WO2018011085A1

WO2018011085A1 - Handling of liquids using a fluid module having a fluid plane that is inclined with respect to a rotation plane

Info

Publication number: WO2018011085A1
Application number: PCT/EP2017/067118
Authority: WO
Inventors: Nils Paust; Markus Rombach; Mark Keller; Felix Von Stetten; Marc Karle
Original assignee: Hahn-Schickard-Gesellschaft für angewandte Forschung e.V.
Priority date: 2016-07-15
Filing date: 2017-07-07
Publication date: 2018-01-18
Also published as: DE102016213000A1

Abstract

A device for handling liquids making use of centrifugal force has a rotation body with a holder for a fluid module, wherein the rotation body has a rotation axis about which the rotation body can be rotated and which defines a rotation plane on which the rotation axis is vertical. A fluid module can be inserted into the holder or attached to the holder. Fluid structures are formed in a fluid plane in the fluid module. When the fluid module is inserted into the holder or attached to the holder, the fluid plane is inclined at an angle to the rotation plane and a) either one of two mutually perpendicular spatial directions that define the fluid plane runs radially with respect to the rotation axis, or b) a straight line in the rotation plane running through the rotation axis, which is perpendicular to one of the two mutually perpendicular spatial directions, does not intersect the fluid module.

Description

Handling of liquids using a Fluidikmoduis with respect to a plane of rotation inclined Fluidikebene

description

Embodiments of the present invention relate to apparatus and methods for handling liquids utilizing centrifugal force, and more particularly to such apparatus and methods in which a fluidic plane of a fluidic module is inclined with respect to a plane of rotation.

Embodiments thus relate to a centrifugal microfluidics related to the handling of liquids in the femtoliter to milliliter range in rotating systems. Such systems are mostly polymer disposable cartridges used in or rather from centrifuge rotors with the intention of automating laboratory processes. Standard laboratory processes such as pipetting, centrifuging, mixing or aliquoting may be implemented in a microfluidic cartridge, which may be referred to as a fluidic module. For this purpose, the cartridges contain channels for fluid guidance, as well as chambers for collecting liquids. The cartridges are subjected to a predefined sequence of rotational frequencies, the frequency protocol, so that the fluids in the cartridges can be moved by the centrifugal force. Centrifugal microfluidics is mainly used in laboratory analysis and mobile diagnostics. The most common cartridges to date are centrifugal microfluidic discs, known for example as "Lab-on-a-disk", "LabDisk", "Lab-on-CD", which are used in special processing equipment.

There are numerous solutions known that allow parallel handling of liquids in multiple cartridges or fluidic modules.

EP 0 778 950 B1 discloses a cartridge or a disposable module for examining biological samples. The cartridge itself is made up of several layers. Microfluidic structures and channels are contained inside the cartridge. The cartridges are designed as segments of a circle so that multiple cartridges can be processed in parallel. For this purpose, the cartridges are arranged side by side on a rotary body, so that they form a circle and are processed horizontally. you can. In other words, the liquid levels of the cartridges are arranged in the plane of rotation.

US 2007/0095393 A1 discloses devices for processing fluids, in which two layers each have microfluidic structures. These two layers are separated by a third layer. Holes may be introduced into the third layer by means of a laser to thereby connect structures or channels of the layers 1 and 2 together. Again, a Fluidikebene is arranged horizontally during processing. From the company "spinX technologies" a so-called "gStack" is known, which represents a container in which several cartridges are arranged. To process liquids using the cartridges, the gStack can be placed in the analyzer, whereupon a gripper removes the individual cartridges and inserts them into a rotor. In the rotor, the cartridges are processed horizontally. During processing, holes are made with a laser as connections between the micro fluidic structures in the layers, in which way the liquids can be controlled during the processing.

Yeo, Joo Chuan; Wang, Zhiping; Lim, Chwee Teck (2015): Microfluidic separation of cells and particles using a swinging centrifuge, in: Biomicrofluidics 9 (5), p. 0541 14. DOI: 10.1063 / 1.4931953, describe microfluidic separation of cells and particles using a swing-bucket rotor. A PDMS chip is placed in a holder of a swing-bucket rotor. Under rotation, the holder swings out with the chip. In the time until the holder swings out, the chip is arranged horizontally and the charged sample is moved further by the centrifugal pressure. In addition, particles are separated by size in the flat separation channel. Larger particles move radially outward faster than smaller particles.

There is a need for devices and methods for handling liquids in which more space is available radially inward for fluidic structures and / or which allow parallelization with an increased integration density.

Embodiments of the present invention cover this need by an apparatus according to claim 1 and a method according to claim 15. Further developments of the invention are set forth in the dependent claims. Embodiments of the invention provide a device for handling liquids using centrifugal force, comprising: a rotary body with a holder for a fluidic module, wherein the rotary body has an axis of rotation about which the rotary body is rotatable and which defines a plane of rotation the axis of rotation is vertical; a fluidic module, which can be introduced into the holder or attached to the holder, in which the fluidic structures are formed, wherein an extension of the Fluidikstruktu- ren in two mutually perpendicular directions in space is many times greater than an extension of the fluidic structures in a third spatial direction, the perpendicular to the first and second spatial directions, wherein the first and second spatial directions define a fluidic plane, wherein, when the fluidic module is inserted into the bracket or attached to the bracket, the fluidic plane is inclined at an angle to the plane of rotation, and either a) one of the two mutually perpendicular spatial directions with respect to the axis of rotation extends radially or b) a line extending through the axis of rotation in the plane of rotation, which is perpendicular to one of the two mutually perpendicular spatial directions, does not intersect the fluidic module.

Embodiments provide a method of handling liquids using a corresponding apparatus comprising introducing a liquid into the fluidic structures and inserting the fluidic module into the rotary body or attaching the fluidic module to the rotary body, and rotating the rotary body to handle the liquid.

Embodiments are based on the finding that by inclining the fluidic plane relative to the plane of rotation radially inside more space is available for the fluidic planes. Furthermore, it has been recognized that it is possible by means of a corresponding arrangement of a fluidic module relative to a plane of rotation to arrange a plurality of fluidic modules in a corresponding arrangement with a higher integration density on the rotation body. As a result, embodiments enable a simultaneous processing of liquids using a larger number of fluidic modules with the same space requirement. Embodiments of the invention are explained below with reference to the accompanying drawings. Show it:

Fig. 1 is a schematic representation of an embodiment of a device for handling liquids with a fluidic module;

FIG. 2 shows a schematic illustration of a device for handling liquids with two fluidic modules; FIG.

3 is a schematic representation of a fluidic module;

Fig. 4 is a schematic representation of an arrangement of a plurality of fluidic modules;

5 shows a schematic representation of an arrangement of a fluidic module relative to a plane of rotation;

6 is a schematic representation of a device having a first axis of rotation and a second axis of rotation;

7 shows a schematic illustration of a device for handling liquids with a drive device;

8a and 8b are schematic representations of a fluidic module;

9 to 12 schematic representation for explaining fluidic structures; and

13 is a schematic representation of an alternative embodiment of a device in which a fluidic module is arranged offset with respect to the radial direction.

In the following description of embodiments of the invention, the same or equivalent elements are provided with the same reference numerals in the figures, so that their description in the different embodiments with each other is interchangeable. Before embodiments of the invention are explained in more detail, it should firstly be pointed out that examples of the invention can be applied in particular in the field of centrifugal microfluidics, which involves the processing of liquids in the femtoliter to milliliter range. Correspondingly, fluidic structures can have suitable dimensions in the micrometer range for handling corresponding volumes of liquid.

When the term "radial" is used herein, it is meant radial with respect to the center of rotation (ie, the axis of rotation) about which the body of revolution and thus the fluidic module is rotatable, thus radially sloping away from the center of rotation in the centrifugal field A fluid passage whose start is closer to the center of rotation than the end thereof is thus radially sloping, while a fluid passage whose beginning is farther from the center of rotation than the end thereof is radially increasing Channel, which has a radially rising portion, thus has directional components that extend radially inward or radially in. It is clear that such a channel does not have to run exactly along a radial line, but at an angle to the radial If this is referred to as a fluid channel, then a structure is gemei nt, whose length dimension is greater from a fluid inlet to a fluid outlet, for example, more than 5 times or more 10 times greater than the dimension or dimensions that define or define the flow cross-section. Thus, a fluid channel has a flow resistance for a flow through it from the fluid inlet to the fluid outlet. In contrast, a fluid chamber herein is a chamber having dimensions such that a relevant flow resistance does not occur in it.

1 shows schematically an embodiment of a device for handling liquids, which has a rotation body 10 with a holder 12 for a fluidic module 14. In the illustration in FIG. 1, the fluidic module 14 is not completely inserted into the holder 12 for purposes of illustration. The holder 12 can be, for example, a recess into which the fluidic module 14 can be introduced so that the module 14 is held in the recess during a rotation of the rotational body. For example, the fluidic module 14 can be introduced from above into the corresponding recess. Alternative mounts are possible, for example a clamping device to which the fluidic module can be attached. In the fluidic module fluidic structures 16 are formed, which are shown in Fig. 1 by dotted lines. In the embodiment shown in Fig. 1, the rotary body 10 has the shape of a circular disc with a center 20 around which the disc 10 is rotatable. The rotation axis 22 of the rotation body 10 extends through the center 20. The rotation axis 22 defines a rotation plane on which the rotation axis 22 is perpendicular.

FIG. 2 shows a schematic illustration of a device for handling liquids, in which two corresponding holders 12 are provided in the rotary body 10, two corresponding fluidic modules 14 being inserted into the holders 12 or attached to the holders 12. In alternative embodiments, any other number of fluidic modules may be appropriately attached to the rotary body 10. In embodiments, the rotary body may be rotationally symmetrical with the attached fluidic modules.

As will be explained in more detail with reference to FIG. 3, the extent of the fluidic structures 16 in two mutually perpendicular spatial directions x and y is many times greater than an extension of the fluidic structures in a third spatial direction z, which is perpendicular to the first and the second spatial direction , wherein the first and the second spatial direction x and y define a Fluidikebene. When the fluidic module 14 is inserted into the bracket 12 or attached to the bracket 12, the fluidic plane is inclined at an angle with respect to the plane of rotation indicated by reference numeral 24 in FIG. In the example shown in FIG. 3, this angle is 90 °, so that one of the two spatial directions, namely the spatial direction y, in the exemplary embodiment shown extends parallel to the axis of rotation 22. Furthermore, in the exemplary embodiment shown in FIG. 1, the other of the spatial directions, namely the spatial direction x, extends radially with respect to the axis of rotation.

In alternative embodiments, the one of the spatial directions is not radial, but may be arranged offset to the radius, as long as a running in the plane of rotation through the axis of rotation straight, which is perpendicular to one of the two mutually perpendicular directions, does not intersect the Fluidikmodul. An example of such an arrangement is shown in FIG. 13, in which a radial direction (radius) is represented by an arrow 26. The fluidic module 14, whose one spatial direction is arranged in the radial direction (as in the example shown in FIG. 1), is shown in dashed lines in FIG. Further, in Fig. 13, a fluidic module 14a is provided to this radial direction is arranged offset, shown. However, the fluidic element 14a is offset only so far with respect to the radial direction that a straight line passing through the axis of rotation, which is perpendicular to one of the two mutually perpendicular spatial directions, does not intersect the fluidic module. An example of such a straight line is shown by the straight line g in FIG. In the example shown in FIG. 13, the fluidic module 14a is arranged parallel to the radial direction 26. However, it is understood that the fluidic element 14a offset from the radial direction could also be disposed at an angle to the radial direction. As shown in FIG. 3, the fluidic structures 16 may include fluid chambers 30a, 30b, 30c and fluid channels 32a, 32b. It should be noted that the fluidic structures shown are purely exemplary of any structures that may be formed in the fluidic module. In exemplary embodiments, the fluidic structures have at least two fluid chambers, which are fluidically connected to one another by at least one fluid channel.

In embodiments, the fluidic module may be formed of any suitable material, for example, a plastic such as PMMA (polymethyl methacrylate), PC (polycarbonate), PVC (polyvinyl chloride) or PDMS (polydimethylsiloxane), glass or the like. In embodiments, the fluidic module has multiple layers, wherein the fluidic structures may be formed in one or more of the layers. In embodiments, the outer layers may be lid layers so that the fluidic structures are closed. One or more filling openings or outlet openings may be provided in the cover layers. These can be lockable.

In embodiments, the fluidic module may have the shape of a plate, wherein the length and the width of the plate are many times greater than the thickness of the plate and wherein the two main surfaces of the plate are parallel to the Fluidikebene. The fluidic module shown in FIGS. 1 and 3 is an example of such a plate-shaped or card-shaped fluidic module. Generally, an area where the fluidic structures are formed in the fluidic module may be plate-shaped, with the layered or plate-shaped portion lying in the fluidic plane. In embodiments, when the fluidic module is inserted into the bracket or attached to the bracket, the fluidic plane is at an angle of 90 degrees with respect to inclined to the plane of rotation. Figs. 1 and 3 show an example of such an arrangement which enables a high integration density. For example, in FIG. 4, a corresponding arrangement of 12 fluid modules 14 is shown, which are arranged about the axis of rotation 22. A rotary body with corresponding holders for the fluidic modules 14 is not shown in FIG. 4. Such an arrangement enables a parallel processing of several fluidic modules simultaneously.

In general, in embodiments of the rotary body on a plurality of holders for the corresponding introduction or attachment of a respective fluidic module, wherein in each of the holders, a corresponding fluidic module can be introduced or attached to the same. The brackets may be arranged such that the center distance of the brackets at a radially inner end thereof in the azimuthal direction with respect to the axis of rotation is less than the extension of the fluidic modules in the fluidic plane. In this regard, reference is made, for example, to the center distance D shown in FIG. 4, which is smaller than the extent of the fluidic modules 14 in the fluidic plane, which is defined by the spatial directions x and y.

In embodiments, the axis of rotation is arranged vertically. In embodiments, processing takes place while the fluidic module (which may also be referred to as a microfluidic cartridge is vertically aligned). In other words, one of the two spatial directions defining the fluidic plane is vertically aligned. The rotation axis can be inside or outside the fluidic module. In the fluidic structures shown in Fig. 3, for example, fluids from the two radially inner chambers 30a can be centrifugally moved through the channels 32a radially outward into the large central chamber 30b. There, the two fluids can be mixed and then be divided by the continuing channel 32b radially outward into the terminal chambers 30c. There, a detection reaction can take place and be read out. A readout can be done, for example, optically, for example by a fluorescence measurement. In order to enable such a reading, at least parts of the rotating body and of the fluidic module can be transparent. Further, mirrors and / or light guides may be disposed in the rotary body to redirect light from a light source to the respective chamber in which a detection reaction occurs and to redirect light from the chamber to a detector. In embodiments of the invention, when the fluidic module is inserted into the fixture or attached to the fixture, the fluidic plane is inclined at an angle in a range of 20 degrees to 70 degrees with respect to the plane of rotation. In embodiments, the fluidic plane is inclined at an angle in a range of 30 degrees to 60 degrees with respect to the plane of rotation. For example, FIG. 5 shows an arrangement of the fluidic module in which the fluidic module 14 is inclined with respect to the plane of rotation 24 by an angle α which is, for example, 45 degrees. As further shown in FIG. 5, the fluidic module or the fluidic plane is inclined at an angle of β with respect to the axis of rotation 22, where α + β = 90 °. It does not require a separate explanation that the respective holder or the respective holders of the rotary body are adapted to hold the fluidic module or the fluidic modules in a corresponding orientation with respect to the plane of rotation. By an inclined arrangement in which the fluidic module is inclined at an angle other than 90 degrees relative to the plane of rotation, for example at an angle of 30 ° to 60 °, on the one hand a high degree of parallelization can be obtained, while on the other hand the fluidic modules without complex Optics can be read directly by a direct light incidence to the fluid chambers in which the reading is to take place, is possible and is not blocked by adjacent fluidic modules. In embodiments, the axis of rotation may be a first axis of rotation, wherein the holder is configured to rotatably support the fluidic module about a second axis of rotation skewed to the first axis of rotation. An example of such an arrangement is shown purely schematically in FIG. As shown in FIG. 6, attached to a corresponding support of the rotary body 10, which is rotatable about the rotation axis 22, a second rotary body 60 is mounted, which is rotatable about a second axis of rotation 62, as indicated by an arrow 64. The rotation axis 62 may, for example, be perpendicular to the rotation axis 22. On the second rotary body 60, one or more fluidic modules 66 are mounted. The fluidic modules 66 may be arranged horizontally with respect to the rotation body 60 and inclined with respect to the rotation plane defined by the rotation axis 22. In embodiments, further rotation axes can thus be used for precision. One of the axes of rotation, the axis of rotation 22, represents the main axis of rotation, while the other axis of rotation, the axis of rotation 62, rotates about the main axis of rotation, wherein the fluidic modules 66 in turn rotate about the second axis of rotation 62. The rotation axes are skewed. Both axes of rotation may be within but also outside the fluidic modules. There is no need for explicit explanation that the rotation body 10 is designed accordingly to a corresponding rotation of the second rotating body 66, for example, by a corresponding recess in the rotating body 10th

FIG. 7 shows schematically an example of a device for handling liquids with a rotary body 10 into which fluidic modules 14 are inserted. A drive device 70 for the rotary body 10 may have a rotating part 72, on which the rotary body 10 is mounted. For example, the rotary body 10 may be attached to the rotating part 72 by means of a hook-and-loop fastener. Alternatively, the rotary body 10 can have a central opening, via which the rotary body 10 can be attached to the rotating part 72 of the drive device 70 by means of a conventional fastening device. The rotating part 72 is rotatably supported on a stationary part 74 of the drive device 70. The drive device 70 can be, for example, a conventional centrifuge with an adjustable rotational speed. A controller 76 may be provided, which is configured to control the drive device 70 in order to apply a predefined sequence of rotational frequencies, the frequency protocol, to the rotational body and thus the fluidic modules in order to achieve the handling of the fluids in the fluidic modules For example, to move and / or process the liquids. As will be appreciated by those skilled in the art, the controller 76 may be implemented by, for example, a suitably programmed computing device or custom integrated circuit.

Referring to Figures 8a and 8b, a simple way of how sample transfer into a fluidic module can take place is described. For example, the fluidic module 14 may have an opening 80, which may be provided in a rear side of the fluidic module 14. Through this opening, a sample can be introduced into the fluidic structures of the fluidic module by means of a charging device 82, for example a pipette tip. In order to close the fluidic module after the sample transfer, the opening 80 must also be closed. This can, as shown in FIGS. 8a and 8b, for example, be done by a strip 84 of self-adhesive film. Alternatively, the opening 80 can also be closed with a plug or more complex closure systems, such as a molded lid with a film hinge. The appropriately sealed fluidic module may then be inserted into the rotary body and processed in the appropriate orientation with respect to the plane of rotation as described herein. In the following, exemplary fluidic structures, which may be provided in the fluidic module, are described with reference to FIGS. 9 to 12. The fluidic structures described with reference to FIGS. 9 to 12 may be used to carry out unit operations in a corresponding fluidic module. However, it is obvious that in addition to the described fluidic structures further fluidic structures may be formed in the respective fluidic modules to implement desired fluidic operations.

Fig. 9 shows fluidic structures in the form of an overflow siphon. The overflow siphon has a radially inner fluid inlet 90, a fluid chamber 92 and a radially outer fluidic outlet 94. The fluidic inlet 90 is connected to the fluid chamber 92 via a fluid channel 96. The fluidic outlet 94 is connected to the fluid chamber 92 via an outlet channel 98. The outlet channel 98 opens into the fluid chamber 92 in an upper and radially outer region of the fluid chamber 92 with respect to the gravitational field. The outlet channel has an earth gravity field rising portion 98a, a radially rising portion 98b, and a radially decreasing portion 98c. The sections 98b and 98c are in turn connected to one another via a channel section rising in the gravitational field. The radially outer fluidic outlet 94 is located radially further outward than the radial position of the outlet of the fluid chamber 92, d. H. the position at which the outlet channel 98 opens into the fluid chamber 92. In operation, the fluid chamber 92 can be filled with rotation via the inlet 90 and the channel 96, wherein from a certain filling volume, when the siphon is exceeded, the chamber 92 can be emptied through the outlet channel 98 again. In addition, in embodiments in a vertical arrangement, the fluid chamber 92 can be filled without it emptying. With no or little rotation, gravity keeps the liquid in the chamber out of contact with the outlet. Only at higher rotational frequencies, the liquid is moved radially outward, in Fig. 9 to the right, filled the outlet channel 98 and can then be transferred through the outlet 94 in downstream fluidic structures. By such a vertical implementation of an overflow siphon, the risk of premature breakthrough by capillary priming of the outlet channel can be significantly reduced.

In order to transfer a sample into the fluidic module 14, a structure as described above with reference to Figs. 8a and 8b may be used. Alternatively, the sample may be introduced from one side of the fluidic module 14, for example, by fluidic structures as shown in FIG. 10. Here is a sample on the side or be introduced from above through an inlet 100 in the fluidic module 14, from which it can be centrifugally moved into an outlet passage 102 of the Ladefluidikstrukturen under rotation. The outlet channel 102 of the loading fluidic structures can in turn be connected to downstream fluidic structures. The loading of the loading fluid structures with a sample can be carried out at standstill or under rotation, for example by inserting, dropping or pipetting. For example, a sample can only be pipetted to the edge of the charging fluidic structures. By rotating the fluidic module, the sample is first thrown into the chamber 104 and then through the same and the outlet channel 102 into subsequent structures. However, the sample may also be pipetted directly into the chamber 104 by inserting the pipette, and then being rotated out of the chamber into subsequent structures.

In embodiments, the fluidic structures include those that implement a Coriolis switch. Such fluidic structures may have a radially sloping channel that branches into a first channel and a second channel, wherein the first channel opens with respect to a center of the radially sloping channel in the third spatial direction on a first side in the radially sloping channel and the second channel opens with respect to the center of the radially sloping channel in the third spatial direction on a second side in the radially sloping channel. An example of such fluidic structures is shown in FIG. In the left part of FIG. 11, the rotation axis 22 is shown, in the middle a schematic side view of the fluidic structures and in the right part a schematic sectional view in the radial direction. The fluidic structures have a radially sloping channel 110 which branches into a first channel 112 and a second channel 114. A center of the radially sloping channel 110 in the third spatial direction is indicated in FIG. 11 by a line 116. As shown in Fig. 11, the radially sloping mother channel 110 divides at a bifurcation 118 in the two daughter channels 112 and 114. Here, starting from the Mutterkana! 110 a daughter channel 112 left, the other daughter channel 114 continued right. By means of the Coriolis force, depending on the direction of rotation, the majority of the liquid can now be directed into the left daughter canal 112 or the right daughter canal 114. In order to disconnect the daughter channels, as shown in Fig. 11, one daughter channel may be led up and the other daughter channel down. Thus, fluidic structures may be configured to implement a Coriolis switch in which the Coriolis force is utilized to switch the liquid into a particular channel. Finally, FIG. 12 shows a sectional view from the axis of rotation onto the fluidic module, ie in the radial direction. The fluidic structures may include a first fluid chamber 120 and a second structure 122 in the form of a second fluid chamber or outlet channel 122. The first fluid chamber 120 may be a sealed chamber in which a liquid is sealed upstream. The seal can be selectively broken so that liquid is released and transferred to the second structure 122. This can be realized for example by a depressible mandrel 124, as indicated in Fig. 12. The operation of this dome can be done manually or automatically before or during the processing of the liquid. By opening the chamber 120 and releasing the previously enclosed liquid, it can be transferred through the opening into the subsequent microfluidic structure 122.

Embodiments of the present invention thus provide a microfluidic cartridge wherein the cartridge is provided with microfluidic structures and the fluidic plane is rotated with respect to the plane of rotation so that more fluidic area is available than area in the plane of rotation is claimed. Under Fluidikebene can be understood the location of the majority of micro-channels. In other words, embodiments of the invention provide a microfluidic cartridge or a microfluidic fluidic module, which is provided with microfluidic structures, wherein the area of the projection of the cartridge on the fluidic plane is greater than the area of the projection on the Rotation axis vertical plane of rotation. In embodiments, the cartridge occupies only up to a percentage of the circumference of the plane of rotation. In embodiments, the fluidic plane is inclined at least 30 degrees with respect to the plane of rotation. Exemplary embodiments can be used for the processing of samples, both preparatively and analytically. In embodiments, the fluidic structures may include a plurality of channels that are parallel to one another.

In embodiments, the fluidic structures are adapted for vertical placement of the fluidic module, as opposed to a horizontal arrangement as used in known systems. While radial channels are used in a horizontal processing, in particular parallel channels can be used in a vertical processing. In horizontal processing, isoradial channels are curved, while in vertical processing the channels can be straight. With horizontal processing, gravitation is typically negligible, while vertical processing uses gravity in large chambers can be. In this regard, gravity is also present in horizontal processing, but due to the small thickness of the horizontally arranged fluidic modules, has no significant influence on the processing. The influence of gravity increases the deeper the chambers become. Thus, the gravity can be used in the vertical arrangement of the fluidic module in the fluidic plane, which allows the use of gravity even with very thin Fluidikmoduien.

The arrangement of the fluidic modules as described herein has numerous advantages over conventional horizontal systems. In the case of a horizontal process, the integration of many unit operations often reaches its limits, especially if radially internal structures are to be or must be implemented. There is only limited space available due to the platform. Although there is sufficient space on the radial outside, the liquids have to be pumped radially inward again with additional space and often under fluidic losses. By arranging the fluidic modules as described herein, this fundamental problem of centrifugal fluidics can be solved. By turning the Fluidikebene is radially inside more space for fluidic structures available. Thus, the problem of the radially inner space shortage can be solved. For horizontal systems, reagents usually had to be stored radially outward for space reasons and pumped radially inward for use. The procedure described herein also allows reagents to be radially in-advance from where they can be used directly for analysis. In addition, the elimination of the pump structures creates more space on the fluidic module or the fluidic module can be made more compact. Another problem with horizontal systems is the processing of many parallel reactions. In particular, in horizontal systems, it is difficult to arrange many fluidic modules on a rotating body, for example, to inspect many samples in parallel on one or a few targets, in contrast, the arrangements of the fluidic modules as described herein allow a high integration density, which indicates that many fluidic modules can be processed in parallel.

Embodiments of the invention thus make it possible to eliminate both said weaknesses of horizontal systems by the rotation of the fluidic plane out of the plane of rotation. The rotation about the radius of the rotation body increases the integration density, so that a larger number of fluidic modules can be processed in parallel. WEI terhin by the rotation radially inside more space for fluidic unit operations available.

Embodiments of the invention enable these advantages without complex structures, such as swing-out rotors. Turning the fluidic plane in swing-bucket rotors reduces or eliminates the centrifugal pressure in the structures, thereby reducing or eliminating fluid drive. More complex analyzes can not be integrated in such a system. In embodiments of the invention, the fluidic modules are firmly inserted into the holder or attached to the holder, so that such problems do not occur. Furthermore, a swing-out mount requires a lot of space, which prevents a high integration density. Embodiments described herein do not require a complex internal mechanism, such as is used in systems where tubes are placed and processed in parallel in a swing-bucket rotor.

Embodiments of the invention thus provide fluidic modules, devices, and methods for the controlled processing of liquids that enable high integration density, meaning that many fluidic modules are parallel processable, with more space available radially inward than is the case with known systems. Embodiments of the invention provide a fluidic module which is rotatable about a center of rotation, wherein the fluidic plane is rotated relative to the plane of rotation and the axis of rotation may be within the fluidic module or outside the fluidic module. The rotation of the fluidic plane with respect to the plane of rotation opens up numerous advantages, for example a processing perpendicular or inclined to the plane of rotation, overlapping of individual fluidic modules, especially radially inward, whereby a denser packing is made possible. In this way, a high degree of parallelization can be achieved. Radially inside there is more space available for fluidic structures or for the pre-storage of reagents. Furthermore, in embodiments, in particular in large fluid chambers, the gravitation can be used for actuation, for example for transport, for mixing or for moving liquids. In embodiments of the invention, the fluidic module may have a size substantially similar to that of a credit card, approximately 75 x 40 x 4 mm ² . Such fluidic modules (cartridges) may be used in a corresponding holder in parallel in a centrifuge or specialized processing apparatus. In the holder integrated heating elements can allow a local temperature of individual structures in the fluidic module. Furthermore, an optical detection (for example fluorescence detection) can be realized by means of mirrors or light guides provided in the rotation body.

Embodiments of the invention may find particular application where several processes are to be executed in parallel. For example, in embodiments, the apparatus and method may be configured to perform digital amplification. In a digital amplification, a plurality of droplets are generated by tearing off at a mouth of a channel in a fluid chamber. A bioreaction to detect DNA can then take place in the droplets.

Although some aspects have been described in the context of a device, it will be understood that these aspects also constitute a description of the corresponding method such that a block or device of a device may also be understood as a corresponding method step or feature of a method step is. Similarly, aspects described in connection with or as a method step also represent a description of a corresponding block or detail or feature of a corresponding device.

The embodiments described above are merely illustrative of the principles of the present invention. It will be understood that modifications and variations of the arrangements and details described herein will be apparent to those skilled in the art. Therefore, it is intended that the invention be limited only by the scope of the appended claims and not by the specific details presented in the description and explanation of the embodiments herein.

Claims

claims

1. A device for handling liquids by utilizing the centrifugal force, comprising: a rotary body (10) with a holder (12) for a fluidic module (14, 66), wherein the rotary body (10) has a rotation axis (22) to the rotation body (10) is rotatable and defines a plane of rotation (24) on which the axis of rotation (22) is perpendicular; a fluidic module (14, 66) which can be introduced into the holder (12) or attached to the holder (12) in which fluidic structures (16) are formed, an extension of the fluidic structures (16) in two mutually perpendicular spatial directions (x , y) is greater than an extension of the fluidic structures (16) in a third spatial direction (z), which is perpendicular to the first and the second spatial direction (x, y), wherein the first and the second spatial direction (x, y) a Define Fluidikebene, wherein, when the fluidic module (14, 66) is inserted into the holder (12) or attached to the holder (12), the Fluidikebene by an angle with respect to the

A) one of the two mutually perpendicular spatial directions (x, y) with respect to the axis of rotation (22) extends radially or b) a through the rotation axis (22) extending straight line (g) in the plane of rotation (24 ), which is perpendicular to one of the two mutually perpendicular spatial directions (x, y), does not intersect the fluidic module (14, 66).

2. Device according to claim 1, wherein, when the fluidic module (14, 66) in the holder (12) introduced or attached to the holder (12), the Fluidikebene inclined by an angle of 90 ° with respect to the plane of rotation (24) is.

3. Device according to claim 1 or 2, wherein, when the fluidic module (14, 66) is introduced into the holder (12) or attached to the holder (12), one of the two main directions (y) defining the fluidic plane, is vertical.

4. Device according to claim 1, wherein, when the fluidic module (14, 66) is introduced into the holder (12) or attached to the holder (12), the fluidic plane is inclined at an angle of 20 ° to 70 ° with respect to the plane of rotation ( 24) is inclined.

Apparatus according to any one of claims 1 to 4, wherein the fluidic module (14, 66) is in the form of a plate, the length and width of the plate being greater than the thickness of the plate, and the two major surfaces of the plate being parallel to the plate Fluidikebene are.

Apparatus according to any one of claims 1 to 5, wherein the axis of rotation (22) is a first axis of rotation (22), and wherein the support (12) is adapted to rotate the fluidic module (66) about a second axis of rotation (62). the skewed to the first axis of rotation (22) is to store.

Apparatus according to claim 6, wherein the second axis of rotation (62) is perpendicular to the first axis of rotation (22).

Apparatus according to claim 5 or 6, wherein the fluidic module (66) is attached to another rotary body (60) on which a plurality of fluidic modules (66) are arranged.

Device according to one of claims 1 to 8, wherein the fluidic structures (16) in the interior of the fluidic module (14, 66) are formed, wherein a filling opening (80) through which a liquid in the fluidic structures (16) can be introduced, is closable ,

Device according to one of claims 1 to 9, wherein the fluid structures (16) at least two Fiuidkammern (30a, 30b, 30c), which are fluidly connected to each other by at least one fluid channel (32a, 32b).

Apparatus according to any one of claims 1 to 10, wherein the fluidic structures (16) comprise an overflow siphon having a radially inner fluid inlet (90), a fluid chamber (92), and an outlet channel (98), one end of the outlet channel (16). 98) opens into the fluid chamber (92) in a region of the fluid chamber (92) which is upper and radially outward relative to the earth's gravitational field, the outlet channel (98) being in contact with the earth's gravitational field. a rising portion (98a), a radially rising portion (98b) and a radially sloping portion (98b), wherein an outlet (94) of the outlet channel (98) is disposed radially further out than the opening into the fluid chamber (92) end thereof ,

12. Device according to one of claims 1 to 11, wherein the fluidic structures (16) have a radially sloping channel (110) which branches into a first channel (112) and a second channel (114), wherein the first channel ( 112) opens with respect to a center of the radially sloping channel (110) in the third spatial direction (z) on a first side in the radially sloping channel (110) and the second channel (114) with respect to the center of the radially sloping channel (110) in the third spatial direction (z) opens on a second side in the radially sloping channel (110).

13. Device according to one of claims 1 to 12, wherein the rotary body (10) has a plurality of holders (12) for the corresponding introduction or attachment of a respective fluidic module (14, 66).

14. The apparatus of claim 13, wherein the brackets (12) are arranged such that the center distance (D) of the brackets (12) at a radially inner end thereof with respect to the axis of rotation (22) azimuthal direction is less than the extent of Fluidic modules (14, 66) in the fluidic plane.

15. A method for handling liquids using a device according to one of claims 1 to 14, comprising:

Introducing a liquid into the fluidic structures (16) and introducing the fluidic module (14, 66) into the rotary body (10) or attaching the fluidic module (14, 66) to the rotary body (10); and

Rotating the rotary body (10) to handle the liquid.