Epitaxial gate type FET (Field Effect Transistor) uric acid sensor and uric acid concentration detection method

Abstract

The invention relates to the field of bioelectrochemical sensors, in particular to an epitaxial gate type FET uric acid sensor and a uric acid concentration detection method. The FET uric acid sensor based on the epitaxial gate type comprises a field effect transistor and an epitaxial gate, the epitaxial grid electrode comprises ITO (Indium Tin Oxide) conductive glass connected with the grid electrode of the field effect transistor, an MXene / Ppy composite modification layer, a polypyrrole layer and a solution tank; the MXene / Ppy composite modification layer and the polypyrrole layer are sequentially deposited on the upper surface of the ITO conductive glass from bottom to top; the polypyrrole layer is provided with a specific imprinting cavity of uric acid to be detected; and the solution tank is arranged on the upper surface of the polypyrrole layer and is used for accommodating detection liquid. According to the invention, rapid, sensitive, accurate and low-cost detection of uric acid molecules in a low-concentration range can be realized.

Description

Technical Field

[0001] This invention relates to the field of bioelectrochemical sensors, specifically to an epitaxial gate-based FET uric acid sensor and a method for detecting uric acid concentration. Background Technology

[0002] With the fast pace of modern life, the incidence of chronic diseases such as gout is rising year by year. Therefore, monitoring uric acid levels is particularly important for the prevention and treatment of gout and other diseases. The level of uric acid in serum is determined by the balance between its formation and excretion. Normal serum uric acid levels are 0.13-0.46 mM, and urinary uric acid levels are 1.49-4.46 mM. Abnormal uric acid concentrations are associated with various diseases, such as hyperuricemia and gout. Hyperuricemia is a state of uric acid accumulation caused by purine metabolism disorders or impaired renal excretion, and it has shown an increasing trend and is affecting younger people in recent years. Gout is a joint disease caused by the deposition of urate crystals. Therefore, uric acid testing is crucial for disease monitoring and management.

[0003] Traditional uric acid testing methods are complex and time-consuming, but rapid testing is crucial for clinical diagnosis and treatment. Therefore, improving testing efficiency and simplifying procedures are key, while also considering cost. Currently used enzyme sensors are expensive, hindering widespread adoption.

[0004] Therefore, developing low-cost, high-performance detection methods will help popularize uric acid testing and has significant clinical and social value. Summary of the Invention

[0005] The technical problem to be solved by the present invention is to overcome the defects of the prior art and provide a FET uric acid sensor based on epitaxial gate type to achieve rapid, sensitive, accurate and low-cost detection of uric acid molecules in a low concentration range.

[0006] To solve the above-mentioned technical problems, the technical solution of the present invention is as follows: a FET uric acid sensor based on an epitaxial gate, comprising a field-effect transistor and an epitaxial gate, wherein the epitaxial gate comprises an ITO conductive glass connected to the gate of the field-effect transistor, an MXene / Ppy composite modification layer deposited sequentially from bottom to top on the upper surface of the ITO conductive glass, a polypyrrole layer having a specific imprint cavity for the uric acid to be measured, and a solution tank disposed on the upper surface of the polypyrrole layer to contain the detection liquid.

[0007] To further facilitate electrical connection with other external components, the epitaxial gate-based FET uric acid sensor also includes a gate electrode, a drain electrode, and a source electrode. The gate electrode is inserted into the detection liquid, the drain electrode is connected to the drain of the field-effect transistor through a current-limiting resistor, and the source electrode is connected to the source of the field-effect transistor.

[0008] To further improve integration, the epitaxial gate-based FET uric acid sensor also includes a PCB board, on which the field-effect transistor, the ITO conductive glass, the drain electrode, the source electrode, and the current-limiting resistor are respectively disposed.

[0009] Furthermore, the method for preparing the MXene / Ppy composite modification layer includes: The prepared MXene dispersion was diluted and then mixed with pyrrole and sodium dodecylbenzenesulfonate to obtain a reaction solution; The reaction solution is dropped into a solution tank, and electrodeposition is performed using a two-electrode system with the ITO conductive glass as the working electrode to form a uniform MXene / Ppy composite modification layer on the upper surface of the ITO conductive glass.

[0010] Furthermore, the parameters for electrodeposition using the two-electrode system with the ITO conductive glass as the working electrode are as follows: The current density is 0.1-10 mA / cm². 2 The reaction time is 5-30 minutes.

[0011] Furthermore, the method for preparing the polypyrrole layer includes: Using pyrrole as a functional monomer and uric acid molecules as template molecules, a molecularly imprinted polymer membrane was prepared on an MXene / Ppy composite modified layer by electrochemical polymerization. The template molecules were then eluted to obtain a polypyrrole layer with a specific imprinted cavity for the uric acid to be tested.

[0012] Furthermore, the specific steps for eluting the template molecule are as follows: Template molecules are removed by utilizing the polarity of anhydrous ethanol.

[0013] This invention also relates to a method for detecting uric acid concentration, using an epitaxial gate-based FET uric acid sensor. The method includes: The source-leakage current change curve over time is used to obtain the uric acid concentration. Alternatively, the uric acid concentration can be obtained by measuring the shift in the uric acid characteristic curve.

[0014] Furthermore, when obtaining uric acid concentration by measuring the relationship between time and source / leakage current changes, the specific steps include: Keeping the voltage between the epitaxial gate and source of the field-effect transistor and the voltage between the source and drain constant, phosphate buffer solution is added to the solution tank until the source-drain current change curve over time stabilizes. The sample solution to be tested is then added to the solution tank, and the uric acid concentration is determined based on the source-drain current change curve over time.

[0015] Furthermore, when using a transfer characteristic curve and obtaining the uric acid concentration by measuring the offset of the transfer characteristic curve, the specific steps include: Keeping the voltage between the epitaxial gate and source of the field-effect transistor and the voltage between the source and drain constant, blank solution and sample solution to be tested are added to the solution bath in sequence, and the transfer characteristic curve is measured. The uric acid concentration is determined by the offset of the transfer characteristic curve after the addition of uric acid solution.

[0016] By adopting the above technical solution, this invention prepares a molecularly imprinted polymer sensitive film as an epitaxial gate, and utilizes the prepared epitaxial gate and a FET to jointly construct a FET-based molecularly imprinted sensing platform. First, a film with a three-dimensional network structure formed by the polymerization of MXene and Ppy is used to increase the specific surface area and improve the sensor's sensitivity. Then, the ability of the molecularly imprinted polymer to capture template molecules in the system through covalent, non-covalent, or semi-covalent interactions is utilized to achieve specific recognition. Finally, the signal amplification function of the FET is used to further improve the detection capability. In summary, this invention enables rapid, sensitive, and accurate detection of uric acid molecules in the low concentration range (pM concentration level). Furthermore, this invention has advantages such as low cost and availability, high stability, long service life, and large-scale production capability, and has broad application prospects. Attached Figure Description

[0017] Figure 1 This is a schematic diagram of the structure of the epitaxial gate-based FET uric acid sensor of the present invention; Figure 2 This is a surface microstructure of the polypyrrole layer in the epitaxial gate-based FET uric acid sensor of the present invention. Figure 3 This is a graph showing the change of source and drain current over time in Embodiment 2 of the present invention; Figure 4 This is a graph showing the transfer characteristics of uric acid at various concentrations in Example 3 of the present invention. Figure 5 This is a schematic diagram of the linear fitting results for detecting uric acid molecules in Example 3 of the present invention; Figure 1 In the diagram, 1. Gate electrode; 2. Detection solution; 3. Solution tank; 4. ITO conductive glass; 5. PCB board; 6. Current limiting resistor; 7. Field effect transistor; 8. Drain electrode; 9. Source electrode. Detailed Implementation

[0018] To make the content of this invention easier to understand, the invention will be further described in detail below with reference to specific embodiments and accompanying drawings. Example

[0019] like Figure 1As shown, a FET uric acid sensor based on an epitaxial gate includes a field-effect transistor 7 and an epitaxial gate. The epitaxial gate includes an ITO conductive glass 4 connected to the gate of the field-effect transistor 7, an MXene / Ppy composite modification layer deposited sequentially from bottom to top on the upper surface of the ITO conductive glass 4, a polypyrrole layer with a specific imprint cavity for the uric acid to be measured, and a solution tank 3 disposed on the upper surface of the polypyrrole layer to contain the detection liquid 2.

[0020] In this embodiment, as Figure 1 As shown, the epitaxial gate-based FET uric acid sensor may also include a gate electrode 1, a drain electrode 8, and a source electrode 9. The gate electrode 1 is inserted into the detection liquid 2, the drain electrode 8 is connected to the drain of the field-effect transistor 7 through a current-limiting resistor 6, and the source electrode 9 is connected to the source of the field-effect transistor 7.

[0021] The conductive path of the epitaxial gate is as follows: gate electrode 1 → detection liquid 2 → polypyrrole layer → MXene / Ppy composite modification layer → ITO conductive glass 4 → gate of field-effect transistor 7. The gate electrode 1 can be supported by an external support device and inserted into the detection liquid 2, or it can be fixed to the solution tank 3.

[0022] This facilitates the electrical connection of the entire epitaxial gate-based FET uric acid sensor with other external components, making it easy to put into use.

[0023] In this embodiment, as Figure 1 As shown, the FET uric acid sensor based on epitaxial gate can also include a PCB board 5, a field-effect transistor 7, an ITO conductive glass 4, a drain electrode 8, a source electrode 9, and a current-limiting resistor 6, which are respectively disposed on the PCB board 5.

[0024] This improves integration and results in a unified sensing platform.

[0025] In this embodiment, as Figure 1 The fabrication method of the epitaxial gate-based FET uric acid sensor shown includes: The first step is to design the PCB board.

[0026] By referring to the FET datasheet, selecting an appropriate current-limiting resistor can effectively optimize circuit efficiency and ensure optimal performance in key parameters such as stability, gain, power consumption, thermal management, and frequency response. PCB board 5 was designed using Altium Designer software and manufactured by the supplier. Components were soldered onto the board using a soldering iron. Figure 1 .

[0027] The second step is to prepare the epitaxial gate.

[0028] First, an MXene / Ppy composite modification layer was constructed on the surface of ITO conductive glass 4 using an electrochemical deposition method. The specific process is as follows: The prepared MXene (two-dimensional transition metal carbide, chemical formula Ti3C2T) was then used. x The dispersion was diluted to 1 mg / ml and then mixed with pyrrole and sodium dodecylbenzenesulfonate at a ratio of 1:10 to obtain a reaction solution; wherein, the ratio of pyrrole monomer to sodium dodecylbenzenesulfonate can be 0.2M:5 mM.

[0029] The reaction solution is dropped into solution tank 3, which can be a silica gel tank. Electrodeposition is performed using a two-electrode system, with ITO conductive glass 4 as the working electrode connected to the positive terminal of a DC power supply, and a platinum electrode as the counter electrode connected to the negative terminal of the DC power supply. The current density is 0.1-10 mA / cm², and the reaction time is 5-30 min. After electrodeposition, a uniform MXene / Ppy black film is formed on the surface of the ITO conductive glass 4. After drying for 1-15 h, the MXene / Ppy composite modified layer is obtained. This electrochemical deposition method can precisely control the thickness and morphology of the composite film, ensuring that MXene and Ppy (polypyrrole) polymers form a uniform interpenetrating network structure, thereby significantly improving the conductivity and detection sensitivity of the epitaxial gate.

[0030] Then, using pyrrole as a functional monomer and uric acid molecules as template molecules, a molecularly imprinted polymer film was prepared on the MXene / Ppy composite modified layer by electrochemical polymerization. The template molecules were then eluted to obtain a polypyrrole layer with a specific imprinted cavity for the uric acid to be tested.

[0031] The conditions for preparing molecularly imprinted polymer films by electrochemical polymerization are as follows: At room temperature, a three-electrode solution system was used, with ITO conductive glass 4 as the working electrode, Ag / AgCl as the reference electrode, and Pt sheet as the auxiliary electrode. Cyclic voltammetry was performed for two cycles within the potential range of -0.6V to 1.2V at a scan rate of 100mV / s. The electrolyte was 5mM uric acid and 50mM pyrrole solution, and the electrolyte was 100mM PCS solution. Uric acid and pyrrole were dissolved in PBS (phosphate buffered saline) and mixed in the electrochemical chamber.

[0032] The specific steps for eluting template molecules are as follows: immerse the molecularly imprinted polymer membrane in anhydrous ethanol for 5-30 minutes to remove template molecules using the polarity of anhydrous ethanol, and obtain a molecularly imprinted sensitive membrane, which is a polypyrrole layer with a specific imprint cavity for the uric acid to be tested.

[0033] Specifically, molecularly imprinted polymers are novel highly selective recognition materials developed by mimicking the principle of antibody-receptor interactions in nature. They use the target molecule as a template and bind it to a functional monomer based on covalent, non-covalent, or semi-covalent interactions. Then, they polymerize to form a polymer of the functional monomer. After removing the template, a molecularly imprinted cavity is left on the imprinted polymer that matches the spatial structure, size, and shape of the target molecule and has an effective site of action. It has the ability to specifically recognize the template molecule and has the advantages of being inexpensive, readily available, highly stable, having a long service life, and being suitable for large-scale production.

[0034] pass Figure 2 It is evident that the molecularly imprinted polymer membrane exhibits a more porous structure after elution, indicating that the template molecules within the imprint were eluted, leaving behind a large number of cavities, and effective imprinted cavities were generated within the molecularly imprinted sensitive membrane.

[0035] Finally, the prepared epitaxial gate and PCB board 5 are connected by wires (that is, the ITO conductive glass 4 is electrically connected to the gate of the field-effect transistor 7) to construct a molecularly imprinted epitaxial gate field-effect sensor for detecting uric acid molecules.

[0036] The third step is to debug the field-effect transistor. Under a fixed gate voltage, the drain voltage (V) provided in the datasheet is used. d The range is scanned to monitor the drain current (I) in real time. ds The curves showing the variation of drain current under different drain voltages are used to determine the optimal drain voltage V at which the drain current reaches its maximum value. d1 Set this optimal drain voltage as the standard operating voltage for subsequent testing. Then apply the standard drain operating voltage to obtain a complete transfer characteristic curve, and set the gate range accordingly.

[0037] The fourth step is to construct a molecularly imprinted epitaxial gate field-effect sensor for detecting uric acid molecules (building a FET-based molecularly imprinted sensing platform). Connect the source of the field-effect transistor 7 to the source electrode 9 on the PCB board 5, and connect the drain to the drain electrode 8 on the PCB board 5 to complete the construction of the molecular imprinted epitaxial gate field-effect sensor.

[0038] The molecularly imprinted epitaxial gate is used to place the sample solution to be tested in the solution tank 3 when using the field-effect sensor to test the sample solution. Example

[0039] A method for detecting uric acid concentration using an epitaxial gate-based FET uric acid sensor as described in Example 1, the method comprising: The first step is the preparation of uric acid molecular analysis solutions: uric acid molecules are prepared into standard solutions of different concentrations using PBS; The second step is the time-current curve testing: The voltage between the gate electrode 1 and the source electrode 9 is fixed at 0.5V, and the voltage between the source electrode 9 and the drain electrode 8 is fixed at 0.1V. Phosphate buffer solution (PBS solution) is first added to solution tank 3 until tI... ds Once the curve (i.e., the source-leakage current versus time curve) stabilizes, adding uric acid molecular analysis solution (PBS solution and uric acid molecular analysis solution can be 10~50μL each, depending on the volume of solution tank 3 and the actual situation) causes a significant change in the curve's direction, such as... Figure 3 As shown, this indicates that the sensor responds to the uric acid molecular analysis solution, thereby testing tI. ds The relationship of change. Based on tI ds The relationship between the changes in uric acid concentration is obtained (generally, the tI of different concentrations of uric acid molecular analytical solution is measured first). ds The relationship between the changes is used for calibration; then, based on the measured tI... ds By comparing the changes with previous calibration, the concentration of uric acid in the uric acid molecular analysis solution can be determined. Example

[0040] A method for detecting uric acid concentration using an epitaxial gate-based FET uric acid sensor as described in Example 1, the method comprising: Step 1: Preparation of uric acid molecular analysis solution: Use PBS to prepare standard solutions of uric acid molecules at different concentrations, ranging from 3 to 694 μM; The second step is to test the device transfer characteristic curve: With the voltage between the gate and source fixed at 0-1V and the voltage between the source and drain at 0.1V, uric acid molecular analysis solution is added sequentially to solution tank 3 to achieve target concentrations of 0.1pM, 100pM, 10nM, 1uM, and 100uM. The transfer characteristic curve of the sensor is then tested, with each test repeated three times at 10-minute intervals. The transfer characteristic curve obtained using phosphate buffered saline (PBS) solution is used as the initial curve. The transfer characteristic curves obtained from testing with different concentrations of uric acid molecular analysis solution are shown below. Figure 4 The initial intercept is the point where the linear region of the initial curve intersects the horizontal axis. The difference between the intercepts of the transfer characteristic curves at different concentrations and the initial intercept represents the amount of change. The offset is used to evaluate the sensor's test results for different concentrations of uric acid molecular analytical solutions. Within the analytical solution concentration range of 1 pM to 100 μM, the logarithm of the analytical solution concentration is taken as the X-axis, and the offset as the Y-axis. The linear relationship between the two can be obtained as follows: Figure 5 As shown.

[0041] The third step, testing, showed that the Vth offset of the prepared molecularly imprinted epitaxial gate field-effect sensor exhibited a very clear and regular change with the uric acid concentration. When the concentration gradient of the analytical solution changed, the offset increased linearly. Therefore, a formula for the change of Vth offset with uric acid concentration can be fitted. During use, after measuring the offset, the uric acid concentration can be calculated by substituting it into the formula.

[0042] Based on the above-described preferred embodiments of the present invention, and through the foregoing description, those skilled in the art can make various changes and modifications without departing from the inventive concept. The technical scope of this invention is not limited to the contents of the specification, but must be determined according to the scope of the claims.

Claims

1. A FET uric acid sensor based on an epitaxial gate, characterized in that, It includes a field-effect transistor (7) and an epitaxial gate. The epitaxial gate includes an ITO conductive glass (4) connected to the gate of the field-effect transistor (7), an MXene / Ppy composite modification layer deposited from bottom to top on the upper surface of the ITO conductive glass (4), a polypyrrole layer with a specific imprint cavity for uric acid to be tested, and a solution tank (3) disposed on the upper surface of the polypyrrole layer to contain the detection liquid (2).

2. The epitaxial gate-based FET uric acid sensor according to claim 1, characterized in that, It also includes a gate electrode (1), a drain electrode (8) and a source electrode (9). The gate electrode (1) is inserted into the detection liquid (2). The drain electrode (8) is connected to the drain of the field-effect transistor (7) through a current-limiting resistor (6). The source electrode (9) is connected to the source of the field-effect transistor (7).

3. The epitaxial gate-based FET uric acid sensor according to claim 2, characterized in that, It also includes a PCB board (5), wherein the field-effect transistor (7), the ITO conductive glass (4), the drain electrode (8), the source electrode (9) and the current-limiting resistor (6) are respectively disposed on the PCB board (5).

4. The epitaxial gate-based FET uric acid sensor according to claim 1, characterized in that, The method for preparing the MXene / Ppy composite modified layer includes: The prepared MXene dispersion was diluted and then mixed with pyrrole and sodium dodecylbenzenesulfonate to obtain a reaction solution; The reaction solution is dropped into the solution tank (3), and electrodeposition is performed using a two-electrode system with the ITO conductive glass (4) as the working electrode to form a uniform MXene / Ppy composite modification layer on the upper surface of the ITO conductive glass (4).

5. The epitaxial gate-based FET uric acid sensor according to claim 4, characterized in that, The parameters for electrodeposition using the two-electrode system with the ITO conductive glass (4) as the working electrode are as follows: The current density is 0.1-10 mA / cm². 2 The reaction time is 5-30 minutes.

6. The epitaxial gate-based FET uric acid sensor according to claim 1, characterized in that, The method for preparing the polypyrrole layer includes: Using pyrrole as a functional monomer and uric acid molecules as template molecules, a molecularly imprinted polymer membrane was prepared on an MXene / Ppy composite modified layer by electrochemical polymerization. The template molecules were then eluted to obtain a polypyrrole layer with a specific imprinted cavity for the uric acid to be tested.

7. The epitaxial gate-based FET uric acid sensor according to claim 6, characterized in that, The specific steps for eluting template molecules are as follows: Template molecules are removed by utilizing the polarity of anhydrous ethanol.

8. A method for detecting uric acid concentration, characterized in that, The detection is performed using the epitaxial gate-based FET uric acid sensor according to any one of claims 1-7, the method comprising: The source-leakage current change curve over time is used to obtain the uric acid concentration. Alternatively, the uric acid concentration can be obtained by measuring the shift in the uric acid characteristic curve.

9. The method for detecting uric acid concentration according to claim 8, characterized in that, When obtaining uric acid concentration by measuring the relationship between time and source / leakage current, the specific steps include: Keep the voltage between the epitaxial gate and source of the field-effect transistor (7) and the voltage between the source and drain constant. Add phosphate buffer solution to the solution tank (3) until the source and drain current change curve with time is stable. Add the sample solution to be tested to the solution tank (3) and determine the uric acid concentration based on the source and drain current change curve with time.

10. The method for detecting uric acid concentration according to claim 8, characterized in that, When using a transfer characteristic curve to obtain uric acid concentration by measuring the offset of the transfer characteristic curve, the specific steps include: Keeping the voltage between the epitaxial gate and source of the field-effect transistor (7) and the voltage between the source and drain constant, blank solution and sample solution to be tested are added to the solution tank (3) in sequence, and the transfer characteristic curve is measured. The uric acid concentration is determined by the offset of the transfer characteristic curve after adding uric acid solution.

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