon S1 is located at the radial position Pi, and an apex of the second inverse siphon S2 is located at the radial position P2. As schematically illustrated in Fig. 2A, the second outlet channel 16 has a fluidic resistance 36.The fluidic resistance 36 is sufficiently large to allow, after a complete transfer of the second liquid volume 32 through the second outlet channel 16, such an overpressure can be built up in the common air volume 12 that the first liquid volume 30 can be transferred through the first outlet channel 14.

[0070] Before describing examples of fluid handling devices according to the invention and examples of methods according to the invention with reference to Figs. 2A to 2D and 3A to 3D and 4 to 8, general features of examples of fluid handling devices according to the invention are first described with reference to Figs. 9A and 9B.

[0071] Figures 9A and 9B show examples of centrifugal microfluidic systems and fluid handling devices, respectively, that utilize or comprise a fluidic module as described herein. In other words, the fluidic module in the systems in Figures 9A and 9B can be any of the fluidic modules described herein. The fluid handling devices each comprise the fluidic module, a drive device, a pressure generating device, and a control device.

[0072] Fig. 9A shows a fluid handling device with a fluidics module 110, a drive device 120, a pressure generating device 140, and a control device 124. The fluidics module 110 is a rotating body having 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 the 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.The control device 124 is designed to control the drive device 120, to subject the rotating body 110 to a rotation or rotations at different rotational frequencies, and to control the pressure generating device 140. As will be apparent to those skilled in the art, the control device 124 can be implemented, for example, by an appropriately programmed computing device or a user-specific integrated circuit. The control device 124 can further be designed to control the drive device 120, in response to manual inputs from a user, to effect the required rotations of the rotating body and / or to control the pressure generating device 140.In any case, the control device 124 can be configured to control the drive device 120 to impart the required rotation to the rotating body 110 and / or to control the pressure generating device 140 to implement embodiments of the invention as described herein. A conventional centrifuge with only one direction of rotation can be used as the drive device 120.

[0073] The rotating body 110 has the fluidic structures as described herein. The required fluidic structures can be formed by cavities and channels in the lid 114, the substrate 112, or in the substrate 112 and the lid 114. In embodiments, for example, fluidic structures can be depicted in the substrate 112, while fill openings and vent openings are formed in the lid 114. In embodiments, the structured substrate (including fill openings and vent openings) is arranged on top and the lid is arranged on the bottom. In examples, the lid can be removable, for example, to allow stick packs to be inserted into the fluid chamber. In examples, the stick packs can be inserted before the lid is removably or permanently attached to the substrate.

[0074] In an alternative embodiment shown in Fig. 9B, 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. Furthermore, the pressure generation device 140, which is controllable by the control device 124, is again shown in Fig. 9B.

[0075] In Figures 9A and 9B, the center of rotation around which the fluidic module or the rotation body can rotate is again denoted by R.

[0076] In embodiments 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 embodiments, 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).

[0077] In examples, the pressure generation device 140 may include a heating device configured to heat the common air volume in the fluid chamber. The heating device may, for example, be configured as a contact heater to heat the fluidic module locally or globally. The heating device may, for example, be provided in the rotating part 118 of the drive device 120 or in the rotor 130. Alternatively, the heating device may also be configured as a contactless heater that heats the fluidic module, for example, using radiant heat.

[0078] Corresponding fluid handling devices may be configured to implement operations and methods as described below.

[0079] As shown in Fig. 2A, in the initial state, the control device 124 controls the drive device 120 to rotate the fluidic module 10 at a rotation frequency fi. During such a rotation, the fluidic module 10 is in the initial state in which the first liquid volume 30 is located in the first chamber region 24 and the second liquid volume 32 is located in the second chamber region 26. The liquid volumes are held in position by the rotation at the frequency fi via centrifugal force. In the examples described below, it is assumed that the pressure generating device is a heating device.In alternative examples, other pressure generating devices may be implemented, for example those having substances in the fluid chamber that are designed to generate the overpressure by a chemical reaction, or those that generate an overpressure by mechanical movement, for example by means of a pumping diaphragm.

[0080] Examples of methods according to the invention are described below with reference to the fluidic modules shown in Figs. 2A to 2D and 3A to 3D. It goes without saying that the control device of the fluid handling device is configured to control the drive device and the pressure generating device, respectively, to implement the corresponding functionalities.

[0081] Starting from the state shown in Fig. 2A, an increase in temperature results in an overpressure p Ge generated in the fluid chamber 12, as shown in Fig. 2B. The heating device is designed to heat at least one region 50 of the fluidic module, which comprises at least part of the fluid chamber 12. As a result of the heating, the common air volume in the fluid chamber 12 expands, thereby generating an overpressure. This overpressure counteracts the centrifugal force acting on the liquid volumes in the channels 14 and 16. The hydrostatic pressure acting on the first liquid volume 30 when the first liquid reaches point P1 is designated Api in Fig. 2B, and the hydrostatic pressure acting on the second liquid volume 32 when the second liquid reaches point P2 is designated Ap2 in Fig. 2B.As can be seen in Figure 2B, the hydrostatic pressure acting on the first liquid volume 30 upon reaching point P1 is greater than the hydrostatic pressure acting on the second liquid volume 32 upon reaching point P2. The pressure generating device is controlled such that the overpressure p. Ge is set such that it is smaller than the hydrostatic pressure Api and greater than the hydrostatic pressure Ap2. As a result, the generated overpressure is not sufficient to overcome the hydrostatic pressure Api and the first fluid volume 30 is not transferred through the first outlet channel 14 and remains in the fluid chamber 12. Since the hydrostatic pressure Ap2 is lower than the overpressure p GeS amt, the second liquid volume 32 is transported through the second outlet channel 16 from the fluid chamber 12, for example, into a further structure (not shown). This is shown in Fig. 2C by an arrow 60. Due to the high fluidic resistance 36 of the second outlet channel 16, sufficient pressure is maintained in the fluid chamber 12, even when the liquid volume 32 has been completely transferred. By reducing the rotation frequency from the frequency fi to a frequency f2, the centrifugal backpressure Api can now be reduced, so that the remaining overpressure p Ge can be used for transporting the liquid volume 30 through the first outlet channel 14 from the fluid chamber 12, as shown in Fig. 2D by an arrow 62. The reduction in the rotation frequency, as shown in Fig. 2D, takes place at a time at which the excess pressure in the fluid chamber 12 has not yet been reduced by the second outlet channel acting as a vent channel.

[0082] Thus, examples of the present disclosure enable transfer of the two liquid volumes 30, 32 from the fluid chamber 12 independently of each other. Examples thus enable sequential transport of two liquid volumes from the same fluid chamber.

[0083] According to examples, the control device is thus designed to control the pressure generating device to generate such an overpressure in the fluid chamber that the second liquid volume, i.e. the second liquid, is transferred from the fluid chamber, but not the first liquid volume. The first liquid volume, i.e. the first liquid, can then be transferred from the fluid chamber in different ways. As described above with reference to Figs. 2A to 2D, the rotation frequency can be reduced to transfer the first liquid volume. Alternatively, the control device can be configured to control the pressure generating device to generate such an overpressure in the fluid chamber after the transfer of the second liquid volume that the first liquid volume is transferred from the fluid chamber.

[0084] A further example of how the first liquid volume can be transferred from the fluid chamber will now be described with reference to Figs. 3A to 3D. Fig. 3A again shows the state as shown in Fig. 2B and described with reference thereto. Due to the overpressure p Ge The second liquid volume 32 is then transferred out of the fluid chamber 12 through the second outlet channel 16. After the second liquid volume has been transferred out of the fluid chamber 12, the second outlet channel 16 acts as a venting channel through which pressure equalization can be carried out under constant rotation, thereby reducing the pressure in the fluid chamber 12, as shown in Fig. 3B. If the fluid chamber is then cooled back to ambient temperature, a negative pressure is created in the fluid chamber 12, which can now also be reduced through the second outlet channel 16, as shown in Fig. 3C. This brings the system back into equilibrium, and other operations can be carried out simultaneously on the fluidic module, the cartridge, without the need for continuous heating.Heating at a simultaneous low rotation frequency can then be used to overcome the relatively low centrifugal backpressure in the first outlet channel 14 by a high pneumatic pressure pcesamt in the fluid chamber 12 and thus initiate the transport of the first liquid volume 30 out of the fluid chamber 12, as shown in Fig. 3D and indicated by an arrow 66. Again, the frame 50 in Figs. 3A to 3D marks a possible jointly heated space.

[0085] In the example shown with reference to Figs. 3A to 3D, the rotation frequency was reduced to transfer the first volume of liquid from the fluid chamber while simultaneously heating. Reducing the rotation frequency to transfer the first volume of liquid is not necessary if the pressure in the fluid chamber 12 is increased to a level higher than the hydrostatic pressure at a constant rotation frequency.

[0086] Fig. 4 shows an example of a fluidic module 10 in which several channels with fluidic resistance lead from the second chamber region 26 into further structures. As shown in Fig. 4, the fluidic module has two second outlet channels 16a and 16b, each having a second inverse siphon S2a and S2b. The radial position of the apex of the inverse siphon channels S2a and S2b lies radially outside the apex of the siphon channel S1 of the first outlet channel 14. The second outlet channel 16a has a fluidic resistance R2.1, and the second outlet channel 16b has a fluidic resistance R2.2. The total fluidic resistance of the plurality of second outlet channels 16a and 16b, i.e. R2.1 -R2.2 / (R2.1 +R2.2), is in turn configured such that an overpressure can be generated in the fluid chamber 12, which makes it possible to transfer the first liquid volume 30 through the first outlet channel 14.In examples, the total fluidic resistance of the plurality of second outlet channels 16a, 16b may be greater than the fluidic resistance of the first outlet channel 14. In examples of the present disclosure, the outlet channels may be configured to have decreasing fluidic resistances with increasing outflow barriers. The further radially inward the position to which the radially inwardly rising channel section of an outlet channel extends, the higher the outflow barrier of that outlet channel. In general, in examples, the channels may have decreasing fluidic resistances with increasing outflow barriers.

[0087] As shown in Fig. 4, one or more region dividing walls 70 extending radially inward from a radially outer end of the second chamber region 26 can be provided in the second chamber region 26. The region dividing wall 70 can separate the second chamber region 26 into different chamber region sections, with the plurality of second outlet channels 16a, 16b opening into different ones of the chamber region sections. Thus, it is possible to transfer separate partial volumes of the second liquid volume from the fluid chamber 12 through the plurality of second outlet channels 16a, 16b.

[0088] In the above examples, the first outlet structure has a first outlet channel. The second outlet structure has one outlet channel in the examples shown in Figures 1 to 3 and two outlet channels in the embodiment shown in Figure 4. In other examples, the first and second outlet structures can have a different number of outlet channels, with the above statements regarding the outlet channels 16a and 16b applying analogously.

[0089] In examples, the fluidic resistance R2 of the second outlet structure and the fluidic resistance R1 of the first outlet structure have a ratio such that a pressure buildup required for transfer of the first liquid through the first outlet structure is possible, even if the second outlet structure, or its outlet channels, are filled with a gas rather than a liquid. In such examples, the resistance ratio R2 / R1 when filled with the same fluid is at least a factor of 30. Mathematically, the resistance ratio can be expressed as: R2 / R1 = Cg2*l2 / A2 2 / (Cg1 *l1 / A1 2 , where Cg1 and Cg2 are constants known to those skilled in the art which depend on the channel cross-section, I1 and I2 are the lengths of the first and second outlet channels, and A1 and A2 are the cross-sectional areas of the first and second outlet channels. In examples, the fluidic module has fluidic structures which are designed to support the generation of an overpressure which is required for the transfer of the first liquid volume, in that the outlet channel(s) of the second outlet structure are at least partially filled with liquid during this transfer. Corresponding examples are described below with reference to Figures 5 to 8. The fluidic structures can ensure that after the transfer of the second liquid through the second outlet structure has been completed, it is possible to refill the second outlet channel(s). As a result, due to the viscosity of the liquid being approximately 50 times higher than that of the gas, e.g.Air, it can be ensured that the fluidic resistance 36 is higher by a factor of approximately 50 than when the second outlet channel is filled with gas.

[0090] Fig. 5 shows an example in which a radially inwardly extending projection 38, which can also be referred to as a partition, is integrated into the chamber region 26, preventing the entire liquid volume 32 from being transferred. By appropriately accelerating or decelerating the fluidic module after the transfer of the liquid volume 32, forces can be generated to overflow this projection and thus enable refilling of the second outlet channel. In examples, the fluid handling device can be designed to effect accelerating or decelerating, by means of which such overflow takes place, so that the portion of the second liquid volume remaining in the chamber region 26 reaches the second outlet channel 16.

[0091] Fig. 6 shows an additional chamber 42, which is connected to the outlet channel 16c, 16d via a channel 40. The chamber 42 can be designed as a compression chamber, but can also be connected to the remaining fluid system or the environment (i.e., vented) via a further channel 44. During the transfer of the liquid volume 32 through the outlet channel 16c, 16d, a portion of the second liquid volume is transported into the chamber 42 according to the resistance ratio of the channels 16d and 40. After the liquid volume 32 has been completely transferred out of chamber 12 by the overpressure in this chamber and the overpressure has been dissipated through the channels 40 and 16d, the volume transferred into the chamber 42 is conveyed back into the outlet channel 16c and 16d by centrifugal force. In alternative examples, the chamber 42 may also be designed merely as a channel widening of the outlet channel 16c, 16d.Since liquid is temporarily stored in the chamber 42, for example between the transfer of the second liquid volume and the transfer of the first liquid volume, it can also be referred to as an intermediate chamber.

[0092] Fig. 7 shows an example in which, after the transfer of the second liquid volume by reheating the chamber 12, a portion of the first liquid volume 30 evaporates, condenses on the chamber walls, and is then conveyed by centrifugation into the sub-chamber 26. From there, the liquid flows into the second outlet channel to at least partially fill it. In such an example, structures can be incorporated into the chamber or chamber wall (48) that allow a large portion of the condensed liquid to be directed into the sub-chamber 26.

[0093] Fig. 8 shows an example in which the connection between the outlet channel 16 and a downstream chamber 52 is designed such that a portion of the transferred liquid volume 32 does not enter the downstream chamber 52, but remains in a chamber region 50 into which the outlet channel 16 opens. The chamber regions 52 and 50 are separated from one another by a barrier 54 that rises radially inward. After the transfer of the liquid volume 32, the liquid volume remaining in the chamber region 50 can be conveyed back into the outlet channel 16 by centrifugation. In examples, the position M2, which is defined by the radially inner end of the barrier 54, can be located radially further inward than the radial position of the siphon S2. In examples, the position M2 can be located radially further outward than the radial position of the siphon S2.Depending on the location of these two positions, either areas of the entire channel 16 or only an area 16e are filled.

[0094] In the examples described above, the pressure generation device comprises a heating device. In alternative examples, the pressure generation device can be designed to chemically generate an overpressure in the chamber. For example, a gas bubble reactor can be used in the fluid chamber to generate an overpressure in the fluid chamber. A reactant can be arranged in the fluid chamber, which, for example, causes a gas generation reaction upon contact with a liquid. The reactant (catalyst) can be provided on wall sections of the fluid chamber. For example, the following reactions can be used by taking place in a chamber of the fluidics module. An overpressure can be generated by generating oxygen, for example via hydrogen peroxide, which is converted into water and oxygen with the help of a catalyst, for example manganese dioxide.Pressure can also be generated by nitrogen, for example by ammonium nitrate, which is converted into water, oxygen, and nitrogen. Pressure can also be generated by carbon dioxide, for example by calcium carbonate, which reacts with hydrogen chloride to form calcium chloride, water, and carbon dioxide. In other examples, pressure can be generated by hydrogen, for example magnesium and water react to form magnesium hydroxide and hydrogen. Another possibility is the electrochemical generation of gas. For example, water can be split into hydrogen and oxygen through electrolysis. The corresponding pressure can be generated in the fluid chamber or in structures fluidly connected to the fluid chamber, as long as it is ensured that the required overpressure can be generated in the fluid chamber.

[0095] Examples of the present disclosure thus provide devices and methods that enable different volumes of liquid to be transferred independently from a fluid chamber. In examples, two stick packs can be arranged in the fluid chamber, which are opened during an automation process by means of centrifugal force and temperature input, and the liquid contained therein is pumped out of the fluid chamber. This enables, in a space-saving and simple manner, the transfer of liquid from two stick packs to various downstream fluidic structures using only one fluid chamber. This enables the corresponding handling of liquids with a smaller space requirement and fewer demands on the analytical device. For example, compared to a case in which two stick pack chambers are provided on a cartridge, only one heating zone is required instead of two.

[0096] The above embodiments comprise two chamber regions, which allow for spatially separated pre-storage of liquids. In alternative embodiments, a larger number of chamber regions, each with associated outlet channels, can be provided.

[0097] Examples of the present disclosure provide a fluidic module that is rotatable about a center of rotation, which has a fluid chamber and two to N outlet channels, wherein in the fluid chamber at least two liquids can be stored geometrically separated by centrifugal force, wherein in the chamber at least two liquids are connected via a common air volume, wherein the liquids can be held in the fluid chamber by hydrostatic pressure through rotation, wherein a first channel and at least one second channel have different outflow barriers with respect to the hydrostatic height, that is to say different radial positions of the highest point of the siphon, wherein the channels can have decreasing fluidic resistances with increasing outflow barrier, and wherein the overpressure in the fluid chamber can be controlled chemically or physically.In examples of such a fluidic module, the temperature of the liquid and the air in the fluid chamber is adjustable by a heating element to control the pressure in the fluid chamber. In examples, a structure adjacent to the channel with the lowest outflow barrier can be vented via a channel. In examples, a structure adjacent to the channel with the lowest outflow barrier can become a compression chamber during transport. In examples, the liquids can be the same liquid or different liquids. In examples, the volume of the liquids in the chamber sections can be definedly distributed via geometric structures and / or an overflow structure in the fluid chamber. In examples, the fluid chamber can be vented through a channel with high fluidic resistance. In examples, a plurality of second outlet channels can have different resistances.In examples, a heating element may be provided to effect the overpressure, wherein the heating element may be configured to adjust the temperature locally, only for the chamber, or globally, for the entire fluidic module.

[0098] In general, the outlet structures can be designed such that, after the transfer of the second liquid, such an overpressure can be generated and maintained in the fluid chamber that the first liquid volume can also be transferred through the first outlet structure. This can be achieved by a correspondingly higher fluidic resistance, for example, at least 50 times higher fluidic resistance of the second outlet structure, so that even if the second outlet structure is filled with a gas, e.g., air, venting occurs so slowly that the overpressure is sufficient to transfer the first liquid volume.In examples in which liquid is arranged in at least parts of the second outlet structure during the transfer of the first liquid volume through the first outlet structure, the resistance ratio between the second outlet structure and the first outlet structure can be significantly lower and, for example, lie in a range of 5 to 10. Although liquid is then transferred through both outlet structures, it is transferred faster through the first outlet structure than through the second outlet structure, so that the first liquid volume can be transferred through the first outlet structure before the liquid in the second chamber region has completely passed through the second outlet structure. In general, the fluidics module can therefore be designed such that when the first liquid is transferred through the first outlet structure, a volume flow through the first outlet structure is greater than a volume flow (gas or liquid) through the second outlet structure.

[0099] 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.

[0100] 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. The examples described above are only 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.< / j>

Claims

Claims 1. Fluidic module (10, 110) for use in a centrifugal microfluidic system with the following features: a fluid chamber (12) with a first chamber region (24) and a second chamber region (26) separated from each other by a partition (28) extending radially inwards with respect to a center of rotation (R), wherein a first liquid volume (30) in the first chamber region (24) can be pre-positioned separately from a second liquid volume (32) in the second chamber region (26), while a common air volume is arranged radially within the first and second liquid volumes (32); a first outlet structure having at least one first outlet channel (14) opening into the first chamber region (24) and providing an outflow barrier for a liquid flow from the first chamber region (24) in the form of a radially inwardly rising channel section (14a) extending to a first radial position (Pi),comprising; and a second outlet structure comprising at least a second outlet channel (16) opening into the second chamber region (26) and providing an outflow barrier for a fluid flow from the second chamber region (26) in the form of a radially inwardly rising channel section (16i) extending to a second radial position (P2), wherein the first radial position (Pi) is located radially further inward than the second radial position (P2), wherein the fluidic module (10, 1 10) is designed such that, starting from a rotation in which a hydrostatic pressure acting on the first and second fluid volumes (32) prevents the fluid volumes from flowing through the first and second outlet structures out of the fluid chamber (12), an overpressure in the common air volume is required to counteract the hydrostatic pressure acting on the first fluid volume (30) of the first fluid volume (30).to transfer the second fluid volume (32) through the first outlet structure from the fluid chamber (12) is greater than the overpressure in the common air volume required to transfer the second fluid volume (32) through the second outlet structure from the fluid chamber (12) against the hydrostatic pressure acting on the second fluid volume (32).

2. Fluidic module (10, 1 10) according to claim 1, wherein the fluidic resistance (36) of the second outlet structure for a fluid flow from the fluid chamber (12) is greater than the fluidic resistance of the first outlet structure for a fluid flow from the fluid chamber (12).

3. Fluidic module (10, 110) according to claim 1 or 2, wherein the second outlet structure has several second outlet channels (16a, 16b) opening into the second chamber region (26), wherein the total fluidic resistance of the several second outlet channels (16a, 16b) for a fluid flow from the fluid chamber (12) is greater than the fluidic resistance of the first outlet structure for a fluid flow from the fluid chamber (12).

4. Fluidic module (10, 110) according to claim 3, wherein the second chamber area (26) is separated into several chamber area sections by at least one radially inwardly extending partition wall (70), wherein one of the several second outlet channels (16a, 16b) opens into each of the chamber area sections.

5. Fluidic module (10, 110) according to one of claims 1 to 4, wherein the first outlet channel (14) has a first inverse siphon channel (S1 ), wherein the first radial position (Pi) is formed by a vertex of the first inverse siphon channel (S1 ), and / or wherein the second outlet channel (16) has a second inverse siphon channel (S2), wherein the second radial position (P2) is formed by the vertex of the second inverse siphon channel (S2).

6. Fluidic module (10, 1 10) according to one of claims 1 to 5, which further comprises a vent channel (34) that connects the fluid chamber (12) to further fluidic structures of the fluidic module (10, 110) or the outside world, wherein the vent channel (34) has a venting resistance that enables it to generate an overpressure in the fluid chamber (12) sufficient to transfer the second fluid volume (32) through the second outlet structure from the fluid chamber (12).

7. Fluidic module (10, 110) according to one of claims 1 to 6, wherein the ratio of the fluidic resistance (36) of the second outlet structure to the fluidic resistance of the first outlet structure when filled with the same fluid is at least a factor of 30, preferably a factor of at least 50.

8. Fluidic module (10, 110) according to one of claims 1 to 7, wherein fluidic structures of the fluidic module (10, 110) are designed to enable the second outlet structure to remain or become at least partially filled with liquid following the transfer of liquid from the second liquid volume (32) through the second outlet structure.

9. Fluidic module (10, 110) according to claim 8, wherein the fluidic structures have a radially inwardly extending projection (38) in an outer chamber wall of the second chamber region (26), which is designed to retain a portion of the liquid of the second liquid volume (32) in the second chamber region (26) during the transfer of the liquid of the second liquid volume (32) through the second outlet structure and to subsequently be flushed over by changing the rotational frequency so that liquid enters the second outlet structure.

10. Fluidic module (10, 110) according to claim 8 in which the fluidic structures have an intermediate chamber (42) which is arranged in the second outlet structure or fluidically coupled to it and is designed to be filled with liquid of the second liquid volume (32) during the transfer of liquid of the second liquid volume (32) through the second outlet structure, and after the transfer to at least partially fill the second outlet channel(s) with the liquid. 1 1. Fluidic module (10, 110) according to claim 8 in which the fluidic structures have an opening of the second outlet channel(s) into a downstream fluid chamber (52) which is designed to retain or return a portion of the fluid of the second fluid volume (32) after transfer through the second outlet structure in the second outlet channel (16) or the second outlet channels (16a, 16b).

12. Fluidic module (10, 110) according to claim 8, wherein the fluidic structures have chamber walls of the fluid chamber (12) which are designed such that, by heating, liquid of the first liquid volume (30) which evaporates and condenses on the chamber walls is at least partially directed into the second chamber area (26) by centrifugation and at least partially fills the second outlet channels (16, 16a, 16b) there.

13. Fluid handling device comprising: a fluid module (10, 110) according to one of claims 1 to 12; a drive device (120) designed to subject the fluid module (10, 110) to rotation; a pressure generating device (140) for generating overpressure in the common air volume of the fluid module (10, 110); and a control device (124) designed to control the drive device (120) to subject the fluid module (10, 110) to rotation, in which the first and second fluid volumes (32) are held in the fluid chamber (12) by the acting hydrostatic pressure, and to control the pressure generating device (140) to generate, from this rotation, an overpressure in the common air volume sufficient to transfer the second fluid volume (32) against the hydrostatic pressure through the second outlet structure from the fluid chamber (12).

14. Fluid handling device according to claim 13, wherein the pressure generating device (140) has a heating device designed to heat the common air volume in the fluid chamber (12) to generate the overpressure.

15. Fluid handling device according to one of claims 13 or 14, wherein the control device (124) is designed to reduce the rotational speed of the fluid module (10, 110) in order to at least assist the transfer of the first fluid volume (30) through the first outlet structure from the fluid chamber (12).

16. Fluid handling device according to claim 15, wherein the control device (124) is designed to control the drive device (120) after the transfer of the second fluid volume (32) through the second outlet structure in order to reduce the rotational speed of the rotation of the fluid module (10, 110) and thus the hydrostatic pressure acting on the first fluid volume (30) so that the overpressure in the air volume in the fluid chamber (12) is sufficient to transfer the first fluid volume (30) against the hydrostatic pressure through the first outlet structure from the fluid chamber (12).

17. Fluid handling device according to one of claims 13 to 16, wherein the control device (124) is designed to control the pressure generating device (140) after the transfer of the second liquid volume (32) through the second outlet structure and after a reduction of the overpressure in the air volume in the fluid chamber (12) in order to generate an overpressure in the air volume in the fluid chamber (12) sufficient to transfer the first liquid volume (30) against the hydrostatic pressure through the first outlet structure from the fluid chamber (12).

18. Fluid handling device according to claim 17, wherein the pressure generating device (140) comprises a heating device, the control device (124) being configured to switch off the heating device after the transfer of the second liquid volume (32) through the second outlet structure, thereby cooling the air volume in the fluid chamber (12), and to control the heating device after the cooling of the air volume in the fluid chamber (12) and a reduction of any resulting negative pressure in the air volume in the fluid chamber (12) in order to heat the air volume in the fluid chamber (12) in order to generate an overpressure in the air volume in the fluid chamber (12) sufficient to transfer the first liquid volume (30) against the hydrostatic pressure through the first outlet structure out of the fluid chamber (12).

19. Method for transferring a first liquid volume (30) from a first chamber region (24) of a fluid chamber (12) through a first outlet structure having a first outlet channel (14), and a second liquid volume (32) from a second chamber region (26) of the fluid chamber (12) through a second outlet structure having a second outlet channel (16), wherein the first chamber region (24) and the second chamber region (26) are separated from each other by a partition (28) extending radially inward with respect to a center of rotation (R), wherein a common air volume is arranged radially within the first and second liquid volumes (32), wherein the first outlet channel (14) opens into the first chamber region (24), and an outflow barrier in the form of a radially inwardly rising channel section (14a) extending to a first radial position (Pi) is provided for a liquid flow from the first chamber region (24).exhibits, wherein the second outlet channel (16) opens into the second chamber area (26) and is designed for a fluid flow from the second, Chamber area (26) has an outflow barrier in the form of a radially inwardly rising channel section (16a) extending to a second radial position (P2), wherein the first radial position (Pi) is radially further inward than the second radial position (P2), such that, starting from a rotation in which a hydrostatic pressure acting on the first and second fluid volumes (32) prevents the fluid volumes from flowing through the first and second outlet structure out of the fluid chamber (12), an overpressure in the common air volume required to transfer the first fluid volume (30) through the first outlet structure out of the fluid chamber (12) against the hydrostatic pressure acting on the first fluid volume (30) is greater than an overpressure in the common air volume required to transfer the second fluid volume (32) against the hydrostatic pressure.which acts on the second fluid volume (32), to transfer through the second outlet structure from the fluid chamber (12), with the following features:, Applying a rotation to the fluid module (10, 1 10) in which the first and second fluid volumes (32) are held in the fluid chamber (12) by the acting hydrostatic pressure, starting from this rotation, generating an overpressure in the common air volume sufficient to transfer the second fluid volume (32) against the hydrostatic pressure through the second outlet structure from the fluid chamber (12), and Transferring the first liquid volume (30) through the first outlet structure from the fluid chamber (12) by creating a ratio of hydrostatic pressure acting on the first liquid volume and overpressure in the fluid chamber (12) such that the first liquid volume is transferred through the first outlet structure from the fluid chamber (12).

20. Method according to claim 19, wherein the generated overpressure, which is sufficient to transfer the second liquid volume (32) against the hydrostatic pressure through the second outlet structure from the fluid chamber (12), is not sufficient to transfer the first liquid volume (30) against the hydrostatic pressure through the first outlet structure from the fluid chamber (12).

21. Method according to claim 19 or 20, wherein the generation of the overpressure sufficient to counteract the hydrostatic pressure of the second liquid volume (32) to transfer through the second outlet structure from the fluid chamber (12), which has the effect of heating the common air volume in the fluid chamber (12).

22. Method according to one of claims 19 to 21, comprising reducing the rotational speed of the fluid module (10, 1 10) to at least assist the transfer of the first fluid volume (30) through the first outlet structure from the fluid chamber (12).

23. Method according to claim 22, which, after transferring the second liquid volume (32) through the second outlet structure, comprises reducing the rotational speed of the fluid module (10, 110) in order to reduce the hydrostatic pressure acting on the first liquid volume (30) such that the overpressure in the air volume in the fluid chamber (12) is sufficient to transfer the first liquid volume (30) against the hydrostatic pressure through the first outlet structure from the fluid chamber (12).

24. A method according to any one of claims 19 to 22, comprising, after transferring the second liquid volume (32) through the second outlet structure and after reducing the overpressure in the air volume in the fluid chamber (12), generating an overpressure in the air volume in the fluid chamber (12) sufficient to transfer the first liquid volume (30) against the hydrostatic pressure through the first outlet structure from the fluid chamber (12).

25. The method of claim 24, comprising, after transferring the second liquid volume (32) through the second outlet structure, switching off a heating device to cool the air volume in the fluid chamber (12), and later, after reducing a negative pressure in the air volume in the fluid chamber (12) caused by cooling, heating the air volume in the fluid chamber (12) to generate an overpressure in the air volume sufficient to transfer the first liquid volume (30) against the hydrostatic pressure through the first outlet structure from the fluid chamber (12).

26. A method according to any one of claims 19 to 25, wherein, following the transfer of the second liquid volume (32) through the second outlet structure, the second outlet structure remains or is at least partially filled with liquid, such that the fluidic resistance of the second outlet structure The transfer of the first liquid volume (30) through the first outlet structure is determined by the viscosity of the liquid in the second outlet structure.

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