DE102015204882A1 - Purification unit for purifying at least one substance from a sample liquid, purification device, method for operating a purification unit and method for producing a purification unit - Google Patents

Abstract

The invention relates to a purification unit (100) for purifying at least one substance (124) from a sample liquid (122). The purification unit (100) comprises a sample chamber (104) for receiving the sample liquid (122), a reagent chamber (102) for receiving a reagent (120), a reagent channel (108) with the reagent chamber (102) and a sample channel ( 110) connected to the sample chamber (104) or connectable filter means (106) for filtering out the substance (124) from the sample liquid (122) using the reagent (120), a holding device (116) for arranging and / or holding a replaceable collecting container (114) under a drain (112) of the filter device (106) to catch the substance (124), and an interface (118) to a pressure controller (302) for controlling a liquid transport within the purification unit (100) by applying the interface ( 118) with a pneumatic pressure.

Description

State of the art

The present invention relates to a purification unit for purifying at least one substance from a sample liquid, to a purification device, to a method for operating a purification unit, to a method for producing a purification unit, to a corresponding device and to a corresponding computer program.

For the implementation of biochemical processes increasingly so-called lab-on-a-chip systems, also called Westentaschenlabore or chip labs are used. These are, for example, microfluidic systems in which all the functionality of a macroscopic laboratory can be accommodated on an approximately plastic-card-sized plastic substrate. In addition, the purification is currently only manually via columns, failures or by automatic pipetting feasible, which is very expensive especially on a laboratory scale.

Disclosure of the invention

Against this background, with the approach presented here, a purification unit for purifying at least one substance from a sample liquid, a purification apparatus, a method for operating a purification unit, a method for producing a purification unit, furthermore a device that uses these methods, and finally a corresponding Computer program presented according to the main claims. Advantageous embodiments emerge from the respective subclaims and the following description.

The approach presented here creates a purification unit for purifying at least one substance from a sample liquid, the purification unit having the following features:
a sample chamber for receiving the sample liquid;
a reagent chamber for receiving a reagent;
a filter means connected to the reagent chamber via a reagent channel and to the sample chamber via a sample channel for filtering the substance from the sample liquid using the reagent;
a holding device for arranging and / or holding a replaceable collecting container at a drain of the filter device in order to collect the substance; and
an interface to a pressure controller for controlling liquid transport within the purification unit by pressurizing the interface with a pneumatic pressure.

The purification unit can be realized, for example, as a composite of a plurality of plastic layers, in particular of polymer substrates and flexible polymer membranes. A substance to be purified may be a biochemical substance such as nucleic acids, in particular DNA, RNA, or proteins. These may be lysed and / or extracted from a matrix either on-chip or off-site, presented in this patent, for example cellular material (blood, cell culture, food, tissues, saliva, body fluids, plants, etc.). The lysis can take place either with reagents by a chemical reaction, and / or thermally and / or electrically and / or by means of ultrasound. A reagent can be understood as meaning a substance which, in conjunction with the sample fluid, causes a chemical reaction. For example, the reagent may be an elution, wash, bind or / and lysis buffer. By a filter device can be understood as a device for generating a mixture of the sample liquid and the reagent and for extracting the substance from the mixture. A collecting vessel can be understood as meaning a microreaction vessel, in particular a sample collecting vessel (eg PCR tubes or "Eppi"). The collecting container can for example be manually inserted into the holding device, in particular einklickbar be. An interface can be understood as meaning a pressure connection for connecting the pressure control device to the purification unit. For example, the interface may be formed to be pneumatically coupled to a pressure port of the pressure control device already when inserting the Aufreinigungseinheit in the pressure control device. A pneumatic pressure can be understood as an overpressure or underpressure, ie a positive or negative relative pressure to an atmospheric pressure, or the atmospheric pressure. The pressure control device can be designed to generate the pneumatic pressure and to pass this over the interface to the Aufreinigungseinheit. Here, different valves and pumping chambers can be controlled pneumatically via a separate pneumatic layer and a flexible membrane. This then takes place, for example, in the form that, by acting on this pneumatic layer of the layer composite, this layer is pressed into the region of the corresponding (for example reagent or sample chamber or the (for example reagent or sample) valve, so that the Volume in the chamber is reduced (and thereby the fluid in the chamber is discharged) or that the passage cross-section in a channel under the pneumatic layer in the region of the valve in question after applying the pneumatic Position is reduced with the compressed air and thus this channel is blocked as a valve.

The approach proposed here is based on the finding that a pressure-controlled lab-on-a-chip cartridge for purifying biochemical substances can have a holder for an exchangeable microreaction vessel. Advantageously, the microreaction vessel held in the cartridge can already be filled with the purified substances during a purification process. Thus, the substances can be processed directly by simply removing the microreaction vessel after completion of the purification process. A manual transfer can thus be omitted. As a result, contamination of the purified substances can be avoided. Even the user is protected from hazardous substances by the completely closed and automated system.

A lab-on-a-chip system typically consists of two main components: a test carrier or a disposable cartridge having structures and mechanisms for performing basic fluidic operations such as mixers consisting of passive components such as channels, reaction chambers, upstream reagents, or active ones Components such as valves or pumps may exist; on the other hand from actuation, detection and control units. Such a system makes it possible, for example, to perform biochemical processes fully automatically.

Also, pressure-controlled systems are known which have a channel structure with valves and pumps for liquid transport. Such functional elements can be realized, for example, by means of two polymer substrates which are separated by a flexible polymer membrane. For example, the polymer membrane may be deflected by pneumatic pressures to displace fluids within the system or to occlude a channel. For this purpose, both positive and negative relative pressures can be generated in an external drive unit and forwarded to the system. An associated control device can provide, for example, negative pressure, overpressure and atmosphere to a pneumatic interface. Such a drive device offers the advantage of a small footprint.

Furthermore, in a pressure-controlled cartridge additional functions, such as a heated purification filter or different chambers, can be realized with relatively little manufacturing effort. For example, required volumes inside the cartridge can be varied across a thickness of the cartridge without major design changes. Also complex biochemical functions such as polymerase chain reaction (PCR) and detection methods, eg. As an optical readout after a hybridization reaction, after a polymerase chain reaction or after enzyme or immunoassays, can be relatively easily and inexpensively integrated into the cartridge.

A purification unit according to the features of the approach described here thus has the advantage that the purification can be carried out fully automatically, as a result of which the processing time during the purification can be significantly reduced in comparison with manual process sequences. Due to the use of interchangeable collecting containers, especially Eppis, handling errors can be avoided. Another advantage arises from the fact that the purification unit can be operated by means of a simple and inexpensive control device. Depending on the embodiment, the control unit can be used not only for DNA purification, but also, for example, for carrying out a full diagnostic process chain with amplification etc.

According to an embodiment described below, the purification unit can also be used, for example, for the parallel purification of nucleic acids, in particular of DNA.

The purification unit can be provided with at least one sample pumping chamber, which can be connected to the sample channel or can be connected and acted upon by the interface with a pneumatic pressure in order to pump the sample liquid through the sample channel. Additionally or alternatively, the sample channel may have at least one closure unit for closing the sample channel, for example a siphon structure or a normally closed valve. Such a sample pumping chamber is easy to implement and allows accurate metering of the sample liquid.

It is also advantageous if the filter device has at least one mixing chamber for mixing the sample liquid and the reagent and a filter for filtering out the substance. The mixing chamber can be connected to the reagent chamber via the reagent channel and to the sample chamber or connected via the sample channel. The filter may be connected or connectable via a drainage channel to the mixing chamber and the drain. In particular, the drainage channel can have at least one drainage valve arranged between the filter and the drain. Such a filter device offers the advantage of a simple and inexpensive construction and a reliable function.

It is particularly favorable when the sample pumping chamber has a control channel with a connected or connectable between the mixing chamber and the filter located portion of the drain channel. In particular, the control channel may have at least one first control valve. Additionally or alternatively, the sample channel may have at least one second control valve arranged between the mixing chamber and the sample pumping chamber for controlling a mixing circuit. By a mixing circuit can be understood, for example, a round pumping of the sample liquid and the reagent through the mixing chamber, the control channel and the sample channel. This allows the sample fluid and the reagent to be mixed thoroughly.

Furthermore, the purification unit can have at least one waste container which can be connected or connectable via a waste channel to a section of the discharge channel located between the filter and the discharge. In particular, the waste channel may have at least one waste valve and, additionally or alternatively, open into the discharge channel between the filter and the discharge valve. By means of such a waste container coupled to the filter device, it is possible to prevent the collecting container placed below the drain from being contaminated with waste products.

According to a further embodiment, the purification unit has at least one reagent pumping chamber which can be connected to the reagent channel or can be connected and acted upon by the interface with a pneumatic pressure in order to pump the reagent through the reagent channel. In particular, the reagent channel can have at least one reagent chamber valve arranged between the reagent chamber and the reagent pump chamber and, additionally or alternatively, a mixing chamber valve arranged between the mixing chamber and the reagent pump chamber. This embodiment allows accurate metering of the reagent during transport into the filter device.

The purification unit may have at least one further reagent chamber for receiving a further reagent. The filter device can be connected via the reagent channel with the other reagent chamber or connectable to filter out the substance using the further reagent from the sample liquid. This embodiment has the advantage that, depending on the nature of the substance to be extracted from the sample liquid, different reagents can be introduced successively into the filter device in order to carry out the purification.

Particularly advantageous is an embodiment in which the purification unit comprises at least one further sample chamber for receiving a further sample liquid, one connected via the reagent channel with the reagent chamber and a further sample channel with the other sample chamber or connectable further filter means for filtering at least one substance from the further sample liquid using the reagent and a further holding device for arranging and / or holding a replaceable further collecting container under a drain of the further filter device. This embodiment enables a parallelized purification of substances from different sample liquids.

In this case, the further filter device can be connected to the further reagent chamber via the reagent channel or can be connectable in order to filter out the substance from the further sample liquid using the further reagent. As a result, parallel purifications with several partial reactions can be carried out without manual intermediate steps.

The approach presented here also creates a purification device with the following features:
at least one purification unit according to one of the embodiments described herein; and
a pressure controller connected to the interface of the purification unit to control liquid transport within the purification unit by pressurizing the interface with a pneumatic pressure.

Furthermore, the approach described here provides a method for operating a purification unit according to one of the embodiments described herein, the method comprising the following step:
Pressurizing the interface with a pneumatic pressure by means of the pressure control device to filter out the substance from the sample liquid using the reagent, wherein the substance is collected by the collecting container.

For example, the interface can be subjected to different pressures in succession in the step of charging in order to effect liquid transport in different directions of flow within the purification device.

Before the substance is discharged from the filter device, the collecting container can be manually placed and fastened in the holding device. Alternatively, the purification unit may be preloaded with the collection container. After filling the collection container, the collection container can be removed. The substance contained therein, for example, in a subsequent Analysis method, which can be carried out locally separated from a purification carried out by means of the purification unit purification process, further investigated.

Finally, the approach proposed here provides a method for producing a purification unit for purifying at least one substance from a sample liquid, the method comprising the following step:

Forming a layer composite, in particular a polymer layer composite, with a sample chamber for receiving the sample liquid, a reagent chamber for receiving a reagent, a reagent via a reagent channel to the reagent chamber and a sample channel connected to the sample chamber or connectable filter device for filtering the substance from the sample liquid using the reagent, a holding device for arranging and / or holding a replaceable collecting container under a drain of the filter device to catch the substance, and an interface to a pressure control device for controlling a liquid transport within the Aufreinigungseinheit by pressurizing the interface with a pneumatic pressure.

By such a method, the purification unit can be produced particularly inexpensively.

The approach presented here also creates a device that is designed to perform the steps of a variant of a method presented here in appropriate facilities to drive or implement. Also by this embodiment of the invention in the form of a device, the object underlying the invention can be solved quickly and efficiently.

In the present case, a device can be understood as meaning an electrical device which processes sensor signals and outputs control and / or data signals in dependence thereon. The device may have an interface, which may be formed in hardware and / or software. In the case of a hardware-based embodiment, the interfaces can be part of a so-called system ASIC, for example, which contains a wide variety of functions of the device. 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 representation of a purification unit according to an embodiment of the present invention;

2 a schematic representation of a purification unit with a plurality of sample and reagent chambers according to an embodiment of the present invention;

3 a schematic representation of a purification device according to an embodiment of the present invention;

4 a flowchart of a method for operating a purification unit according to an embodiment of the present invention;

5 a flowchart of a method for manufacturing a purification unit according to an embodiment of the present invention;

6 a schematic representation of an apparatus for operating a purification unit according to an embodiment of the present invention; and

7 a schematic representation of an apparatus for producing a Aufreinigungseinheit 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 representation of a purification unit 100 according to an embodiment of the present invention. The purification unit 100 has a reagent chamber 102 . a sample chamber 104 and a filter device 106 on. The filter device 106 is via a reagent channel 108 with the reagent chamber 102 and via a sample channel 110 with the sample chamber 104 fluidly coupled. Below a process 112 the filter device 106 there is a collection container 114 from a holding device 116 is held such that an opening of the collecting container 114 the process 112 opposite. Depending on the embodiment, the collecting container 114 in the holding device 116 be inserted, mounted or clicked.

The purification unit 100 is also with an interface 118 formed, which is pneumatically coupled with a pressure control device for generating a pneumatic pressure. About the interface 118 can the pneumatic pressure through the purification unit 100 be routed to liquids within the purification unit 100 to transport. This transporting of the liquid can be effected, for example, by a pneumatic layer of the layer composite of the purification unit 100 is subjected to a pneumatic pressure and is thereby depressed. This depression causes the volume in the chamber located below the depressed area of the pneumatic layer to be reduced so that the liquid in that chamber is then discharged. If a channel is arranged below the depressed area of the pneumatic layer, this area can be used as a valve, since the channel is then closed or the passage is considerably impaired by the depressed part of the pneumatic layer.

the interface 118 can be acted upon in such a way with the pneumatic pressure that one in the reagent chamber 102 reagent present 120 through the reagent channel 108 in the filter device 106 is pumped and one in the sample chamber 104 located sample liquid 122 through the sample channel 110 in the filter device 106 is pumped. The filter device 106 For example, it serves a mixture of the two liquids 120 . 122 to form and from this mixture a substance 124 to extract that over the expiration 112 in the collection container 114 directed and collected there. The for purifying the substance 124 in the filter device 106 performed purification process is via the interface 118 pneumatically controllable.

2 shows a schematic representation of a purification unit 100 with multiple sample and reagent chambers according to an embodiment of the present invention. At the purification unit 100 For example, it is one based on 1 described purification unit. According to the in 2 embodiment shown has the filter device 106 a mixing chamber 200 and a filter 202 on, via a drainage channel 204 with the mixing chamber 200 and the process 112 is fluidically connected. The drainage channel 204 may be at least partially in a second level of the purification unit 100 be formed. One over the interface 118 Reagent pump chamber to be pressurized with a pneumatic pressure 206 is above the reagent channel 108 both with the reagent chamber 102 as well as with the mixing chamber 200 fluidly connected. By means of the reagent pumping chamber 206 the reagent can pass through the reagent channel 108 into the mixing chamber 200 be pumped. For controlling a flow of fluid between the reagent chamber 102 and the reagent pumping chamber 206 indicates between the reagent chamber 102 and the reagent pumping chamber 206 extending portion of the reagent channel 108 a reagent chamber valve 208 on. In addition, the reagent pump chamber is in one 206 with the mixing chamber 202 connecting portion of the reagent channel 108 a mixing chamber valve 210 arranged to control a flow of liquid between the Reagenzpumpkammer 206 and the mixing chamber 200 serves.

The sample channel 110 is with one over the interface 118 be subjected to a pneumatic pressure sample pump chamber 212 fluidly connected. The sample pumping chamber 212 is also via a control channel 216 with a the mixing chamber 200 with the filter 202 connecting subsection of the drainage channel 202 fluidly connected. In the control channel 216 is a first control valve 218 for controlling a fluid flow between the drainage channel 204 and the sample pumping chamber 212 arranged. Likewise, one between the sample pumping chamber 212 and the sample chamber 104 located subsection of the sample channel 110 via a second control valve 220 with the mixing chamber 200 connected. The second control valve 220 serves to control a liquid flow between the mixing chamber 200 and the sample pumping chamber 212 or the sample chamber 104 , The sample pumping chamber 212 on the one hand serves to pump the sample liquid into the mixing chamber 200 , On the other hand, the sample pumping chamber 212 be used to in the mixing chamber 200 located liquids, such as the reagent and the sample liquid, over the sample channel 110 and the control channel 216 Pump in a circle to mix the liquids together. Subsequently, the mixture over the filter 202 be passed to filter out the substance from the mixture.

According to the in 2 embodiment shown, the sample channel 110 between the second control valve 220 and the sample chamber 104 additionally a closure unit 222 on, For example, a normally-closed valve or a siphon structure.

Below the collection container 114 , here one in the holding device 116 clicked Eppis, there is a waste container 224 that's over a waste channel 226 into one the filter 202 with the process 112 connecting subsection of the drainage channel 204 empties. A liquid flow through the waste channel 220 is by means of a waste valve 228 controllable. Between the expiration 112 and a connection point between waste channel 226 and drainage channel 204 has the drainage channel 204 a drain valve 230 which is adapted to a flow of liquid between the filter 202 and the process 112 to control.

In addition to the reagent chamber 102 the purification unit is exemplary with four further reagent chambers 232 . 234 . 236 . 238 to preload other reagents. Depending on the embodiment, in the reagent chamber 102 an elution buffer, in the further reagent chamber 232 a wash buffer 2 in the further reagent chamber 234 a wash buffer 1 in the further reagent chamber 236 a binding buffer and in the other reagent chamber 238 a lysis buffer with enzymes upstream.

The other reagent chambers are above the reagent channel 108 with the reagent pump chamber 206 fluidly connected. More specifically, the further reagent chambers are each via a partial branch with a main branch of the reagent channel 108 connected. In the sub-branches are more Reagenzkammerventile 240 . 242 . 244 . 246 for controlling a fluid flow between the further reagent chambers and the main branch of the reagent channel 108 arranged.

According to 2 has the purification unit 100 another sample chamber 248 for receiving a further sample liquid. The further sample chamber 248 is via another sample channel 250 with a further filter device 252 fluidly connected. The further filter device 252 For example, corresponds to the above with reference to 2 described filter device 106 , A mixing chamber of the further filter device 252 is above the reagent channel 108 fluidic with the reagent pumping chamber 206 connected so that in the reagent chambers 102 to 238 located reagents by means of the reagent pumping chamber 206 if necessary also in the mixing chamber of the further filter device 252 can be pumped.

Below a process 254 the further filter device 252 there is another collection container 256 , here also an Eppi, of another holding device 258 is held such that an opening of the further collecting container 256 the process 254 opposite, so that one by means of the further filter device 2250 substance purified by using one or more reagents from the further sample liquid when discharging from the filter device 252 from the further collection container 256 is caught.

As in 2 To recognize, a through the sample chamber 104 , the filter device 106 and the holding device 116 formed first purification strand 260 and one through the other sample chamber 248 , the other filter device 252 and the further holding device 258 formed second purification strand 262 be carried out substantially identical.

In 2 are in addition to the two purification lines 260 . 262 by way of example, a third purification column 264 with another sample chamber 266 , another filter device 268 , another holding device 270 and another collecting container 272 and a fourth purification strand 274 with another sample chamber 276 , another filter device 278 , another holding device 280 and another collecting container 282 shown. The purification strands 264 . 274 can be identical to the second purification line 262 be built up, wherein the respective mixing chambers of the other filter devices 252 . 268 . 278 via the reagent channel 108 with the reagent pump chamber 206 are fluidically coupled.

According to one embodiment, the in 2 shown schematic plan view of an exemplary lab-on-a-chip design for the parallel purification of several different samples, here exemplified by four samples. This contains the purification unit 100 for example, a cartridge, five common reagent pre-storage chambers 102 . 232 . 234 . 236 . 238 with the reagent pump chamber 206 , a waste reservoir 224 and four sample input chambers 104 . 248 . 266 . 276 with the associated sample pumping chambers 212 , Mixing chambers 200 , Filters 202 , such as silica filter, and clickable Eppis as a container 114 . 256 . 272 . 282 ,

Depending on the embodiment, the purification unit 100 have more or less than five reservoirs for pre-storage of reagents in liquid form. The reagents may be packaged in stick packs or blisters.

The four different samples can be in liquid form in the four sample chambers 104 to 276 be entered. The size of the chambers may vary depending on the amount of liquid used. For example, the size may be between 100 μl and 5 ml, in particular about 500 μl. The Volume can be adjusted by varying the cartridge thickness.

Furthermore, the purification unit comprises 100 a fluidic network of channels, valves, and active pumping chambers to move the reagents into the mixing chambers 200 to transport and mix over the filters 202 to conduct and finally in the clickable micro reaction vessels 114 catch. For example, silica filters can be used as a filter for DNA binding 202 be used.

3 shows a schematic representation of a purification device 300 according to an embodiment of the present invention. The purification device 300 includes a pressure controller 302 and a purification unit 100 , For example, a purification unit, as described above with reference to 1 and 2 is described. According to this embodiment, the purification unit 100 such in the pressure control device 302 that inserted the interface 118 with a pressure connection 304 of the pressure control device 302 is pneumatically coupled. The pressure control unit 302 is trained to interface 118 with those for transporting liquids in the purification unit 100 to apply required pneumatic pressures.

According to one embodiment, the pressure control device 302 designed to set three different pressure levels, for example, to control one by means of the purification unit 100 can serve feasible DNA purification. This has the advantage that the pressure control unit 302 can be carried out particularly inexpensive, since additional functions such as a temperature control or an optical evaluation unit can be omitted.

4 shows a flowchart of a method 400 for operating a purification unit according to an embodiment of the present invention. The procedure 400 For example, in connection with a preceding on the basis of 1 to 3 be carried out purification unit described. The procedure 400 includes a step 401 in that the interface of the purification unit is subjected to a pneumatic pressure by means of the pressure control device in order to filter out the substance from the sample liquid using the reagent. The substance is thereby collected by the holding device held by the holding device.

According to one embodiment, the method 400 for performing a DNA purification process in the purification unit. Such a DNA purification process may consist of the following steps.

In a first step, a liquid sample is introduced into the sample chamber, wherein the reagents required for the purification may be upstream in the corresponding reagent chambers of the purification unit. The purification unit is then closed and placed in a corresponding control device, such as a pressure control device described above.

In a second step, the reagent containers, also called reagent chambers, are opened.

In a third step, a binding buffer is transported to the mixing chamber. An amount of the binding buffer can be adjusted to provide suitable binding conditions for attaching DNA to the silica filter.

In a fourth step, the sample is transported from the sample chamber into the mixing chamber.

In a fifth step, the total amount of sample and binding buffer is mixed by circular pumping in a mixing loop.

In a sixth step, the contents of the mixing chamber are transported via the silica filter. A dwell time can be inserted between individual pumping strokes. The residence time may correspond to a binding time required for binding the DNA to the silica filter. The DNA is bound on the integrated filter.

In a seventh step, a first wash buffer is transported over the silica filter. This frees the DNA from contaminants such as proteins. Meanwhile, the DNA remains bound to the integrated filter. A liquid conducted through the filter is collected in a waste chamber, also called waste bin above.

In an eighth step, a second wash buffer is transported over the silica filter. A further purification step takes place in which the DNA is again freed of impurities while it remains bound to the filter. Again, a liquid conducted through the filter is collected in the waste chamber.

In a ninth step, an elution buffer is transported over the silica filter. The elution buffer removes the DNA from the silica filter and collects it in Eppis, which are clicked into the purification unit.

In a tenth step, the Eppis are removed with the purified sample.

Steps three through nine may be part of the step 401 be carried out by applying the interface of the Aufreinigungseinheit with appropriate pneumatic pressures.

Optionally, a further pumping chamber may be inserted in each purification strand to allow multiple elution through the filters by reciprocating.

According to another embodiment, the filters and the mixing chambers may be heated during the purification process to increase the purification efficiency.

5 shows a flowchart of a method 500 for producing a purification unit according to an embodiment of the present invention. The procedure 500 can be performed, for example, to a preceding on the basis of 1 to 4 to produce the described purification unit. The procedure 500 includes a step 501 forming a layer composite, in particular a polymer layer composite, with a sample chamber for receiving the sample liquid, a reagent chamber for receiving a reagent, a reagent channel connected to the reagent chamber via a reagent channel and a sample channel connected to the sample chamber or filter means for filtering out the substance from the sample below Use of the reagent, a holding device for arranging and / or holding an interchangeable collecting container under a drain of the filter device to collect the substance, and an interface to a pressure control device for controlling a liquid transport within the Aufreinigungseinheit by pressurizing the interface with a pneumatic pressure. With the aid of this pneumatic pressure, a part of the layered assembly, in particular a pneumatic layer, can then be pressed into the (for example reagent or sample) chamber or the (for example reagent or sample) channel of the purification unit, whereby a discharge of the material in this chamber located fluid or a liquid located in this chamber is effected from the chamber. However, it is also conceivable by the depression of the pneumatic layer of the layer composite blocking a channel or reducing the channel cross-section to prevent, reduce or at least complicate a passage of liquid through this channel.

6 shows a device 600 for operating a purification unit according to an embodiment of the present invention. The device 600 includes a unit 601 adapted to provide a signal to pressurize the interface of the purification unit with a pneumatic pressure. The device 600 can for example be used to control a pressure control device described above. Here, the device 600 be implemented depending on the embodiment as a component of the pressure control device or as an external unit.

7 shows a device 700 for producing a purification unit according to an embodiment of the present invention. The device 700 has a unit 701 auf, for example, to control, implementation and / or implementation of a manufacturing step in a based on 5 described method is used.

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 an "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.

Claims (15)

Purification unit ( 100 ) for purifying at least one substance ( 124 ) from a sample liquid ( 122 ), wherein the purification unit ( 100 ) has the following features: a sample chamber ( 104 ) for receiving the sample liquid ( 122 ); a reagent chamber ( 102 ) for receiving a reagent ( 120 ); one via a reagent channel ( 108 ) with the reagent chamber ( 102 ) and via a sample channel ( 110 ) with the sample chamber ( 104 ) connected or connectable filter device ( 106 ) for filtering out the substance ( 124 ) from the sample liquid ( 122 ) using the reagent ( 120 ); a holding device ( 116 ) for arranging and / or holding a replaceable collecting container ( 114 ) on a process ( 112 ) of the filter device ( 106 ) to the substance ( 124 ) to catch; and an interface ( 118 ) to a pressure control device ( 302 ) for controlling a liquid transport within the purification unit ( 100 ) by Loading the interface ( 118 ) with a pneumatic pressure. Purification unit ( 100 ) according to claim 1, characterized by at least one sample pumping chamber ( 212 ) connected to the sample channel ( 110 ) or is connectable and via the interface ( 118 ) can be acted upon with a pneumatic pressure to the sample liquid ( 122 ) through the sample channel ( 110 ) to pump. Purification unit ( 100 ) According to one of the preceding claims, characterized in that the filter device ( 106 ) at least one mixing chamber ( 200 ) for mixing the sample liquid ( 122 ) and the reagent ( 120 ) and a filter ( 202 ) for filtering out the substance ( 124 ), wherein the mixing chamber ( 200 ) via the reagent channel ( 108 ) with the reagent chamber ( 102 ) and via the sample channel ( 110 ) with the sample chamber ( 104 ) is connectable or connectable, the filter ( 202 ) via a drainage channel ( 204 ) with the mixing chamber ( 200 ) and the process ( 112 ) is connected or connectable, in particular wherein the drainage channel ( 204 ) at least one between the filter ( 202 ) and the process ( 112 ) arranged drain valve ( 230 ) having. Purification unit ( 100 ) according to claims 2 and 3, characterized in that the sample pumping chamber ( 212 ) via a control channel ( 216 ) with one between the mixing chamber ( 200 ) and the filter ( 202 ) section of the drainage channel ( 204 ) is connected or connectable, in particular wherein the control channel ( 216 ) at least a first control valve ( 218 ) and / or the sample channel ( 110 ) at least one between the mixing chamber ( 200 ) and the sample pumping chamber ( 212 ) arranged second control valve ( 220 ) for controlling a mixing circuit. Purification unit ( 100 ) according to claim 3 or 4, characterized by at least one waste container ( 224 ), which has a waste channel ( 226 ) with one between the filter ( 202 ) and the process ( 112 ) section of the drainage channel ( 204 ) is connected or connectable, in particular wherein the waste channel ( 226 ) at least one waste valve ( 228 ) and / or between the filter ( 202 ) and the drain valve ( 230 ) into the drainage channel ( 204 ) opens. Purification unit ( 100 ) according to one of the preceding claims, characterized by at least one reagent pumping chamber ( 206 ) with the reagent channel ( 108 ) or is connectable and via the interface ( 118 ) is subjected to a pneumatic pressure to the reagent ( 120 ) through the reagent channel ( 108 ), in particular wherein the reagent channel ( 108 ) at least one between the reagent chamber ( 102 ) and the reagent pump chamber ( 206 ) arranged reagent chamber valve ( 208 ) and / or at least one between the mixing chamber ( 200 ) and the reagent pump chamber ( 206 ) arranged mixing chamber valve ( 210 ) having. Purification unit ( 100 ) according to one of the preceding claims, characterized by at least one further reagent chamber ( 232 . 234 . 236 . 238 ) for receiving a further reagent, wherein the filter device ( 106 ) via the reagent channel ( 108 ) with the further reagent chamber ( 232 . 234 . 236 . 238 ) or connectable to the substance ( 124 ) using the further reagent from the sample liquid ( 122 ) filter out. Purification unit ( 100 ) according to one of the preceding claims, characterized by at least one further sample chamber ( 248 . 266 . 276 ) for receiving a further sample liquid, one via the reagent channel ( 108 ) with the reagent chamber ( 102 ) and via another sample channel ( 250 ) with the further sample chamber ( 248 . 266 . 276 ) connected or connectable further filter device ( 252 . 268 . 278 ) for filtering out at least one substance from the further sample liquid using the reagent ( 120 ) and a further holding device ( 258 . 270 . 280 ) for arranging and / or holding a replaceable further collecting container ( 256 . 272 . 282 ) under a procedure ( 254 ) of the further filter device ( 252 . 268 . 278 ) to catch the substance. Purification unit ( 100 ) according to claim 7 and 8, characterized in that the further filter device ( 252 . 268 . 278 ) via the reagent channel ( 108 ) with the further reagent chamber ( 232 . 234 . 236 . 238 ) or connectable to filter out the substance using the further reagent from the further sample liquid. Purification device ( 300 ) having the following features: at least one purification unit ( 100 ) according to one of the preceding claims; and a pressure control device ( 302 ) connected to the interface ( 118 ) of the purification unit ( 100 ) to facilitate liquid transport within the purification unit ( 100 ) by loading the interface ( 118 ) with a pneumatic pressure control. Procedure ( 400 ) for operating a purification unit ( 100 ) according to any one of claims 1 to 9, wherein the process ( 400 ) comprises the following step: 401 ) of the interface ( 118 ) with a pneumatic pressure by means of the pressure control device ( 302 ) to the substance ( 124 ) from the Sample liquid ( 122 ) using the reagent ( 120 ), whereby the substance ( 124 ) from the collecting container ( 114 ) is caught. Procedure ( 500 ) for producing a purification unit ( 100 ) for purifying at least one substance ( 124 ) from a sample liquid ( 122 ), the process ( 500 ) comprises the following step: forming ( 501 ) a layer composite, in particular a polymer layer composite, with a sample chamber ( 104 ) for receiving the sample liquid ( 122 ), a reagent chamber ( 102 ) for receiving a reagent ( 120 ), one via a reagent channel ( 108 ) with the reagent chamber ( 102 ) and via a sample channel ( 110 ) with the sample chamber ( 104 ) connected or connectable filter device ( 106 ) for filtering out the substance ( 124 ) from the sample liquid ( 122 ) using the reagent ( 120 ), a holding device ( 116 ) for arranging and / or holding a replaceable collecting container ( 114 ) under a procedure ( 112 ) of the filter device ( 106 ) to the substance ( 124 ) and an interface ( 118 ) to a pressure control device ( 302 ) for controlling a liquid transport within the purification unit ( 100 ) by loading the interface ( 118 ) with a pneumatic pressure. Contraption ( 600 . 700 ), which is designed to handle all the steps of a process ( 400 . 500 ) according to claim 11 or 12 perform, implement and / or to control. Computer program adapted to perform, implement and / or control all steps of a method according to claim 11 or 12. A machine-readable storage medium having a computer program stored thereon according to claim 14.

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