WO2022136243A1

WO2022136243A1 - Cartridge and analysis system for testing a sample

Info

Publication number: WO2022136243A1
Application number: PCT/EP2021/086744
Authority: WO
Inventors: Axel Niemeyer
Original assignee: Boehringer Ingelheim Vetmedica Gmbh
Priority date: 2020-12-21
Filing date: 2021-12-20
Publication date: 2022-06-30

Abstract

A cartridge and an analysis system for testing an in particular biological sample are proposed. The cartridge or analysis system comprises a sensor apparatus for detecting analytes and/or amplification products of the sample, the sensor apparatus comprising a support and a plurality of electrodes arranged on the support. The support has a temperature-control structure for temperature-controlling the sensor apparatus and/or support. Further, a corresponding method is proposed.

Description

Cartridge and analysis system for testing a sample

The present invention relates to a cartridge according to the preamble of claim 1 and to an analysis system according to the preamble of claim 23.

Preferably, the present invention deals with analysing and testing a sample, in particular from a human or animal, particularly preferably for analytics and diagnostics, for example with regard to the presence of diseases and/or pathogens and/or for determining blood counts, antibodies, hormones, steroids or the like. Therefore, the present invention is in particular within the field of bioanalytics. A food sample, environmental sample or another sample may optionally also be tested, in particular for environmental analytics or food safety and/or for detecting other substances.

In particular, by means of the present invention, at least one analyte (target analyte) of a sample, preferably a nucleic-acid product, such as a particular nucleic- acid sequence, can be determined, identified or detected. In particular, the sample can be tested for qualitatively or quantitatively determining at least one analyte, for example in order for it to be possible to detect a disease and/or pathogen.

The present invention deals in particular with what are known as point-of-care systems, i.e. with systems, devices and other apparatuses, and deals with methods for carrying out tests on a sample at the sampling site and/or independently or away from a central laboratory or the like.

EP 1 362 827 B1 discloses a microfluidic device comprising heater elements that are positioned on one of the walls of a fluidic conduit in order to change the temperature of the fluid that is present in or passes through the conduit. The heater elements are formed by a thin layer of a patterned conductive material.

WO 2018/056102 A1 discloses an analysis system and a method for testing a sample. The analysis system comprises an analysis device and a cartridge that can be inserted into the analysis device. The cartridge comprises a sensor apparatus having a plurality of electrodes that are arranged on a support, the sensor apparatus being designed to identify, to detect and/or to determine analytes of the sample. The analysis device comprises a sensor temperature-control apparatus that is assigned to the sensor apparatus and designed to temperature-control fluids located in or on the sensor apparatus, in particular analytes of the sample or the like. The sensor temperature-control apparatus comprises a heating element that can be pressed against the sensor apparatus to temperature-control the sensor apparatus.

WO 2015/003722 A1 relates to a single-used device comprising a laminate having at least three layers of a thin flexible material. A reaction chamber is formed in a middle layer which is then closed off by the two other layers. A heating element for heating a test sample is contained on at least one of the xxx surfaces of the upper and lower layers of the laminate. Chemical sensor electrodes for sensing an electric chemical activity inside the reaction chamber may be arranged in the device.

WO 2017/201315 A1 relates to quantitative real time PCR amplification using an electrowetting-based device. The device may comprise at least one inductive heating element and at least one detection zone that may detect electric chemical and/or fluorescence signals.

It is an object of the present invention to provide an improved cartridge, analysis system and/or method for testing an in particular biological sample, which allow or facilitate testing of the sample that is as efficient, reliable, rapid and/or precise as possible.

The above object is solved by a cartridge according to claim 1 or by an analysis system according to claim 23. Advantageous developments are the subject of the dependent claims.

The cartridge according to the proposal is preferably designed and/suitable for testing a sample, in particular a biological sample.

The proposed cartridge has a sensor apparatus for detecting analytes of the sample and/or amplification products of said analytes. The sensor apparatus comprises a support having a plurality of electrodes, which are preferably arranged on the support and/or form a, preferably outermost, layer of the support. The electrodes are preferably designed for detecting analytes of the sample to be tested and/or amplification products thereof.

According to the proposal, the support preferably has a temperature-control structure for temperature-controlling the sensor apparatus and/or support. Preferably, the sensor apparatus and/or temperature-control structure is designed for temperature-controlling, in particular heating and/or cooling, a fluid that is to be tested or sensed with the sensor apparatus, preferably the fluid being in direct contact with the sensor apparatus, in particular the electrodes, and/or being present in a sensor compartment of the sensor apparatus.

The fluid preferably contains the analytes and/or amplification products.

The temperature-control structure allows a quick, efficient, precise and/or reliable temperature-control of the sensor apparatus, the support and/or the fluid that is to be tested and/or is in contact with the sensor apparatus or electrodes.

Preferably, the temperature of the temperature-control structure and/or the support is controllable by applying an electric voltage and/or current to the temperaturecontrol structure. In other words, the temperature-control structure is preferably actively and/or directively heatable and/or coolable by applying an electric field, in particular in form of applying a voltage and/or an electric current, directly to the temperature-control structure. This makes the temperature-control of the temperature-control structure particularly easy, efficient, precise and reliable.

Particularly preferably, the temperature-control structure is a resistive heating structure, in particular having or being formed by at least one resistive heating element, and/or is designed to be heated by resistive heating and/or has, in particular consists of, an electrically conductive material. Designing the temperature-control structure in this way constitutes an especially simple way of integrating a temperature-control structure in the support and makes it especially easy to temperaturecontrol the sensor apparatus and/or support.

“Resistive heating” in the sense of the present invention is also known under the term “Joule heating” and preferably means a process in which the passage of an electric current through a material, in particular a conductor, produces heat, particular preferably due to the electrical resistance of the material.

However, it is also possible that the temperature-control structure has or is formed by a Peltier element. A Peltier element is also an element that can be temperature- controlled by applying a voltage and/or electric current thereto. Alternatively or additionally, the temperature-control structure is an inductive heating structure and/or is designed to be heated by induction heating and/or comprises a ferromagnetic material and/or a metal. Designing the temperature-control structure in this way has the advantage that the temperature can the temperaturecontrol structure can be very quickly and precisely controlled. Further, heating by induction heating is highly efficient.

“Induction heating” in the sense of the present invention preferably means a process of heating a material, preferably a metal and/or ferromagnetic material, by subjecting the material to an, in particular alternating, electromagnetic field. The electromagnetic field will then give rise eddy currents in the material that lead to a heating of the material.

Preferably, the temperature-control structure is either a resistive heating structure or an inductive heating structure. However, it is in principle also possible to design the temperature-control structure as a both resistive and inductive heating structure, for example by the temperature-control structure having a material which is both electrically conductive and heatable by induction heating, in particular ferromagnetic, for example iron, nickel, cobalt, an alloy comprising one or more of these elements, alloys such as Alnico or the like.

The temperature-control structure can have or be formed by one or more temperature-control elements, preferably a plurality of temperature-control elements. The temperature-control elements preferably have a finger-like, comb-like, interengaging and/or meandering structure This is conducive for making the surface of the temperature-control structure as large as possible, so that the temperature may be controlled in a particularly quick and/or efficient way.

It is preferred that the temperature-control structure be designed to be planar or laminar. This is conducive to a compact design and an economic manufacturing process.

Preferably, the temperature-control structure is electrically isolated from the electrodes. This makes it possible to control the electrodes and the temperature-control structure separately from one another. In particular, it can be avoided in this way that the detection of analytes with the electrodes interferes with the control of the temperature-control structure. Particularly preferably, the support has a layered structure having a plurality of layers, the temperature-control structure forming a layer of the plurality of layers. Preferably, the temperature-control structure is an inner layer of the plurality of layers, i.e. at least one layer is arranged on each side of the temperature-control structure and/or the temperature-control structure is sandwiched between other layers. In other words, the temperature-control structure is preferably not an outermost of the plurality of layers. In particular, the support is designed as a chip, in particular a CMOS chip, having a plurality of layers. Designing the temperature-control structure as one of a plurality of layers results in a temperature-control structure, support and/or sensor apparatus that can be easily and/or quickly manufactured, in particular in an automated process and/or processes well-known in the field of semiconductor device fabrication.

It is preferred that the support has a circuit layer having one or more electronic circuits, in particular integrated circuits.

Preferably, a passivation layer is arranged between the temperature-control structure and the circuit layer and/or the temperature-control structure is electrically isolated from the circuit layer. The passivation layer preferably isolates the temperature-control structure from the circuit layer.

According to a preferred aspect, the temperature-control structure is electrically connected to the circuit layer, in particular by one or more vias and/or conductive tracks. In this case, the passivation layer preferably only partially isolates the temperature-control structure from the circuit layer.

Thus, when a passivation layer is arranged between the circuit layer and the temperature-control structure, the isolation layer does not necessarily completely isolate the temperature-control structure from the circuit layer, but the temperaturecontrol structure can still be electrically connected to the circuit layer, as explained.

According to another preferred aspect, the temperature-control structure is, in particular completely, electrically isolated from the circuit layer, particularly by the passivation layer arranged between the temperature-control structure and the circuit layer. Preferably, the temperature-control structure has one or more electrical connections for connecting the temperature-control structure separately from the circuit layer, the connection/connections in particular having or being formed by bond pads and/or wire bonds.

According to another aspect, which can also be implemented independently, an analysis system for testing an in particular biological sample is proposed.

The analysis system has a sensor apparatus for detecting analytes of the sample and/or amplification products of the analytes, wherein the sensor apparatus has a support and a plurality of electrodes arranged on the support. Further, the analysis system has a sensor temperature-control apparatus that is designed for temperature-controlling the support.

According to the proposal, the support preferably has a temperature-control structure, wherein the sensor temperature-control apparatus is designed to control, in particular temperature-control, the temperature-control structure. In other words, the sensor temperature-control apparatus is preferably designed to set the temperature of the temperature-control structure. The temperature-control structure is preferably a resistive and/or inductive heating structure. The sensor temperaturecontrol apparatus and the temperature-control structure are preferably designed in such a way that the temperature-control structure can be temperature-controlled by the sensor temperature-control apparatus. This is conducive to a quick, efficient, precise and/or reliable temperature-control of the sensor apparatus, the support and/or the fluid that is to be tested and/or is in contact with the sensor apparatus or electrodes.

Particularly preferably, the analysis system has an analysis device and a cartridge, the cartridge being separate from the analysis device and preferably being insertable into the analysis device, wherein the cartridge has the sensor apparatus and/or the analysis device has the sensor temperature-control apparatus. Thus, particularly, the cartridge comprises the sensor apparatus with the temperature-control structure integrated in its support and the analysis device comprises the sensor temperature-control apparatus for controlling the temperature-control structure.

The cartridge is particularly preferably designed as explained above. Preferably, the sensor temperature-control apparatus comprises contacting means for electrically contacting the temperature-control structure and a voltage and/or current source for applying a voltage and/or an electric current to the temperaturecontrol structure via the contacting means.

According to another preferred aspect, the sensor temperature-control apparatus comprises a field-generating device for generating a magnetic, in particular electromagnetic, field designed for induction heating of the temperature-control structure.

According to a further aspect, which can also implemented independently, a method for testing an in particular biological sample is proposed.

In the method, analytes of the sample and/or amplification products of the analytes are bonded to capture molecules on a support of a sensor apparatus and the bonded analytes and/or amplification products are detected by means of the sensor apparatus. Preferably, the sensor apparatus has electrodes that are arranged on the support and/or comprise the capture molecules.

According to the proposal, the sensor apparatus is preferably temperature- controlled by temperature-controlling a temperature-control structure that is integrated into the support, wherein the temperature-control structure is temperature- controlled by applying a voltage, an electric current and/or an electromagnetic field to the temperature-control structure. In particular the temperature-control structure is heated by resistive and/or inductive heating. In this way, the method can be made particularly quick, efficient, precise and/or reliable.

The method is preferably performed with a cartridge and/or an analysis system according to the proposal.

The above-mentioned aspects and features of the present invention and the aspects and features of the present invention that will become apparent from the claims and the following description can in principle be implemented independently from one another, but also in any combination or order. Other aspects, advantages, features and properties of the present invention will become apparent from the claims and the following description of preferred embodiments with reference to the drawings, in which:

Fig. 1 is a schematic section through a proposed analysis system or analysis device comprising a proposed cartridge received therein;

Fig. 2 is a schematic view of the cartridge;

Fig. 3 is a schematic front view of a proposed sensor apparatus of the analysis system and/or cartridge;

Fig. 4 is an enlarged detail from Fig. 3 illustrating a sensor field of the sensor apparatus;

Fig. 5 is a schematic rear view of the sensor apparatus;

Fig. 6 is a schematic sectional view of the sensor apparatus;

Fig. 7 is schematic sectional view of a support of the sensor apparatus;

Fig. 8 is a schematic view of a preferred embodiment of an element of a temperature-control structure; and

Fig. 9 is a schematic view of a further preferred embodiment of an element of a temperature-control structure.

In the Figures, which are only schematic and sometimes not to scale, the same reference signs are used for the same or similar parts and components, corresponding or comparable properties and advantages being achieved even if these are not repeatedly described.

Fig. 1 is a highly schematic view of a proposed analysis system 1 and analysis device 200 for testing an in particular biological sample P, preferably by means of or in an apparatus or cartridge 100. Fig. 2 is a schematic view of a preferred embodiment of the proposed apparatus or cartridge 100 for testing the sample P. The apparatus or cartridge 100 in particular forms a handheld unit, and in the following is merely referred to as a cartridge.

The term "sample" is preferably understood to mean the sample material to be tested, which is in particular taken from a human or animal. In particular, within the meaning of the present invention, a sample is a fluid, such as saliva, blood, urine or another liquid, preferably from a human or animal, or a component thereof. Within the meaning of the present invention, a sample may be pretreated or prepared if necessary, or may come directly from a human or animal or the like, for example. A food sample, environmental sample or another sample may optionally also be tested, in particular for environmental analytics, food safety and/or for detecting other substances, preferably natural substances, but also biological or chemical warfare agents, poisons or the like.

Preferably, the analysis system 1 or analysis device 200 controls the testing of the sample P in particular in or on the cartridge 100 and/or is used to evaluate the testing or the collection, processing and/or storage of measured values from the test.

By means of the proposed analysis system 1 or analysis device 200 or by means of the cartridge 100 and/or using the proposed method for testing the sample P, preferably an analyte A of the sample P, in particular a nucleic-acid product, such as a certain nucleic-acid sequence, or particularly preferably a plurality of analytes A of the sample P, can be determined, identified or detected. Said analytes are in particular detected and/or measured not only qualitatively, but particularly preferably also quantitatively.

Therefore, the sample P can in particular be tested for qualitatively or quantitatively determining at least one analyte A, for example in order for it to be possible to detect a disease and/or pathogen or to determine other values, which are important for diagnostics, for example.

Particularly preferably, a molecular-biological test is made possible by means of the analysis system 1 and/or analysis device 200 and/or by means of the cartridge 100. Particularly preferably, a molecular and/or PCR assay, in particular for detecting DNA and/or RNA, i.e. nucleic-acid products and/or sequences, is made possible and/or carried out.

Preferably, the sample P or individual components of the sample P or analytes A can be amplified if necessary, in particular by means of PCR, and tested, identified or detected in the analysis system 1 , analysis device 200 and/or in the cartridge 100. Preferably, amplification products V of the analyte A or analytes A are thus produced.

In the following, further details are first given on a preferred construction of the cartridge 100, with features of the cartridge 100 preferably also directly representing features of the analysis system 1 , in particular even without any further explicit explanation.

The cartridge 100 is preferably separate from the analysis device 200 and/or insertable into the analysis device 200.

The cartridge 100 is preferably at least substantially planar, flat and/or plate-shaped and/or card-like.

The cartridge 100 preferably comprises an in particular at least substantially flat, planar, plate-shaped and/or card-like main body 101 , the main body 101 in particular being made of and/or injection-moulded from plastics material, particularly preferably polypropylene.

The cartridge 100 preferably comprises at least one film or cover 102 for covering the main body 101 and/or cavities and/or channels formed therein at least in part, in particular on the front 100A, and/or for forming valves or the like, as shown by dashed lines in Fig. 2.

The analysis system 1 or cartridge 100 or the main body 101 thereof, in particular together with the cover 102, preferably forms and/or comprises a fluidic system 103, referred to in the following as the fluid system 103.

The cartridge 100 and/or the fluid system 103 thereof is preferably at least substantially vertically oriented in the operating position and/or during the test, in particular in the analysis device 200, as shown schematically in Fig. 1. In particular, the main plane or surface extension of the cartridge 100 thus extends at least substantially vertically in the operating position.

The cartridge 100 and/or the fluid system 103 preferably comprises a plurality of cavities, in particular at least one receiving cavity 104, at least one metering cavity 105, at least one intermediate cavity 106, at least one mixing cavity 107, at least one storage cavity 108, at least one reaction cavity 109, at least one intermediate temperature-control cavity 110 and/or at least one collection cavity 111 , as shown in Fig. 1 .

The cartridge 100 and/or the fluid system 103 also preferably comprises at least one pump apparatus 112 and/or at least one sensor apparatus 113.

Some, most or all of the cavities are preferably formed by chambers and/or channels or other depressions in the cartridge 100 and/or the main body 101 , and particularly preferably are covered or closed by the film or cover 102. However, other structural solutions are also possible.

In the example shown, the cartridge 100 or the fluid system 103 preferably comprises two metering cavities 105A and 105B, a plurality of intermediate cavities 106A to 106G, a plurality of storage cavities 108A to 108E and/or a plurality of reaction cavities 109, which can preferably be loaded independently from one another, in particular a first reaction cavity 109A, a second reaction cavity 109B and an optional third reaction cavity 109C, as can be seen in Fig. 2.

The reaction cavity/cavities 109 is/are used in particular to carry out an amplification reaction, in particular PCR, or several, preferably different, amplification reactions, in particular PCRs. It is preferable to carry out several, preferably different, PCRs, i.e. PCRs having different primer combinations or primer pairs, in parallel and/or independently and/or in different reaction cavities 109.

The amplification products V and/or other portions of the sample P forming in the one or more reaction cavities 109 can be conducted or fed to the connected sensor apparatus 113, in particular by means of the pump apparatus 112. The sensor apparatus 113 is used or designed in particular for detecting, particularly preferably qualitatively and/or quantitatively determining, the analyte A or analytes A of the sample P, in this case particularly preferably the amplification products V of the analytes A. Alternatively or additionally, however, other values may also be collected or determined.

In particular, the pump apparatus 112 comprises or forms a tube-like or bead-like raised portion, in particular by means of the film or cover 102, particularly preferably on the back of the cartridge, as shown schematically in Fig. 1.

The cartridge 100, the main body 101 and/or the fluid system 103 preferably comprise a plurality of channels 114 and/or valves 115, as shown in Fig. 2.

By means of the channels 114 and/or valves 115, the cavities 104 to 111 , the pump apparatus 112 and/or the sensor apparatus 113 can be temporarily and/or permanently connected and/or separated from one another, as required and/or optionally or selectively, in particular such that they are controlled by the analysis system 1 or the analysis device 200.

The cavities 104 to 111 are preferably each fluidically linked by a plurality of channels 114. Particularly preferably, each cavity is linked or connected by at least two associated channels 114, in order to make it possible for fluid to fill, flow through and/or drain from the respective cavities as required.

The fluid transport or the fluid system 103 is preferably not based on capillary forces, or is not exclusively based on said forces, but in particular is essentially based on the effects of gravity and/or pumping forces and/or compressive forces and/or suction forces that arise, which are particularly preferably generated by the pump or pump apparatus 112. In this case, the flows of fluid or the fluid transport and the metering are controlled by accordingly opening and closing the valves 115 and/or by accordingly operating the pump or pump apparatus 112, in particular by means of a pump drive 202 of the analysis device 200.

Preferably, each of the cavities 104 to 110 has an inlet at the top and an outlet at the bottom in the operating position. Therefore, if required, only liquid from the respective cavities can be removed via the outlet. Preferably, at least one valve 115 is assigned to each cavity, the pump apparatus 112 and/or the sensor apparatus 113 and/or is arranged upstream of the respective inlets and/or downstream of the respective outlets.

Preferably, the cavities 104 to 111 or sequences of cavities 104 to 111 , through which fluid flows in series or in succession for example, can be selectively released and/or fluid can selectively flow therethrough by the assigned valves 115 being actuated, and/or said cavities can be fluidically connected to the fluid system 103 and/or to other cavities.

In particular, the valves 115 are formed by the main body 101 and the film or cover

102 and/or are formed in another manner, for example by additional layers, depressions or the like.

Particularly preferably, one or more valves 115A are provided which are preferably tightly closed initially or when in storage, particularly preferably in order to seal liquids or liquid reagents F, located in the storage cavities 108, and/or the fluid system

103 from the open receiving cavity 104 in a storage-stable manner.

The valves 115A assigned to the receiving cavity 104 seal the fluid system 103 and/or the cartridge 100 in particular fluidically and/or in a gas-tight manner until the sample P is inserted and the receiving cavity 104 or a connection 104A of the receiving cavity 104 is closed.

As an alternative or in addition to the valves 115A (which are initially closed), one or more valves 115B are preferably provided which are not closed in a storagestable manner and/or which are open initially and/or which can be closed by actuation. These valves are used in particular to control the flows of fluid during the test.

The cartridge 100 is preferably designed as a microfluidic card and/or the fluid system 103 is preferably designed as a microfluidic system. In the present invention, the term "microfluidic" is preferably understood to mean that the respective volumes of individual cavities, some of the cavities or all of the cavities 104 to 111 and/or channels 114 are, separately or cumulatively, less than 5 ml or 2 ml, particularly preferably less than 1 ml or 800 pl, in particular less than 600 pl or 300 pl, more particularly preferably less than 200 pl or 100 pl. Particularly preferably, a sample P having a maximum volume of 5 ml, 2 ml or 1 ml can be introduced into the cartridge 100 and/or the fluid system 103, in particular the receiving cavity 104.

Preferably, reagents and liquids which are preferably introduced or provided before the test in liquid form as liquids or liquid reagents F and/or in dry form as dry reagents S are required for testing the sample P, as shown in the schematic view according to Fig. 2.

Furthermore, other liquids F, in particular in the form of a wash buffer, solvent for dry reagents S and/or a substrate SU, for example in order to form detection molecules and/or a redox system, are also preferably required for the test, the detection process and/or for other purposes and are in particular provided in the cartridge 100, i.e. are likewise introduced before use, in particular before delivery. At some points in the following, a distinction is not made between liquid reagents and other liquids, and therefore the respective explanations are accordingly also mutually applicable.

The analysis system 1 or the cartridge 100 preferably contains all the reagents and liquids required for carrying out one or more amplification reactions or PCRs and/or for carrying out the test, and therefore, particularly preferably, it is only necessary to receive the optionally pretreated sample P.

The cartridge 100 and/or the fluid system 103 preferably comprises a bypass 114A that can optionally be used, in order for it to be possible, if necessary, to conduct or convey the sample P or components thereof past the reaction cavities 109 and, by bypassing the optional intermediate temperature-control cavity 110, also directly to the sensor apparatus 113, and/or in order for it to be possible to convey or pump liquids or liquid reagents F2-F5 out of the storage cavities 108B-108E into the sensor apparatus 113, in particular in the opposite direction to the analytes A and/or amplification products V, when the bypass 114A is open, more specifically when the valve 115B of the bypass 114A is open.

The cartridge 100 or the fluid system 103 or the channels 114 preferably comprise sensor portions 116 or other apparatuses for detecting liquid fronts and/or flows of fluid. It is noted that various components, such as the channels 114, the valves 115, in particular the valves 115A that are initially closed and the valves 115B that are initially open, and the sensor portions 116 in Fig. 2 are, for reasons of clarity, only labelled in some cases, but the same symbols are used in Fig. 2 for each of these components.

The collection cavity 111 is preferably used for receiving excess or used reagents and liquids and volumes of the sample. It is preferably given appropriate large dimensions and/or is only provided with inputs or inlets, in particular such that liquids cannot be removed or pumped out again in the operating position.

The receiving cavity 104 preferably comprises a connection 104A for introducing the sample P. After the sample P is introduced into the receiving cavity 104, said cavity and/or the connection 104A is closed.

The cartridge 100 can then be inserted into the proposed analysis device 200 and/or received thereby, as shown in Fig. 1 , in order to test the sample P. Alternatively, the sample P could also be fed in later.

In the following, further details are given on a preferred construction of the sensor apparatus 113 with reference to Fig. 3 to Fig. 9.

The sensor apparatus 113 preferably allows and/or is designed for electrochemical measurement and/or redox cycling.

In particular, the sensor apparatus 113 is designed to identify, to detect and/or to determine (identical or different) analytes A bonded to capture molecules M or products derived therefrom, in particular amplification products V of the analyte A or different analytes A.

Preferably, the sensor apparatus 113 has a measuring side and a connection side, which are preferably arranged on opposite sides, in particular flat sides, of the sensor apparatus 113.

The sensor apparatus 113 preferably comprises a sensor array 113A comprising a plurality of sensor regions or sensor fields 113B, as shown schematically in Fig. 3, which schematically shows the measuring side of the sensor apparatus 113 and/or the sensor array 113A. Fig. 4 is an enlarged detail from Fig. 3. Fig. 5 shows a connection side and Fig. 6 is a schematic section through the sensor apparatus 113.

Preferably, the sensor apparatus 113 or the sensor array 113A comprises more than 10 or 20, particularly preferably more than 50 or 80, in particular more than 100 or 120 and/or less than 1000 or 800 sensor fields 113B.

Preferably, the sensor apparatus 113 or the sensor array 113A comprises a plurality of electrodes 113C. At least two electrodes 113C are preferably arranged in each sensor region or sensor field 113B. In particular, at least two electrodes 113C in each case form a sensor field 113B.

The electrodes 113C are preferably made of metal, in particular of noble metal, such as platinum or gold, and/or said electrodes are coated, in particular with thiols.

Preferably, the electrodes 113C are finger-like and/or engage in one another, as can be seen from the enlarged detail of a sensor field 113B according to Fig. 4. However, other structural solutions or arrangements are also possible.

The sensor apparatus 113 preferably comprises a support 113D, in particular a chip or CMOS chip or printed circuit board (PCB), the electrodes 113C preferably being arranged on the support 113D and/or being integrated in the support 113D. The formulation that the electrodes 113C are “arranged on the support” does not exclude that the electrodes 113C form a part or element of the support 113D. In particular, the electrodes 113C, which are arranged on the support, preferably form a layer SL of the support 113D, as will be explained in more detail later. In this sense, “arranged on the support” preferably means the electrodes form an outermost element or layer SL of the support 113D.

The support 113D is only very schematically depicted in Fig. 6. Fig. 7 is a more detailed depiction of the support 113D.

The sensor apparatus 113 and/or support 113D is preferably produced from a wafer, preferably a silicon wafer. The wafer is in particular an 8” wafer.

The sensor apparatus 113 and/or support 113D is preferably a microelectromechanical system (MEMS) or comprises such. The measuring side comprises the electrodes 113C and/or is the side that faces the fluid, the sample P, the amplification products V and/or a sensor compartment 113G, and/or is the side of the sensor apparatus 113 and/or the support 113D comprising capture molecules M (as shown in Fig. 6) to which the analytes A and/or amplification products V are bonded.

The connection side of the sensor apparatus 113 and/or the support 113D is preferably opposite the measuring side and/or is the side that faces away from the fluid, the sample P and/or the amplification product V.

Particularly preferably, the measuring side and the connection side of the sensor apparatus 113 and/or the support 113D each form one flat side of the in particular planar and/or plate-like support 113D.

The sensor apparatus 113, in particular the support 113D, preferably comprises a plurality of, in this case eight, electrical contacts or contact surfaces 113E, the contacts 113E preferably being arranged on the connection side and/or forming the connection side, as shown in Fig. 5.

Preferably, the sensor apparatus 113 can be contacted on the connection side and/or by means of the contacts 113E and/or can be electrically connected to the analysis device 200. In particular, an electrical connection can be established between the cartridge 100, in particular the sensor apparatus 113, and the analysis device 200, in particular the control apparatus 207, by electrically connecting the contacts 113E to the contact elements 203A.

Preferably, the contacts 113E are arranged laterally, in the edge region and/or in a plan view or projection around the electrodes 113C and/or the sensor array 113A, and/or the contacts 113E extend as far as the edge region of the sensor apparatus 113, in particular such that the support 113D can be electrically contacted, preferably by means of the connection apparatus 203 or contact elements 203A thereof, as will be explained below, laterally, in the edge region and/or around a sensor temperature-control apparatus 204C, which can preferably be positioned centrally or in the middle on the support 113D. Preferably, the sensor fields 113B are separated from one another, as shown in the schematic view from Fig. 6. In particular, the sensor apparatus 113 comprises barriers or partitions between each of the sensor fields 113B, which are preferably formed by an in particular hydrophobic layer 113F having corresponding recesses for the sensor fields 113B. However, other structural solutions are also possible.

The cartridge 100 and/or the sensor apparatus 113 comprises or forms a sensor compartment 113G. In particular, the sensor compartment 113G is formed between the sensor array 113A, the sensor apparatus 113 and/or the support 113D, or between the measuring side on one side and a sensor cover 113H on the other side.

The sensor apparatus 113 preferably defines the sensor compartment 113G by means of its measuring side and/or the sensor array 113A. The electrodes 113C are therefore in the sensor compartment 113G.

Preferably, the cartridge 100 and/or the sensor apparatus 113 comprises the sensor cover 113H, the sensor compartment 113G in particular being defined or delimited by the sensor cover 113H on the flat side.

Particularly preferably, the sensor cover 113H can be lowered onto the partitions and/or layer 113F for the actual measurement.

The sensor apparatus 113 or the sensor compartment 113G is fluidically linked to the fluid system 103, in particular to the reaction cavity/cavities 109, preferably by connections, such that the (treated) sample P, the analytes A or amplification products V can be admitted to the measuring side of the sensor apparatus 113 or sensor array 113A.

The sensor compartment 113G can thus be loaded with fluids and/or said fluids can flow therethrough.

The sensor apparatus 113, in particular the support 113D, preferably comprises at least one, preferably a plurality of, electronic or integrated circuits, the circuits in particular being designed to detect electrical currents or voltages that are preferably generated at the sensor fields 113B, particularly preferably in accordance with the redox cycling principle. Particularly preferably, the measurement signals from the different sensor fields 113B are separately collected or measured by the sensor apparatus 113 and/or the circuits.

Particularly preferably, the sensor apparatus 113 and/or the integrated circuits directly convert the measurement signals into digital signals or data, which can in particular be read out by the analysis device 200.

Particularly preferably, the sensor apparatus 113 and/or the support 113D is at least essentially constructed as described in EP 1 636 599 B1.

The sensor apparatus 113 preferably comprises a plurality of in particular different capture molecules M, different capture molecules M preferably being arranged and/or immobilised in or on different sensor fields 113B and/or preferably being assigned to different sensor fields 113B.

Particularly preferably, the electrodes 113C are provided with capture molecules M, in this case via bonds B, in particular thiol bonds, in particular in order to bond and/or detect or identify suitable analytes A and/or amplification products V.

Different capture molecules M1 to M3 are preferably provided for the different sensor fields 113B and/or the different electrode pairs and/or electrodes 113C, in order to specifically bond different analytes A and/or amplification products V, in Fig. 6 the amplification products V1 and V2, in the sensor fields 113B.

Particularly preferably, the sensor apparatus 113 or sensor array 113A allows the amplification products V bonded in each sensor field 113B to be qualitatively or quantitatively determined.

Preferably, the sensor apparatus 113 comprises capture molecules M having different hybridisation temperatures, preferably in order to bond the amplification products V to the corresponding capture molecules M at different hybridisation temperatures.

According to the present invention, the sensor apparatus 113, in particular the support 113D thereof, comprises a temperature-control structure 1131. In particular, the temperature-control structure 1131 is integrated into the sensor apparatus 113, in particular the support 113D. The temperature-control structure 1131 is designed for controlling and/or setting the temperature of the sensor apparatus 113, in particular of the electrodes 113C, the support 113D, the sensor compartment 113G, in particular the fluid therein, and/or the cover 113H.

The temperature-control structure 1131 is schematically shown in Fig. 7 in a sectional view of the support 113D.

The temperature-control structure 1131 or the temperature thereof is preferably controllable or controlled by means of the analysis device 200, in particular the sensor temperature-control apparatus 204C. This will be explained in more detail later.

By temperature-controlling the temperature-control structure 1131, in particular hybridisation can be achieved and/or the hybridisation temperature or different hybridisation temperatures can be set.

At this point, it should be noted that the terms “temperature-control”, “controlling the temperature”, “controlling the temperature-control structure” and the like are to be understood in a broad sense. In particular, any setting or controlling of the temperature and/or the temperature-control structure is encompassed by these terms, particularly preferably also a feedback-control of the temperature and/or the temperature-control structure. In particular, a control is carried out by applying an electric, magnetic and/or electromagnetic field to the temperature-control structure and/or exposing the temperature-control structure to such a field, in particular by directly applying a voltage and/or electric current to the temperature-control structure and/or by exposing the temperature-control structure to a magnetic field. In contrast, heating and/or cooling the sensor apparatus 113, support 113D and/or temperature-control structure 1131 by thermal conduction is preferably not a controlling in the sense of the present invention.

The temperature of the temperature-control structure 1131 is preferably directly and/or electrically controllable. In particular, the temperature of the temperaturecontrol structure 1131 is controllable by applying a voltage and/or an electric current to the temperature-control structure 1131. This is preferably done by an external device or device that is separate from the sensor apparatus 113, in particular separate from the cartridge 100, preferably by the analysis device 200 and/or the sensor temperature-control apparatus 204C, as will be explained later. In particular, the temperature-control structure 1131 is controllable or heatable by applying a voltage and/or electric current thereto, in particular heatable to a defined, predetermined and/or desired temperature, most preferably a hybridisation temperature of the analytes A and/or amplification products V to be detected by the sensor apparatus 113. However, it may also be possible to cool the temperaturecontrol structure 1131 by applying a voltage and/or electric current thereto, in particular by using a Peltier element as temperature-control structure 1131.

Preferably, however, the temperature-control structure 1131 is a resistive heating structure and/or designed to be heated by resistive heating and/or comprises or is formed by and electrically conductive material. In particular, the temperature-control structure 1131 comprises one or more resistive heating elements or heating resistors.

Resistive heating is a process in which the material is heated by converting electrical energy into heat energy due to the electrical resistance of the material. This process is also known as Joule heating.

It is preferred that the temperature-control structure 1131 has a high specific resistance and/or that the material from which the temperature-control structure 1131 is built has a high specific resistivity. In particular, the specific resistivity of the tern- peratu re-control structure 1131 or its material is higher than 0.1 — , preferably higher than 0.3 ^{n mm} , and/or lower than 2 ^{n mm} , preferably lower than 1.5 ^{n mm} , m m m in particular at a temperature of 20 °C. This is conducive to an efficient conversion of electrical energy to heat.

The temperature-control structure 1131 preferably comprises tungsten, aluminium nitride, aluminium oxide, nickel, chromium, manganese and/or an alloy comprising or consisting of at least two of nickel, chromium, copper and manganese. However, other materials are also possible here.

According to another preferred aspect, the temperature-control structure 1131 is an inductive heating structure and/or is designed to be heated by induction heating and/or comprises a ferromagnetic material. Induction heating in the sense of the present invention is the process of heating a material or object, in particular the temperature-control structure 1131, by electromagnetic induction. In this process, the material or object, in particular the temperature-control structure 1131, is exposed to a magnetic or electromagnetic field, in particular an alternating field. The field preferably induces eddy currents in the material or object which leads to a heating thereof.

A ferromagnetic material in the sense of the present invention preferably is a material with a Curie temperature of at least 20 °C, preferably at least 50 °C, in particular at least 80 °C, most preferably at least 100 °C. However, considerably higher Curie temperatures, in particular of several hundred °C or even above 1000 °C, are also possible and preferred.

The temperature-control structure 1131 preferably comprises or is formed by nickel, iron, cobalt and/or an alloy comprising or consisting of at least two of these elements, preferably all of these elements.

Preferably, the temperature-control structure 1131 is either a resistive heating structure or an inductive heating structure. However, it may also be possible for the temperature-control structure 1131 to be a combined resistive and inductive heating structure, for example by manufacturing the temperature-control structure 1131 from a material that is both electrically conductive and ferromagnetic.

The temperature-control structure 1131 is preferably at least substantially flat, planar, laminar and/or two-dimensional. Preferably, a length and width of the temperature-control structure 1131 are considerably larger than a height or thickness of the temperature-control structure 1131, in particular by at least a factor of 5 or 10.

The temperature-control structure 1131 can have or be formed by one temperaturecontrol element or can have a plurality of separate temperature-control elements that together form the temperature-control structure 1131.

Preferably, the temperature-control structure 1131 comprises more than 10 or 20, particularly preferably more than 50 or 80, in particular more than 100 or 120 and/or less than 1000 or 800 temperature-control elements. Particularly preferably, the number of temperature-control elements is the same as the number of sensor fields 113B and/or electrodes 113C and/or each temperature-control element is assigned to a (single) sensor field 113B and/or electrode 113C.

Preferably, the temperature-control element has a pair of structures that finger-like or comb-like and/or engage into one another. This is in particular shown in Fig. 8.

As an alternative or in addition, the temperature-control element preferably is designed to be meandering or having a plurality of meanders. This is in particular shown in Fig. 9.

Preferably, the temperature-control structure 1131 has several regions that are separately controllable or temperature-controllable. In particular, different temperatures can be set for different regions of the temperature-control structure 1131.

Particularly preferably, each of the regions is assigned to and/or arranged under one or more of the sensor fields 113B and/or electrodes 113C, so that different temperatures, in particular hybridization temperatures, can be set in or for different sensor fields 113B and/or electrodes 113C.

This enhances or makes possible a quick and/or parallel detection of different analytes A and/or amplification products V or groups thereof, in particular with different hybridization temperatures.

Particularly preferably, the separately controllable regions are formed by the separate temperature-control elements.

In particular, each temperature-control element forms a separately controllable region.

The temperature-control elements are in particular separately connectable and/or have separate connections, so that different voltages and/or currents and/or different magnetic fields can be applied to each of the temperature-control elements, in particular in order to set different temperatures for each of the temperature-control elements.

As an alternative or in addition, the different temperature-control elements of the temperature-control structure 1131 may be manufactured from different materials and/or may have different sizes and/or dimensions, so that different temperatures result from the same applied voltage or current or magnetic field.

It is preferred that the temperature-control structure 1131 is electrically isolated from the electrodes 113C, in particular by at least the isolation layer SL4 described below.

The support 113D preferably has a layered structure and/or a plurality of layers SL, in particular two, three or more layers SL. For simplicity, the layers SL are not shown in Fig. 6, but are in particular shown in Fig. 7. It should be noted that Fig. 7 is a very schematic drawing and has the main purpose of visualising the layered structure of the support 113D. In particular, the thicknesses of different layers SL are not to scale and different layers SL may have considerably different thicknesses, deviating from the depiction in Fig. 7.

The temperature-control structure 1131 preferably forms a layer SL of the plurality of layers SL. In particular, the temperature-control structure 1131 is a heating layer SL3 for heating the support 113D, sensor apparatus 113 and/or sensor compartment 113G.

The temperature-control structure 1131 or heating layer SL3 is preferably a middle layer SL of the support 113D and/or is arranged between two other layers SL of the support 113D. Preferably, the temperature-control structure 1131 is not an outermost layer SL of the support 113D.

The electrodes 113C preferably also constitute a layer SL of the support 113D, in particular an outermost layer and/or measuring layer SL7.

Preferably, the support 113D has a circuit layer SL1. The circuit layer SL1 is preferably an outermost layer SL of the support 113D and/or arranged on the side of the support 113D that is opposite the electrodes 113C or measuring layer SL7. The circuit layer SL1 preferably has one or more electronic circuits, in particular the integrated circuits mentioned above. The circuit layer SL1 and/or the circuit(s) is/are preferably fabricated using CMOS technology.

The circuit layer preferably comprises or forms or is in direct contact and/or directly adjacent the contacts 113E. The support 113D preferably has an isolation layer SL4, in particular for electrically isolating the temperature-control structure 1131 or heating layer SL3 from the electrodes 113C or measuring layer SL7.

The isolation layer SL4 is preferably arranged on the side of the temperaturecontrol structure 1131 facing the electrodes 113C and/or opposite the circuit layer SL1. The isolation layer SL4 is preferably arranged directly adjacent to the temperature-control structure 1131 and/or is in contact with the temperature-control structure 1131. Preferably, the isolation layer SL4 comprises or is formed by silicon nitride, in particular SisN4, polyimide, and/or benzocyclobutene (BCB).

The support 113D preferably has a passivation layer SL2, in particular for electrically isolating the circuit layer SL1 from the further layers SL of the support 113D, in particular the temperature-control structure 1131 or heating layer SL3. The passivation layer is preferably arranged between the circuit layer SL1 and the temperature-control structure 1131 or heating layer SL3. In particular, the passivation layer SL2 is in contact with and/or arranged directly adjacent to the circuit layer SL1 and/or the temperature-control structure 1131 or heating layer SL3. The passivation layer SL2 preferably has or is formed by silicon nitride, in particular SisNzj.

Thus, preferably, the temperature-control structure 1131 or heating layer SL3 is arranged between the isolation layer SL4 and the passivation layer SL2, preferably wherein the isolation layer SL4 and the passivation layer SL2 are each in contact and/or directly adjacent to the temperature-control structure 1131 or heating layer SL3.

Further, the temperature-control structure 1131 or heating layer SL3 is preferably arranged between the electrodes 113C or measuring layer SL7 and the circuit layer SL1.

Moreover, the support 113D preferably has one or more diffusion barrier layers SL5, SL6, in the example shown two diffusion barrier layers SL5, SL6. The diffusion barrier layer/layers SL5, SL6 are in particular designed or provided for preventing diffusion of atoms between different layers, in particular metal atoms, most particularly copper atoms. The diffusion barrier layer SL5, SL6 preferably comprises or is formed by tantalum and/or platinum. Preferably, the support 113D has one diffusion barrier layer SL5 comprising or being formed by tantalum and one diffusion barrier layer SL6 comprising or being formed by platinum. When more than one diffusion barrier layer SL5, SL6 is provided, the diffusion barrier layers SL5, SL6 are preferably in contact and/or directly adjacent to each other.

The diffusion barrier layer(s) SL5, SL6 is/are preferably arranged adjacent to the electrodes 113C or measuring layer SL7 and/or between, one the one hand, the electrodes 113C and, on the other hand, the circuit layer SL1 , passivation layer SL2 and/or temperature-control structure 1131 or heating layer SL3. In particular, the diffusion barrier layer(s) SL5, SL6 is/are in contact and/or directly adjacent to the electrodes 113C or measuring layer SL7 and/or the isolation layer SL4.

Particularly preferably, the sequence of layers SL is as follows: Circuit layer SL1 , passivation layer SL2, temperature-control structure 1131 or heating layer SL3, isolation layer SL4, diffusion barrier layer(s) SL5, SL6, electrodes 113C or measuring layer SL7. Preferably, additional layers SL can be provided and/or one or more of the listed layers SL may be omitted.

The layers SL preferably form an integrated component. Preferably, the component or support 113D cannot be disassembled and/or the layers SL cannot be separated from one another without destruction of the component or the support 113D.

The temperature-control structure 1131 is preferably electrically contactable for controlling the temperature-control structure 1131 and/or the temperature thereof, in particular if the temperature-control structure 1131 is designed to be controllable by applying a voltage and/or an electric current and/or if the temperature-control structure 1131 is a resistive heating structure.

Preferably, the temperature-control structure 1131 is electrically connected to the circuit layer SL1 , in particular by one or more vias 113 J and/or conductive tracks 113K. The via/vias 113J in particular extend(s) through the passivation layer SL2.

“Via” is the short word for “vertical interconnected access” and denotes an electrical connection between different layers in a physical electronic circuit, in particular a printed circuit board, the via going through the plane of one or more adjacent layers. The term “conductive track” in particular denotes an electrical connection within one layer SL of the support 113D.

The via/vias 113 J connecting the temperature-control structure 1131 are preferably isolated from other potentially existing vias, in particular vias for connecting the electrodes 113C.

According to another preferred aspect, the temperature-control structure 1131 comprises one or more electrical connections 113L for connecting the temperaturecontrol structure 1131 separately from the circuit layer SL1. The connections 113L preferably have or are designed as bond pads and/or wire bonds. Particularly, the connections 113L are arranged in an edge region of the support 113D, in particular the chip. Preferably, the connections 113L connect the temperature-control structure 1131 to the contacts 113E. This makes it possible to control the temperaturecontrol structure 1131 and/or to supply the temperature-control structure 1131 with power separately from the circuit layer SL1 .

In principle, it is also possible that the temperature-control structure 1131 is connected to the circuit layer SL1 , in particular by vias 113 J and/or conductive tracks 113K, and that additionally further electrical connections 113D for connection of the temperature-control structure 1131 separately from the circuit layer SL1 are provided.

However, it can also be preferred for the temperature-control structure 1131 to be not electrically contactable and/or to be, in particular completely, isolated from the circuit layer SL1 , in particular by the passivation layer SL2. This is in particular the case if the temperature-control structure 1131 is designed as an inductive heating structure. Nevertheless, the temperature-control structure 1131 can also be designed to be electrically contactable if it is designed as an inductive heating structure.

In the following, some features and aspects of the analysis device 200 are explained in greater detail. The features and aspects relating to the analysis device 200 are preferably also directly features and aspects of the proposed analysis system 1 , in particular even without any further explicit explanation. Fig. 1 shows the analysis system 1 in a ready-to-use state for carrying out a test on the sample P received in the cartridge 100. In this state, the cartridge 100 is therefore linked to, received by and/or inserted into the analysis device 200.

The analysis system 1 or analysis device 200 preferably comprises a mount or receptacle 201 for mounting and/or receiving the cartridge 100.

Preferably, the cartridge 100 is fluidically, in particular hydraulically, separated or isolated from the analysis device 200. In particular, the cartridge 100 forms a preferably independent and in particular closed fluidic and/or hydraulic system 103 for the sample P and the reagents and other liquids.

Preferably, the analysis device 200 is designed to actuate the pump apparatus 112 and/or valves 115, to have a thermal effect and/or to detect measured data, in particular by means of the sensor apparatus 113 and/or sensor portions 116.

The analysis system 1 or analysis device 200 preferably comprises a pump drive 202, the pump drive 202 in particular being designed for mechanically actuating the pump apparatus 112.

Preferably, a head of the pump drive 202 can be rotated in order to rotationally axially depress the preferably bead-like raised portion of the pump apparatus 112. Particularly preferably, the pump drive 202 and pump apparatus 112 together form a pump, in particular in the manner of a hose pump or peristaltic pump and/or a metering pump, for the fluid system 103 and/or the cartridge 100.

Preferably, the capacity and/or discharge rate of the pump can be controlled and/or the conveying direction of the pump and/or pump drive 202 can be switched. Preferably, fluid can thus be pumped forwards or backwards as desired.

The analysis system 1 or analysis device 200 preferably comprises a connection apparatus 203 for in particular electrically and/or thermally connecting the cartridge 100 and/or the sensor apparatus 113.

As shown in Fig. 1 , the connection apparatus 203 preferably comprises a plurality of electrical contact elements 203A, the cartridge 100, in particular the sensor ap- paratus 113, preferably being electrically connected or connectable to the analysis device 200 by the contact elements 203A.

The analysis system 1 or analysis device 200 preferably comprises one or more temperature-control apparatuses 204 for temperature-controlling the cartridge 100 and/or having a thermal effect on the cartridge 100, in particular for heating and/or cooling.

Preferably, at least one of the one or more temperature-control apparatuses 204 has or is formed by a heating element and/or a Peltier element. Preferably, different temperature-control apparatuses are designed differently, as will be explained in more detail below.

Individual temperature-control apparatuses 204, some of these apparatuses or all of these apparatuses can preferably be positioned against the cartridge 100, the main body 101 , the cover 102, the sensor apparatus 113 and/or individual cavities and/or can be thermally coupled thereto and/or can be integrated therein and/or in particular can be operated or controlled electrically by the analysis device 200. In the example shown, in particular the temperature-control apparatuses 204A, 204B and/or 204C are provided.

Preferably, the temperature-control apparatus 204A, referred to in the following as the reaction temperature-control apparatus 204A, is assigned to the reaction cavity 109 or to a plurality of reaction cavities 109, in particular in order for it to be possible to carry out one or more amplification reactions and/or PCRs therein.

The reaction cavities 109 are preferably temperature-controlled simultaneously and/or uniformly, in particular by means of one common reaction temperaturecontrol apparatus 204A or two reaction temperature-control apparatuses 204A.

More particularly preferably, the reaction cavity/cavities 109 can be temperature- controlled from two different sides and/or by means of two or the reaction temperature-control apparatuses 204A that are preferably arranged on opposite sides.

Alternatively, for reaction cavities 109, each reaction cavity 109 can be temperature-controlled independently and/or individually. The temperature-control apparatus 204B, referred to in the following as the intermediate temperature-control apparatus 204B, is preferably assigned to the intermediate temperature-control cavity 110 and/or is designed to temperature-control the intermediate temperature-control cavity 110 or a fluid located therein, in particular the amplification products V, preferably to a preheat temperature.

The intermediate temperature-control cavity 110 and/or temperature-control apparatus 204B is preferably arranged upstream of or (immediately) before the sensor apparatus 113, in particular in order for it to be possible to temperature-control or preheat, in a desired manner, fluids to be fed to the sensor apparatus 113, in particular analytes A and/or amplification products V, particularly preferably immediately before said fluids are fed.

Particularly preferably, the intermediate temperature-control cavity 110 and/or temperature-control apparatus 204B is designed or intended to denature the sample P or analytes A and/or the amplification products V produced, and/or to divide any double-stranded analytes A or amplification products V into single strands and/or to counteract premature bonding and/or hybridising of the amplification products V, in particular by the addition of heat.

The intermediate temperature-control cavity 110 is preferably designed to actively temperature-control, particularly preferably to heat, fluids, in particular the amplification products V, preferably to a melting point or melting temperature, as explained in greater detail in the following.

The intermediate temperature-control apparatus 204B assigned to the intermediate temperature-control cavity 110 is preferably designed to (actively) temperature control, in particular heat, the intermediate temperature-control cavity 110.

Preferably, the intermediate temperature-control apparatus 204B comprises a heating element, in particular a heating resistor or a Peltier element, or is formed thereby.

The intermediate temperature-control apparatus 204B is preferably planar and/or has a contact surface which is preferably elongate and/or rectangular allowing for heat transfer between the intermediate temperature-control apparatus 204B and the intermediate temperature-control cavity 110. Preferably, the intermediate temperature-control apparatus 204B can be externally positioned against, in particular pressed against, the cartridge 100, the main body 101 and/or the cover 102, in the region of the intermediate temperature-control cavity 110 or on the intermediate temperature-control cavity 110, preferably over the entire surface thereof.

In particular, the analysis device 200 comprises the intermediate temperaturecontrol apparatus 204B. However, other structural solutions are also possible in which the intermediate temperature-control apparatus 204B is arranged in the cartridge 100 or integrated in the cartridge 100, in particular in the intermediate temperature-control cavity 110.

Preferably, the analysis system 1 , analysis device 200 and/or the cartridge 100 and/or one or each temperature-control apparatus 204 comprise/comprises a temperature detector and/or temperature sensor (not shown), in particular in order to make it possible to control and/or regulate temperature.

One or more temperature sensors may for example be assigned to the sensor portions 116 and/or to individual channel portions or cavities, i.e. may be thermally coupled thereto.

Particularly preferably, a temperature sensor is assigned to each temperaturecontrol apparatus 204A, 204B and/or 204C, for example in order to measure the temperature of the respective temperature-control apparatuses 204 and/or the contact surfaces thereof. This allows in particular a feedback-control.

The temperature-control apparatus 204C, referred to in the following as the sensor temperature-control apparatus 204C, is in particular assigned to the sensor apparatus 113 and/or is designed to temperature-control fluids located in or on the sensor apparatus 113 and/or sensor compartment 113G, in particular analytes A and/or amplification products V, reagents or the like, in a desired manner, preferably to a hybridisation temperature.

The sensor temperature-control apparatus 204C is preferably designed differently than the intermediate temperature-control apparatus 204B and/or the reaction temperature-control apparatus 204A. In particular, the design of the sensor temperature-control apparatus 204C is an aspect that is independently realisable. The sensor temperature-control apparatus 204C can be provided without any of the other temperature-control apparatuses 204, in particular without the reaction temperature-control apparatus 204A and the intermediate temperature-control apparatus 204B.

Preferably, the analysis device 200 comprises the sensor temperature-control apparatus 204C.

Particularly preferably, the sensor temperature-control apparatus 204C is associated to the sensor apparatus 113, in particular the temperature-control structure 1131.

The sensor temperature-control apparatus 204C is in particular configured to control the temperature-control structure 1131, in particular to control or set the temperature of the temperature-control structure 1131.

The sensor temperature-control apparatus 204C and the temperature-control structure 1131 are in particular designed in such a way that the temperature-control structure 1131 can be temperature-controlled by the sensor temperature-control apparatus 204C.

Preferably, the sensor temperature-control apparatus 204C comprises contacting means for electrically contacting the support 113D and/or the temperature-control structure 1131, in particular when the temperature-control structure 1131 is a resistive heating structure. In particular, the contacting means are designed for indirectly contacting the temperature-control structure 1131, for example by contacting the circuit layer SL1 , thereby contacting the temperature-control structure 1131 indirectly by the above-mentioned vias and/or conductive tracks, and/or by contacting the above-mentioned connection/connections of the support 113D or temperaturecontrol structure 1131.

The contacting means preferably comprise and/or are formed by the contact elements 203A.

In particular, the contacting means may be omitted when the temperature-control structure 1131 is an inductive heating structure. The sensor temperature-control apparatus 204C preferably comprises a voltage and/or current source 204D for applying a voltage and/or an electric current to the temperature-control structure 1131, in particular via the contacting means and/or in order to control or temperature-control the temperature-control structure 1131. The sensor temperature-control apparatus 204C, in particular the voltage and/or current source, is preferably designed for resistive heating of the sensor apparatus 113, in particular the temperature-control structure 1131.

According to another preferred aspect, the sensor temperature-control apparatus 204C comprises a field-generating device 204D for generating a magnetic or electro-magnetic field designed for induction heating of the temperature-control structure. The field is in particular an alternating field. This allows to induce eddy currents in the temperature-control structure 1131 and/or to heat the temperaturecontrol structure 1131 by induction heating. By using a magnetic field or induction heating to heat the temperature-control structure 1131, a direct physical contact between the temperature-control structure 1131 and the sensor temperature-control apparatus 204C can be dispensed with.

It is also possible that the sensor temperature-control apparatus 204C comprises both a a voltage and/or current source 204D for resistive heating of the temperature-control structure 1131 and a a field-generating device 204E for inductive heating of the temperature-control structure 1131.

Thus, particularly preferably, the analysis system 1 has the analysis device 200 and the cartridge 100, wherein the cartridge 100 has the sensor apparatus 113 and/or the analysis device 200 has the sensor temperature-control apparatus 204C, particularly wherein the sensor temperature-control apparatus 204C controls or is designed to control the temperature-control structure 1131 and/or the temperature thereof.

In principle, however, an analysis device 1 with a sensor apparatus 113 comprising a temperature-control apparatus 1131 integrated into a support 113D of the sensor apparatus 113 and a sensor temperature-control apparatus 204C that is separate from the sensor apparatus 113 can also be realized without the division of the analysis system 1 into an analysis device 200 and a cartridge 100. In addition, the sensor temperature-control apparatus 204C may also be designed to temperature-control, in particular heat and/or cool, the sensor apparatus 113, in particular the support 113D, the temperature-control structure 1131 and/or the sensor compartment 113G, by direct contact and/or thermal conduction. Preferably, in this case, the sensor temperature-control apparatus 204C is usable or used to temperature-control the sensor compartment 113G by being in contact with the connection side, in particular such that the desired or required hybridisation temperature is reached on the measuring side, in the sensor compartment 113G and/or in the fluid.

Preferably, the sensor temperature-control apparatus 204C comprises a Peltier element for temperature-controlling, in particular heating and/or cooling, the sensor apparatus 113, by direct contact and/or thermal conduction, in particular between the support 113D and the sensor temperature-control apparatus 204C. The Peltier element can in particular be provided in addition to other means for controlling the temperature-control structure 1131, such as the contacting means, the voltage and/or current source and/or the field-generating device 204E.

The combination of the resistive and/or inductive temperature-control structure 1131 with the sensor temperature-control apparatus 204C comprising a Peltier element, is particularly conducive to a quick, efficient and/or precise setting of the temperature in the sensor apparatus 113, support 113D, temperature-control structure 1131 and/or sensor compartment 113G. Particularly preferably, a heating by resistive and/or inductive heating can be supported and/or accelerated with the heating by thermal conduction and/or the Peltier element, and/or the Peltier element and/or thermal conduction allows a cooling.

Particularly preferably, the connection apparatus 203 comprises the sensor temperature-control apparatus 204C, and/or the connection apparatus 203 together with the sensor temperature-control apparatus 204C can be linked to, in particular pressed against, the cartridge 100, in particular the sensor apparatus 113.

More particularly preferably, the connection apparatus 203 and the sensor temperature-control apparatus 204C (together) can be moved toward and/or relative to the cartridge 100, in particular the sensor apparatus 113, and/or can be positioned against the cartridge 100, preferably in order to both electrically and thermally cou- pie the analysis device 200 to the cartridge 100, in particular the sensor apparatus 113 or the support 113D thereof.

Preferably, the sensor temperature-control apparatus 204C is arranged centrally on the connection apparatus 203 or a support thereof and/or is arranged between the contact elements 203A.

In particular, the contact elements 203A are arranged in an edge region of the connection apparatus 203 or a support thereof or are arranged around the sensor temperature-control apparatus 204C, preferably such that the connection apparatus 203 is connected or connectable to the sensor apparatus 113 thermally in the centre and/or electrically on the outside or in the edge region. However, other solutions are also possible here.

Preferably, in the operating state, the sensor temperature-control apparatus 204C rests on the support 113D in a planar manner and/or centrally and/or so as to be opposite the sensor array 113A and/or rests on one or more contacts 113E at least in part.

The analysis system 1 or analysis device 200 preferably comprises one or more actuators 205 for actuating the valves 115. Particularly preferably, different (types or groups of) actuators 205A and 205B are provided which are assigned to the different (types or groups of) valves 115A and 115B for actuating each of said valves, respectively.

The analysis system 1 or analysis device 200 preferably comprises one or more sensors 206. In particular, the sensors 206A are designed or intended to detect liquid fronts and/or flows of fluid in the fluid system 103. Particularly preferably, the sensors 206A are designed to measure or detect, for example optically and/or capacitively, a liquid front and/or the presence, the speed, the mass flow rate/volume flow rate, the temperature and/or another value of a fluid in a channel and/or a cavity, in particular in a respectively assigned sensor portion 116, which is in particular formed by a planar and/or widened channel portion of the fluid system 103.

The analysis system 1 or analysis device 200 preferably comprises a control apparatus 207, in particular comprising an internal clock or time base for controlling the sequence of a test and/or for collecting, evaluating and/or outputting or providing measured values in particular from the sensor apparatus 113, and/or from test results and/or other data or values.

The control apparatus 207 preferably controls or regulates the pump drive 202, the temperature-control apparatuses 204 and/or actuators 205, in particular taking into account or depending on the desired test and/or measured values from the sensor apparatus 113 and/or sensors 206.

Generally, it is noted that the cartridge 100, the fluid system 103 and/or the conveying of fluid preferably do not operate on the basis of capillary forces, but at least essentially or primarily under the effects of gravity and/or the effect of the pump or pump apparatus 112.

In the operating position, the liquids from the respective cavities are preferably removed, in particular drawn out, via the outlet that is at the bottom in each case, it being possible for gas or air to flow and/or be pumped into the respective cavities via the inlet that is in particular at the top. In particular, relevant vacuums in the cavities can thus be prevented or at least minimised when conveying the liquids.

The flows of fluid are controlled in particular by accordingly activating the pump or pump apparatus 112 and actuating the valves 115.

Optionally, the analysis system 1 or analysis device 200 comprises an input apparatus 208, such as a keyboard, a touch screen or the like, and/or a display apparatus 209, such as a screen.

The analysis system 1 or analysis device 200 preferably comprises at least one interface 210, for example for controlling, for communicating and/or for outputting measured data or test results and/or for linking to other devices, such as a printer, an external power supply or the like. This may in particular be a wired or wireless interface 210.

The analysis system 1 or analysis device 200 preferably comprises a power supply 211 , preferably a battery or an accumulator, which is in particular integrated and/or externally connected or connectable. Preferably, an integrated accumulator is provided as a power supply 211 and is (re)charged by an external charging device (not shown) via a connection 211 A and/or is interchangeable.

The analysis system 1 or analysis device 200 preferably comprises a housing 212, all the components and/or some or all of the apparatuses preferably being integrated in the housing 212. Particularly preferably, the cartridge 100 can be inserted or slid into the housing 212, and/or can be received by the analysis device 200, through an opening 213 which can in particular be closed, such as a slot or the like.

The analysis system 1 or analysis device 200 is preferably portable or mobile. Particularly preferably, the analysis device 200 weighs less than 25 kg or 20 kg, particularly preferably less than 15 kg or 10 kg, in particular less than 9 kg or 6 kg.

In the following, a preferred sequence of a test or analysis using the proposed analysis system 1 and/or analysis device 200 and/or the proposed cartridge 100 and/or in accordance with the proposed method is explained in greater detail by way of example.

The analysis system 1 , the cartridge 100 and/or the analysis device 200 is preferably designed to carry out the proposed method.

During the proposed method for testing a sample P, at least one analyte A of the sample P is preferably amplified or copied, in particular by means of PCR. The amplified analyte A and/or the amplification products V produced in this way is/are then bonded and/or hybridised to corresponding capture molecules M. The bonded amplification products V are then detected, in particular by means of electronic or electrochemical measurement.

The method may be used in particular in the field of medicine, in particular veterinary medicine, in order to detect diseases and/or pathogens.

Within the context of the method according to the invention, a sample P having at least one analyte A on the basis of a fluid or a liquid from the human or animal body, in particular blood, saliva or urine, is usually first introduced into the receiving cavity 104 via the connection 104A, in order to detect diseases and/or pathogens, it being possible for the sample P to be pretreated. Once the sample P has been received, the receiving cavity 104 and/or the connection 104A thereof is fluidically closed, in particular in a liquid-tight and/or gas-tight manner.

Preferably, the cartridge 100 together with the sample P is then linked or connected to the analysis device 200, in particular is inserted or slid into the analysis device 200.

The method sequence, in particular the flow and conveying of the fluids, the mixing and the like, is controlled by the analysis device 200 or the control apparatus 207, in particular by accordingly activating and actuating the pump drive 202 or the pump apparatus 112 and/or the actuators 205 or valves 115.

Preferably, the sample P, or a part or supernatant of the sample P, is removed from the receiving cavity 104 via the outlet 104C and/or the intermediate connection 104D and is fed to the mixing cavity 107 in a metered manner.

Preferably, the sample P in the cartridge 100 is metered, in particular in or by means of the first metering cavity 105A and/or second metering cavity 105B, before being introduced into the mixing cavity 107. Here, in particular the upstream and/or downstream sensor portions 116 are used together with the assigned sensors 206 in order to make possible the desired metering. However, other solutions are also possible.

In the mixing cavity 107, the sample P is prepared for further analysis and/or is mixed with a reagent, preferably with a liquid reagent F1 from a first storage cavity 108A and/or with one or more dry reagents S1 , S2 and/or S3, which are preferably provided in the mixing cavity 107.

The liquid and/or dry reagents can be introduced into the mixing cavity 107 before and/or after the sample P. In the example shown, the dry reagents S1 to S3 are preferably introduced into the mixing cavity 107 previously and are optionally dissolved by the sample P and/or the liquid reagent F1.

The liquid reagent F1 may in particular be a reagent, in particular a PCR master mix, for the amplification reaction or PCR. Preferably, the PCR master mix contains nuclease-free water, enzymes for carrying out the PCR, in particular at least one DNA polymerase, nucleoside triphosphates (NTPs), in particular deoxynucleotides (dNTPs), salts, in particular magnesium chloride, and/or reaction buffers.

The dry reagents S1 , S2 and/or S3 may likewise be reagents required for carrying out an amplification reaction or PCR, which are in a dry, in particular lyophilised, form. Preferably, the dry reagents S1 , S2 and/or S3 are selected in particular from lyophilised enzymes, preferably DNA polymerases, NTPs, dNTPs and/or salts, preferably magnesium chloride.

The dissolving or mixing in the mixing cavity 107 takes place or is assisted in particular by introducing and/or blowing in gas or air, in particular from the bottom. This is carried out in particular by accordingly pumping gas or air in the circuit by means of the pump or pump apparatus 112.

Subsequently, a desired volume of the sample P that is mixed and/or pretreated in the mixing cavity 107 is preferably fed to one or more reaction cavities 109, particularly preferably via (respectively) one of the upstream, optional intermediate cavities 106A to 106C and/or with different reagents or primers, in this case dry reagents S4 to S6, being added or dissolved.

Particularly preferably, the (premixed) sample P is split into several sample portions, preferably of equal size, and/or is divided between the intermediate cavities 106A to 106C and/or reaction cavities 109, preferably evenly and/or in sample portions of equal size.

Different reagents, in the present case dry reagents S4 to S6, particularly preferably primers, in particular those required for the PCR or PCRs, in particular groups of different primers in this case, are preferably added to the (premixed) sample P in the intermediate cavities 106A to 106C and/or different reaction cavities 109, respectively.

The primers in the different groups differ in particular in terms of the hybridisation temperatures of the amplification products V produced by the respective primers. As a result, in particular the different group temperatures of the groups of analytes A and/or amplification products V are produced, as already mentioned at the outset. Particularly preferably, marker primers are used in the sense already specified at the outset.

In the embodiment shown, the reagents or primers S4 to S6 are contained in the intermediate cavities 106A to 106C. However, other solutions are also possible, in particular those in which the reagents or primers S4 to S6 are contained in the reaction cavities 109.

According to a preferred embodiment, the intermediate cavities 106A to 106C each contain primers for amplifying/copying one analyte A, preferably two different analytes A and more preferably three different analytes A. However, it is also possible for four or more different analytes A to be amplified/copied per reaction cavity 109.

Particularly preferably, the reaction cavities 109 are filled in succession with a specified volume of the (pretreated) sample P or with respective sample portions via the intermediate cavities 106A to 106C that are each arranged upstream. For example, the first reaction cavity 109A is filled with a specified volume of the pretreated sample P before the second reaction cavity 109B and/or the second reaction cavity 109B is filled therewith before the third reaction cavity 109C.

In the reaction cavities 109, the amplification reactions or PCRs are carried out to copy/amplify the analytes A. This is carried out in particular by means of the assigned, preferably common, reaction temperature-control apparatus(es) 204A and/or preferably simultaneously for all the reaction cavities 109, i.e. in particular using the same cycles and/or temperature (curves/profiles).

The PCR or PCRs are carried out on the basis of protocols or temperature profiles that are essentially known to a person skilled in the art. In particular, the mixture or sample volume located in the reaction cavities 109 is preferably cyclically heated and cooled.

Preferably, nucleic-acid products are produced from the analytes A as amplification products V in the reaction cavity/cavities 109.

During the pretreatment, reaction and/or PCR or amplification, a label L is directly produced (in each case) and/or is attached to the amplification products V. This is in particular achieved by using corresponding, preferably biotinylated, primers. However, the label L can also be produced and/or bonded to the amplification products V separately or later, optionally also only in the sensor compartment 113G and/or after hybridisation.

The label L is used in particular for detecting bonded amplification products V. In particular, the label L can be detected or the label L can be identified in a detection process.

Preferably, it is possible for a plurality of amplification reactions or PCRs to be carried out in parallel and/or independently from one another using different primers S4 to S6 and/or primer pairs, such that a large number of (different) analytes A can be copied or amplified in parallel and subsequently analysed.

After carrying out the PCR and/or amplification, corresponding fluid volumes and/or amplification products V and/or the groups are conducted out of the reaction cavities 109 in succession to the sensor apparatus 113 and/or to the sensor compartment 113G, in particular via a group-specific and/or separate intermediate cavity 106E, 106F or 106G (respectively) and/or via the optional (common) intermediate temperature-control cavity 110.

The intermediate cavities 106E to 106G may contain further reagents, in this case dry reagents S9 and S10, respectively, for preparing the amplification products V for the hybridisation, e.g. a buffer, in particular an SSC buffer, and/or salts for further conditioning. On this basis, further conditioning of the amplification products V can be carried out, in particular in order to improve the efficiency of the subsequent hybridisation (bonding to the capture molecules M). Particularly preferably, the pH of the sample P is set or optimised in the intermediate cavities 106E to 106G and/or by means of the dry reagents S9 and S10.

Preferably, the sample P or the analytes A and/or amplification products V or groups formed thereby is/are, in particular immediately before being fed to the sensor apparatus 113 and/or between the reaction cavities 109 and the sensor apparatus 113, actively temperature-controlled (in particular in advance and/or before being temperature-controlled in the sensor apparatus 113), preferably preheated, in particular by means of and/or in the intermediate temperature-control cavity 110 and/or by means of the intermediate temperature-control apparatus 204B. Preferably, the groups and/or analytes A or amplification products V of the individual reaction cavities 109 are actively temperature-controlled (in particular in advance and/or before being temperature-controlled in the sensor apparatus 113) and/or fed to the intermediate temperature-control cavity 110 in succession. The groups are in particular fed to the sensor apparatus 113 and/or the sensor compartment 113G in succession being temperature-controlled, in particular in advance and/or before being temperature-controlled in the sensor apparatus 113.

Preferably, the groups and/or amplification products V are actively temperature- controlled, in particular heated, (exclusively) in or on the sensor apparatus 113, and/or brought to the corresponding hybridisation temperature, preferably solely by means of the sensor temperature-control apparatus 204C. In particular, both the denaturing of any hybridised amplification products V and the (subsequent) hybridisation of the amplification products V and the corresponding capture molecules M can take place in or on the sensor apparatus 113. In this case, previous (intermediate) temperature control before the sensor apparatus 113 can therefore be omitted.

However, the sample P and/or the groups or analytes A and/or amplification products V is/are, in particular immediately before being fed to the sensor apparatus 113 and/or between the reaction cavities 109 and the sensor apparatus 113, actively temperature-controlled (in particular in advance and/or before being temperature- controlled in the sensor apparatus 113) and/or brought to the preheat temperature, preferably by means of the intermediate temperature-control apparatus 204B, and, after being fed to the sensor apparatus 113 and/or in the sensor apparatus 113, is/are subsequently and/or again temperature-controlled (in particular after being temperature-controlled in the intermediate temperature-control cavity 110) and/or brought to the corresponding hybridisation temperature and/or group temperature, preferably by means of the sensor temperature-control apparatus 204C. In this case, any hybridised amplification products V are thus denatured before being fed to and/or outside the sensor apparatus 113.

In particular, the sample P and/or the groups and/or amplification products V is/are brought to the respective hybridisation temperatures and/or group temperatures in multiple stages or more rapidly after leaving the reaction cavity/cavities 109, preferably the amplification products V being, in a first stage, temperature-controlled, in particular in the intermediate temperature-control cavity 110 and/or in advance and/or before being temperature-controlled in the sensor apparatus 113, to a temperature above the hybridisation temperature and/or to the preheat temperature and/or being denatured at the melting point or melting temperature, and, in a second stage, being subsequently and/or again temperature-controlled, in particular heated and/or cooled, to the corresponding hybridisation temperature and/or group temperature, in particular in the sensor apparatus 113 and/or after being temperature-controlled in the intermediate temperature-control cavity 110.

By means of the sensor temperature-control apparatus 204C, the sensor apparatus 113 is in particular preheated such that in particular undesired cooling of the sample P that is preheated, in this case in the intermediate temperature-control cavity 110, and/or groups, in particular to below the respective hybridisation temperatures and/or group temperatures, can be prevented.

Particularly preferably, the sensor apparatus 113 is preheated in each case at least substantially to the hybridisation temperature of the respective analytes A and/or amplification products V, and/or to the respective group temperatures or to a slightly higher or lower temperature. Owing to the relatively large thermal mass of the sensor apparatus 113, the desired and/or optimal temperature for the hybridisation can be (rapidly) reached when the preferably warmer sample P and/or group is fed into the sensor apparatus 113 and/or the sensor compartment 113G thereof.

After the sample P and/or the amplification products V are fed to the sensor apparatus 113, the amplification products V are hybridised to the capture molecules M.

Once the sample P, groups, analytes A and/or amplification products V are hybridised and/or bonded to the capture molecules M, detection follows, in particular by means of the preferably provided labels L, or in another manner.

In the following, a particularly preferred variant of the detection is described in greater detail, specifically electrochemical detection, but other types of detection, for example optical detection, capacitive detection or the like, may also be carried out.

Following the respective bondings/hybridisations, preferably an optional washing process takes place and/or additional reagents or liquids, in particular from the storage cavities 108B to 108E, are optionally fed in. In particular, it may be provided that sample residues and/or unbonded amplification products V, reagents and/or remnants of the PCR and other substances that may disrupt the rest of the method sequence are removed.

Washing or flushing may in particular take place using a fluid and/or reagent F3, in particular a wash buffer, particularly preferably a sodium-citrate buffer or SSC buffer, which is preferably contained in the storage cavity 108C. Unbonded analytes A and/or amplification products V, and substances which could disrupt subsequent detection, are preferably removed from the sensor apparatus 113 and/or fed to the collection cavity 111 by the wash buffer.

Subsequently and/or after the washing process, in accordance with a preferred variant of the method, detection of the amplification products V bonded to the capture molecules M takes place.

In order to detect the amplification products V bonded to the capture molecules M, a reagent F4 and/or detector molecules D, in particular alkaline phospha- tase/streptavidin, is/are fed to the sensor apparatus 113, preferably from the storage cavity 108D.

The reagents F4 and/or detector molecules D can bond to the bonded amplification products V, in particular to the label L of the bonded amplification products V, particularly preferably to the biotin marker, as shown in Fig. 6.

In the context of detection, it may also be provided that additional liquid reagents F3 and/or F5 are fed from the storage cavities 108C and/or 108E to the sensor apparatus 113.

Optionally, subsequently or after the reagents F4 and/or detector molecules D have bonded to the amplification products V and/or the labels L, an (additional) washing process and/or flushing takes place, preferably by means of the fluid and/or reagent F3 and/or wash buffer, in particular in order to remove unbonded reagents F4 and/or detector molecules D from the sensor apparatus 113.

Preferably, a reagent S7 and/or S8 and/or substrate SU for the detection, in particular from the storage cavity 106D, is lastly fed to the sensor apparatus 113, pref- erably together with a fluid or reagent F2 (in particular a buffer), which is suitable for the substrate SU, particularly preferably for dissolving the reagent S7 and/or S8 and/or substrate SU, the fluid or reagent F2 in particular being taken from the storage cavity 106B. In particular the reagent S7 and/or S8 can form or can comprise the substrate SU.

After adding the substrate SU, the cover 113H is preferably lowered in order to isolate the sensor fields 113B from one another and/or to minimise the exchange of substances therebetween.

Preferably, p-aminophenyl phosphate (pAPP) is used as the substrate SU.

The substrate SU preferably reacts on and/or with the bonded amplification products V and/or detector molecules D and/or allows these to be electrochemically measured.

Preferably, the substrate SU is split by the bonded detector molecules D, in particular the alkaline phosphatase of the bonded detector molecules D, preferably into a first substance SA, such as p-aminophenol, which is in particular electrochemically active and/or redox active, and a second substance SP, such as phosphate.

Preferably, the first or electrochemically active substance SA is detected in the sensor apparatus 113 or in the individual sensor fields 113B by electrochemical measurement and/or redox cycling.

Particularly preferably, by means of the first substance SA, specifically a redox reaction takes place at the electrodes 113C, the first substance SA preferably discharging electrons to or receiving electrons from the electrodes 113C.

In particular, the presence of the first substance SA and/or the respective amounts in the respective sensor fields 113B is detected by the associated redox reactions. In this way, it can be determined qualitatively and in particular also quantitatively whether and how many analytes A and/or amplification products V are bonded to the capture molecules M in the respective sensor fields 113B. This accordingly gives information on which analytes A are or were present in the sample P, and in particular also gives information on the quantity of said analytes A. In particular, by means of the redox reaction with the first substance SA, an electrical current signal or power signal is generated at the assigned electrodes 113C, the current signal or power signal preferably being detected by means of an assigned electronic circuit and/or the circuit layer SL1 of the sensor apparatus 113 or support 113D.

Depending on the current signal or power signal from the electrodes 113C that is generated in this way, it is determined whether and/or where hybridisation to the capture molecules M has occurred.

The measurement is preferably taken just once and/or for the entire sensor array 113A and/or for all the sensor fields 113B, in particular simultaneously or in parallel. In particular, the bonded groups and/or amplification products V from all the groups and/or reaction cavities 109 are detected, identified or determined simultaneously or in parallel in a single or common detection process.

In other words, the amplification products V from the individual reaction cavities 109 that are bonded at different and/or specifically selected hybridisation temperatures are detected together and/or in parallel, such that rapid measurement is possible, and high specificity in relation to the hybridisation of the analytes A and/or amplification products V to the capture molecules M is nevertheless also achieved on the basis of the hybridisation temperature that is set in a targeted manner in each case.

However, in principle, it is also possible to measure a plurality of sample portions in the sensor apparatus 113 or in a plurality of sensor apparatuses 113 in succession or separately.

The hybridisation temperature and/or temperature of the sensor apparatus 113, support 113D and/or sensor compartment 113G is preferably set or controlled by controlling a temperature-control structure 1131 that is integrated into the support 113D. This is in particular an independently realisable aspect of the proposed method.

The temperature-control structure 1131 is preferably controlled and/or temperature- controlled by applying a voltage, an electric current and/or a magnetic field to the temperature-control structure 1131. The magnetic field is in particular an alternating field and/or an electromagnetic field. The temperature-control structure 1131 is preferably heated by resistive and/or inductive heating.

The voltage, electric current and/or magnetic field is preferably generated in the sensor temperature-control apparatus 204C of the analysis device 200, in particular in or by the voltage and/or current source 204D and/or the field-generating device 204E.

Preferably, the temperature-control structure 1131 is designed as described above. Thus, the temperature-control structure 1131 preferably is a resistive and/or inductive temperature-control structure or heating element and/or is temperature- controlled, in particular heated, by resistive heating and/or induction heating.

As an alternative or in addition to first performing an amplification and/or PCR and subsequently transferring the sample P to the sensor apparatus 113 and performing a hybridisation with the sensor apparatus 113 for detecting the analytes A and/or amplification products V, it is also possible to perform a PCR in or with the sensor apparatus 113. In this case, the steps described above in connection with performing the amplification and/or PCR are preferably performed in or with the sensor apparatus 113. In particular, the sensor temperature-control apparatus 204C and/or the temperature-control structure 1131 are in this case used for performing the respective heating and/or cooling steps.

The test results or measurement results are in particular electrically transmitted to the analysis device 200 or the control apparatus 207 thereof, preferably by means of the electrical connection apparatus 203, and are accordingly prepared, analysed, stored, displayed and/or output, in particular by the display apparatus 209 and/or interface 210.

After the test has been carried out, the cartridge 100 is preferably disconnected from the analysis device 200 and/or is released and/or ejected therefrom, and is in particular disposed of.

Individual aspects and features of the present invention and individual method steps and/or method variants may be implemented independently from one another, but also in any desired combination and/or order. In particular, the present invention relates to the following aspects, which can also be combined with the afore-mentioned aspects and features:

1 . Cartridge (100) for testing an in particular biological sample (P), the cartridge (100) comprising a sensor apparatus (113) for detecting analytes (A) of the sample (P) and/or amplification products (V) of the analytes (A), the sensor apparatus (113) comprising a support (113D) with a plurality of electrodes (113C), characterised in that the support (113D) has a temperature-control structure (1131) for temperaturecontrolling the sensor apparatus (113) and/or support (113D).

2. Cartridge, preferably according to aspect 1 , characterised in that a temperature of the temperature-control structure (1131) and/or the support (113D) is controllable by applying an electric voltage and/or current to the temperature-control structure (1131).

3. Cartridge, preferably according to aspect 1 or 2, characterised in that the temperature-control structure (1131) is a resistive heating structure and/or is designed to be heated by resistive heating and/or comprises an electrically conductive material.

4. Cartridge, preferably according to one of the preceding aspects, characterised in that the temperature-control structure (1131) is an inductive heating structure and/or is designed to be heated by induction heating and/or comprises a ferromagnetic material.

5. Cartridge, preferably according to one of the preceding aspects, characterised in that the temperature-control structure (1131) has one or more temperaturecontrol elements having a finger-like, comb-like, inter-engaging and/or meandering structure.

6. Cartridge, preferably according to one of the preceding aspects, characterised in that the temperature-control structure (1131) is designed to be planar or laminar. 7. Cartridge, preferably according to one of the preceding aspects, characterised in that the temperature-control structure (1131) is electrically isolated from the electrodes (113C).

8. Cartridge, preferably according to one of the preceding aspects, characterised in that the support (113D) has a layered structure having a plurality of layers (SL), the temperature-control structure (1131) forming a layer (SL), in particular a heating layer (SL3), of the plurality of layers (SL).

9. Cartridge, preferably according to one of the preceding aspects, characterised in that the support (113D) has a circuit layer (SL1 ) having one or more electronic circuits, in particular integrated circuits, preferably wherein the support (113D) has a passivation layer (SL2) that is arranged between the temperature-control structure (1131) and the circuit layer (SL1 ) and/or wherein the temperature-control structure (1131) is electrically connected to the circuit layer (SL1 ), in particular by one or more vias (113J) and/or conductive tracks (113K).

10. Cartridge, preferably according to one of aspects 1 to 8, characterised in that the support (113D) has a circuit layer (SL1 ) having one or more electronic circuits, in particular integrated circuits, wherein the temperature-control structure (1131) is electrically isolated from the circuit layer (SL1 ), in particular by a passivation layer (SL2) arranged between the temperature-control structure (1131) and the circuit layer (SL1 ), and/or wherein the support (113D) and/or the temperature-control structure (1131) has one or more electrical connections (113L) for connecting the temperature-control structure (1131) separately from the circuit layer (SL1 ), the connection/connections (113L) in particular having bond pads and/or wire bonds.

11 . Analysis system (1 ) for testing an in particular biological sample (P), the analysis system (1 ) having a sensor apparatus (113) for detecting analytes (A) of the sample (P) and/or amplification products (V) of the analytes (A), the sensor apparatus (113) having a support (113D) and a plurality of electrodes (113C) arranged on the support (113D), the analysis system (1 ) having a sensor temperature-control apparatus (204C) for temperature-controlling the support (113D), characterised in that the support (113) has a preferably resistive and/or inductive temperaturecontrol structure (1131), wherein the sensor temperature-control apparatus (204C) is designed to control the temperature-control structure (1131).

12. Analysis system, preferably according aspect 11 , characterised in that the analysis system (1 ) has an analysis device (200) and a cartridge (100), wherein the cartridge (100) has the sensor apparatus (113) and/or the analysis device (200) has the sensor temperature-control apparatus (204C), in particular wherein the cartridge (100) is separate from and/or insertable into the analysis device (200) and/or wherein the cartridge (100) is configured according to one of claims 1 to 10.

13. Analysis system, preferably according to aspect 11 or 12, characterised in that the sensor temperature-control apparatus (204C) has contacting means for electrically contacting the support (113D) and/or the temperature-control structure (1131) and has a voltage and/or current source (204D) for applying a voltage and/or an electric current to the temperature-control structure (1131) via the contacting means.

14. Analysis system, preferably according to one of aspects 11 to 13, characterised in that the sensor temperature-control apparatus (204C) has a field-generating device (204E) for generating a, preferably alternating, magnetic, in particular electromagnetic, field designed for induction heating of the temperature-control structure (1131).

15. Method for testing an in particular biological sample (P), wherein analytes (A) of the sample (P) and/or amplification products (V) of the analytes (A) are bonded to capture molecules (M) on a support (113D) of a sensor apparatus (113) and the bonded analytes (A) and/or amplification products (V) are detected by means of the sensor apparatus (113), characterised in that the sensor apparatus (113) is temperature-controlled by temperaturecontrolling a temperature-control structure (1131) that is integrated into the support (113D), wherein the temperature-control structure (1131) is temperature-controlled by applying a voltage, an electric current and/or a magnetic, in particular an alternating and/or electromagnetic, field to the temperature-control structure (1131), in particular wherein the temperature-control structure (1131) is heated by resistive and/or inductive heating.

List of Reference Signs: analysis system cartridge A front main body cover fluid system receiving cavity A connection B inlet C outlet D intermediate connection metering cavity A first metering cavity B second metering cavity (A-G) intermediate cavity mixing cavity (A-E) storage cavity reaction cavity A first reaction cavity B second reaction cavity C third reaction cavity intermediate temperature-control cavityA inlet B outlet collection cavity pump apparatus sensor apparatus A sensor array B sensor field C electrode D support E contact F layer G sensor compartment 113H sensor cover 1131 temperature-control structure 113J via 113K conductive track 113L connection 114 channel 114A bypass 115 valve

115A initially closed valve 115B initially open valve 116 sensor portion 118 sensor compartment 119 inlet 120 outlet

200 analysis device 201 receptacle 202 pump drive

203 connection apparatus 203A contact element 204 temperature-control apparatus

204A reaction temperature-control apparatus 204B intermediate temperature-control apparatus 204C sensor temperature-control apparatus 204D voltage and/or current source 204E field-generating device 205 (valve) actuator 205A (valve) actuator for 115A

205B (valve) actuator for 115B 206 sensor

206A fluid sensor 206B other sensor 207 control apparatus 208 input apparatus 209 display apparatus 210 interface 211 power supply 211A connection 212 housing 213 opening

A analyte B bond D detector molecule F(1-5) liquid reagent L label M(1-3) capture molecule P sample S(1-10) dry reagent SL layer (support) SL1 circuit layer SL2 passivation layer SL3 heating layer SL4 isolation layer SL5 diffusion barrier layer SL6 diffusion barrier layer SL7 measuring layer SU substrate SA first substance SP second substance V(1-2) amplification product

Claims

55 Claims:

1 . Cartridge (100) for testing an in particular biological sample (P), the cartridge (100) comprising a sensor apparatus (113) for detecting analytes (A) of the sample (P) and/or amplification products (V) of the analytes (A), the sensor apparatus (113) comprising a support (113D) with a plurality of electrodes (113C) for detecting analytes (A) of the sample (P) to be tested, characterised in that the support (113D) has a temperature-control structure (1131) for temperaturecontrolling the sensor apparatus (113) and/or support (113D).

2. Cartridge according to claim 1 , characterised in that a temperature of the temperature-control structure (1131) and/or the support (113D) is controllable by applying an electric voltage and/or current to the temperature-control structure (1131).

3. Cartridge according to claim 1 or 2, characterised in that the temperaturecontrol structure (1131) is a resistive heating structure and/or is designed to be heated by resistive heating and/or comprises an electrically conductive material.

4. Cartridge according to one of the preceding claims, characterised in that the temperature-control structure (1131) is an inductive heating structure and/or is designed to be heated by induction heating and/or comprises a ferromagnetic material.

5. Cartridge according to one of the preceding claims, characterised in that the temperature-control structure (1131) has one or more temperature-control elements having a finger-like, comb-like, inter-engaging and/or meandering structure.

6. Cartridge according to one of the preceding claims, characterised in that the temperature-control structure (1131) is designed to be planar or laminar.

7. Cartridge according to one of the preceding claims, characterised in that the temperature-control structure (1131) is electrically isolated from the electrodes (113C). 56

8. Cartridge according to one of the preceding claims, characterised in that the support (113D) has a layered structure having a plurality of layers (SL), the temperature-control structure (1131) forming a layer (SL), in particular a heating layer (SL3), of the plurality of layers (SL).

9. Cartridge according to one of the preceding claims, characterised in that the support (113D) has a circuit layer (SL1 ) having one or more electronic circuits, in particular integrated circuits, the circuits in particular being designed to detect electrical currents or voltages.

10. Cartridge according to claim 9, characterised in that the circuit layer (SL1 ) is an outermost layer (SL) of the support (113D).

11. Cartridge according to claim 9 or 10, characterised in that the support (113D) has a passivation layer (SL2) that is arranged between the temperature-control structure (113I) and the circuit layer (SL1 ).

12. Cartridge according to one of claims 9 to 11 , characterised in that the temperature-control structure (1131) is electrically connected to the circuit layer (SL1 ), in particular by one or more vias (113J) and/or conductive tracks (113K).

13. Cartridge according to one of claims 9 to 12, characterised in that the temperature-control structure (1131) is electrically isolated from the circuit layer (SL1 ), in particular by a passivation layer (SL2) arranged between the temperature-control structure (113I) and the circuit layer (SL1 ).

14. Cartridge according to one of claims 9 to 13, characterised in that the support (113D) and/or the temperature-control structure (1131) has one or more electrical connections (113L) for connecting the temperature-control structure (1131) separately from the circuit layer (SL1 ), the connection/connections (113L) in particular having bond pads and/or wire bonds.

15. Cartridge according to one of claims 9 to 14, characterised in that temperaturecontrol structure (1131) is arranged between the electrodes (113C) and the circuit layer (SL1 ). 57

16. Cartridge according to one of the preceding claims, characterised in that temperature-control structure (1131) is a middle layer (SL) of the support (113D) and/or is arranged between two other layers (SL) of the support (113D).

17. Cartridge according to one of the preceding claims, characterised in that the electrodes (113C) constitute an outermost layer and/or measuring layer (SL7) of the support (113D).

18. Cartridge according to one of the preceding claims, characterised in that the sensor apparatus (113) has a measuring side and a connection side which are arranged on opposite sides of the sensor apparatus (113), preferably wherein the measuring side comprises the electrodes (113C) and/or is the side that faces the sample (P) and/or a sensor compartment (113G).

19. Cartridge according to one of the preceding claims, characterised in that the support (113D) has an isolation layer (SL4) for electrically isolating the temperature-control structure (1131) from the electrodes (113C).

20. Cartridge according to one of the preceding claims, characterised in that the support (113D) has one or more diffusion barrier layers (SL5, SL6).

21. Cartridge according to one of the preceding claims, characterised in that the sensor apparatus (113) comprises a sensor cover (113H) and a sensor compartment (113G), wherein the sensor compartment (113G) is formed between the support (113D) on one side and the sensor cover (113H) on the other side.

22. Cartridge according to one of the preceding claims, characterized in that the electrodes (113C) are arranged on the support (113D) and/or integrated in the support (113D).

23. Cartridge according to one of the preceding claims, characterised in that the sensor apparatus (113) comprises a sensor array (113A) comprising a plurality of sensor fields (113B) that are preferably separated from one another, wherein the temperature-control structure (1131) has several regions that are separately controllable, wherein each of the regions is assigned to one or more of the sensor fields (113B), so that different temperatures, in particular hybridization temperatures, can be set in or for different sensor fields (113B). 58

24. Cartridge according to one of the preceding claims, characterised in that the cartridge (100) comprises a main body (101 ) that is injection-moulded from plastics material.

25. Cartridge according to one of the preceding claims, characterised in that the support (113D) is a chip or CMOS chip or printed circuit board.

26. Cartridge according to one of the preceding claims, characterised in that the sensor apparatus (113) and/or support (113D) is produced from a wafer, preferably a silicon wafer.

27. Analysis system (1 ) for testing an in particular biological sample (P), the analysis system (1 ) having a sensor apparatus (113) for detecting analytes (A) of the sample (P) and/or amplification products (V) of the analytes (A), the sensor apparatus (113) having a support (113D) and a plurality of electrodes (113C) for detecting analytes of the sample (P) to be tested, the electrodes (113C) being arranged on the support (113D), wherein the support (113D) is a chip or CMOS chip or printed circuit board, the analysis system (1 ) having a sensor temperature-control apparatus (204C) for temperature-controlling the support (113D), characterised in that the support (113) has a preferably resistive and/or inductive temperaturecontrol structure (1131), wherein the sensor temperature-control apparatus (204C) is designed to control the temperature-control structure (1131).

28. Analysis system according claim 27, characterised in that the analysis system (1 ) has an analysis device (200) and a cartridge (100), wherein the cartridge (100) has the sensor apparatus (113) and/or the analysis device (200) has the sensor temperature-control apparatus (204C).

29. Analysis system according to claim 28, characterised in that the cartridge (100) is separate from and/or insertable into the analysis device (200).

30. Analysis system according to claim 28 or 29, characterised in that the cartridge (100) is configured according to one of claims 1 to 26.

31. Analysis system according to one of claims 27 to 30, characterised in that the sensor temperature-control apparatus (204C) has contacting means for electrically contacting the support (113D) and/or the temperature-control structure (1131) and has a voltage and/or current source (204D) for applying a voltage and/or an electric current to the temperature-control structure (1131) via the contacting means.

32. Analysis system according to one of claims 27 to 31 , characterised in that the sensor temperature-control apparatus (204C) has a field-generating device (204E) for generating a, preferably alternating, magnetic, in particular electromagnetic, field designed for induction heating of the temperature-control structure (1131).