An EISCAP-Type Biochemical Sensor Based on Saturated Excitation

Abstract

The present invention discloses a biochemical sensor of EISCAP type based on saturation excitation, which uses a DC bias voltage with a constant amplitude and an AC excitation voltage with a sufficiently large and constant amplitude as the excitation. The AC excitation amplitude should ensure that the MOS capacitor periodically enters the accumulation region, depletion region and inversion region. A compensation circuit composed of a compensation AC signal, a compensation capacitor and a compensation resistor is used to compensate the current background signal flowing through the MOS capacitor. A transimpedance amplifier, a frequency-selective amplifier, a rectifier whose structure is determined by the measurement reference point and a low-pass filter are used to process the compensated signal, and an output voltage linearly related to the measured quantity is obtained. This sensor has the characteristics of high signal-to-noise ratio, fast detection speed and good linearity.

Description

Technical Field

[0001] The present invention belongs to the field of sensors, and particularly relates to an EISCAP type biochemical sensor. Background Art

[0002] The EISCAP (Electrolyte-Insulator-Semiconductor Capacitor) type biochemical sensor is a biochemical sensor based on the semiconductor field effect principle, and can be used to detect biochemical quantities such as pH value, glucose, urea, DNA, etc. This kind of sensor usually realizes measurement by applying a variable DC bias voltage and an AC small-signal excitation voltage. Specifically, the method is to successively change the magnitude of the DC bias voltage, and measure the magnitude of the MOS capacitance under each DC bias voltage respectively, to form a relationship curve between the bias voltage and the MOS capacitance value, that is, the V-C characteristic curve. The measured biochemical quantity is detected by comparing the displacement of the measured V-C curve along the bias voltage direction relative to the V-C curve of the known quantity. This kind of sensor requires relatively expensive equipment and takes a long time to complete one measurement. The literature “A closed-loop detectionsystem based on orthogonal phase locking for EISCAP sensor,” Journal ofElectro-analytical Chemistry, vol.860, pp.

[0003] 113925, Mar. 2020.” discloses a closed-loop EISCAP type pH sensor based on orthogonal phase locking, which can directly output a voltage signal proportional to the measured biochemical quantity. In order to ensure working in the linear section of the V-C curve, this kind of sensor also adopts the AC small-signal excitation method, and there are problems of small signal amplitude and low measurement linearity. Summary of the Invention

[0004] In order to solve the problems of the prior art, the present invention adopts a DC bias voltage with a constant amplitude and a saturated AC excitation voltage that can make the MOS capacitance repeatedly enter the accumulation region and the inversion region, and provides an EISCAP type biochemical sensor with a large signal amplitude, a fast detection speed, and good linearity.

[0005] The solution adopted by the present invention to solve its technical problems is as follows: An EISCAP-type biochemical sensor based on saturated excitation includes a DC bias voltage 1 with a constant amplitude, an AC excitation voltage 2 with a sufficiently large amplitude, a reference electrode 3, a solution cell 4, a detection silicon wafer 5, a transimpedance amplifier 14, a frequency-selective amplifier 16, a rectifier 18, a low-pass filter 19, a compensation AC signal 11, a compensation capacitor 12, and a compensation resistor 13. The technical characteristics of the present invention are: The amplitude of the DC bias voltage remains constant; the amplitude of the AC excitation voltage remains constant, and the amplitude of the AC excitation voltage is large enough to ensure that the MOS capacitor periodically enters the accumulation region, depletion region, and inversion region; the compensation circuit generates a compensation current I m whose amplitude is equal to that of the fundamental wave component in I c and has a phase difference of 180°; the compensated signal is subjected to transimpedance amplification, frequency-selective amplification, rectification, and low-pass filtering to obtain an output signal linearly related to the measured quantity.

[0006] The detection silicon wafer 5 of the present invention can be a p-type silicon wafer or an n-type silicon wafer. When different sensitive films are used, it can be applied to detect biochemical quantities such as pH value, glucose, urea, DNA, etc. When describing the technical characteristics of the present invention below, taking an n-type silicon wafer as the detection silicon wafer and measuring the pH value as an example, and referring to reference appendices Figure 1 appendix Figure 2 appendix Figure 3 appendix Figure 4 appendix Figure 5 appendix Figure 6 and appendix

[0007] The relationship between the various parts of the present invention is as shown in appendix Figure 1 Appendix Figure 2 is the working principle diagram of the present invention, where appendix Figure 2 (a) is the V-C characteristic curve of the MOS capacitor of the detection silicon wafer 5; U i is the voltage across the MOS capacitor at the boundary between the inversion region and the depletion region in the V-C characteristic curve; U a is the voltage across the MOS capacitor at the boundary between the accumulation region and the depletion region in the V-C characteristic curve; The waveform of the AC excitation voltage 2 adopted by the present invention can be a sine wave or a triangular wave, and the frequency is between 1 kHz and 100 kHz. When a sine wave excitation is adopted, the voltage U MOS applied across the MOS capacitor is:

[0008] U MOS =U b +Um sinωt

[0009] Where: U m and ω are the amplitude and frequency of the AC excitation respectively.

[0010] U b is the DC component of the voltage applied across the MOS capacitor, called the DC operating point voltage, and its value is the algebraic sum of the externally applied constant DC voltage 1 (denoted by U 0 ), the reference electrode voltage U r and the membrane potential U ph formed at the interface of the sensitive membrane (silicon nitride layer 6) due to the pH value of the solution to be measured, that is:

[0011] U b = U 0 + U r + U ph

[0012] Attached Figure 2 (c) is the waveform of the AC excitation voltage 2, and its amplitude is large enough to ensure that the maximum value of the AC excitation voltage can make the MOS capacitor enter the accumulation region; the minimum value of the AC excitation voltage can make the MOS capacitor enter the inversion region, that is, simultaneously satisfy:

[0013] U m > U b - U i

[0014] U m > U a - U b

[0015] Under the action of U MOS , the capacitance value of the MOS capacitor changes according to the law of Attached Figure 2 (b), and the current I m flowing through the MOS capacitor changes according to Attached Figure 2 (d). The result of this saturation excitation method is that the current I m flowing through the MOS capacitor is much larger than that in the small-signal AC excitation method, and its current waveform is distorted relative to the AC excitation. When the pH is 4.0, 7.0, and 10.0 respectively, the waveform of the current I m flowing through the MOS capacitor is as shown in Attached Figure 3 . The fundamental component of the current I m flowing through the MOS capacitor has the same frequency as the AC excitation voltage 2, and its amplitude has a linear relationship with the DC operating point voltage U b in a large range, as shown in Attached Figure 4 . Near the middle position (U bThe linearity is best near ≈ -1.2V, and this is taken as the DC operating point. Since the constant DC voltage U applied externally during operation 0 and the voltage U of the reference electrode r remain unchanged, the membrane potential U of the sensitive membrane ph has a linear relationship with the pH value. Therefore, at this position (U b ≈ -1.2V), the linear relationship between the fundamental component of I m and the pH value is also the best.

[0016] The present invention uses a compensation AC signal 11, a compensation capacitor 12, and a compensation resistor 13 to form a compensation circuit to compensate for the background signal in the MOS capacitor current I m . The specific compensation method is to first select a measurement reference point in the Figure 4 linear segment. The position is set according to actual needs. For example, pH = 0 or pH = 7 or pH = 14 can be selected as the measurement reference point, or other settings can also be chosen. At the measurement reference point, the parameters of the compensation capacitor 12 and the compensation resistor 13 are adjusted so that the compensation current I c and the current I of the MOS capacitor m have equal fundamental component amplitudes and a phase difference of 180°. The addition of the compensation current I c at the measurement reference point and the current I of the MOS capacitor m , after being amplified by the transimpedance amplifier 14, a voltage signal (represented by U t ) is obtained at its output terminal 15, and its voltage value is:

[0017] U t = R f (I m + I c )

[0018] The waveforms of the output voltages of the transimpedance amplifier when pH is 4.0, 7.0, and 10.0 are as Figure 5 shown. At the measurement reference point, the fundamental component is zero, and the amplitude of the fundamental component varies linearly with pH, and it also contains second harmonic and higher harmonic components. The present invention uses a frequency-selective amplifier 16 to filter out the second harmonic and higher harmonic components in the output signal of the transimpedance amplifier, and a signal containing only the fundamental frequency (represented by U f ) is obtained at the output terminal 17 of the frequency-selective amplifier 16:

[0019] U f = K(pHx - pHr)cosωt

[0020] where: K is a constant related to the gains of the transimpedance amplifier 14 and the frequency-selective amplifier 16; pHx is the pH value of the solution to be measured; pHr is the pH value of the solution at the measurement reference point.

[0021] In the present invention, the rectifier 18 and the low-pass filter 19 are used to convert the output signal of the frequency-selective amplifier into a DC signal for output. The type or structure of the rectifier 18 can select different rectification circuits according to the selection position of the measurement reference point. When the measured quantity corresponding to the measurement reference point is less than the minimum value of the measurement range or greater than the maximum value of the measurement range, the phase of the output signal of the frequency-selective amplifier 16 will not change by 180°. An absolute value circuit can be selected to achieve rectification. When the measurement reference point is within the measurement range and the pH value of the measured solution may be greater than or less than the pH value of the measurement reference point, a phase-sensitive rectification circuit is selected to achieve rectification. When a phase-sensitive rectification circuit is selected, a reference signal is required. The frequency of the reference signal is the same as the fundamental component of the AC excitation voltage (2), the phase is the same as the output voltage 17 of the frequency-selective amplifier, and the waveform can be a sine wave, a square wave or a triangular wave.

[0022] The beneficial effects of the present invention compared with the prior art are as follows:

[0023] (1) The large-amplitude excitation voltage increases the amplitude of the detection signal. After the background signal is eliminated by the compensation circuit, the gain of the processing circuit can be further increased, and the signal-to-noise ratio of the sensor is high;

[0024] (2) The excitation with a constant-amplitude DC bias voltage and a constant-amplitude AC excitation voltage avoids the time for detecting by successively changing the DC bias voltage and the cost of signal processing;

[0025] (3) There is a good linearity between the output voltage and the measured quantity. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] FIG Figure 1 is the overall structure diagram of the EISCAP type biochemical sensor based on saturated excitation.

[0027] FIG Figure 2 is a waveform diagram illustrating the principle of the EISCAP type biochemical sensor based on saturated excitation, where FIG Figure 2 (a) is the V-C characteristic curve of the MOS capacitor of the detection wafer 5, FIG Figure 2 (b) is the variation law of the capacitance value of the MOS capacitor under the action of the DC bias voltage (1) and the AC excitation voltage (2), FIG Figure 2 (c) is the waveform of the AC excitation voltage 2, FIG Figure 2 (d) is the current I flowing through the MOS capacitor m waveform.

[0028] FIG Figure 3 is the waveform of the current I flowing through the MOS capacitor when the pH values are 4.0, 7.0 and 10.0 respectively m waveform.

[0029] Attached Figure 4 is the relationship diagram of the amplitude of the fundamental component of the current I flowing through the MOS capacitor and the DC operating point voltage U m b .

[0030] Attached Figure 5 is the waveform diagram of the output voltage 15 of the transimpedance amplifier when the pH values are 4.0, 7.0, and 10.0 respectively.

[0031] Attached Figure 6 is the waveform diagram of the output voltage 17 of the frequency selective amplifier when the pH values are 4.0, 7.0, and 10.0 respectively. Detailed implementation manners

[0032] A saturation excitation-based EISCAP-type biochemical sensor includes a DC bias voltage 1 with a constant amplitude, an AC excitation voltage 2 with a large enough amplitude, a reference electrode 3, a solution cell 4, a detection silicon wafer 5, a transimpedance amplifier 14, a frequency selective amplifier 16, a rectifier 18, a low-pass filter 19, a compensating AC signal 11, a compensating capacitor 12, and a compensating resistor 13.

[0033] Referring to Attached Figure 1 and Attached Figure 2 , the circuit and component design of each part of the sensor includes but is not limited to the following structure selection and parameter setting methods.

[0034] Example 1

[0035] (1) The detection silicon wafer 5 uses an n-type silicon wafer, the sensitive film uses a silicon nitride thin film, and the working electrode uses an Au thin film.

[0036] (2) When pH = 7, change the voltage value of the externally applied DC bias voltage 1, measure the V-C characteristic curve of the MOS capacitor, and set the voltage value of the externally applied DC bias voltage 1 to the externally applied DC voltage corresponding to the midpoint of the V-C characteristic curve, and keep it unchanged in subsequent tests.

[0037] (3) Use a sine wave generation circuit to generate a sine wave signal with a frequency of 12.5 kHz as the AC excitation voltage 2; add this sine voltage to the DC bias voltage 1 and connect it to the solution cell through the reference electrode 3; adjust the amplitude of the AC excitation voltage 2, and observe the waveform I of the current flowing through the MOS capacitor with an oscilloscope m , and adjust the amplitude of the AC excitation voltage 2 to 1.2 times when the waveform appears Attached Figure 2 (d) distorted, and keep this amplitude unchanged in subsequent tests.

[0038] (4) Design the center frequency of the frequency selective amplifier 16 to be 12.5 kHz and the Q value to be 10.

[0039] ​(5) The alternating current excitation voltage 2 is amplified in reverse to obtain a compensated alternating current signal 11; at pH = 7, the compensation capacitor 12 and the compensation resistor 13 are adjusted, and the output voltage 17 of the frequency-selective amplifier 16 is measured. When the output voltage 17 of the frequency-selective amplifier is zero, record the capacitance value and resistance value of the compensation capacitor 12 and the compensation resistor 13 at this time, and keep this value unchanged in subsequent tests.

[0040] (6) The rectifier 18 is designed as a phase-sensitive rectification circuit. The alternating current excitation voltage is phase-shifted so that its phase is in phase with the voltage signal at the output terminal 17 of the frequency-selective amplifier at pH = 10, serving as the reference signal for phase-sensitive rectification.

[0041] (7) The cut-off frequency of the low-pass filter is designed to be 300 Hz.

[0042] Example 2

[0043] (1) The silicon wafer 5 for detection uses an n-type silicon wafer, the sensitive film uses a silicon nitride thin film, and the working electrode uses an Au thin film.

[0044] (2) At pH = 7, change the voltage value of the externally applied DC bias voltage 1, measure the V-C characteristic curve of the MOS capacitor, set the voltage value of the externally applied DC bias voltage 1 to the externally applied DC voltage corresponding to the midpoint of the V-C characteristic curve, and keep it unchanged in subsequent tests.

[0045] (3) Use a triangular wave generation circuit to generate a triangular wave signal with a frequency of 6 kHz as the alternating current excitation voltage 2; add this triangular wave voltage to the DC bias voltage 1 and connect it to the solution cell through the reference electrode 3; adjust the amplitude of the alternating current excitation voltage 2, and observe the waveform I of the current flowing through the MOS capacitor with an oscilloscope m , and adjust the amplitude of the alternating current excitation voltage 2 to 1.5 times when the waveform appears Figure 2 (d) distorted, and keep this amplitude unchanged in subsequent tests.

[0046] (4) The center frequency of the frequency-selective amplifier 16 is designed to be 6 kHz, and the Q value is designed to be 15.

[0047] (5) Use a sine wave generation circuit to generate a sine wave signal with a frequency of 6 kHz and a phase difference of 180° from the alternating current excitation voltage 2, and use it as the compensated alternating current signal 11; superimpose a 500 mV DC voltage on the externally applied DC bias voltage 1, adjust the compensation capacitor 12 and the compensation resistor 13, and measure the output voltage 17 of the frequency-selective amplifier. When the output voltage 17 of the frequency-selective amplifier is zero, record the capacitance value and resistance value of the compensation capacitor 12 and the compensation resistor 13 at this time, and keep this value unchanged in subsequent tests.

[0048] (6) The rectifier 18 is designed as an absolute value circuit.

[0049] (7) The cut-off frequency of the low-pass filter is designed to be 150 Hz.

Claims

1. An EISCAP type biochemical sensor based on saturated excitation, characterized in that a DC bias voltage (1) that keeps the V-C characteristic curve of the sensor chip at the midpoint position and an AC excitation voltage (2) with an amplitude large enough to make the MOS capacitor periodically enter the accumulation region, depletion region, and inversion region are selected as the excitation. The waveform of the AC excitation voltage (2) is selected as a sine wave or a triangular wave. The DC bias voltage (1) remains constant, and the amplitude of the AC excitation voltage (2) remains constant. A compensation AC signal (11), a compensation capacitor (12), and a compensation resistor (13) are used as a compensation circuit. The values of the compensation capacitor (12) and the compensation resistor (13) should ensure that the amplitude of the fundamental wave component in the compensation current Ic generated by the compensation circuit is equal to that of the current Im of the MOS capacitor, and the phase difference is 180°. A transimpedance amplifier (14), a frequency-selective amplifier (16), a rectifier (18), and a low-pass filter (19) are used to process the compensated signal to obtain an output voltage signal (20) that is linearly related to the measured quantity.

2. The EISCAP type biochemical sensor based on saturated excitation according to claim 1, characterized in that: the frequency of the AC excitation voltage (2) is between 1 kHz and 100 kHz.

3. The EISCAP type biochemical sensor based on saturated excitation according to claim 1, characterized in that: the compensation AC signal (11) is a sine wave, and the phase is 180° different from that of the AC excitation voltage (2).

4. The EISCAP type biochemical sensor based on saturated excitation according to claim 1, characterized in that: the center frequency of the frequency-selective amplifier (16) is equal to the fundamental wave frequency of the AC excitation voltage (2), the Q value is between 5 and 20, and the gain at the center frequency is set according to the amplitude requirement of the output signal.

5. The EISCAP type biochemical sensor based on saturated excitation according to claim 1, characterized in that: when the measurement reference point is selected to be less than the minimum value of the measurement range or the measurement reference point is selected to be greater than the maximum value of the measurement range, an absolute value circuit is used to achieve rectification; when the measurement reference point is selected within the measurement range, the measurement reference point is greater than the minimum value of the measurement range and less than the maximum value of the measurement range, a phase-sensitive rectification circuit is used to achieve rectification.

6. The EISCAP type biochemical sensor based on saturated excitation according to claim 1, characterized in that: the frequency of the reference signal of the phase-sensitive rectification circuit is the same as that of the AC excitation voltage (2), the phase is the same as the output voltage (17) of the frequency-selective amplifier, and the waveform is one of a sine wave, a square wave, and a triangular wave.

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