DE102016213000A1 - Handling of liquids using a fluidic module having a plane of fluidity inclined with respect to a plane of rotation - Google Patents

Abstract

A device for handling liquids by utilizing the centrifugal force has 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 on which the axis of rotation is perpendicular. A fluidic module can be introduced into the holder or attached to the holder. Fluidic structures are formed in a fluidic plane in the fluidic module. When the fluidic module is inserted into the mount or attached to the mount, the fluidic plane is inclined at an angle to the plane of rotation, and a) extends either one of two mutually perpendicular spatial directions that define the fluidic plane radially or b) with respect to the axis of rotation a plane passing through the axis of rotation straight line in the plane of rotation, which is perpendicular to one of the two mutually perpendicular directions in space, not the fluidic module.

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 in place of 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.

From the EP 0 778 950 B1 a cartridge or a disposable module for examining biological samples is known. 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 rotating body, so that they form a circle and can be processed horizontally. In other words, the fluidic planes of the cartridges are arranged in the plane of rotation.

From the US 2007/0095393 A1 are devices for processing fluids known 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 the processing, holes are introduced with a laser as connections between the microfluidic 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 size separation of cells and particles using a swinging bucket centrifuge, in: Biomicrofluidics 9 (5), p. 054114. DOI: 10.1063 / 1.4931953 , describe a 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 to swing out of the holder, the chip is arranged horizontally and the charged sample is moved 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 liquid handling apparatuses and methods in which more space is available radially inward for fluidic structures and / or that allows for parallelization with 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 by utilizing the 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 on which Rotation axis 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 the fluidic structures in two mutually perpendicular spatial directions is many times greater than an extension of the fluidic structures in a third spatial direction, which is perpendicular to the first and the second spatial direction, wherein the first and the second spatial direction define a fluidic plane,
wherein, when the fluidic module is inserted into the mount or attached to the mount, the fluidic plane is inclined at an angle to the plane of rotation, and either a) one of the two mutually perpendicular spatial directions is radial with respect to the axis of rotation, or b) one passing through the axis of rotation Especially in the plane of rotation, which is perpendicular to one of the two mutually perpendicular spatial directions, the fluidic module does not intersect.

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 recognition that by tilting the fluidic plane relative to the plane of rotation radially inside more space is available for the Fluidikebenen. 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:

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

2 a schematic representation of a device for handling liquids with two fluidic modules;

3 a schematic representation of a fluidic module;

4 a schematic representation of an arrangement of a plurality of fluidic modules;

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

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

7 a schematic representation of a device for handling liquids with a drive device;

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

9 to 12 schematic representation for explaining fluidic structures; and

13 a schematic representation of an alternative embodiment of an apparatus 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. Accordingly, fluidic structures may have suitable dimensions in the micrometer range for handling corresponding volumes of fluid.

When the term "radial" is used herein, it is meant in each case radial with respect to the center of rotation (ie the axis of rotation) about which the rotational body and thus the fluidic module is rotatable. Thus, in the centrifugal field, a radial direction is radially sloping away from the center of rotation and a radial direction toward the center of rotation is radially increasing. A fluid channel, the beginning of which is closer to the center of rotation than the end, is thus radially sloping, while a fluid channel, the beginning of which is farther from the center of rotation than its end, is radially increasing. A channel, which has a radially rising portion, thus has directional components that extend radially inward or radially inward. It is clear that such a channel does not have to run exactly along a radial line, but can run at an angle to the radial line or bent.

As used herein, a fluid channel means a structure 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 defining the flow area define. Thus, a fluid channel has a flow resistance for flowing through it from the fluid inlet to the fluid outlet. In contrast, a fluid chamber herein is a chamber having dimensions such that a relevant flow resistance does not occur in it.

1 schematically shows an embodiment of a device for handling liquids, which is a rotational body 10 with a holder 12 for a fluidic module 14 having. When displayed in 1 is the fluidic module 14 not completely in the holder for purposes of illustration 12 brought in. At the bracket 12 it may, for example, be 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 rotary body. For example, the fluidic module 14 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 are fluidic structures 16 formed in 1 are shown by dotted lines. At the in 1 the embodiment shown has the rotary body 10 the shape of a circular disk with a center 20 to which the disc 10 is rotatable. Through the center 20 the axis of rotation runs 22 of the rotational body 10 , The rotation axis 22 defines a rotation plane on which the rotation axis 22 is vertical.

2 shows a schematic representation of a device for handling liquids, in which two corresponding holders 12 in the rotation body 10 are provided, wherein two corresponding fluidic modules 14 in the brackets 12 introduced or on the brackets 12 are attached. In alternative embodiments, any other number of fluidic modules may be correspondingly attached to the rotary body 10 to be appropriate. In embodiments, the rotary body may be rotationally symmetrical with the attached fluidic modules.

As referring to 3 is explained in more detail, is the extension of the fluidic structures 16 in two mutually perpendicular spatial directions x and y by a multiple 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 fluidic plane. If the fluidic module 14 in the holder 12 inserted or on the holder 12 is attached, the fluidic plane is at an angle with respect to the plane of rotation, which in 3 by the reference numeral 24 is indicated, inclined. At the in 3 As shown, this angle is 90 °, so that one of the two spatial directions, namely the spatial direction y, in the embodiment shown, parallel to the axis of rotation 22 runs. Furthermore, runs in the in 1 shown embodiment, the other of the spatial directions, namely the spatial direction x, with respect to the axis of rotation radially.

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 in 13 shown in a radial direction (radius) by an arrow 26 is shown. The fluidic module 14 whose one spatial direction is arranged in the radial direction (as in the in 1 shown example) is in 13 shown in dashed lines. Furthermore, in 13 a fluidic module 14a , which is arranged offset to this radial direction shown. The fluidic element 14a However, with respect to the radial direction only offset so far that a running through the axis of rotation straight line, which is perpendicular to one of the two mutually perpendicular directions in space, does not intersect the fluidic module. An example of such a straight line is the straight line g in 13 shown. At the in 13 The example shown is the fluidic module 14a parallel to the radial direction 26 arranged. However, it is clear that the fluidic element offset from the radial direction 14a could also be arranged at an angle to the radial direction.

As in 3 shown, the fluidic structures 16 fluid chambers 30a . 30b . 30c and fluid channels 32a . 32b exhibit. 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 exemplary embodiments, the fluidic module has a plurality of layers, wherein the fluidic structures in one or more several of the layers can be formed. 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. That in the 1 and 3 shown fluidic module is an example of such a plate 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 fixture or attached to the fixture, the fluidic plane is inclined at an angle of 90 degrees with respect to the plane of rotation. The 1 and 3 show an example of such an arrangement, which allows a high integration density. For example, in 4 a corresponding arrangement of 12 fluid modules 14 shown around the axis of rotation 22 are arranged. A rotating body with corresponding holders for the fluidic modules 14 is in 4 not shown. 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, for example, refer to the in 4 referenced center distance D, which is less than the extension 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 oriented vertically). 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. At the in 3 Fluidic structures shown, for example, fluids from the two radially inner chambers 30a centrifugally through the channels 32a radially outward into the large central chamber 30b to be moved. There, the two fluids can be mixed and then through the secondary channel 32b radially outward into the terminal chambers 30c be split. 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, shows 5 an arrangement of the fluidic module, in which the fluidic module 14 with respect to the plane of rotation 24 is inclined by an angle α, which is for example 45 degrees. As further in 5 is shown, the fluidic module or the Fluidikebene by an angle of β with respect to the axis of rotation 22 inclined, 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 purely schematic in FIG 6 shown. As in 6 is shown is on a corresponding holder of the rotating body 10 that is about the axis of rotation 22 is rotatable, a second body of revolution 60 attached, which is about a second axis of rotation 62 is rotatable, as by an arrow 64 is indicated. The rotation axis 62 can for example be perpendicular to the axis of rotation 22 be. On the second rotation body 60 are one or more fluidic modules 66 appropriate. The fluidic modules 66 can with respect to the rotation body 60 be arranged horizontally and with respect to the through the axis of rotation 22 defined rotation plane inclined. 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 rotated about the main axis of rotation, the fluidic modules 66 turn around the second axis of rotation 62 rotate. The axes of rotation are skewed. Both axes of rotation may be within but also outside the fluidic modules. It needs no explicit explanation that the body of revolution 10 is formed corresponding to a corresponding rotation of the second body of revolution 66 to allow, for example, by a corresponding recess in the rotary body 10 ,

7 shows schematically an example of a device for handling liquids with a rotary body 10 , in the fluidics modules 14 are used. A drive device 70 for the rotation body 10 can be a rotating part 72 to which the body of revolution 10 is attached have. For example, the rotational body 10 by means of a hook and loop fastener on the rotating part 72 to be appropriate. Alternatively, the rotational body 10 have a central opening through which the rotary body 10 by means of a conventional fastening device on the rotating part 72 the drive device 70 can be appropriate. The rotating part 72 is rotatable on a stationary part 74 the drive device 70 stored. In the drive device 70 it may be, for example, a conventional centrifuge with adjustable rotational speed. A controller 76 may be provided, which is designed to drive the drive 70 to control the rotational body and thus the fluidic modules with a predefined sequence of rotational frequencies, the frequency protocol, in order to achieve the handling of the fluids in the fluidic modules, for example, to move and / or process the fluids. The control 76 As can be appreciated by those skilled in the art, for example, it may be implemented by a suitably programmed computing device or user-specific integrated circuit.

Referring to the 8a and 8b a simple way is described how a sample transfer into a fluidic module can take place. For example, the fluidic module 14 an opening 80 have, in a back of the fluidic module 14 can be provided. Through this opening can by means of a charging device 82 , For example, a pipette tip, a sample are introduced into the fluidic structures of the fluidic module. To close the fluidic module after the sample transfer, the opening must also 80 getting closed. This can, as in the 8a and 8b is shown, for example, by a strip 84 self-adhesive film done. Alternatively, the opening 80 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, referring to the 9 to 12 exemplary fluidic structures that may be provided in the fluidic module are described. The reference to the 9 to 12 described fluidic structures may serve to perform unitary 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.

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 via a fluid channel 96 with the fluid chamber 92 connected. The fluidic outlet 94 is via an outlet channel 98 with the fluid chamber 92 connected. The outlet channel 98 opens into an upper and a radially outer region of the fluid chamber with respect to the earth's gravitational field 92 into the fluid chamber 92 , The outlet channel has a rising portion with respect to the earth's gravitational field 98a , a radially rising portion 98b and a radially sloping portion 98c on. The sections 98b and 98c are in turn connected to each other via a rising in the gravitational field channel section. The radially outer fluidic outlet 94 is radially outward than the radial position of the outlet of the fluid chamber 92 ie the position at which the outlet duct 98 into the fluid chamber 92 empties. In operation, the fluid chamber 92 under rotation over the inlet 90 and the channel 96 be filled, starting from a certain filling volume when the siphon is exceeded, the chamber 92 over the outlet channel 98 can be emptied again. In addition, in embodiments in a vertical arrangement, the fluid chamber 92 be filled without 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 9 to the right, fills the outlet channel 98 and then through the outlet 94 be converted into 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.

To add a sample to the fluidic module 14 can transfer a structure, as described above with reference to the 8a and 8b has been described. Alternatively, the sample may be from one side of the fluidic module 14 be introduced, for example by fluidic structures, as in 10 are shown. Here is a sample from the side or from above through an inlet 100 into the fluidic module 14 be introduced, from where they rotate centrifugally into an outlet channel 102 the loading fluidic structures can be moved. The outlet channel 102 the charging fluidic structures can in turn be connected to downstream fluidic structures. The loading of the loading fluidic structures with a sample can be carried out at standstill or under rotation, and be done 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 introduced into the chamber 104 and then through the same and the exhaust duct 102 thrown into subsequent structures. The sample may also be obtained by inserting the pipette into the chamber 104 are pipetted directly into this, to then be moved under rotation from 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 in 11 shown. In the left part of 11 is the axis of rotation 22 shown in the middle of a schematic side view of the fluidic structures and in the right part of a schematic sectional view in the radial direction. The fluidic structures have a radially sloping channel 110 on that turns into a first channel 112 and a second channel 114 branched. A center of the radially sloping channel 110 in the third spatial direction is in 11 through a line 116 indicated. As in 11 is shown, the radially sloping mother channel divides 110 at a bifurcation 118 in the two daughter channels 112 and 114 , In this case, starting from the mother channel 110 a daughter channel 112 left, the other daughter channel 114 continued right. By means of the Coriolis force can now, depending on the direction of rotation, the majority of the liquid in the left daughter channel 112 or the right daughter channel 114 be steered. To separate the daughter channels, as in 11 is shown, which is a daughter channel 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 shows 12 a sectional view from the axis of rotation to the fluidic module, ie in the radial direction. The fluidic structures may be a first fluid chamber 120 and a second structure 122 in the form of a second fluid chamber or an outlet channel 122 exhibit. 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 into the second structure 122 is transferred. This can, for example, by a depressible mandrel 124 be realized, as in 12 is indicated. The operation of this mandrel can be done manually or automatically before or during the processing of the liquid. By opening the chamber 120 and the release of the previously entrapped liquid may pass through the opening into the subsequent microfluidic structure 122 be transferred.

Embodiments of the present invention thus provide a microfluidic cartridge, wherein the cartridge is provided with microfluidic structures, and the fluidic plane is rotated relative to the plane of rotation, so that more fluidic surface is available than surface 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 plane perpendicular to the rotation axis , 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. Embodiments may be used to process samples, both preparative and analytical. 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, gravity is typically negligible, while in vertical processing gravity can be used in large chambers. In this regard, the gravity is also present in the horizontal processing, but has no significant influence on the processing due to the small thickness of the horizontally arranged fluidic modules. The influence of gravity increases the deeper the chambers become. Thus, the gravity in the vertical arrangement of the fluidic module can be used in the Fluidikebene, which allows the use of gravity even with very thin Fluidikmodulen.

The arrangement of the fluidic modules as described herein has numerous advantages over conventional horizontal systems. In the case of horizontal processing, the integration of many unit operations often reaches its limits when, above all, radially internal structures are or have to 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 examine many samples in parallel on one or a few targets. In contrast, the arrangements of the fluidic modules as described herein enable a high density of integration, meaning 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. Furthermore, there is more room for fluidic unit operations due to the rotation radially inward.

Embodiments of the invention provide 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 bracket 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 for fluidic Structures or for the pre-storage of reagents available. 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 should be understood that these aspects also constitute a description of the corresponding method such that a block or device of a device is also to be understood as a corresponding method step or feature of a method step. 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.

QUOTES INCLUDE IN THE DESCRIPTION

This list of the documents listed by the applicant has been generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

Cited patent literature

• EP 0778950 B1 [0004]
• US 2007/0095393 A1 [0005]

Cited non-patent literature

• Yeo, Joo Chuan; Wang, Zhiping; Lim, Chwee Teck (2015): Microfluidic size separation of cells and particles using a swinging bucket centrifuge, in: Biomicrofluidics 9 (5), p. 054114. DOI: 10.1063 / 1.4931953 [0007]

Claims (15)

Apparatus for handling liquids utilizing centrifugal force, comprising: a body of revolution ( 10 ) with a holder ( 12 ) for a fluidic module ( 14 . 66 ), wherein the rotational body ( 10 ) a rotation axis ( 22 ), around which the rotary body ( 10 ) is rotatable and the one rotation plane ( 24 ) on which the axis of rotation ( 22 ) is vertical; a fluidic module ( 14 . 66 ), which fits into the holder ( 12 ) or on the holder ( 12 ) is attachable, in the fluidic structures ( 16 ), wherein an extension of the fluidic structures ( 16 ) in two mutually perpendicular spatial directions (x, y) is greater by a multiple 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) define a fluidic plane, wherein when the fluidic module ( 14 . 66 ) in the holder ( 12 ) or on the holder ( 12 ), the fluidic plane at an angle with respect to the plane of rotation ( 24 ) and either a) one of the two mutually perpendicular spatial directions (x, y) with respect to the axis of rotation ( 22 ) extends radially or b) one through the axis of rotation ( 22 ) running straight line (g) in the plane of rotation ( 24 ), which is perpendicular to one of the two mutually perpendicular spatial directions (x, y), the fluidic module ( 14 . 66 ) does not cut. Apparatus according to claim 1, wherein when the fluidic module ( 14 . 66 ) in the holder ( 12 ) or on the holder ( 12 ), the fluidic plane at an angle of 90 ° with respect to the plane of rotation ( 24 ) is inclined. Apparatus according to claim 1 or 2, wherein when the fluidic module ( 14 . 66 ) in the holder ( 12 ) or on the holder ( 12 ), one of the two main directions (y) defining the fluidic plane is vertical. Apparatus according to claim 1, wherein when the fluidic module ( 14 . 66 ) in the holder ( 12 ) or on the holder ( 12 ), the Fluidikebene by an angle of 20 ° to 70 ° with respect to the plane of rotation ( 24 ) is inclined. Device according to one of claims 1 to 4, in which the fluidic module ( 14 . 66 ) has 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. Device according to one of claims 1 to 5, in which the axis of rotation ( 22 ) a first axis of rotation ( 22 ), and in which the holder ( 12 ) is adapted to the fluidic module ( 66 ) rotatable about a second axis of rotation ( 62 ), which skewed to the first axis of rotation ( 22 ) is to be stored. Device according to Claim 6, in which the second axis of rotation ( 62 ) perpendicular to the first axis of rotation ( 22 ). Apparatus according to claim 5 or 6, wherein the fluidic module ( 66 ) at a further rotation body ( 60 ), on which several fluidic modules ( 66 ) are arranged. Device according to one of claims 1 to 8, in which the fluidic structures ( 16 ) inside 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, in which the fluid structures ( 16 ) at least two fluid chambers ( 30a . 30b . 30c ), which by at least one fluid channel ( 32a . 32b ) are fluidly connected to each other. Device according to one of claims 1 to 10, in which the fluidic structures ( 16 ) have an overflow siphon having a radially inward fluid inlet ( 90 ), a fluid chamber ( 92 ), and an outlet channel ( 98 ), wherein one end of the outlet channel ( 98 ) in a respect to the Erdgravitationsfelds upper and radially outer region of the fluid chamber ( 92 ) into the fluid chamber ( 92 ), wherein the outlet channel ( 98 ) a section rising in relation to the earth's gravitational field ( 98a ), a radially rising portion ( 98b ) and a radially sloping section ( 98b ), wherein an outlet ( 94 ) of the outlet channel ( 98 ) is arranged radially further out than that in the fluid chamber ( 92 ) end of the same. Device according to one of claims 1 to 11, in which the fluidic structures ( 16 ) a radially sloping channel ( 110 ) extending into a first channel ( 112 ) and a second channel ( 114 ) branches, whereby the first channel ( 112 ) 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) on a second side in the radially sloping channel ( 110 ) opens. Device according to one of claims 1 to 12, wherein the rotary body ( 10 ) several brackets ( 12 ) for the corresponding introduction or attachment of a respective fluidic module ( 14 . 66 ) having. Device according to Claim 13, in which the holders ( 12 ) are arranged such that the center distance (D) of the holders ( 12 ) at a radially inner end thereof with respect to the axis of rotation ( 22 ) azimuthal direction is less than the extension of the fluidic modules ( 14 . 66 ) in the fluidic plane. A method of handling liquids using a device according to any one of claims 1 to 14, comprising: introducing a liquid into the fluidic structures ( 16 ) and introduction of the fluidic module ( 14 . 66 ) in the rotary body ( 10 ) or attaching the fluidic module ( 14 . 66 ) on the rotary body ( 10 ); and rotating the rotating body ( 10 ) to handle the liquid.

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