Automatic calibration loop for bio-FET

Abstract

The invention relates to a biosensor field effect transistor (bio-FET) and a biosensor device. The present disclosure proposes a biosensor device that includes one or more bio-FETs and one or more readout circuits, where each readout circuit is connected to a source node of one bio-FET. Each readout circuit is configured to generate a readout signal based on a bias current of the bio-FET. In addition, each readout circuit is configured to calibrate the bio-FET to which it is connected. To this end, each readout line is configured to generate a calibration signal based on a current difference between a bias current and a reference current of the bio-FET, and to control a bias of a source node of the bio-FET in accordance with the calibration signal.

Description

Technical Field

[0001] The present disclosure relates to biosensor devices, particularly biosensor devices based on biosensor field effect transistors (bio-FETs). The present disclosure presents a biosensor device that includes a bio-FET and a readout circuit that is connected to the bio-FET and configured to read the bio-FET and automatically calibrate the bio-FET. Background Art

[0002] FET-based biosensor devices are becoming increasingly popular because their readout interfaces are easy to integrate with CMOS technology. Biosensor devices can be used in a wide range of applications, including electrochemical sensing, DNA sequencing, protein detection, etc. Biosensor devices include one or more bio-FETs, such as nanopore FETs.

[0003] For some applications, such as DNA or protein detection using nanopore FETs, the signals are very fast (about 100 ns per base). Therefore, the readout circuit of the nanopore FET also needs to be very fast (e.g., it should have a bandwidth of 10 MHz or higher) in order to be able to correctly capture the sensing signal. In addition, due to non-ideality in the manufacturing process and the influence of external factors, bio-FETs may suffer from problems such as offset and drift of the bias current. Usually, several compensation techniques, such as calibration methods, are used to solve these problems.

[0004] However, some traditional compensation techniques are only applicable to cases where the signal bandwidth is very low, such as can be used for ion-sensitive field effect transistor (ISFET)-based biosensor devices. These compensation techniques cannot be applied to bio-FETs with higher bandwidth requirements. Some other traditional compensation techniques require access to the gate of the FET, which is impossible for many bio-FETs, such as for nanopore FETs because they are liquid-gated.

[0005] Traditional readout circuits for bio-FETs can typically achieve a bandwidth of up to 1 MHz. Therefore, they are not suitable for faster applications such as DNA or protein analysis where the bandwidth requirement is higher than 1 MHz. In addition, traditional broadband readout circuits cannot be fully integrated into integrated circuits (ICs) and thus cannot be used for biosensor devices with large arrays including bio-FETs. Summary of the Invention

[0006] In view of the above, the present disclosure aims to improve compensation techniques. The objective is to provide a circuit and method that can be used to calibrate a bio-FET. Specifically, the objective is to provide a readout circuit for a bio-FET that is configured to automatically calibrate the bio-FET. Thus, the goal is to address the non-idealities of the bio-FET, such as compensating for the offset or drift of the bias current of the bio-FET. This should even be possible for applications with bandwidth requirements of, for example, 1 MHz or higher. Another objective is that the readout circuit can be used for large arrays comprising multiple bio-FETs.

[0007] These and other objectives are achieved by the solution of the present disclosure provided in the independent claims. Advantageous embodiments are described in the dependent claims.

[0008] A first aspect of the present disclosure provides a biosensor device comprising one or more bio-FETs; and one or more readout circuits, wherein each readout circuit is connected to the source node of one of the bio-FETs among the respective bio-FETs and is configured to: generate a readout signal based on the bias current of the bio-FET; generate a calibration signal based on the current difference between the bias current of the bio-FET and a reference current; and control the bias of the source node of the bio-FET according to the calibration signal.

[0009] By showing the readout signal, the readout circuit is configured to read out the signal generated by the bio-FET during a sensing operation. By generating the calibration signal and by controlling the bias of the source node according to the calibration signal, the readout circuit is configured to calibrate the bio-FET. Specifically, the control of the bias of the source node can be accomplished by providing a control signal to the source node. In this way, the readout circuit can compensate for the offset and / or drift of the bias current of the bio-FET. Thus, the readout circuit can be used to read out and automatically calibrate the bio-FET. The readout circuit of the first aspect is compatible with signal bandwidth requirements of 1 MHz or higher and can be fully integrated into an IC.

[0010] In the implementation of the biosensor device, the readout signal is generated based on the high-frequency variation of the bias current of the bio-FET; and the calibration signal is generated based on the low-frequency variation and / or drift of the bias current of the bio-FET.

[0011] Thus, faster (higher frequency) signal variations generated when the bio-FET is sensing can be correctly reflected in the readout signal. At the same time, a calibration signal can be used to compensate for slower (lower frequency) variations and / or slow drifts of the bias current of the bio-FET. The frequency value of the faster signal variations can be adjusted according to the cut-off frequency set by the optional filter circuit described below and can vary, for example, in the range of 1 - 1000 Hz (e.g., for DNA / protein sequencing) or within the range of 1 - 10000 Hz. That is, any signal faster than the cut-off frequency of the filter circuit can be transmitted to the output. Similarly, any signal slower than the cut-off frequency of the filter circuit can not be transmitted to the output, but the calibration signal can be determined.

[0012] In an implementation of the biosensor device, the readout circuit includes a current comparator circuit configured to generate a calibration signal based on the bias current of the bio-FET and a reference current.

[0013] The reference current can be provided to the readout circuit or can be generated by the readout circuit. Calibration of the bio-FET based on the difference between these two currents is fast and can be adjusted automatically.

[0014] In an implementation of the biosensor device, the readout circuit includes a filter circuit; the filter circuit is configured to act as a low-pass filter in the calibration signal path of the readout circuit to prevent high-frequency variations of the bias current of the bio-FET from being used to generate the calibration signal; and the filter circuit is configured to act as a high-pass filter in the readout signal path of the readout circuit to prevent low-frequency variations and / or drifts of the bias current of the bio-FET from being used to generate the readout signal.

[0015] Thus, the filter circuit is arranged as a low-pass filter in the calibration signal path (also known as the feedback path). The filter circuit can be part of the current comparator circuit. The filter circuit acts as a high-pass filter that suppresses the offset and / or drift (lower frequency) of the bias current in the readout signal path to the output of the readout circuit. In addition, the readout circuit can naturally act like a low-pass filter (in the readout signal path to the output). Thus, the combined effect can be the effect of a band-pass filter that only allows signals within a specific frequency range to pass to the output.

[0016] In the implementation of a biosensor device, a current comparator circuit includes a first amplifier and a pair of transistors connected in series, wherein the midpoint of the pair of transistors connected in series is connected to the inverting input of the first amplifier; a reference voltage is connected to the non-inverting input of the first amplifier; the pair of transistors is configured to provide the current difference between the bias current of the bio-FET and the reference current as a voltage difference compared to the reference voltage to the inverting input of the first amplifier; and the first amplifier is configured to provide a calibration signal at its output.

[0017] The pair of transistors connected in series can be an inverter.

[0018] In one implementation, the biosensor device further includes a capacitor connected to the inverting input and the output of the first amplifier; a pseudo-resistor connected between the midpoint of the pair of transistors connected in series and the inverting input of the first amplifier; wherein the capacitor, the pseudo-resistor, and the first amplifier form a filter circuit.

[0019] Therefore, the filter circuit can be integrated with the current comparator circuit. Generally, as described above, the readout circuit provides a filtering function and a current comparator function. These two functions can be integrated into a single physical circuit system, namely the current comparator circuit. However, it is possible to separate these two functions into two separate circuits.

[0020] In the implementation of a biosensor device, the readout circuit includes a first current mirror circuit, the first current mirror circuit includes a first transistor and a second transistor and is configured to mirror a reference current from the first transistor to the second transistor; the readout circuit includes a second current mirror circuit, the second current mirror circuit includes a third transistor and a fourth transistor and is configured to mirror the bias current of the bio-FET from the third transistor to the fourth transistor; and the pair of transistors connected in series is formed by the second transistor and the fourth transistor.

[0021] In the implementation of a biosensor device, the readout circuit further includes an output transistor; the third transistor and the fourth transistor are connected to the output transistor; and the output transistor is configured to generate a readout signal based on the bias current of the bio-FET.

[0022] The output transistor is connected to both the third transistor and the fourth transistor, which means it receives the mirrored current from the third transistor and the fourth transistor, and the fourth transistor receives the current mirror from the third transistor.

[0023] In the implementation of a biosensor device, the readout circuit further includes a control circuit configured to control the bias of the source node of the bio-FET according to the calibration signal provided by the current comparator circuit.

[0024] The control circuit can output a control signal generated based on a calibration signal. The control signal can be provided to the source node of the bio-FET to calibrate the bio-FET. It is noted that the calibration signal may be the same as the control signal. The control of the source node bias can change the bias current in the bio-FET and thereby can compensate for the offset and / or drift of the bias current.

[0025] In the implementation of the biosensor device, the control circuit includes a second amplifier; the output terminal of the first amplifier is connected to the non-inverting input terminal of the second amplifier; and the source node of the bio-FET is connected to the inverting input terminal of the second amplifier.

[0026] In the implementation of the biosensor device, the readout circuit further includes an input transistor; the input transistor is connected between the source node of the bio-FET and the third transistor of the second current mirror circuit; and the gate of the input transistor is connected to the output terminal of the second amplifier.

[0027] In the implementation of the biosensor device, each of the one or more bio-FETs includes a liquid gate.

[0028] In the implementation of the biosensor device, the one or more bio-FETs include one or more nanopore FETs.

[0029] In the implementation of the biosensor device, the biosensor device includes a bio-FET array and a readout circuit array connected to the bio-FET array.

[0030] Since the readout circuit can be fabricated using CMOS technology and integrated into an IC, it is also compatible with biosensor devices having a large number of bio-FETs.

[0031] In the implementation of the biosensor device, the readout circuit array includes one or more groups of readout circuits; and each group of readout circuits is connected to one or more multiplexers.

[0032] A second aspect of the present disclosure provides a method for calibrating a biosensor device, the biosensor device including one or more bio-FETs and one or more readout circuits, wherein each readout circuit is connected to the source node of one of the bio-FETs, and the method includes: generating a readout signal based on the bias current of the bio-FET using the readout circuit; generating a calibration signal based on the current difference between the bias current of the bio-FET and a reference current; and controlling the bias of the source node of the bio-FET according to the calibration signal.

[0033] The method of the second aspect is a calibration method for a bio-FET. The method of the second aspect achieves the same advantages as those of the biosensor device of the first aspect, and can be extended by corresponding implementations corresponding to the above-mentioned implementation of the biosensor device of the first aspect. Specifically, any feature of the first aspect can be correspondingly implemented in the second aspect.

[0034] Summarizing the above aspects and implementations, the present disclosure proposes a readout circuit having a current conveyor architecture with an automatic calibration signal path. In the calibration signal path, the readout circuit senses the error in the bias current of the bio-FET (relative to a reference current) and controls the source node of the bio-FET to bias it with a desired current amplitude, for example.

[0035] The readout circuit is designed such that slow-moving and DC artifacts (such as offsets and drifts) are attenuated, while fast-moving signals of interest are passed to the output. The calibration signal path includes a low-pass filter, which acts as a high-pass filter in the readout signal path. The calibration signal path can be specifically configured according to the desired passband corner frequency. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] The above aspects and implementations are further explained in the following detailed description with reference to the accompanying drawings below:

[0037] Figure 1 A biosensor device according to an embodiment of the present disclosure is shown.

[0038] Figure 2 An exemplary biosensor device according to an embodiment of the present disclosure is shown.

[0039] Figure 3 Compensation for offsets and drifts in the readout signal of a bio-FET in a biosensor device according to an embodiment of the present disclosure is shown.

[0040] Figure 4 Examples of (a) a first amplifier, (b) a second amplifier, and (c) a pseudo-resistor of a biosensor device according to an embodiment of the present disclosure are shown.

[0041] Figure 5 A biosensor device according to an embodiment of the present disclosure having a bio-FET array and a readout circuit array is shown.

[0042] Figure 6 A calibration method for calibrating a bio-FET of a biosensor device according to an embodiment of the present disclosure is shown. DETAILED DESCRIPTION

[0043] Figure 1FIG. 0 shows a biosensor device 10 according to an embodiment of the present disclosure. The biosensor device 10 is a FET-based biosensor device that includes a readout circuit system compatible with CMOS technology and can be integrated into an IC. The biosensor device 10 can be used for electrochemical sensing, DNA sequencing, protein detection, or similar applications.

[0044] The biosensor device 10 includes at least one bio-FET 11 and at least one readout circuit 15 ( Figure 1 one of each of them is shown in FIG. 5), where the readout circuit 15 is connected to the source node 13 of the bio-FET 11. The bio-FET 11 can be a liquid-gated bio-FET, i.e., it can include a liquid gate. For example, the bio-FET 11 can be a nanopore FET.

[0045] The bio-FET 11 includes a drain node 12 and a source node 13, and can have a channel disposed between the drain node 12 and the source node 13. In the case of a liquid gate, the surface above the channel can be exposed to the liquid. The bio-FET 11 can be gated by a change in the surface potential of the channel surface, where such a change can be caused by, for example, charged molecules in the liquid gate. These charged molecules can bind to the sensor surface. The charged molecules can affect the charge distribution of the semiconductor material below the channel surface (which can be a dielectric surface) and can cause a change in the bias current flowing between the drain node 12 and the source node 13 of the bio-FET 11.

[0046] The nanopore FET can be a nanopore sensor that includes a FET (e.g., a bio-FET). A nanopore sensor is a device that can have a sensing region within the nanopore or at another location in the device. The nanopore can be disposed outside the channel of the FET. In one embodiment, the FET is embedded in the nanopore. In another embodiment, the sensor is a sensing layer (which can be a conductive layer that at least surrounds and / or wraps the nanopore) and is electrically coupled to the FET. The nanopore is nanoscale, i.e., the cross-sectional diameter is less than 1 μm. For a circular cross-section of the nanopore, its diameter can be less than 1000 nm.

[0047] Thus, the nanopore FET can combine a nanopore with a bio-FET, where the nanopore can be a nanoribbon, a nanotube, or a nanowire. The nanopore can also be embedded within the channel of the bio-FET. The nanopore FET can be used to sense single molecules with a bio-FET, where a single molecule translocates through the nanopore. The nanopore FET is particularly suitable for DNA sequencing or other applications with MHz bandwidth. The advantages of the nanopore FET over biological nanopores are its mechanical robustness, higher throughput, and higher signal-to-noise ratio.

[0048] The readout circuit 15 is configured to read out the signal generated by the bio-FET 11 during the sensing operation (e.g., as described above, the bio-FET 11 generates a switching of the bias current due to the presence of charged molecules), and is also configured to calibrate the bio-FET 11, as will be explained below. The biosensor device 10 may also include, for example, a plurality of bio-FETs 11 and a plurality of readout circuits 15 arranged in a sensing array. In this case, each readout circuit 15 is configured as Figure 1 shown and is connected to the source node 13 of one of the bio-FETs.

[0049] The readout circuit 15, or each readout circuit 15 in the case of a plurality of readout circuits 15, is configured to generate a readout signal 16 based on the bias current 14 of the bio-FET 11 to which it is connected. In this way, the readout circuit 15 can read out the signal generated according to the sensing of the bio-FET 11. Specifically, the readout signal 16 may be generated based on the high-frequency variation of the bias current 14 of the bio-FET 11, which may be caused by the bio-FET 11 sensing charged molecules on its sensor surface.

[0050] In addition, the readout circuit 15 is configured to generate a calibration signal and control the bias of the source node 13 of the bio-FET 11 according to the calibration signal, for example, by providing a control signal 17 depending on the calibration signal to the source node 12. In this way, the readout circuit 15 can calibrate the bio-FET 11. The readout circuit 15 is configured to generate a calibration signal based on the current difference between the detected bias current 14 of the bio-FET 11 and a reference current. The reference current may be provided to the readout circuit 15 externally, or may be generated by the readout circuit 15. Specifically, the calibration signal may be generated based on the low-frequency variation of the bias current 14 and / or based on the drift of the bias current 14 of the bio-FET 11.

[0051] Figure 2 shows a specific biosensor device 10 constructed according to an embodiment of the present disclosure on Figure 1 the embodiment shown. Figure 1 and Figure 2 The same elements in Figure 2 share the same reference numerals and may be implemented identically. Specifically, Figure 2 shows an exemplary implementation of the readout circuit 15 connected to the bio-FET 11. As described above, the biosensor device 10 may include a plurality of such readout circuits 15, each of which is connected to one of the plurality of bio-FETs 11.

[0052] Figure 2The exemplary readout circuit 15 shown in [Figure 0] includes various sub - circuits. Specifically, the readout circuit 15 includes a current comparator circuit 23a configured to generate a calibration signal 21 based on the bias current 14 of the bio - FET 11 and a reference current 22. In addition, the biosensor device 10 includes a control circuit 23b configured to control the bias of the source node 13 of the bio - FET 11 according to the calibration signal 21 provided by the current comparator circuit 23a. The readout circuit 15 further includes a first current mirror circuit formed by a first transistor 27a and a second transistor 27b and configured to mirror the reference current 22 from the first transistor 27a to the second transistor 27b. The readout circuit 15 also includes a second current mirror circuit formed by a third transistor 27c and a fourth transistor 27d and configured to mirror the bias current 14 of the bio - FET 11 from the third transistor 27c to the fourth transistor 27d.

[0053] Figure 2 An exemplary implementation of the above - mentioned sub - circuits is shown, which will be explained below. It should be noted that the electrical components of the readout circuit 15 can belong to more than one sub - circuit.

[0054] The exemplary current comparator circuit 23a includes a first amplifier 26 and a transistor pair connected in series formed by a second transistor 27b and a fourth transistor 27d. The mid - point of the series - connected transistor pair, i.e., the mid - point between the second transistor 27b and the fourth transistor 27d, is connected to the inverting input of the first amplifier 26. A reference voltage (Vref) is connected to the non - inverting input of the first amplifier 26. The series - connected transistor pair is configured to generate a current difference between the bias current 14 and the reference current 22 and provide the generated current difference as a voltage difference between the voltage at the mid - point of the series - connected transistor pair and the reference voltage to the first amplifier 26. Based on these inputs to the inverting input and the non - inverting input, the first amplifier 26 is configured to provide the calibration signal 21 at its output, specifically to provide it to the control circuit 23b.

[0055] It should be noted that, as Figure 2 shown, a pseudo - resistor 24 is connected between the mid - point of the series - connected transistor pair and the inverting input of the first amplifier 26; however, the pseudo - resistor 24 does not function in the current comparison but functionally serves to provide a filter circuit.

[0056] Specifically, the current comparator circuit 23a further includes a capacitor 25, which is connected to the inverting input terminal and the output terminal of the first amplifier 26, respectively. The capacitor 25, together with the pseudo resistor 25 and the first amplifier 26, forms a filter circuit. This filter circuit is designed to act as a low-pass filter in the calibration signal path of the readout circuit 15. In this way, the filter circuit can prevent high-frequency variations of the bias current 14 of the bio-FET 11 from being used to generate the calibration signal 21. The pseudo resistor can be designed to achieve the desired pole frequency and passband corner frequency.

[0057] As described above, the readout circuit 15 provides a filtering function and a current comparator function. In Figure 2 the illustrated embodiment, these two functions are integrated into the current comparator circuit 23a. However, it is possible to separate these two functions into two separate circuits.

[0058] Figure 4 Exemplary implementations of the first amplifier 26 and the pseudo resistor are shown in (a) and (c), respectively.

[0059] The exemplary control circuit 23b includes a second amplifier 29. The output terminal of the first amplifier 26 is connected to the non-inverting input terminal of the second amplifier 29. The source node 13 of the bio-FET 11 is connected to the inverting input terminal of the second amplifier 29. The control circuit 23b further includes an input transistor 28a connected between the source node 13 and the third transistor 27c. The gate of the input transistor 28a is connected to the output terminal of the second amplifier 29.

[0060] Figure 4 An exemplary implementation of the second amplifier 29 is shown in (b).

[0061] The readout circuit 15 further includes an output transistor 28b, which is connected to the third transistor 27c and the fourth transistor 27d. The output transistor 28b is configured to generate a readout signal 16. The filter circuit in the current comparator circuit 23b is also designed to act as a high-pass filter in the readout signal path of the readout circuit 15. In this way, the filter circuit can prevent low-frequency variations of the bias current 14 of the bio-FET 11 and / or drifts of the bias current 14 from being used to generate the readout signal 16.

[0062] Figure 2Exemplary readout circuit 15 combines a current conveyor (readout signal path, via a second current mirror circuit and output transistor 28b and control circuit 23b) with a feedback calibration loop (calibration signal path, via current comparator circuit 23a and control circuit 23b; note that control circuit 23b can be part of both the readout signal path and the calibration signal path). This allows high-frequency signals to be replicated by the second current mirror circuit while blocking DC offsets and low-frequency drifts. Additionally, slow variations in the bias current 14 of bio-FET 11 can be compensated for, particularly by biasing the source node 13 of bio-FET 11 according to calibration signal 21.

[0063] Figure 3 This compensation for offset and drift in the bias current of bio-FET 11 is shown. Figure 3 (a) shows the gate voltage of bio-FET 11, particularly showing the gate voltage V G ’, due to the sensing of the bio-FET, the gate voltage V G ’ drifts slowly and exhibits higher-frequency variations. The drift is reflected in the bias current. The gate voltage without drift would be as V G shown. V G ’s drift can be compensated for by biasing the source node 13 of bio-FET 11, i.e., by adjusting the source voltage V S at source node 12, as shown in Figure 3 (b). In the readout signal 16 of readout circuit 15, in this case, in Figure 3 the output current I shown in (d) out , the drift is suppressed. Figure 3 (c) shows the voltage at the midpoint of the series-connected pair of transistors. When the bias current in bio-FET 11 is the same as the reference current 22, this voltage remains at the reference voltage (connected to the non-inverting input of the first amplifier 26). Due to variations in the bias current of bio-FET 11, compared to the reference voltage, the voltage at the midpoint may deviate because of a loss of balance. In this case, calibration signal 21 is generated at this time and can be used to restore balance.

[0064] Figure 5FIG. 0 shows a biosensor device 10, which includes a plurality of bio-FETs 11 and a plurality of readout circuits 15, as described above. The bio-FETs 11 may be arranged in an array of bio-FETs 11, while the readout circuits 15 may be arranged in an array of readout circuits 15. The array of readout circuits 15 is connected to the array of bio-FETs 11. For example, the array of bio-FETs 11 may include sixteen nanopore FETs. A plurality of the readout circuits 15 of the array grouped together may be connected to at least one multiplexer 51. In this way, the corresponding bio-FETs 11 can be read out in a multiplexed manner, and the biosensor device 10 can be designed more compactly. Each of the readout circuits 15 may perform automatic calibration of its connected bio-FET 11, particularly handling offsets and drifts in the corresponding bias currents. Using the exemplary biosensor device 10, a bandwidth of 10 MHz or higher can be achieved.

[0065] Figure 6 FIG. 4 shows a flowchart of a calibration method 60 according to an embodiment of the present disclosure. The calibration method 60 can be used to calibrate the bio-FET 11, which is connected to the readout circuit 15 through its source node 13, as Figure 1 shown. The calibration method 60 can also be used to calibrate a plurality of bio-FETs 11 by using a plurality of readout circuits 15, for example, as Figure 5 shown in the biosensor device 10.

[0066] According to Figure 6 the flowchart, method 60 includes step 61 of generating a readout signal 16 based on the bias current 14 of the bio-FET 11. As described above, the readout signal 16 is generated by the readout circuit 15. Method 60 also includes step 62 of generating a calibration signal 21 based on the current difference between the bias current 14 of the bio-FET 11 and a reference current 22, and step 63 of controlling the bias of the source node 13 of the bio-FET 11 according to the calibration signal 21.

[0067] This automatic calibration method 60 does not require any digital-to-analog converter (DAC), and does not require a separate calibration step before starting to record the readout signal from the bio-FET 11. The readout circuit can be operated to provide the readout signal 16 and simultaneously perform calibration of the bio-FET 11. This reduces the design overhead required for large bio-FET arrays.

[0068] Possible applications of the biosensor device 10 according to the embodiments of the present disclosure are DNA / protein detection and sequencing using nanopore FETs as bio-FETs 11, or applications that require a large signal bandwidth.

[0069] In the claims as well as in the description of the present disclosure, the word "comprising" does not exclude other elements or steps, and the indefinite article "a" or "an" does not exclude a plurality. A single element may perform the functions of several entities or items recited in the claims. The mere fact that certain measures are stated in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage.

Claims

1. A biosensor device (10) comprising: one or more biosensor field effect transistors bio-FETs (11); and one or more readout circuits (15), wherein each readout circuit (13) is connected to the source node (13) of one of the bio-FETs (11) and is configured to generate a readout signal (16) based on the bias current (14) of the one bio-FET (11); generate a calibration signal (21) based on the current difference between the bias current (14) of the one bio-FET (11) and a reference current (22); and control (17) the bias of the source node (13) of the one bio-FET (11) according to the calibration signal.

2. The biosensor device (10) according to claim 1, characterized in that: the readout signal (16) is generated based on the high-frequency variation of the bias current (14) of the one bio-FET; and the calibration signal (21) is generated based on the low-frequency variation and / or drift of the bias current (14) of the one bio-FET (11).

3. The biosensor device (10) according to claim 1 or 2, characterized in that: the readout circuit (15) includes a current comparator circuit (23a), and the current comparator circuit (23a) is configured to generate the calibration signal (21) based on the bias current (14) of the one bio-FET (11) and the reference current (22).

4. The biosensor device (10) according to any one of claims 1 to 3, characterized in that: the readout circuit (15) includes filter circuits (24, 25, 26); the filter circuits (24, 25, 26) are configured to act as a low-pass filter for the calibration signal path of the readout circuit (15) to prevent the high-frequency variation of the bias current (14) of the one bio-FET (11) from being used to generate the calibration signal (21); and the filter circuits (24, 25, 26) are configured to act as a high-pass filter for the readout signal path of the readout circuit (15) to prevent the low-frequency variation and / or drift of the bias current (14) of the one bio-FET (11) from being used to generate the readout signal (16).

5. The biosensor device (10) according to claim 3 or 4, characterized in that: the current comparator circuit (23a) includes a first amplifier (26) and a pair of transistors (27b, 27d) connected in series, wherein the midpoint of the pair of transistors (27b, 27d) connected in series is connected to the inverting input of the first amplifier (26); a reference voltage (Vref) is connected to the non-inverting input of the first amplifier (26); The transistor pair (27b, 27d) is configured to provide the current difference between the bias current (14) of the one bio-FET (11) and the reference current (22) as a voltage difference compared to the reference voltage (Vref) to the inverting input of the first amplifier (26); and The first amplifier (26) is configured to provide the calibration signal (21) at its output terminal.

6. The biosensor device (10) according to claims 4 and 5, characterized in that, Further comprising: A capacitor (25), the capacitor (25) being connected to the inverting input of the first amplifier (26) and the output of the first amplifier (26); And A pseudo-resistor (24), the pseudo-resistor (24) being connected between the midpoint of the serially connected transistor pair (27b, 27d) and the inverting input of the first amplifier (26); Wherein the capacitor (25), the pseudo-resistor (24), and the first amplifier (26) form the filter circuit (24, 25, 26).

7. The biosensor device (10) according to claim 5 or 6, characterized in that: The readout circuit (15) includes a first current mirror circuit, the first current mirror circuit including a first transistor (27a) and a second transistor (27b) and being configured to mirror the reference current (22) from the first transistor (27a) to the second transistor (27b); The readout circuit (15) includes a second current mirror circuit, the second current mirror circuit including a third transistor (27c) and a fourth transistor (27d) and being configured to mirror the bias current (14) of the one bio-FET (11) from the third transistor (27c) to the fourth transistor (27d); and The serially connected transistor pair (27b, 27d) is formed by the second transistor (27b) and the fourth transistor (27d).

8. The biosensor device (10) according to claim 7, characterized in that: The readout circuit (15) further includes an output transistor (28); The third transistor (27c) and the fourth transistor (27d) are connected to the output transistor (28); and The output transistor (28) is configured to generate the readout signal (16) based on the bias current (14) of the one bio-FET (11).

9. The biosensor device (10) according to any one of claims 3 to 8, characterized in that: The readout circuit (15) further includes a control circuit (23b), the control circuit (23b) being configured to control the bias of the source node (13) of the one bio-FET (11) according to the calibration signal (21) provided by the current comparator circuit (23a).

10. The biosensor device (10) according to claims 5 and 9, characterized in that: The control circuit (23b) includes a second amplifier (29); The output of the first amplifier (26) is connected to the non-inverting input of the second amplifier (29); and The source node (13) of the one bio-FET (11) is connected to the inverting input of the second amplifier (29).

11. The biosensor device (10) according to claim 10, characterized in that: The readout circuit (15) further comprises an input transistor (28a); The input transistor (28a) is connected between the source node (13) of the one bio-FET (11) and the third transistor (27c) of the second current mirror circuit; and The gate of the input transistor is connected to the output of the second amplifier (29).

12. The biosensor device (10) according to any one of claims 1 to 11, characterized in that: Each of the one or more bio-FETs (11) comprises a liquid gate.

13. The biosensor device (10) according to any one of claims 1 to 12, characterized in that: The one or more bio-FETs (11) comprise one or more nanopore FETs.

14. The biosensor device (10) according to any one of claims 1 to 13, characterized in that, The biosensor device (10) comprises a bio-FET array (11) and a readout circuit array (15) connected to the bio-FET array (11).

15. The biosensor device (10) according to claim 14, characterized in that: The readout circuit array (15) comprises one or more sets of readout circuits (15); and Each set of readout circuits (15) is connected to one or more multiplexers (51).

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