Sample analyzer

Abstract

The invention relates to an analyzer (100) for receiving and processing a disposable diagnostic article (10), which comprises a sample container (12) and a microfluidic cartridge (20) connected to the sample container. The microfluidic cartridge (20) contains a fluid reservoir (32) with a sample receiving fluid (52), a fluid interface (30) for connection to the sample container (12), a pumping device (36) for bidirectional pumping of fluid between the fluid reservoir (32) and the fluid interface (30), a reaction chamber (46) for amplifying an analyte to be detected from the sample container (12), and a detection chamber (44) for detecting the analyte by means of a biochip (54) integrated in the cartridge. The analyzer (100) comprises: - an openable and closable receiving device (110) for the disposable diagnostic article (10), which, when closed, fixes the cartridge (20) in an analysis position, - a pump control device (130) for actuating the pump device (36) of the cartridge in the analysis position, - a heating / cooling device for generating a cyclic temperature profile in the reaction chamber (46) of the cartridge in the analysis position, and - a measuring / reading device for controlling and reading the biochip (54) of the cartridge in the analysis position.

Description

[0001] The invention relates to an analytical device for receiving and processing a disposable diagnostic article, comprising a sample container and a microfluidic cartridge connected to the sample container.

[0002] Many questions in molecular biology research and molecular diagnostics require the determination of the quantity or concentration of specific biomolecules, such as certain nucleic acids, in a sample. In this context, the term nucleic acid also includes nucleic acid sequences. High-performance and rapid detection methods employ array technology using so-called DNA chips or biochips, which enable surface-sensitive detection of nucleic acid oligomer hybridization events. Often, an amplification step is added prior to the actual, already highly sensitive detection process, in which the nucleic acids to be detected are multiplied so that they are ultimately present in a concentration above the detection limit of the chosen detection method.

[0003] Various methods for such specific amplification of nucleic acids are known in the prior art, for example the polymerase chain reaction (PCR). For details and background information on PCR, reference is made to the applicant's publication DE 10 2011 056 606 B3, the disclosure content of which is incorporated into the present application.

[0004] A microfluidic cartridge for the detection of bioparticles is known from the publication DE 10 2015 001 998 B3.

[0005] Publication WO 2016 / 077364 A2 concerns an instrument and a cartridge for carrying out tests in a closed sample preparation and reaction system.

[0006] Based on this, the invention aims to provide an analysis device for a disposable diagnostic article, comprising a sample container and a microfluidic cartridge connected to the sample container, with which an automatic analysis of a patient's swab sample contained in the sample container can be carried out quickly and without laboratory work.

[0007] In particular, an analyzer for a disposable diagnostic article is to be specified, the microfluidic cartridge of which contains a fluid reservoir with a sample receiving fluid, a fluid interface for connection to the sample container, a pumping device for bidirectional pumping of fluid between the fluid reservoir and the fluid interface, a reaction chamber for amplifying an analyte to be detected from the sample container, and a detection chamber for detecting the analyte by means of a biochip integrated in the cartridge.

[0008] This problem is solved by the features of the independent claims. Further developments of the invention are the subject of the dependent claims.

[0009] The invention provides an analyzer for receiving and processing a disposable diagnostic article, which comprises a sample container and a microfluidic cartridge connected to the sample container. The microfluidic cartridge contains a fluid reservoir with a sample receiving fluid, a fluid interface for connection to the sample container, a pumping device for bidirectional pumping of fluid between the fluid reservoir and the fluid interface, a reaction chamber for amplifying an analyte to be detected from the sample container, and a detection chamber for detecting the analyte by means of a biochip integrated in the cartridge. According to the invention, the analyzer comprises at least the following components: - an openable and closable receiving device for the disposable diagnostic article, which, when closed, fixes the cartridge in an analysis position, - a pump control device for actuating the cartridge's pumping mechanism in the analysis position, - a heating / cooling device for generating a cyclic temperature profile in the reaction chamber of the cartridge in the analysis position, and - a measuring / reading device for controlling and reading the biochip of the cartridge in the analysis position.

[0010] In an advantageous embodiment, the analyzer further includes a heating / sonification device for applying heat and / or ultrasound to a sample contained in the sample container, in particular for denaturation or inactivation of inhibitors, or for lysis of an analyte.

[0011] The sample container of the disposable diagnostic article is preferably a swab with a swab stick and a swab sleeve.

[0012] The measuring / readout unit advantageously includes a potentiostat for performing electrochemical measurements on contact pads of the biochip.

[0013] The pump control device advantageously includes a dowel pin that engages in a pin receptacle of the cartridge's pumping unit and controls the pumping steps of the pumping unit by means of a stepper motor.

[0014] In an advantageous embodiment, it is provided that a dead-end branch of the fluidic system of the cartridge contains the said detection chamber, the said reaction chamber and a dead-end pressure chamber, and that the pump control device is designed and configured to pump an analysis sample into the dead-end branch until the reaction chamber is completely filled and the dead-end pressure chamber is partially filled with liquid.

[0015] According to a preferred embodiment, the analyzer further includes an activation unit for activating an activatable closure for a fluidic system of the cartridge, in particular in the form of a movable plunger, with which a ball can be moved from a ball channel into a valve area for separating the fluid interface from the rest of the fluidic system of the cartridge.

[0016] In an advantageous embodiment, the receiving device comprises two pivotable jaws with which interacting devices of a module group are brought into contact with corresponding sub-areas of the cartridge when the receiving device is fired.

[0017] The module group advantageously includes one or more, in particular all, of the following facilities as interacting institutions: - two heating units of a heating / cooling device for contacting the reaction chamber of the cartridge, - a heating block for opening a fluidic transition between the fluid reservoir and the fluid interface by melting a fusible material, - a contact head for contacting the biochip of the cartridge, - a chip heating block for the biochip of the cartridge, and - a movable valve plunger for the activatable closure.

[0018] In an advantageous embodiment, the analyzer is designed as a table-top device with a horizontal base.

[0019] Advantages of the invention and further embodiments are explained below with reference to the figures, in the representation of which a scale and proportion-accurate reproduction has been omitted in order to increase clarity.

[0020] They show: Fig. 1. A perspective view of a point-of-care analyzer according to an embodiment of the invention. Fig. 2. A microfluidic disposable diagnostic article (disposable) in perspective view, Fig. 3 a schematic representation of a microfluidic disposable diagnostic article according to Fig. 2, Fig. 4. The process steps that are advantageously carried out in a sample analysis, Fig. 5 a schematic representation of the recording device of the analyzer, in (a) with the device cover open and in (b) with the device cover closed, Fig. 6. Schematically, the facilities of the module group that interact with the cartridge, Fig. 7 in (a) and (b) a schematic representation of the squeezing of the swab tube in the analysis position, where (a) shows the state with the instrument flap open and (b) the state with the instrument flap closed, Fig. 8 a schematic representation of the liquid transfer device for moving the reservoir liquid, and Fig. 9 A schematic representation of a Peltier heating block of the heating / cooling device of the analyzer.

[0021] Fig. Figure 1 shows a perspective view of a point-of-care analyzer 100 according to an embodiment of the invention. The analyzer 100 serves to receive and process a microfluidic disposable diagnostic article 10, in particular to detect biomolecules in a swab sample from a patient contained in the disposable diagnostic article 10.

[0022] The microfluidic single-use diagnostic article 10, also referred to in this description as "Disposable", is in Fig. 2 in perspective view and in Fig. 3 for the explanation of its main components and their function shown in a schematic representation.

[0023] The analyzer 100 automatically performs a series of process steps on the Disposable 10 in the manner described in more detail below and can quickly and without laboratory work perform multiparametric tests on the contained swab sample in order to determine the presence or absence of detectable biomolecules in the swab sample.

[0024] With regard to the Fig. 2 and Fig. 3 The Disposable 10 consists of a swab tube 12 and a microfluidic cartridge 20 attached to the swab tube. The swab tube 12 contains a swab sleeve 16 and a hollow swab stick 14, at the distal end of which a swab head 18 carries a cotton ball with the patient's swab sample 50 to be examined.

[0025] The microfluidic cartridge 20 attached to the swab tube 12 has a cartridge body 22 in which a fluid interface 30 for fluid connection with the hollow swab stick 14 and a fluidic system 24 for microbiological and molecular diagnostic examinations of the prepared swab sample of the swab tube 12 are formed.

[0026] More precisely, the fluidic system 24 of the cartridge 20 contains a main branch 26 for connection to the swab 14 and a dead-end branch 28 for sample analysis. The main branch 26 comprises a fluid reservoir 32 with a sample receiving fluid 52, a main fluid channel 34 connecting the fluid reservoir 32 to the fluid interface 30, and a pumping device 36 for bidirectional pumping of a fluid between the fluid reservoir 32 and the fluid interface 30 through the main fluid channel 34.

[0027] Between the fluid reservoir 32 and the fluid interface 30 there is an activatable closure 38 for closing the connection of the main fluid channel 34 to the fluid interface 30. Fig. Figure 3 shows the closure 38 in its open state. Furthermore, the fluid reservoir 32 is separated from the rest of the fluidic system 24 by a constriction, which is sealed with a fusible separating material 35 in the cartridge's delivery state.

[0028] The secondary branch 28 of the fluidic system 24 contains a secondary fluid channel 40, which branches off from the main fluid channel 34 at a junction 42 located between the activatable closure 38 and the fluid reservoir 32. It also includes a detection chamber 44, a reaction chamber 46, and a pressure chamber 48. The reaction chamber 46 serves to amplify an analyte contained in an analytical sample, for example, by (RT-)PCR. The amplified analyte is then detected in the detection chamber 44 using a biochip 54 inserted into the cartridge 20. The pressure chamber 48, located at the end of the secondary branch 28, is designed as a dead-end chamber with only a fluid inlet and no fluid outlet. During (RT-)PCR, it serves to generate back pressure to suppress unwanted gas bubble formation in the reaction chamber 46.

[0029] For automated sample analysis, the Analyzer 100 includes features for performing the tasks necessary to receive a swab sample in a Disposable 10, transfer the swab sample in a suitable form into the microfluidic cartridge, and perform an assay there to detect biomolecules. Specifically, the Analyzer 100 provides the following functionalities for this purpose: i) the Disposable 10 can be fixed in an analysis position in the analyzer 100 and ejected again; ii) in the area of ​​the fluid reservoir 32 a piston can be grasped and moved; iii) a transition area of ​​the fluidics between fluid reservoir 32 and closure 38 can be heated; iv) a valve of the closure 38 can be closed; v) the reaction chamber 44 can be cyclically heated and cooled; and vi) a biochip 54 can be heated, cooled, electrically contacted and the analytical material present on contact pads of the biochip can be measured using a potentiostat.

[0030] In addition, the analyzer 100 features control electronics, a user interface, software and external interfaces.

[0031] By performing these tasks, the analyzer 100 contains, in particular, the following units: - Devices for opening and closing the analyzer and for inserting, positioning and ejecting the disposables 10; - a potentiostat for performing electrochemical measurements with a contact head 176, which ensures electrical contact to the biochip 54 of the cartridge 20; - a heating / cooling device with a Peltier-controlled chip heating unit 174, which serves to adjust the temperature on the biochip 54; - a heating / cooling device with two Peltier-controlled heating units 140, which are pressed against the cartridge 20 from opposite sides and can generate rapid cyclic temperature changes in the reaction chamber 46 of the cartridge; - a heating / sonification device 120 with an ultrasonic probe 122 and a heating block 124, with which bacteria / viruses / microorganisms can be disrupted in the swab tube 12; - a syringe pump 130 for gripping and moving a piston inserted into the cartridge 20; - a heating block 170 for opening a sealed fluid passage; - a movable plunger 172 for closing a valve in the cartridge 20; - a 106-inch monitor with touchpad as the user interface; - a barcode scanner for identifying patient, user, test and other data and for entering assay parameters - a control electronics unit with integrated microprocessor, power supply and electronic interfaces; and - an integrated software that controls the process steps, evaluates the electrochemical data, and displays and saves the result.

[0032] In the embodiment, the analyzer 100 is operated by the user via a Graphic User Interface (GUI) which is displayed on the monitor 106 with integrated touchpad.

[0033] The procedural steps carried out in a sample analysis are now described with reference to Fig. Section 4 describes in more detail the structure and function of some of the aforementioned features of the analyzer 100. In a preferred procedure, the analyzer 100 performs the following steps: Step 300: Insert disposable Step 302: Position, fix and contact the disposable Step 304: Open fluidic transition Step 306: Pump liquid into swab Step 308: Heat the swab and treat with ultrasound Step 310: Withdraw the liquid Step 312: Close the valve Step 314: Pump liquid into PCR area, create overpressure. Step 316: Perform PCR, heat and cool cyclically. Step 318: Pump liquid into sensor area Step 320: Electrochemical detection with biochip, measuring signals. Step 322: Evaluation of the results. Step 324: Data presentation and storage Step 326: Eject cartridge

[0034] As preparation, a swab sample 50 is taken from a patient using a swab 12 before using the point-of-care analyzer 100. The microfluidic cartridge 20 is attached to the swab tube 12 to form the disposable microfluidic diagnostic article 10 to be examined.

[0035] In a first step 300, after reading user, patient, and test data as well as assay parameters, the analyzer 100 opens the initially closed device cover 102, allowing the user to insert the disposable 10 into the device. An opening in the front panel 101, adapted to the shape of the cartridge 20, prevents incorrect insertion of the disposable 10. Inside the device, the disposable is pre-positioned more precisely by another internal opening, which is finely adjustable laterally and vertically. A guide tube provides the disposable with further stability, and a position sensor indicates that a disposable has been inserted into the analyzer 100. A stop is provided at the lower end of the disposable 10 in the longitudinal direction; this stop can be designed as a plunger driven by a motor, allowing the disposable 10 to be pushed out of the analyzer 100 after the test is complete. Fig. Figure 1 shows the analyzer 100 in the form of a table-top device after inserting a disposable 10 with the flap 102 still open.

[0036] If the position sensor detects that a disposable 10 has been inserted into the analyzer 100, the user is prompted in step 302 to close the device cover 102. As shown in the schematic diagram of the Fig. As shown in Figure 5, the analyzer 100 contains a receiving device 110 for fixing the disposable 10, which, triggered by closing the flap 102, securely fixes the disposable 10 in an analysis position in the device and automatically brings various sub-areas of the cartridge 20 into contact with interacting devices of a module group 114.

[0037] The devices of module group 114, described in more detail below, are suspended on two pivoting jaws with guide rollers 112 and, with reference to the schematic representation of the Fig. 6 in particular heating units 140 of a heating / cooling device for contacting the reaction chamber 46, a heating block 170 for opening the fluidic transition 35, a contact head 176 for contacting the biochip 54 of the cartridge 20, a chip heating block 174, a movable valve plunger 172 for the activatable closure 38 and a piston gripper 132 for the syringe pump 130.

[0038] The device flap 102 is designed with a guide 103 located inside the device, which presses the pivoting jaws together when the flap 102 is closed, thereby bringing the devices of the module group 114 into contact with the corresponding sub-areas of the cartridge 20 at precisely predefined positions. Fig. Figure 5 shows in (a) the device flap 102 in the open state and in (b) the device flap 102 in the closed state, in which the cartridge 20 is fixed in the analysis position and is contacted via the two jaws by the devices of the module group 114.

[0039] As a special feature, the Disposable 10 is fixed in the analyzer 100 in an analysis position 104 that is inclined against the direction of gravity, which in Fig. 1 is shown schematically by the dashed line. In the table-top analyzer 100, the disposable 10 is thereby fixed in a position inclined to the horizontal base 105 of the analyzer.

[0040] The inclined position of the analyzer offers several advantages during the processing of the disposable 10. For example, the inclined position of the disposable 10 in the analyzer 100 allows only a small amount of liquid to be pumped into and withdrawn from the swab tube. The inclined position also facilitates the dissolution of the swab sample 50 with the heating / sonification device 120 and, finally, allows for an advantageous design of the reaction chamber 46 of the cartridge 20 with upper bulges for receiving wax that melts during processing and rises against gravity.

[0041] With reference to the schematic drawing of the Fig. 7 The receiving device 110 contains, in addition to the elements described above, an attachment 116 mounted on the device flap 102, which, when the device flap is closed, i.e., when transitioning from Fig. 7(a) to 7(b), the heating device 124 presses against the swab casing 16 and brings it into intimate contact. The mounted heating block 124 of the heating / sonification device 120, which has a resistance heater and a temperature sensor for temperature monitoring and control, is pressed downwards against the swab tube in a linear motion, possibly against spring support, when the lid is closed, as shown in Fig. 7(b) shown.

[0042] In the cartridge 20, the fluid reservoir 32 is separated from the rest of the fluidic system 24 by a constriction, which is initially sealed with the fusible separation material 35. In step 304, the separation material 35 melts, opening a fluidic transition from the fluid reservoir 32 to the fluidic system 24. The separation material 35, which is solid at room temperature, liquefies upon temperature increase and can be pumped out. Module 114 of the analyzer 100 contains a heating block 170, optionally spring-mounted, which presses against the transition area of ​​the cartridge 20 containing the separation material 35 after the device cover 102 is closed. Defined temperatures can be set on the heating block 170 via a power resistor and a temperature sensor and transferred locally to the cartridge.

[0043] After opening the fluidic interface, in step 306 the sample collection fluid 52 is pumped from the fluid reservoir 32 into the swab tube 12. With reference to Fig. The analyzer 100 contains a syringe pump 130, which can be used to move liquid in the disposable 10. For this purpose, a dowel pin 132, which is also referred to as a "piston gripper" in this description and is attached to a linear rail 131, is inserted into a circular opening 37 of the pumping device 36 of the cartridge 20.

[0044] The linear rail 131 is mounted in two linear slides 134 attached to the device and can be moved by a motor 135. A further dowel pin 136 on the linear rail, acting as a sensor trigger, can, together with a position switch 138, specify a defined position of the piston gripper 132 and is used to initialize the motor. In this way, a syringe piston of the pump unit 36 ​​of the cartridge 20 can be moved to any desired position within the fluid reservoir 32. At the same time, the travel distance is chosen to be so small that there is no risk of pulling the syringe piston out of the cartridge 20.

[0045] By actuating the syringe pump 130, the sample collection fluid 52 is pumped from the fluid reservoir 32 through the hollow shaft of the swab stick 14 into the swab tube 12. Due to the inclined position of the disposable 10 and the swab sheath 16 being pressed against the ultrasonic nozzle 122, a small amount of fluid is sufficient to collect the swab sample 50. The fluid can also be pumped back and forth several times to thoroughly mix the sample material of the swab sample 50 and the sample collection fluid 52. Since the fluid reservoir 32 in the cartridge 20 is usually partially filled with sample collection fluid 52 and partially with air, the sample collection fluid 52 can be completely pumped into the swab tube without any residual fluid remaining in the fluid system of the cartridge or in the shaft of the swab stick 14.

[0046] In step 308, the sample collection fluid 52 and the swab sample 50 in the swab 12 are heated with a heating block 124 of the heating / sonification device and / or set into high-frequency vibrations with the ultrasonic probe 122 of the heating / sonification device to facilitate lysis and release of DNA from the swab sample 50.

[0047] After lysis of the swab sample, the sample receiving fluid 52 contains the analyte to be detected from the swab sample 50 and is therefore subsequently referred to as the analytical sample. In step 310, the analytical sample containing the analyte is almost completely withdrawn into the cartridge 20 by means of the syringe pump 130. First, air is extracted from the swab 14 and the fluid passage area, and then the analytical sample is withdrawn into the liquid reservoir 32. By precisely adjusting the pumping steps, the fluid passage area can be filled with either liquid or air. In particular, the air-filled portion of the fluid reservoir 32 can be precisely controlled.

[0048] In step 312, the activatable closure 38 is closed to seal the fluid connection between the fluid interface 30 with the connected swab tube 12 and the fluidic system 24 of the cartridge 20. For this purpose, a plunger 172 of module group 114, driven by a stepper motor, pushes a pre-inserted rubber ball into the valve area of ​​the cartridge 20 and seals the outlet of the main fluid channel 34 to the swab tube 12, so that only the secondary branch 28 remains in contact with the fluid reservoir 32. To increase the pressure tightness of the cartridge 20, the plunger can remain in the extended position during the remainder of the assay and prevent the rubber ball from shifting.

[0049] In step 314, a portion of the analysis sample is pumped from the fluid reservoir 32 into the dead-end branch 28 of the fluidic system 24 using the syringe pump 130, until the reaction chamber 46 is completely filled and the pressure chamber 48 is partially filled with liquid. This creates an overpressure in the pressure chamber 48, the exact magnitude of which depends on the size of the air bubble in the fluid reservoir 32. Optionally, step 314 also checks whether the sensor area of ​​the biochip 54 in the detection chamber 44 is completely wetted or whether air bubbles are still present. An electrochemical measurement can be performed using the potentiostat for this purpose. If individual electrodes of the biochip 54 do not provide a signal response, the air bubble can be displaced by further movement of the syringe pump 130 until the sensor area is completely wetted.

[0050] To perform an (RT-)PCR, the reaction chamber 46 is then cyclically heated and cooled in step 316 using the pressed-on heating blocks 140 of module group 114. With reference to Fig. Each of the heating blocks 140 contains a Peltier element 142 and a low-mass metal heating plate 146 with an integrated temperature sensor 148, which is bonded to the cold side with a thermally conductive adhesive 144. Due to the low heat capacity, very rapid temperature changes can be generated. The temperature sensor 148 can be, for example, a Pt100, Pt1000, NTC, K, or J sensor, or another type of sensor element.

[0051] A heat sink 150 is attached to the hot side of the Peltier element 142 using thermally conductive adhesive 144. The heat sink is positioned in an air duct 152 and is sufficiently dissipated by an airflow generated by a fan 154. A temperature sensor 156 attached to the heat sink 150 monitors whether the supplied energy is within a desired range. If not, the fan speed can be increased or the Peltier element power reduced.

[0052] The heating block unit 140 is suspended by a spring 158 in a cage 160, which is firmly connected to the jaws of the analyzer 100. When the device flap 102 is closed as described above, the heating plates 146 are pressed firmly onto the PCR area of ​​the inserted cartridge 20, in particular the reaction chamber 46, thereby ensuring high heat transfer.

[0053] In an optional configuration, a cable fixing 162 ensures that the unit is stable over the long term and that no cable breaks occur. This cable fixing can be achieved by clamping, potting, or other means. The cables 164 can lead to a spring-loaded adapter board 166 attached to the heating block unit 140 or be connected directly to the main board.

[0054] The module group 114 also contains another such Peltier heating block unit as chip heater 174, which, after closing the device flap 102, contacts the area of ​​the biochip 54 on one side opposite the potentiostat and can set defined temperatures there.

[0055] To perform a (RT-)PCR, the heating blocks 140 of the heating / cooling unit are first used to heat chemical reservoirs in the cartridge 20 to release the chemicals required for the PCR. Subsequently, the heating blocks 140 are used to cyclically generate a temperature in the reaction chamber 46 between a high denaturation temperature (approx. 90-98°C) and a medium primer hybridization temperature (approx. 50-70°C). A PID controller ensures that both the block temperatures and the temperatures in the cartridge 20 reach their set point within a few seconds, allowing a cycle to be completed in a very short time (less than 30 s). It is also possible to integrate a third temperature into the cycles, for example, an elongation temperature in the range of 65-78°C, if the assay requires it.

[0056] The overpressure generated by the dead-end pressure chamber 48 prevents air or vapor bubbles from forming in the reaction chamber 46 during the denaturation cycles and forcing this liquid out of the PCR area.

[0057] The analyzer 100 can optionally be calibrated, for example, with a sample cartridge with an integrated temperature sensor, and the temperature transfer to cartridge 20 can be determined. For this purpose, a sensor can, for example, be embedded in the sample cartridge with adhesive or be freely suspended in an air chamber or a liquid-filled chamber.

[0058] Optionally, before measuring the amplicon on the biochip 54 after PCR, an initial electrochemical measurement is performed on the biochip 54 to determine data on the chip's initial state. If air bubbles are found to be present, the liquid level can be adjusted using the syringe pump 130.

[0059] After amplification, in step 318 a portion of the amplified analysis sample is drawn over the sensor area of ​​the biochip 54 using the syringe pump 130, and in step 320 the presence of analytes is determined by electrochemical measurements.

[0060] The potentiostat used for electrochemical measurements contains circuit boards with the electronic components required for electrochemical measurements, a contact unit, and a housing. A potentiostat locating pin protrudes from a contact head 176 of the potentiostat, its position corresponding to a positioning bore on the cartridge 20. When a disposable 10 containing a cartridge 20 is inserted into the analyzer 100, the potentiostat locating pin engages the corresponding positioning bore of the cartridge and guides the potentiostat, with its spring-loaded pin connections, into a position precisely above the contact pads of the biochip. When the device cover 102 of the analyzer 100 is closed, the potentiostat is then pressed against the biochip in such a way that reliable electrical contact with the biochip 54 is ensured.

[0061] The biochip 54 contains a series of contact pads located in a dry area of ​​the chip. These contact pads are connected via insulated conductor tracks to a microelectrode array consisting of, for example, 10 working electrodes, one counter electrode, and one reference electrode, which are located in the liquid-fillable detection chamber 44 of the cartridge.

[0062] In this exemplary embodiment, the potentiostat is designed as a 10-channel potentiostat for 10 working electrodes, one counter electrode, and one reference electrode. During an electrochemical measurement, a ramp of potential steps is generated by changing the potential between the working and reference electrodes and measuring the resulting current between the counter and working electrodes at frequencies of 1–25 kHz. Each electrode can be individually switched on or off using semiconductor relays. Operational amplifiers convert the measured current into a voltage and transmit it to a potentiostat adapter board, where analog-to-digital conversion and data processing take place on an FPGA.

[0063] In step 322, the results of the electrochemical measurement are evaluated and it is determined whether a detectable analyte is present in the analysis sample.

[0064] In step 324, the data is presented and stored. After the assay is complete, the result determined in step 322 is displayed on the screen. Additionally, the result, along with all relevant data and parameters, is stored in the analyzer 100. Several options are available for accessing the stored results via USB and TCP / IP interfaces 108. For example, a printer can be connected to the analyzer 100 to print the result, the data can be exported to an external USB flash drive, or the analyzer 100 can be integrated into a hospital information system via the TCP / IP interface.

[0065] Finally, in step 328, after the result is acknowledged on the touchscreen 106, the disposable 10 is ejected and the user is prompted to dispose of it. After the position sensor detects that the disposable has been removed, the analyzer 100 prompts the user to close the device cover 102. Once the cover is closed, the analyzer 100 returns to its initial state and a start screen is displayed on the monitor 106. The analyzer 100 is now ready to perform the next test.

Claims

[1] An analysis device for receiving and processing a disposable diagnostic article comprising a sample container and a microfluidic cartridge connected to the sample container, the microfluidic cartridge comprising a fluid reservoir with a sample receiving liquid, a fluid interface for connection to the sample container, a pumping device for bidirectionally pumping fluid between the fluid reservoir and the fluid interface, a reaction chamber for amplifying an analyte to be detected from the sample container, and a detection chamber for detecting the analyte by means of a biochip integrated in the cartridge, the analysis device comprising: - an openable and closable holding device for the disposable diagnostic article, which, when closed, fixes the cartridge in an analysis position, - a pump control device for actuating the pump device of the cartridge in the analysis position, - a heating / cooling device for generating a cyclic temperature profile in the reaction chamber of the cartridge in the analysis position, and - a measuring / reading device for controlling and reading the biochip of the cartridge in the analysis position. [2] Analysis device according to claim 1, with a heating / sonication device for applying heat and / or ultrasound to a sample contained in the sample container, in particular for denaturing or inactivating inhibitors, or for lysing an analyte. [3] Analysis device according to claim 1 or 2, characterized by that the sample container of the disposable diagnostic device is a swab with a swab stick and a swab cover. [4] Analysis device according to at least one of claims 1 to 3, characterized by that the measuring / readout unit comprises a potentiostat for carrying out electrochemical measurements on contact pads of the biochip. [5] Analysis device according to at least one of claims 1 to 4, characterized by that the pump control device comprises a dowel pin which engages in a pin receptacle of the pump device of the cartridge and controls the pumping steps of the pump device by means of a stepper motor. [6] Analysis device according to at least one of claims 1 to 5, characterized by that a secondary branch of the fluidic system of the cartridge, designed as a dead-end, contains said detection chamber, said reaction chamber and a dead-end pressure chamber, and that the pump control device is designed and arranged to pump an analysis sample into the secondary branch until the reaction chamber is completely filled and the dead-end pressure chamber is partially filled with liquid. [7] Analysis device according to at least one of claims 1 to 6, with an activation unit for activating an activatable closure for the fluidic system of the cartridge, in particular in the form of a movable plunger, with which a bead can be displaced from a ball passage into a valve area for separating the fluid interface from the remaining fluidic system of the cartridge. [8] Analysis device according to at least one of claims 1 to 7, characterized by that the receiving device comprises two pivoting jaws with which interacting devices of a module group are brought into contact with corresponding parts of the cartridge when the receiving device is fired. [9] Analysis device according to claim 8, characterized by that the module group comprises one or more, in particular all, of the following facilities as interacting facilities: - two heating units of a heating / cooling device for contacting the reaction chamber of the cartridge, - a heating block for opening a fluidic transition between the fluid reservoir and the fluid interface by melting a fusible material, - a contact head for contacting the biochip of the cartridge, - a chip heating block for the cartridge's biochip, and - a movable valve tappet for the activatable closure. [10] Analysis device according to at least one of claims 1 to 9, characterized by that the analyzer is designed as a table-top device with a horizontal base.

Images