DE102014221412A1 - Analysis unit for analyzing a fluid, analysis device, method for operating an analysis unit and method for producing an analysis unit - Google Patents

Abstract

The invention relates to an analysis unit (102) for analyzing a fluid. The analysis unit (102) comprises a housing (108) having at least a first housing opening (110) and a second housing opening (112). Furthermore, the analysis unit (102) comprises at least a first body (114) and a second body (116) for receiving the fluid, wherein the first body (114) and the second body (116) about an axis of rotation (118) and / or in Direction of the axis of rotation (118) are arranged relative to each other movable in or on the housing (108). The first body (114) is configured to move about the rotational axis (118) and / or through the first housing opening (110) by a first drive element (104) which is movable about the rotation axis (118) and / or in the direction of the rotation axis (118) to be moved in the direction of the axis of rotation (118). The second body (116) is configured to move about the rotational axis (118) and / or through the second housing opening (112) by a second drive element (106) which is movable about the rotation axis (118) and / or in the direction of the rotation axis (118) to be moved in the direction of the axis of rotation (118). In this way, the first body (114) and the second body (116) can be fluidly coupled together.

Description

State of the art

The present invention relates to an analysis unit for analyzing a fluid, to an analysis device, to a drive element holder for an analysis device, to a method for operating an analysis unit, to a method for producing an analysis unit, to a corresponding control device and to a corresponding computer program.

The implementation of biochemical processes is usually based on the handling of liquids. The liquids can be handled either manually with tools such as pipettes, reaction vessels, active probe surfaces or laboratory equipment, or at least partially automated using pipetting robots or special equipment.

The DE 10 2010 003 223 A1 describes a system in which different cartridges in the format of a standard centrifuge tube axially superimposed and can be inserted into a centrifuge. The switching of the liquids takes place via an integrated ballpoint pen mechanism, which is triggered by the centrifugal force.

Disclosure of the invention

Against this background, with the approach presented here, an analysis unit for analyzing a fluid, an analysis device, a drive element holder for an analysis device, a method for operating an analysis unit, a method for producing an analysis unit, furthermore a control device which uses these methods, and finally a corresponding computer program according to the main claims presented. Advantageous embodiments emerge from the respective subclaims and the following description.

The approach proposed here provides an analysis unit for analyzing a fluid, the analysis unit having the following features:
a housing having at least a first housing opening and a second housing opening; and
at least a first body and a second body for receiving the fluid, wherein the first body and the second body are arranged around a rotation axis and / or in the direction of the rotation axis relative to each other movable in and / or on the housing, wherein the first body is formed to be moved by the first housing opening from a about the axis of rotation and / or in the direction of the axis of rotation movable first drive member about the axis of rotation and / or in the direction of the axis of rotation, and wherein the second body is formed to pass through the second housing opening of a to be moved about the axis of rotation and / or in the direction of the axis of rotation movable second drive element about the axis of rotation and / or in the direction of the axis of rotation to fluidly couple the first body and the second body with each other.

An analysis unit can be understood as a unit for the biochemical analysis of a fluid. A fluid may be a liquid or a gas. Under a housing, an outer sleeve of the analysis unit can be understood. The housing can be realized, for example, as a cylindrical cartridge. A housing opening may be a through opening in the housing. Alternatively, under a housing opening and a blind hole, d. H. an opening in a housing surface. Under a body, in particular, a rotationally symmetrical body, such as a revolver or a drum can be understood. The two bodies can, for example, be rotated about the axis of rotation by 30, 60, 90, 180, 270 or 360 degrees. The bodies can be rotated both clockwise and anticlockwise. The bodies can be designed with different cavities and channels for receiving or transporting the fluid. For example, the bodies may be stacked in the housing and aligned coaxially with the axis of rotation. In this case, the housing can serve for the axial guidance of the body. The axis of rotation can each correspond to a central axis of the body. At the same time, the axis of rotation can correspond to a longitudinal axis of the housing. A drive element can be understood to be a separate or separable element from the analysis unit, such as a plunger, which can be arranged to be movable on the respective housing openings of the analysis unit about the axis of rotation or in the direction of the axis of rotation. Depending on the embodiment, the drive elements and the body by the respective housing openings form, force or cohesively be connected or connected to each other. By rotating the bodies relative to each other, for example, the respective cavities or channels of the bodies can be brought into coincidence with each other. By moving the body, the bodies can be fluidly connected to each other. In this way, the fluid can flow between the respective cavities or channels of the two bodies.

The approach presented here is based on the recognition that it is possible to control a fluid flow within a cartridge for the biochemical processing of fluids by individual cartridge processing units from the outside or outside of the housing by means of independently rotatable and displaceable tools relative to each other and be moved. A Such external adjustment of the processing units can be realized very cost-effectively with a few components that are easy to produce. Complicated and correspondingly expensive adjusting mechanisms within the cartridge can thus be dispensed with.

So-called lab-on-a-chip systems, also known as vest pocket or chip laboratories, are microfluidic systems, by means of which all the functionality of a macroscopic laboratory can be accommodated on a plastic card-sized plastic substrate. Lab-on-a-chip systems typically have two major components. A test carrier or disposable cartridge may include structures and mechanisms for performing basic fluidic operations, such as mixers, which may include passive components such as channels, reaction chambers, upstream reagents, or even active components such as valves or pumps. A second major component may include actuation, detection and control units. By means of such systems biochemical processes can be fully automated.

In principle, the systems can be divided into two categories. On the one hand, pipetting robots are known, with the help of which liquids can be precisely measured by means of pipettes and transferred into various functional reaction vessels. For processing other components such as centrifuges can be used. On the other hand, there are cartridge-based systems in which the liquids can typically be processed in a special device within a cartridge.

Current lab-on-a-chip systems usually consist of flat plastic card-sized plastic cartridges. In these cartridges, a complete biochemical process chain can be mapped, d. For example, liquids are measured, mixed and passed sequentially sequentially into chambers. The liquids can be actively controlled by valves, switches or pumps.

The approach presented here now allows fluids to be mechanically stationary, d. H. not movable, z. As centrifugal to process, for example, for the purification of nucleic acids and proteins.

This has the advantage that components required for processing can be made less complex and therefore significantly cheaper compared to conventional cartridge-based lab-on-a-chip systems. For example, it is possible to dispense with the use of springs.

The approach presented here also allows processing without external connections.

According to one embodiment, the housing and the second body can be made in one piece. As a result, the analysis unit can be produced overall with fewer components and thus particularly cost-effectively.

The analysis unit may be provided with at least one sealing element which is arranged between the first body and the second body. A sealing element may for example be an O-ring or a lip of a fluid-tight, flexible material. By the sealing element can be prevented that the fluid escapes through a gap between the first and the second body in an interior of the housing.

It is advantageous if the first body has at least one first receiving element for receiving the drive element. Alternatively or additionally, the second body may have at least one second receiving element for receiving the second drive element. A receiving element can be understood as meaning an element having a contour which can be positively connected to a correspondingly shaped mating contour of a respective drive element. As a result, the first or second body can be coupled mechanically with little effort to the first and second drive element.

According to a further embodiment, the analysis unit may comprise at least one third body for receiving the fluid. The third body may be rotationally disposed in the housing and configured to be fluidly coupled to the first body by moving the first body about the axis of rotation or in the direction of the axis of rotation. Additionally or alternatively, the third body may be configured to be fluidically coupled by moving the second body about the axis of rotation or in the direction of the axis of rotation with the second body. With the help of the third body, the number of process steps that can be carried out in the analysis unit can be increased with only a small additional outlay. By a rotationally fixed fixation of the third body, an uncontrolled relative rotation of the body can be prevented.

The third body may be disposed between the first body and the second body. Alternatively, the second body may be disposed between the first body and the third body. In particular, in the latter case, the first body may be arranged rotationally fixed in the housing. For example, the third body may be arranged coaxially to the axis of rotation. As a result, the analysis unit can be made particularly compact. By the flexible arrangement of the body in the housing, the analysis unit can be adapted to different applications.

Advantageously, the analysis unit can be provided with at least one latching element. The latching element may be formed on an inner wall surface of the housing to fix the first body and, alternatively or additionally, the third body rotationally fixed in the housing. The locking element may for example be a projection or a recess. Depending on the embodiment, the latching element may be formed to positively or non-positively engage in the first and third body. As an alternative or in addition to the latching element, the first or third body can be connected to the housing in a material-locking manner, for example by means of gluing or welding. By means of the locking element precise positioning of the first and third body is ensured in the housing.

The present approach also provides an analysis device having the following features:
an analysis unit according to one of the embodiments described herein;
a first drive element which is movable about the rotation axis and / or in the direction of the rotation axis and which is designed to move the first body through the first housing opening about the rotation axis and / or in the direction of the rotation axis; and
a second drive element which is movable about the rotation axis and / or in the direction of the rotation axis and which is designed to move the second body through the second housing opening about the rotation axis and / or in the direction of the rotation axis.

Advantageously, the analyzer can be operated without a centrifuge. As a result, in contrast to centrifugal processing, in which usually only the rotational frequency is controlled, a flexible control of various process parameters possible, such as to carry out a polymerase chain reaction, short PCR, where the temperatures are fast and cyclical, for example, from 94 ° C to 54 ° C and 72 ° C are adjusted.

This means that other components such as electrical detection methods can be integrated very flexibly. For example, an electrical contact can be easily realized via cable to a monitoring or evaluation.

It is also advantageous if the first drive element has at least one first gripping element for the form-locking gripping of the first receiving element. Alternatively or additionally, the second drive element may have at least one second gripping element for the form-locking gripping of the second receiving element. In this case, at least the first drive element may have at least one pressure channel which is shaped to be fluidically coupled by moving the first drive element about the axis of rotation and, alternatively or additionally, in the direction of the axis of rotation with a pressure port of the first body. The gripping element may be formed to engage (for example, form-fitting) in the receiving element of the respective body and / or to embrace this (for example, form-fitting). For example, the gripping element may be a pin, a hook, an eyelet or any other element familiar to a person skilled in the art for producing a positive connection. By means of the gripping elements can be realized with little effort, a reliable mechanical coupling of the drive elements and the body. The fact that the pressure can be applied via the drive element to the pressure port, additional external connections can be omitted.

Furthermore, the approach presented here creates a drive element holder for an analysis device according to one of the embodiments described here. The drive member holder may be configured to hold the first drive element and the second drive element during operation of the analysis device. Alternatively or additionally, the drive element holder may be designed to move the two drive elements about the axis of rotation or in the direction of the axis of rotation. A drive element holder can be understood to mean a device with units for gripping, positioning or driving the drive elements. For example, the drive elements may each be part of an adjustable support arm and rotatably mounted on the support arms. The drive member holder may be configured to vary a vertical or horizontal distance between the drive elements. As a result, the drive element holder can be used with analysis units of very different dimensions.

The proposed approach also provides a method of operating an analysis unit according to one of the embodiments described herein, the method comprising the steps of:
Providing the analysis unit; and
Moving the first body by means of the first drive element about the axis of rotation and / or in the direction of the axis of rotation and moving the second body by means of the second drive element about the axis of rotation and / or in the direction of the axis of rotation to fluidly couple the first body and the second body together ,

Such a method enables the positioning and fluidic coupling of cavities with non-complex structures. As a result, a cost-efficient mechanical processing can be realized.

Furthermore, the presented approach provides a method for producing an analysis unit for analyzing a fluid, the method comprising the following steps:
Providing a housing having at least a first housing opening and a second housing opening, and a first body and a second body for receiving the fluid; and
Inserting the first body and the second body into the housing, wherein the first body and the second body are disposed about a rotation axis and / or in the direction of the rotation axis relative to each other movable in the housing, wherein the first body is formed to pass through the first Housing opening of a about the axis of rotation and / or in the direction of the axis of rotation movable first drive member to be moved about the axis of rotation and / or in the direction of the axis of rotation, and wherein the second body is adapted to move through the second housing opening from one about the axis of rotation and / or in the direction of the axis of rotation movable second drive element to be moved about the axis of rotation and / or in the direction of the axis of rotation to fluidly couple the first body and the second body with each other.

The approach presented here also creates a control unit which is designed to execute, to control or to implement the steps of a variant of a method presented here in corresponding devices. Also by this embodiment of the invention in the form of a control device, the object underlying the invention can be achieved quickly and efficiently.

In the present case, a control device can be understood as meaning an electrical device which processes sensor signals and outputs control and / or data signals in dependence thereon. The control unit may have an interface, which may be formed in hardware and / or software. In the case of a hardware-based design, the interfaces can be part of a so-called system ASIC, for example, which contains various functions of the control unit. However, it is also possible that the interfaces are their own integrated circuits or at least partially consist of discrete components. In a software training, the interfaces may be software modules that are present, for example, on a microcontroller in addition to other software modules.

Also of advantage is a computer program product or computer program with program code which can be stored on a machine-readable carrier or storage medium such as a semiconductor memory, a hard disk memory or an optical memory and for carrying out, implementing and / or controlling the steps of the method according to one of the embodiments described above is used, especially when the program product or program is executed on a computer or a device.

The approach presented here will be explained in more detail below with reference to the accompanying drawings. Show it:

1 a schematic cross-sectional view of an analysis device according to an embodiment of the present invention;

2a . 2 B schematic cross-sectional views of an analysis device according to an embodiment of the present invention;

3 a schematic cross-sectional view of an analysis device according to an embodiment of the present invention;

4 a schematic cross-sectional view of an analysis device according to an embodiment of the present invention;

5 a flowchart of a method for operating an analysis unit according to an embodiment of the present invention; and

6 a flowchart of a method for producing an analysis unit according to an embodiment of the present invention.

In the following description of favorable embodiments of the present invention, the same or similar reference numerals are used for the elements shown in the various figures and similar acting, with a repeated description of these elements is omitted.

1 shows a schematic cross-sectional view of an analysis device 100 according to an embodiment of the present invention. The analyzer 100 includes an analysis unit 102 , a first drive element 104 and a second drive element 106 , The analysis unit 102 is exemplary with a hollow cylinder as a housing 108 executed, also called outer sleeve. In this case, the housing has 108 at a first end a first housing opening 110 and a second housing opening at a second end opposite the first end 112 on. The housing openings 110 . 112 allow access to the interior of the case 108 ,

In the case 108 are a first body 114 and a second body 116 arranged one above the other. The two bodies 114 . 116 are trained to receive a fluid to be biochemically examined. The body 114 . 116 are coaxial with a rotation axis 118 arranged. In 1 corresponds to the axis of rotation 118 a respective central axis of the body 114 . 116 and a longitudinal axis of the housing 108 , According to this embodiment, the bodies are 114 . 116 around the axis of rotation 118 and in the direction of the axis of rotation 118 relatively movable in (or on) the housing 108 arranged. In a one-piece embodiment of the housing 108 with the second body 116 is the first body 114 opposite the composite of the second body 116 and housing 108 movable, that is rotatable and / or displaceable.

The two drive elements 104 . 106 are movable at the respective housing openings 110 . 112 arranged. By way of example only, the first drive element 104 counterclockwise and the second drive element 106 clockwise about the axis of rotation 118 rotatable, the here a respective central axis of the drive elements 104 . 106 equivalent. In addition, the drive elements 104 . 106 each in the direction of the axis of rotation 118 displaceable. The drive elements 104 . 106 can also be referred to as a ram.

By way of example, the drive elements 104 . 106 each having a T-shaped cross section with a wide and a narrow section. Here is a narrow portion of the first drive element 104 in the first housing opening 110 displaceable or rotatable and a narrow portion of the second drive element 106 in the second housing opening 112 displaceable or rotatable.

The first drive element 104 is trained to be with the first body 114 be mechanically coupled. The second drive element 106 is trained to work with the second body 116 be mechanically coupled. For example, the first drive element 104 and the first body 114 by a displacement of the first drive element 104 in the direction of the first body 114 or the second drive element 106 and the second body 116 by a displacement of the second drive element 106 in the direction of the second body 116 non-positively or positively connected. Alternatively or additionally, the drive elements 104 . 106 cohesively with the respective bodies 114 . 116 be connected. This can be the first body 114 by a rotation of the first drive element 104 or the second body 116 by a rotation of the second drive element 116 around the axis of rotation 118 to be turned around.

According to this embodiment, the first drive element 104 trained to be the first body 114 by moving along the axis of rotation 118 against the second body 116 to press. In this case, the second drive element 106 trained to the second body 116 by moving along the axis of rotation 118 against the first body 114 to press. By pushing the bodies against each other 114 . 116 becomes a contact area between the bodies 114 . 116 fluidly sealed. In this way one can prevent one between the bodies 114 . 116 flowing fluid into the interior of the housing 108 escapes. Alternatively, the contact area may also be sealed by only one of the two bodies 114 . 116 by means of the respective drive element 104 . 106 is moved.

Alternatively, the housing 108 and the second body 116 designed in one piece, wherein the second drive element 106 is designed to cover the entire case 108 relative to the first body 114 to move.

The 2a and 2 B show schematic cross-sectional views of an analysis device 100 according to an embodiment of the present invention. At the analyzer 100 For example, it is an analysis device as described by 1 is described. According to this embodiment, the analysis unit 102 a third body 200 up, between the first body 114 and the second body 116 is arranged. Here is the third body 200 coaxial with the two bodies 114 . 116 arranged.

An inner wall surface of the housing 108 is exemplary with two opposing locking elements 202 formed in the 2a and 2 B are shown schematically as locking lugs. The locking elements 202 serve for the rotational fixation of the third body 200 in the case 108 , The third body points to this 200 two locking recesses 204 on, in which the locking elements 202 interlock positively. The two locking elements 202 are exemplified executed with a slope which is in a substantially perpendicular to the axis of rotation 118 running stop goes over. For example, the slope is shaped to cause a slight movement of the third body 200 in the direction of the second body 116 to enable. The stop can serve to move the third body 200 in the direction of the first body 114 to block.

The analysis unit 102 includes by way of example a first sealing element 206 and a second sealing element 208 , The two sealing elements 206 . 208 , also called gaskets, are between the first body 114 and the second body 116 arranged. More specifically, the first sealing element 206 between the first body 114 and the third body 200 and the second sealing element 208 between the third body 200 and the second body 116 arranged. The first sealing element 206 is designed to be a contact area between the first body 114 and the third body 200 sealed fluid-tight. The second sealing element 108 is designed to be a contact area between the third body 200 and the second body 116 sealed fluid-tight. The sealing elements 206 . 208 are made for example of a fluid-tight, compressible plastic.

By way of example, the first drive element 104 with two pins arranged parallel to each other as the first gripping elements 210 realized. The first gripping elements 210 are at an edge of the narrow portion of the first drive element 104 arranged opposite each other and formed to each in a first receiving element 212 of the first body 114 intervene positively. The first two receptacles 212 are for example blind holes in the first body 114 realized.

Analogous to this is the second drive element 106 with two second gripping elements 214 executed, each in a second receiving element 216 in the second body 116 interlock positively.

According to this embodiment, one of the first housing opening 110 facing end portion of the first body 114 made with a width that is slightly smaller than a width of the first housing opening 110 , Likewise, one of the second housing opening 112 facing end portion of the second body 116 made with a width that is slightly smaller than a width of the second housing opening 112 , The end sections of the two bodies 114 . 116 are thus in the respective housing opening 110 . 112 displaceable, as in particular in 2 B to recognize. For example, the body can 114 . 116 each have a circumferential groove through which a respective cross-section of the body 114 . 116 in the direction of the respective housing opening 110 . 112 tapered stepwise.

Alternatively, the third body 200 and the case 108 in one piece, be realized as a low-cost injection molded part.

In 2a is the analysis unit 102 shown in a sealed condition. This is the first body 114 by means of the first drive element 104 parallel to the axis of rotation 118 initiated force F ₁ against the third body 202 pressed so that the first sealing element 206 is slightly compressed and the contact area between the first body 114 and the third body 200 is fluidically sealed.

In the same way, the second body 116 by means of the second drive element 106 initiated force F ₂ , which is opposite to the force F ₁ , against the third body 200 pressed to the contact area between the second body 116 and the third body 200 by means of the second sealing element 208 fluidly seal.

In the 2a and 2 B is the first drive element 104 by way of example with two pressure channels 218 shown parallel to the axis of rotation 118 are lost and shaped to one of the first body 114 opposite side of the first drive element 104 with a first body 114 facing side of the first drive element 104 fluidly connect. In the in 2a shown sealed state of the analysis unit 102 are the two pressure channels 218 each with a seal 220 , such as an O-ring, each with a channel 222 in the first body 114 fluidly coupled. The seals 220 are for example on a first drive element 104 facing surface of the first body 114 attached, as in 2 B to recognize where the seals are 220 are shown in a relaxed condition. The pressure channels 218 For example, they act as compressed air or vacuum ports that serve the first body 114 to apply a pressure difference. According to one embodiment, alternatively or additionally, the second drive element 106 with one or more pressure channels 218 executed to the second body 116 to apply a pressure difference.

2 B shows the analysis unit 102 in a rotatable state. In this state, no axial force acts on the two outer bodies 114 . 116 , This forms between the first sealing element 206 and the first body 114 and between the second sealing element 208 and the second body 116 depending on a small gap, the free rotation of the body 114 . 116 relative to the third body 200 allows. A respective length of the gripping elements 210 . 214 is such that it is also in the rotatable state of the analysis unit 102 in the respective receiving elements 212 . 216 interlock positively.

3 shows a schematic cross-sectional view of an analysis device 100 according to an embodiment of the present invention. The analyzer 100 corresponds to the in the 2a and 2 B shown analysis device, with the difference that the second body 116 between the first body 114 and the third body 200 is arranged. Here is the second body 116 both about the axis of rotation 118 as well as in the direction of the axis of rotation 118 movable. The second body 116 is, so to speak, floating between the first body 114 and the third body 200 stored. 3 shows the analyzer 100 in a rotatable state, as judged by 2 B is described.

The second body 116 is with a perpendicular to the axis of rotation 118 extending recess 300 realized, which is shaped to a plunger as a second drive element 106 take. In 3 is the recess 300 laterally offset from the central axis of the second body 116 arranged. For example, the second drive element 106 slidable in the recess 300 arranged. The second housing opening (not visible) is in a lateral surface of the housing 108 configured to be an insertion of the second drive element 106 into the recess 300 to enable. The second body 116 is configured to move by a displacement of the second drive element 116 in the recess 300 around the axis of rotation 118 to be turned.

According to this embodiment, the sealing elements 206 . 208 on the second body 116 attached, wherein the first sealing element 206 the first body 114 and the second sealing element 108 the third body 200 is facing.

The third body 200 is using the locking elements 202 twisting and displaceable in the housing 108 fixed. The first body 114 is by means of two further locking elements 302 rotationally fixed in the housing 108 fixed. The two other locking elements 302 are shaped to a slight movement of the first body 114 along the axis of rotation 118 to allow, for example, in a way as described above with reference to the locking elements of the 2a and 2 B is described in more detail.

The first drive element 104 has the pressure channels 218 on. Unlike the 2a and 2 B is the first drive element 104 executed without the first gripping elements. Accordingly, the first body 114 executed without the first recording elements. Similar to the one based on 1 described embodiment, the first drive element 104 a T-shaped cross section having a wide portion and a narrow portion, wherein the narrow portion of the first body 114 is facing. The narrow section is significantly narrower than the first housing opening 110 executed.

The second housing opening 112 is through a floor plate 304 covered, for example, to set up the analysis unit 102 serves on a flat surface. The bottom plate 304 can with the case 108 be materially connected by gluing or welding. In the same way, the bottom plate 304 through the second housing opening 112 in addition to the third body 200 cohesively connected to slipping of the third body 200 in the case 108 to prevent.

The first drive element 104 is trained to be the first body 114 over the narrow section of the floating second body 116 to press. This will be the second body 116 against the third body fixed in the housing 200 pressed so that the first body 114 with the second body 116 as well as the second body 116 with the third body 200 is fluidically coupled.

The body 114 . 116 . 200 can also be pressed against each other by alternatively or additionally to the displacement of the first drive element 104 the housing 108 together with the third body fixed in it 200 in the direction of the first drive element 104 is moved. In this case, the first drive element 104 by means of a suitable holder in the direction of the axis of rotation 118 be fixed.

In the following, two embodiments of an inventive analysis device for mechanical actuation of a fluidic tube, also called analysis unit, based on the 2a to 3 described.

2a shows a starting point of a system in which the first body 114 and the second body 116 towards a solid third body 200 are rotatable in the middle. The third body 200 is through structures, here by the locking elements 202 in which case 108 recorded. At the top and bottom of the analysis unit 102 are two pestles 104 . 106 arranged. At least one of the pestles 104 . 106 is with channels 218 for supplying media, such as compressed air or vacuum executed. The pestles 104 . 106 show cones 210 . 214 on that in the body 114 . 116 intervention.

If a force F ₁ , F ₂ parallel to the axis of rotation 118 put on, so will the seals 206 between the first body 114 and third body 200 and the seals 208 between third body 200 and second body 116 compressed. In addition, gaskets 220 compressed at the media feeds. This makes it possible to get fluids inside the body 114 . 116 . 200 by pneumatic or vacuum actuation or to perform other pressure-driven functions.

To turn the body 114 . 116 become the pestles 104 . 106 on the bodies 114 . 116 twisted with little or no force in the axial direction, as in 2 B shown. To the configuration of the body 114 . 116 . 200 to change, are the pestles 104 . 106 and thus also the intervening seals 206 . 208 at least partially relieved, so that the body 114 . 116 with the help of the recessed pegs 210 . 214 or else by a kind of bracket outside the body 14 . 116 can be twisted. The outer sleeve 108 is trained to Prevent contamination and the axial alignment of the body 114 . 116 . 200 sure.

In 3 are the first body 114 and the third body 200 firmly; the second body 116 is rotatable. Shown is a relaxed state in which the second body 116 can be turned. The body 114 . 200 be through the structures 202 . 302 in the sleeve 108 recorded. The rotation of the second body 116 is according to this embodiment via a perpendicular to the axis of rotation 118 arranged ram 106 , which pushes for the rotation forward and back, scored. Alternatively, the second body 116 be rotated by a rotation movement by means of clamp.

The analyzer 100 For example, it is used to purify DNA or proteins using columns or bead-based methods. Furthermore, the analysis device is suitable 100 for performing further tests such as immunoassays or DNA amplifications and detections.

4 shows a schematic cross-sectional view of an analysis device 100 according to an embodiment of the present invention. At the analyzer 100 it is, for example, an analysis device, as they are based on the 2a and 2 B is described.

According to this embodiment, the analysis device is 100 realized as a 3D LoC process device with mechanical actuator in cost-effective form. The analyzer 100 includes the analysis unit 102 and the two drive elements 104 . 106 , In the case 108 the analysis unit 102 are three revolvers as a body 114 . 116 . 200 arranged. The body 114 . 116 . 200 have various chambers, upstream reagents, sedimentation structures, mixers, siphons or solid phases for fluidic unit operations, as explained in more detail below.

According to the in 4 Embodiment shown are in the first body 114 Reagents and lysate in separate chambers 400 . 401 upstream. The third body 200 includes an incubation chamber 402 which is filled with a sample reagent. The incubation chamber 402 is through a lid 403 locked. The lid 403 has two lid openings, for example, each by a lancet-shaped element 404 are covered. The lancet-shaped elements 404 are trained to the chambers 400 . 401 to open when the first body 114 and the third body 200 pressed against each other. In this way, the reagents and the lysate pass through the lid openings into the incubation chamber 402 , On a bottom surface of the incubation chamber 402 is a variety of beads 405 distributed. The incubation chamber 402 has an opening in the area of the bottom surface which passes through a filter membrane 406 is covered. Alternative to the membrane 406 can also have a purification column in the third body 200 be integrated. The second body 116 includes a cavity 408 for collecting waste products and a recess 410 which is shaped to a replaceable micro reaction vessel 412 , also called Eppi, for collecting purified proteins.

For coupling or spatial positioning of the body 114 . 116 . 200 is the analysis device 100 designed to be an axial distance of the body 114 . 116 . 200 and their azimuthal positioning to each other by rotation or rotation of the body 114 . 116 . 200 to change. The analyzer 100 can thus be operated independently of centrifugal forces. Furthermore, no external pressure connections are necessary. The analysis unit 102 can also be referred to as fluidic tube, 3D LoC tube or short 3D LoC.

The mechanical actuation of the analysis unit 102 fulfills two tasks. For one, a lateral force is applied to the body 114 . 116 . 200 exerted so that they are rotated against each other to actuate the Fluidikwege. On the other hand, a volume is displaced, creating a flow of liquids or gases.

As materials for housing 108 and body 114 . 116 . 200 For example, polymers such as cycloolefin polymer (COP), cycloolefin copolymer (COC), polycarbonates (PC), polyamides (PA), polyurethanes (PU), polypropylene (PP), polyethylene terephthalate (PET) or polymethyl methacrylate (PMMA) can be used.

In 4 is a basic structure of the analysis device 100 shown. The three bodies 114 . 116 . 200 are designed to be mechanically rotated against each other. As a body 114 . 116 . 200 For example, plain cylindrical revolvers without ballpoint mechanical components can be used. In addition to the mechanical actuation of the analysis unit 102 It is necessary to transfer the fluids through the respective chambers of the body 114 . 116 . 200 to move. The analysis unit 102 For example, has flat gaskets or O-rings as sealing elements, which are adapted to the body 114 . 116 . 200 at pressure in the direction of the axis of rotation 118 seal against each other. For moving liquids, gases or solids, the analyzer 100 be operated with a conventional syringe principle or with compressed air.

The syringe principle can be realized for example by a piston for displacing gases or liquids. The piston is like that designed such that its cross-section is smaller than a smallest Kavitätenquerschnitt in the first body 114 , For example, less than 2 to 5 mm. This allows the piston in the chambers 400 . 401 in the first body 114 plunge. For example, the chambers 400 . 401 sealed by sealing materials upwards. A deflection of the inner piston can be between 1 and 3 cm or even more than 3 cm.

Each of the chambers 400 . 401 in the upper body 114 is capped at its top. The cap is, for example, by a press fit of a lid segment in the chambers 400 . 401 realized. Alternatively, the first body 114 Segments, which are solved by the breaking of a predetermined breaking point and the same cross-sectional shape as the respective underlying chamber 400 . 401 exhibit. The piston makes contact with the cover segment during its deflection and presses it into the respective chamber 400 . 401 , which increases the volume in each chamber 400 . 401 reduced. This corresponds to the principle of a classic syringe.

The lid segment can be made of thermoplastic materials or have a thermoplastic core and have an outer seal similar to a sealing ring made of elastomers or thermoplastic elastomers. Further, the lid segment may have on its surface a support structure in which the inner piston is immersed, whereby tilting of the lid segment when moving in the chambers 400 . 401 is avoided. Alternatively, the inner piston may have a widened end, in cross-section similar to a T-format.

Thus, liquids can be stored in the chambers 400 . 401 are upstream, directly displace and in cavities in the third body 200 , here the incubation chamber 402 , convict. But it can also be displaced a gas volume. Because the body 114 . 200 In this Aktuationszustand are in contact and the contact surface is sealed, can by the displaced gas volume in the first body 114 also a volume of liquid or gas in the third body 200 be displaced. The sealing takes place via the plane-parallel surfaces or partial surfaces, for example a border, the two revolver sides and a resulting pressure of the thermoplastic materials. Alternatively, one of the two bodies 114 . 200 a surface with an elastomer or a thermoplastic elastomer as a sealing surface, in the simplest case an O-ring.

The gas flow is controlled by a rate at which the piston is deflected. Alternatively, the gas flow can be controlled via outlet openings of a chamber via the fluidic resistance and the construction of a capacity by compression of the gas volume. For example, the gas flow may be used to dry a filter, such as the membrane 406 , are used.

Alternatively, in the first body 114 a gas overpressure reservoir integrated by mechanical actuation, such as the lancet-shaped elements 404 , is punctured when the two bodies 114 . 200 are in gastight contact. Thus, an increased pressure is released in the third body 200 is induced.

Instead of the syringe principle, the processing of the liquids can also be carried out using compressed air or gas.

Into the analysis unit 102 For example, further elements for carrying out biochemical processes can be integrated. For example, heating elements can be integrated to the chambers 400 . 401 to temper, buffer preheat or perform a lysis, the filter membrane 406 to dry or a temperature in the second body 116 to vary cyclically to perform a polymerase chain reaction or at steady temperature an isothermal DNA amplification. Furthermore, at least one optical read-out unit can be integrated to detect color change reactions, absorption measurements or fluorescence measurements in at least one of the chambers of the analysis unit 102 perform.

In 4 is the analysis unit 102 in a drive element holder 414 arranged, which is formed according to this embodiment, to the drive elements 104 . 106 during operation of the analyzer 100 at the respective housing openings of the analysis unit 102 to keep. For example, the drive element holder 414 electric servomotors on the adjustment of the drive elements 104 . 106 around the axis of rotation 118 and in the direction of the axis of rotation 118 serve. Alternatively or additionally, the drive element holder 414 a manually operable adjusting mechanism for adjusting the drive elements 104 . 106 on.

The heating elements and the optical readout unit may be in the drive element holder 414 be integrated.

The analysis unit 102 can be placed on a shaker, such as a vortex mixer, which serves to hold the analyzer 102 to shake to mix liquids. The in the incubation chamber 402 upstream beads 402 Also called beads, in combination with the vibrator, can aid in lysing sample materials similar to a bead mill.

5 shows a flowchart of a method 500 for operating an analysis unit according to an embodiment of the present invention. By means of the procedure 500 For example, you can use the 1 to 4 be operated described analysis unit. It is in one step 501 provided the analysis unit. In one step 502 the first body is moved about the axis of rotation by means of the first drive element and, alternatively or additionally, in the direction of the axis of rotation. Furthermore, the second body is moved by means of the second drive element about the axis of rotation and, alternatively or additionally, in the direction of the axis of rotation. As a result, the two bodies are fluidly coupled together. The two bodies can be moved simultaneously or in any order one after the other.

6 shows a flowchart of a method 600 for producing an analysis unit according to an embodiment of the present invention. The procedure 600 can be performed, for example, to an analysis unit, as based on the 1 to 4 is described to produce. In the process 600 be in one step 601 a housing having at least a first housing opening and a second housing opening, and a first body and a second body for receiving a fluid provided. In one step 602 the first body and the second body are introduced into and / or to the housing so that the two bodies are movable in the housing about an axis of rotation and, alternatively or additionally, in the direction of the axis of rotation relative to one another. In this case, the first body is designed to be moved by the first housing opening of a about the axis of rotation and, alternatively or additionally, in the direction of the axis of rotation movable first drive element about the axis of rotation or in the direction of the axis of rotation. The second body is in this case designed to be moved by the second housing opening of a about the axis of rotation and, alternatively or additionally, in the direction of the axis of rotation movable second drive element about the axis of rotation or in the direction of the axis of rotation.

The embodiments described and shown in the figures are chosen only by way of example. Different embodiments may be combined together or in relation to individual features. Also, an embodiment can be supplemented by features of another embodiment.

Furthermore, the method steps presented here can be repeated as well as executed in a sequence other than that described.

If an exemplary embodiment comprises a "and / or" link between a first feature and a second feature, then this is to be read so that the embodiment according to one embodiment, both the first feature and the second feature and according to another embodiment either only first feature or only the second feature.

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

• DE 102010003223 A1 [0003]

Claims (15)

Analysis unit ( 102 ) for analyzing a fluid, wherein the analysis unit ( 102 ) has the following features: a housing ( 108 ), the at least one first housing opening ( 110 ) and a second housing opening ( 112 ) having; and at least a first body ( 114 ) and a second body ( 116 ) for receiving the fluid, wherein the first body ( 114 ) and the second body ( 116 ) about a rotation axis ( 118 ) and / or in the direction of the axis of rotation ( 118 ) movable relative to each other in and / or on the housing ( 108 ), wherein the first body ( 114 ) is formed to pass through the first housing opening ( 110 ) of one about the axis of rotation ( 118 ) and / or in the direction of the axis of rotation ( 118 ) movable first drive element ( 104 ) about the axis of rotation ( 118 ) and / or in the direction of the axis of rotation ( 118 ), and wherein the second body ( 116 ) is formed to pass through the second housing opening ( 112 ) of one about the axis of rotation ( 118 ) and / or in the direction of the axis of rotation ( 118 ) movable second drive element ( 106 ) about the axis of rotation ( 118 ) and / or in the direction of the axis of rotation ( 118 ) to be moved to the first body ( 114 ) and the second body ( 116 ) to fluidly couple with each other. Analysis unit ( 102 ) according to claim 1, characterized in that the housing ( 108 ) and the second body ( 116 ) are made in one piece. Analysis unit ( 102 ) according to one of the preceding claims, characterized by at least one sealing element ( 206 . 208 ), which is between the first body ( 114 ) and the second body ( 116 ) is arranged. Analysis unit ( 102 ) according to one of the preceding claims, characterized in that the first body ( 114 ) at least a first receiving element ( 212 ) for receiving the first drive element ( 104 ) and / or the second body ( 116 ) at least one second receiving element ( 216 ) for receiving the second drive element ( 106 ) having. Analysis unit ( 102 ) according to one of the preceding claims, characterized by at least one third body ( 200 ) for receiving the fluid, wherein the third body ( 200 ) rotationally fixed in the housing ( 108 ) is arranged and adapted to move by moving the first body ( 114 ) about the axis of rotation ( 118 ) and / or in the direction of the axis of rotation ( 118 ) with the first body ( 114 ) to be fluidly coupled and / or by moving the second body ( 116 ) about the axis of rotation ( 118 ) and / or in the direction of the axis of rotation ( 118 ) with the second body ( 116 ) be fluidly coupled. Analysis unit ( 102 ) according to claim 5, characterized in that the third body ( 200 ) between the first body ( 114 ) and the second body ( 116 ) or the second body ( 116 ) between the first body ( 114 ) and the third body ( 200 ), in particular wherein the first body ( 114 ) rotationally fixed in the housing ( 108 ) is arranged. Analysis unit ( 102 ) according to claim 5 or 6, characterized by at least one latching element ( 202 ; 302 ), which on an inner wall surface of the housing ( 108 ) is shaped to the first body ( 114 ) and / or the third body ( 200 ) rotationally fixed in the housing ( 108 ) to fix. Analysis device ( 100 ) comprising: an analysis unit ( 102 ) according to one of the preceding claims; one around the axis of rotation ( 118 ) and / or in the direction of the axis of rotation ( 118 ) movable first drive element ( 104 ), which is designed to be the first body ( 114 ) through the first housing opening ( 110 ) about the axis of rotation ( 118 ) and / or in the direction of the axis of rotation ( 118 ) to move; and one around the axis of rotation ( 118 ) and / or in the direction of the axis of rotation ( 118 ) movable second drive element ( 106 ) which is adapted to the second body ( 116 ) through the second housing opening ( 112 ) about the axis of rotation ( 118 ) and / or in the direction of the axis of rotation ( 118 ) to move. Analysis device ( 100 ) according to claim 8, comprising an analysis unit ( 102 ) according to claim 4, characterized in that the first drive element ( 104 ) at least a first gripping element ( 210 ) for positive engagement of the first receiving element ( 212 ) and / or the second drive element ( 106 ) at least one second gripping element ( 216 ) for positive engagement of the second receiving element ( 214 ), and / or wherein at least the first drive element ( 104 ) at least one pressure channel ( 218 ), which is shaped to move by moving the first drive element ( 104 ) about the axis of rotation ( 118 ) and / or in the direction of the axis of rotation ( 118 ) with a pressure connection ( 222 ) of the first body ( 114 ) be fluidly coupled. Drive element holder ( 414 ) for an analysis device ( 100 ) according to claim 8 or 9, wherein the drive element holder ( 414 ) is formed around the first drive element ( 104 ) and the second drive element ( 106 ) during operation of the analyzer ( 100 ) and / or to move. Procedure ( 500 ) for operating an analysis unit ( 102 ) according to one of claims 1 to 7, wherein the method ( 500 ) comprises the following steps: providing ( 501 ) of the analysis unit ( 102 ); and moving ( 502 ) of the first body ( 114 ) by means of the first drive element ( 104 ) about the axis of rotation ( 118 ) and / or in the direction of the axis of rotation ( 118 ) and moving the second body ( 116 ) by means of the second drive element ( 106 ) about the axis of rotation ( 118 ) and / or in the direction of the axis of rotation ( 118 ) to the first body ( 114 ) and the second body ( 116 ) to fluidly couple with each other. Procedure ( 600 ) for producing an analysis unit ( 102 ) for analyzing a fluid, the method ( 600 ) comprises the following steps: providing ( 601 ) of a housing ( 108 ), the at least one first housing opening ( 110 ) and a second housing opening ( 112 ), and a first body ( 114 ) and a second body ( 116 ) for receiving the fluid; and introduction ( 602 ) of the first body ( 114 ) and the second body ( 116 ) in the housing ( 108 ), the first body ( 114 ) and the second body ( 116 ) about a rotation axis ( 118 ) and / or in the direction of the axis of rotation ( 118 ) movable relative to each other in and / or on the housing ( 108 ), the first body ( 114 ) is formed to pass through the first housing opening ( 110 ) of one about the axis of rotation ( 118 ) and / or in the direction of the axis of rotation ( 118 ) movable first drive element ( 104 ) about the axis of rotation ( 118 ) and / or in the direction of the axis of rotation ( 118 ), and wherein the second body ( 116 ) is formed to pass through the second housing opening ( 112 ) of one about the axis of rotation ( 118 ) and / or in the direction of the axis of rotation ( 118 ) movable second drive element ( 106 ) about the axis of rotation ( 118 ) and / or in the direction of the axis of rotation ( 118 ) to be moved to the first body ( 114 ) and the second body ( 116 ) to fluidly couple with each other. Control device that is designed to handle all steps of a process ( 500 ; 600 ) according to claim 11 or 12 to control and / or implement. Computer program adapted to perform all steps of a procedure ( 500 ; 600 ) according to claim 11 or 12 to control and / or implement. A machine-readable storage medium having a computer program stored thereon according to claim 14.

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