TWI806211B - Biosensor measurement system and method thereof for detecting human uric acid - Google Patents

Abstract

A biosensor measurement method for detecting human uric acid (UA) includes: measuring a human uric acid sample with a uric acid biosensor member to obtain a uric acid measurement signal; electrically connecting a uric acid signal processing circuit with the uric acid biosensor member; electrically processing the uric acid measurement signal via the uric acid signal processing circuit to obtain a processed uric acid measurement signal; electrically connecting a signal readout circuit with the uric acid signal processing circuit; and amplifying the processed uric acid measurement signal via the signal readout circuit to obtain an amplified uric acid measurement signal.

Description

Measuring system and method of biomedical sensor for uric acid detection

The present invention relates to a biomedical sensor (biosensor) measurement system and method for (blood) uric acid (human uric acid) detection; in particular, an extension of a biomedical sensor for uric acid detection Extended-Gate Field Effect Transistor [EGFET, Extended-Gate Field Effect Transistor] resistance voltage-dividing measurement system and method thereof; more particularly, a ruthenium dioxide [Ruthenium Dioxide] film biomedicine for uric acid detection Sensor measurement system and its method.

For example, conventionally used vitamin C biosensors, such as the invention patent of the Republic of China Patent Publication No. TW-I374267 "Vitamin C Sensor Calibration Measurement System and Calibration Method", which discloses a vitamin C sensor A calibration measurement system, and the calibration measurement system of the vitamin C sensor includes a vitamin C sensor, a reference electrode, an amplifier, an analog-to-digital converter and a programmable logic gate array module.

Continuing from the above, the amplifier of the aforementioned TW-I374267 has a positive input terminal, a negative input terminal and an output terminal, and the reference electrode is selectively connected to the positive input terminal of the amplifier, and a sensing element is selectively connected to the The negative input terminal of the amplifier, and the analog-to-digital converter is selectively connected to the output terminal of the amplifier.

Continuing from the above, the programmable logic gate array module of the aforementioned TW-I374267 is selectively connected to the analog-to-digital converter, and the programmable logic gate array module includes a control chip, and the programmable logic gate The array module further includes a controller, a multi-segment display and a light-emitting diode lamp, and the controller, the multi-segment display and the light-emitting diode lamp are respectively connected to the control chip.

Another conventional bio-sensing element, such as the invention patent of the Republic of China Patent Publication No. TW-I377342 "Formation Method of Sensing Element of Extended Gate Field-Effect Transistor and Sensing Element Formed", which discloses an extended The sensing element of the extended gate field effect transistor, and the sensing element of the extended gate field effect transistor includes a substrate, a ruthenium-doped titanium dioxide sensing film and a wire.

As mentioned above, the ruthenium-doped titanium dioxide sensing film of the aforementioned TW-I377342 is formed on the substrate, and the ruthenium-doped titanium dioxide sensing film is a nano-crystal surface, and the size of the nano-crystal surface is about 37-61nm, and the wire is extended from the ruthenium-doped titanium dioxide sensing film, which serves as an external electrical contact.

Continuing from the above, the sensing element of the extended gate field effect transistor of the aforementioned TW-I377342 alternatively includes a substrate, a titanium dioxide, ruthenium-doped titanium dioxide or ruthenium oxide sensing film, a calcium ion sensing film and a wire.

Inheriting from the above, the wire of the aforementioned TW-I377342 can alternatively be extended from the titanium dioxide, ruthenium-doped titanium dioxide or ruthenium oxide sensing film sensing film, which serves as an electrical contact to the outside, and the calcium ion A sensing film is formed on the ruthenium-doped titanium dioxide sensing film.

However, the aforementioned ROC Patent Publication No. TW-I374267 for the vitamin C sensor and TW-I377342 for the sensing element of the extended gate field-effect transistor did not disclose how to use it for blood uric acid detection or related methods, Therefore, there must be a need for how to detect blood uric acid or provide related methods.

Another conventional urea biosensor, such as US Patent Publication No. US-20060096858 "Potentiometric urea sensor based on The invention patent application of ion-selective electrode", which discloses a potentiometric [potentiometric] urea biosensor based on ion-selective electrode [ion-selective electrode], and the potentiometric urea biosensor based on ion-selective electrode The detector is a potentiometric urea sensing element.

As above, the potentiometric urea sensing element of the aforementioned US-20060096858 includes a substrate, a sensing film, a conductive wire, an encapsulating colloid, and a urea enzyme. The substrate has a surface, and a conductive layer is formed on the surface. The sensing film is located on one surface of the conductive layer of the substrate, and the sensing film forms an ion sensing electrode, and the sensing film has a sensing area and a non-sensing area.

Based on the above, the conductive wire of the aforementioned US-20060096858 is extended from the conductive layer so as to form an outward electrical contact. The packaging colloid covers the non-sensing area of the sensing film and forms a sensing window on the sensing area. The urease is fixed on the sensing film and placed in the sensing window.

Another conventional method for manufacturing urea biosensors, such as the invention patent of the Republic of China Patent Publication No. TW-588159 "Potentiometric Urea Sensing Element and Its Manufacturing Method", discloses a manufacturing method of a potentiometric urea sensing element . The manufacturing method of the potentiometric urea sensing element includes the steps of: providing a substrate, and forming a conductive layer on the substrate.

Based on the above, the manufacturing method of the potentiometric urea sensing element of the aforementioned TW-588159 further includes the step of: forming a sensing film on one surface of the conductive layer of the substrate, so that the sensing film forms an ion sensing electrode , and the ion sensing electrode of the sensing thin film has a sensing area and a non-sensing area.

Continuing from the above, the manufacturing method of the potentiometric urea sensing element of the aforementioned TW-588159 further includes steps: extending a conductive wire from the conductive layer so as to form an outward electrical contact; Covering the non-sensing area of the sensing film, and forming a sensing window on the sensing area; finally, fixing a urease in the sensing window on the sensing film.

Another conventional urea biosensor signal processing method, such as the invention patent of the Republic of China Patent Publication No. TW-I276798 "Solid-state urea biosensor and its signal acquisition method", which discloses a solid-state urea biosensor The method of detecting signal acquisition. The signal acquisition method of the solid-state urea biosensor includes: using a solid-state urea biosensor to measure from an object to be tested to obtain a signal (ie, urea measurement signal); then, using a meter The amplifier picks up the signal measured by the solid-state urea biosensor.

Continuing from the above, the signal acquisition method of the solid-state urea biosensor of the aforementioned TW-I276798 further includes: transmitting the signal to a low-pass filter to remove high-frequency noise of the signal, so as to obtain an already removing the noise signal; then, transmitting the noise-removed signal to a computer via a data acquisition card.

Continuing from the above, the signal acquisition method of the solid-state urea biosensor of the aforementioned TW-I276798 further includes: outputting the noise-removed signal in the computer to an output potential display panel in real time, and analyzing the signal with a signal The program analyzes the signal, and the signal analysis program includes an analysis function and a parameter setting panel for real-time calibration of calculation parameters and calculation of the concentration of the analyte; finally, an operation result is displayed in a concentration of the analyte display panel.

Another conventional urea biosensor, such as the invention patent of the Republic of China Patent Publication No. TW-I328115 "solid-state urea biosensor", discloses a solid-state urea biosensor. The solid-state urea biosensor includes a substrate, a conductive layer, an acid-base sensing film, an ammonium ion selective film and an enzyme film.

Continuing from the above, the conductive layer of the aforementioned TW-I328115 is suitable Covering is formed on the substrate to form a covering layer. The acid-base sensing film has a pH value measuring area, and a part of the acid-base sensing film is selectively covered on the conductive layer, and the pH value measuring area is used to measure one of a solution to be measured pH value.

As mentioned above, the ammonium ion selective membrane of No. TW-I328115 has an ammonium ion measurement area, and the ammonium ion measurement area is used to measure the ammonium ion concentration value of the solution to be tested, and A part of the ammonium ion selective film is optionally covered on the acid-base sensing film, so that the pH value measuring area of the acid-base sensing film can be properly exposed relative to the ammonium ion selective film.

Succeeding above, the enzyme film of the aforementioned TW-I328115 is used to measure a urea concentration value of the solution to be tested, and a part of the enzyme film is selectively covered and formed on the ammonium ion-selective film, so that it can be compared with the enzyme The film can properly expose the ammonium ion measuring area of the ammonium ion selective film.

However, the aforementioned U.S. Patent Publication No. US-20060096858 patent application, the Republic of China Patent Publication No. TW-588159, No. TW-I276798 and No. TW-I328115 urea biosensors, their manufacturing methods and the amount of urea The detection signal processing method does not disclose how to use it for blood uric acid detection or its related methods, so there must be a demand for how to use it for blood uric acid detection or provide its related methods.

Another commonly used uric acid sensing element, such as the invention patent of the Republic of China Patent Announcement No. TW-I241906 "Disposable Electrochemically Modified Screen Printed Electrode Uric Acid Detection Test Strip, Its Preparation Method and Application", which discloses a disposable electrochemical modification Screen-printed electrode uric acid detection test piece, and the disposable electrochemically modified screen-printed electrode uric acid detection test piece includes an electrically insulating back plate, a conductive film and an insulating layer.

As mentioned above, the conductive film of the aforementioned TW-I241906 is covered on the electrically insulating backplane, and the conductive film forms several electrodes, and several of the The electrode includes an electrode joint, a working electrode and a reference electrode, and the insulating layer is covered on the conductive film, and the electrically insulating back plate can be made of polyethylene, polypropylene synthetic paper, plastic or ceramic sheet.

Continuing from the above, the conductive film of the aforementioned TW-I241906 includes a wire layer and an electrode layer, and the wire layer can be selected to be made of silver or silver chloride, and the wire layer is covered on the electrically insulating layer by screen printing. The back plate, and the electrode layer can be made of a mixture of carbon powder, graphite powder and metal particles, and the electrode layer is covered on the wire layer by screen printing.

However, the aforementioned Republic of China Patent Announcement No. TW-I241906 of the disposable electrochemically modified screen-printed electrode uric acid detection test piece only provides electrochemical technology to process the screen-printed electrode technology, and it does not disclose how to measure blood uric acid Detection data (for example: extended gate sensing field-effect transistor resistance voltage-dividing measurement method) or related methods, so there must be a need for how to measure blood uric acid detection data or provide related methods.

In short, the aforementioned ROC Patent Announcements No. TW-I374267, No. TW-I377342, US Patent Publication No. US-20060096858, and ROC Patent Announcements No. TW-588159, No. TW-I276798, No. No. TW-I328115 and No. TW-I241906 are only for reference of the technical background of the present invention and to illustrate the current state of technological development, and are not intended to limit the scope of the present invention.

In view of this, in order to meet the above technical problems and needs, the present invention provides a biomedical sensor measurement system and method for uric acid detection, which uses a uric acid sensing element to measure and obtain a uric acid measurement signal , and the uric acid sensing element is electrically connected to a uric acid signal processing circuit, so that the uric acid measurement signal is processed by the uric acid signal processing circuit to obtain a processed uric acid measurement signal, and the uric acid signal is processed The circuit is electrically connected to a signal readout circuit, so that the processed uric acid measurement signal is amplified through the signal readout circuit to obtain an amplified The uric acid measurement signal, therefore, can achieve the purpose of providing accurate measurement of uric acid, improving sensing characteristics and measurement stability compared with conventional uric acid sensing elements.

The main purpose of the present invention is to provide a biomedical sensor measurement system and method for uric acid detection, which uses a uric acid sensing element to measure and obtain a uric acid measurement signal, and connects the uric acid sensing element to an electric current. Sexually connected to a uric acid signal processing circuit, so that the uric acid measurement signal is processed by the uric acid signal processing circuit to obtain a processed uric acid measurement signal, and the uric acid signal processing circuit is electrically connected to a signal readout The circuit, in this way, amplifies the processed uric acid measurement signal through the signal readout circuit to obtain an amplified uric acid measurement signal, so as to achieve the functions of providing accurate measurement of uric acid, improving sensing characteristics and measurement stability.

In order to achieve the above purpose, the measurement method of the biomedical sensor for uric acid detection according to the preferred embodiment of the present invention includes:

Using a uric acid sensing element to measure a uric acid sample to obtain a uric acid measurement signal;

The uric acid sensing element is electrically connected to a uric acid signal processing circuit;

Process the uric acid measurement signal through the uric acid signal processing circuit to obtain a processed uric acid measurement signal;

electrically connecting the uric acid signal processing circuit to a signal readout circuit; and

The processed uric acid measurement signal is amplified through the signal readout circuit to obtain an amplified uric acid measurement signal.

The uric acid sensing element in a preferred embodiment of the present invention is a ruthenium dioxide thin film uric acid sensing element.

The uric acid signal processing circuit in a preferred embodiment of the present invention includes an extended gate sensing field effect transistor and a voltage divider resistor, so that the extended gate sensing field effect transistor is formed as a resistor, or the uric acid signal office The management circuit includes an NMOS extended gate sensing field effect transistor and a voltage dividing resistor, so that the NMOS extended gate sensing field effect transistor is formed as a resistor.

In the preferred embodiment of the present invention, the amplified uric acid measurement signal is converted from an analog signal to a digital signal.

In a preferred embodiment of the present invention, the uric acid measurement signal is directly proportional to a uric acid measurement concentration.

In order to achieve the above object, the measurement system of the biomedical sensor for uric acid detection according to the preferred embodiment of the present invention includes: a uric acid sensing element, which includes a substrate; several sensing electrodes, which are arranged on the uric acid On the substrate of the sensing element, and the sensing electrode is used for measuring a uric acid sample to be measured, so as to obtain a uric acid measurement signal; at least one uric acid signal processing circuit, which is electrically connected to the uric acid sensing element; and at least one signal readout circuit electrically connected to the uric acid signal processing circuit; The uric acid measurement signal is processed by the uric acid signal processing circuit to obtain a processed uric acid measurement signal, and then the processed uric acid measurement signal is amplified by the signal readout circuit to obtain an amplified uric acid measurement signal Measure the signal.

The substrate of the preferred embodiment of the present invention is selected from a flexible substrate or a non-flexible substrate.

In a preferred embodiment of the present invention, the plurality of sensing electrodes form an electrode array, and the electrode array includes several sensing electrode groups.

The uric acid signal processing circuit in a preferred embodiment of the present invention includes an extended gate sensing field effect transistor and a voltage divider resistor, or the uric acid signal processing circuit includes an NMOS extended gate sensing field effect transistor and A divider resistor.

The signal readout circuit of a preferred embodiment of the present invention includes a positive terminal voltage follower, a negative terminal voltage follower and a differential amplifier.

1: Uric acid sensing element

11: Substrate

12: Circuit layout layer

121: Reference electrode

122: metal electrode layer

123: Sensing electrode

124: Sensing signal output electrode

13: Insulation pattern layer

100: uric acid sample to be tested

2: Uric acid signal processing circuit

21:Extended gate sensing field effect transistor

22: Divider resistor

3: Signal readout circuit

31: Positive terminal voltage follower

32: Negative terminal voltage follower

33: Differential amplifier

4: Analog conversion digital circuit

9: The uric acid measurement signal has been amplified

a: Epoxy resin layer

b: Aminopropyltrioxysilane layer

c: glutaraldehyde layer

d: uricase layer

Figure 1: A schematic block diagram of a biomedical sensor measurement system for uric acid detection in a preferred embodiment of the present invention.

Figure 2: Schematic flow chart of the measurement method of the biomedical sensor for uric acid detection in a preferred embodiment of the present invention.

Fig. 3: A schematic circuit diagram of a biomedical sensor measurement system for uric acid detection in the first preferred embodiment of the present invention using a combination of uric acid sensing elements and measurement circuits.

Figure 4: A schematic front view of a uric acid sensing element used in a measurement system of a biomedical sensor for uric acid detection according to a preferred embodiment of the present invention.

Fig. 5: A schematic side view of the uric acid sensing element used in the measurement system of the biomedical sensor for uric acid detection in a preferred embodiment of the present invention.

Fig. 6: A schematic circuit diagram of a uric acid signal processing circuit used in a measurement system of a biomedical sensor for uric acid detection according to a preferred embodiment of the present invention.

Fig. 7: A schematic circuit diagram of a signal readout circuit used in a measurement system of a biomedical sensor for uric acid detection according to a preferred embodiment of the present invention.

Figure 8: A schematic diagram of the relationship between the sensing voltage and the concentration of uric acid in the measurement system and method of the biomedical sensor for uric acid detection in a preferred embodiment of the present invention.

Fig. 9: A schematic diagram of the relationship between response voltage and time of the biomedical sensor measurement system and method for uric acid detection in a preferred embodiment of the present invention.

Fig. 10: The measurement system of the biomedical sensor for uric acid detection according to the second preferred embodiment of the present invention adopts the circuit schematic diagram of the combination of uric acid sensing element and measurement circuit.

In order to fully understand the present invention, preferred embodiments will be described below in detail together with the accompanying drawings, which are not intended to limit the present invention.

The biomedical sensor measurement system and method for uric acid detection in the preferred embodiments of the present invention are suitable for the measurement or comparison of various [blood] uric acid biomedical sensing circuit components, various [blood] ] The measurement operation or comparison operation of uric acid biomedical sensing chip or the measurement operation and related measurement operation or comparison operation of various (blood) uric acid biomedical sensing systems, but it is not intended to limit the scope of the present invention application range.

FIG. 1 shows a schematic block diagram of a biomedical sensor measurement system for uric acid detection according to a preferred embodiment of the present invention. Please refer to Figure 1, for example, the measurement system of the biomedical sensor for uric acid detection in a preferred embodiment of the present invention mainly includes a uric acid sensing element 1, at least one or several uric acid [quantity Measurement] signal processing circuit 2 and at least one or several signal readout circuits (that is, uric acid measurement signal readout circuit) 3, as shown on the left side of Figure 1.

Figure 2 shows a schematic flow chart of the measurement method of the biomedical sensor for uric acid detection in a preferred embodiment of the present invention, which corresponds to the measurement system of the biomedical sensor for uric acid detection in Figure 1 . Figure 3 discloses a schematic circuit diagram of a combination of uric acid sensing elements and measurement circuits used in the measurement system of the biomedical sensor for uric acid detection according to the first preferred embodiment of the present invention, which corresponds to Figures 1 and 2 Measurement system and method of biomedical sensor for uric acid detection.

Please refer to Figures 1, 2 and 3, the measurement method of the biomedical sensor for uric acid detection according to the preferred embodiment of the present invention includes step S1: for example, first, using the uric acid sensing element 1 [For example: ruthenium dioxide [RuO ₂ ] thin film uric acid sensing element or other uric acid sensing element] Measure a response voltage [response voltage] in a uric acid sample 100 to be tested, for example: high level or low level, Obtain a uric acid measurement signal, as shown on the left side of Figure 3.

FIG. 4 shows a schematic front view of a uric acid sensing element used in a measurement system of a biomedical sensor for uric acid detection according to a preferred embodiment of the present invention. FIG. 5 shows a schematic side view of a uric acid sensing element used in a measurement system of a biomedical sensor for uric acid detection according to a preferred embodiment of the present invention, which corresponds to a schematic front view of the uric acid sensing element in FIG. 4 .

Please refer to Figures 1, 2, 3, 4 and 5 again. For example, the uric acid sensing element 1 includes a substrate 11, a circuit layout layer (printed circuit layer) 12 and an insulating pattern layer (for example: epoxy resin layer] 13, and the substrate [for example: polyethylene terephthalate or other flexible or non-flexible material] 11 is selected from a flexible substrate or a non-flexible substrate, And the circuit layout layer 12 includes several reference electrodes [L-shaped pattern, which can be selected to be made of silver or other metal materials] 121, several metal electrode layers [sensing metal film layer] 122, several sensing electrodes [ Working electrode, I-shaped pattern] 123 and several sensing signal output electrodes 124 for subsequent uric acid measurement signal processing.

Please refer to Figures 1, 3, 4 and 5 again. For example, the metal electrode layer 122 is selected to be made of ruthenium dioxide material or other materials, and the sensing electrode 123 is selected to be made of a composite material [for example: Composite uricase and silver nanoparticle materials or other composite materials], and several sensing electrodes 123 form an electrode array or an electrode array sensing window, and the electrode array or electrode array sensing window includes Several sensing electrode groups are used to simultaneously use multiple uric acid measurement signals for subsequent signal processing operations.

Please refer to Figures 1, 3, 4 and 5 again. For example, the sensing electrode 123 further includes an epoxy resin layer a, an aminopropyl trioxysilane layer [can be selected as an enzyme immobilization layer ] b, a glutaraldehyde layer [can be selected as an enzyme immobilization layer] c and a uricase layer [Uricase, which can be fixed by cross-linking method] d, and the epoxy resin layer a, aminopropyl three The sensing electrode 123 is sequentially formed with an oxysilane layer b, a glutaraldehyde layer c and a uricase layer d.

Please refer to Figures 1, 2, 3, 4 and 5 again, the measurement method of the biomedical sensor for uric acid detection according to the preferred embodiment of the present invention includes step S2: for example, then, with appropriate Technical means The uric acid sensing element 1 (for example: sensing signal output electrode 124) is electrically connected (electrically connected) to the uric acid signal processing circuit 2 or other related circuits, so as to perform a uric acid signal processing operation, as shown in Section 3 Shown on the left side of the figure.

FIG. 6 shows a schematic circuit diagram of a uric acid signal processing circuit used in a measurement system of a biomedical sensor for uric acid detection according to a preferred embodiment of the present invention. Please refer to Figures 1, 3 and 6. For example, the uric acid signal processing circuit 2 includes an extended gate sensing field effect transistor 21 [or an NMOS extended gate sensing field effect transistor can be selected. ] and a voltage dividing resistor [for example: a variable resistor or an element with a variable resistor function can be selected] 22, so that the extended gate sensing field effect transistor 21 is formed as a resistor, and the uric acid signal processing circuit 2 It has a positive supply voltage V _DD , a negative supply voltage V _SS and an output voltage V _EG , and the output voltage V _EG is output from the voltage dividing resistor 22 . The preferred embodiment of the present invention can choose to use the calculation formula of the output voltage V _EG as follows:

Where V _DD is a positive supply voltage, V _SS is a negative supply voltage, R _EGFET is a resistance formed by an extended gate sensing field effect transistor, and R _D is a voltage dividing resistor.

Please refer to Figures 1, 3 and 6 again. For example, the uric acid measurement signal of the uric acid sensing element 1 has a sensing voltage, and the sensing voltage can cause changes in the extension of the uric acid signal processing circuit 2. The gate senses a resistance value of the field effect transistor 21 so as to change the output voltage V _EG generated by the voltage dividing resistor 22 .

Please refer to again shown in Fig. 1, 2 and 3, the preferred embodiment of the present invention The measurement method of the biomedical sensor for uric acid detection in the embodiment includes step S3: for example, then, for example, then, the uric acid measurement signal is properly processed through the uric acid signal processing circuit 2, Obtain a processed uric acid measurement signal, and appropriately output the processed uric acid measurement signal to one or several other circuits, so as to properly perform other subsequent signal processing operations (for example: signal readout operation, signal amplification operation, signal Calibration work or other signal processing work].

Please refer to Figures 1, 2 and 3 again. The measurement method of the biomedical sensor for uric acid detection according to the preferred embodiment of the present invention includes step S4: using appropriate technical means to convert one or several uric acid signals The processing circuit 2 is electrically connected to one or several signal readout circuits 3 to perform a signal amplification operation, as shown on the right side of FIG. 3 . In addition, the signal readout circuit 3 can reduce the noise interference of the processed uric acid measurement signal.

FIG. 7 shows a schematic circuit diagram of a signal readout circuit used in a measurement system of a biomedical sensor for uric acid detection according to a preferred embodiment of the present invention. Please refer to Figures 1, 3 and 7, for example, the signal readout circuit 3 includes a positive terminal voltage follower 31, a negative terminal voltage follower 32 and a differential amplifier 33, and the signal The readout circuit 3 has a positive terminal input voltage V ₊ , a negative terminal input voltage V ₋ and an output voltage V _OUT , and the output voltage V _OUT is output from the differential amplifier 33 of the signal readout circuit 3, as shown in the seventh Shown on the right side of the figure.

Please refer to Figures 1, 3 and 7 again. For example, the positive terminal voltage follower 31, the negative terminal voltage follower 32 and the differential amplifier 33 are properly connected to form the signal readout circuit 3, and the The positive terminal voltage follower 31, the negative terminal voltage follower 32 and the differential amplifier 33 are properly connected to form a two-stage operational amplifier device, and the uric acid signal processing circuit 2 and the signal readout circuit 3 can be optionally integrated into one A single chip or a single circuit device, which can be optionally combined with at least one or several CMOS integrated circuits to improve its circuit characteristics.

Please refer to Fig. 7 again. For example, the positive terminal voltage follower 31 includes a first operational amplifier and a resistance of the first follower (as shown in the lower left side of Fig. 7), and the Negative terminal voltage follower 32 comprises a second operational amplifier and a resistance of the second follower (as shown in the upper left side of Fig. 7), and this differential amplifier 33 comprises a third operational amplifier and four differential The resistance of the moving amplifier (as shown on the right side of Figure 7).

Please refer to Figures 1, 2, 3 and 7 again, the measurement method of the biomedical sensor for uric acid detection in the preferred embodiment of the present invention includes step S5: for example, then, with appropriate technical means Properly read and amplify the processed uric acid measurement signal through one or several signal readout circuits 3 to obtain an amplified uric acid measurement signal (that is, the amplified response voltage) 9, and the amplified The uric acid measurement signal 9 can be selected to be properly output to the outside (exterior) or to perform signal conversion (for example: analog conversion to digital).

FIG. 8 shows a schematic diagram of the relationship between the sensing voltage and the concentration of uric acid in the measurement system and method of the biomedical sensor for uric acid detection according to a preferred embodiment of the present invention. Please refer to Figures 1, 3 and 8. For example, the uric acid measurement signal is directly proportional to a uric acid measurement concentration, and the linearity (linearity) of the uric acid signal processing circuit 2 is 0.997, and the uric acid signal The average sensitivity [sensitivity] of the processing circuit 2 is 12.69 mV/(mg/dL), but it is not intended to limit the scope of application of the present invention.

FIG. 9 shows a schematic diagram of the relationship between response voltage and time of the biomedical sensor measurement system and method for uric acid detection according to a preferred embodiment of the present invention. Please refer to Figures 1 and 9, for example, the initial voltage of the uric acid signal processing circuit 2 is about 32mV, and it generates a voltage transition (voltage transition) to 96.6mV in about 30 seconds, and reaches the voltage in about 38 seconds For 95% conversion, the response time (response time) is about 8 seconds, but it is not intended to limit the scope of application of the present invention.

Figure 10 discloses the measurement system of the biomedical sensor for uric acid detection in the second preferred embodiment of the present invention using uric acid sensing elements and measurement Circuit diagram of the circuit combination. Please refer to Figures 1 and 10, compared to the first embodiment, the measurement system of the biomedical sensor used for uric acid detection in the second preferred embodiment of the present invention includes an analog conversion digital circuit 4, and uses The analog conversion digital circuit 4 converts the amplified uric acid measurement signal 9 from an analog signal into a digital signal.

The above experimental data are preliminary experimental results obtained under specific conditions, which are only used for easy understanding or reference to the technical content of the present invention, and other related experiments are still required. The experimental data and its results are not intended to limit the scope of the present invention.

The above-mentioned preferred embodiments only illustrate the present invention and its technical characteristics, and the technology of this embodiment can still be implemented in various substantially equivalent modifications and/or replacements; therefore, the scope of rights of the present invention depends on the appended patent application The scope defined by the scope shall prevail. The copyright in this case is restricted to be used for patent applications in the Republic of China.

1: Uric acid sensing element

100: uric acid sample to be tested

2: Uric acid signal processing circuit

3: Signal readout circuit

9: The uric acid measurement signal has been amplified

Claims (10)

A measurement method of a biomedical sensor for uric acid detection, which includes: using a uric acid sensing element to measure a uric acid sample to obtain a uric acid measurement signal; electrically charging the uric acid sensing element Sexually connected to a uric acid signal processing circuit; the uric acid measurement signal is processed through the uric acid signal processing circuit to obtain a processed uric acid measurement signal; the uric acid signal processing circuit is electrically connected to a signal readout circuit; and amplifying the processed uric acid measurement signal through the signal readout circuit to obtain an amplified uric acid measurement signal, and integrating the uric acid signal processing circuit and the signal readout circuit into a single chip; wherein the uric acid The sensing element includes a sensing electrode, and the sensing electrode can be made of a compound uricase and silver nanoparticle material, and the uric acid sensing element is a ruthenium dioxide thin film uric acid sensing element. A measurement method of a biomedical sensor for uric acid detection, which includes: using a uric acid sensing element to measure a uric acid sample to obtain a uric acid measurement signal; electrically charging the uric acid sensing element Sexually connected to a uric acid signal processing circuit; the uric acid measurement signal is processed through the uric acid signal processing circuit to obtain a processed uric acid measurement signal; the uric acid signal processing circuit is electrically connected to a signal readout circuit; And the processed uric acid measurement signal is amplified by the signal readout circuit to obtain an amplified uric acid measurement signal; wherein the uric acid sensing element is a ruthenium dioxide thin film uric acid sensing element. The measurement method of the biomedical sensor for uric acid detection according to item 1 or 2 of the patent application, wherein the uric acid signal processing circuit includes an extended gate sensing field effect transistor and a voltage dividing resistor , so that the extended gate sensing field effect transistor is formed as a resistor, or the uric acid signal processing circuit includes an NMOS extended gate sensing field effect transistor and a voltage dividing resistor, so that the NMOS extended gate The sensing field effect transistor is formed as a resistor. The measurement method of the biomedical sensor for uric acid detection according to item 1 or 2 of the scope of the patent application, wherein the amplified uric acid measurement signal is converted from an analog signal to a digital signal. The measurement method of the biomedical sensor for uric acid detection according to claim 1 or 2 of the patent application, wherein the uric acid measurement signal is directly proportional to a uric acid measurement concentration. A measurement system of a biomedical sensor for uric acid detection, which includes: a uric acid sensing element, which includes a substrate; several sensing electrodes, which are arranged on the substrate of the uric acid sensing element, and the Several sensing electrodes are used for measuring a uric acid sample to be tested to obtain a uric acid measurement signal, and one of the plurality of sensing electrodes can be selected to be made of a composite uricase and silver nanoparticle material; At least one uric acid signal processing circuit, which is electrically connected to the uric acid sensing element; and at least one signal readout circuit, which is electrically connected to the uric acid signal processing circuit; wherein the uric acid measurement signal passes through the uric acid signal processing circuit process to obtain a processed uric acid measurement signal, and then amplify the processed uric acid measurement signal through the signal readout circuit to obtain an amplified uric acid measurement signal, and process the uric acid signal processing circuit and signal The readout circuit is integrated into a single chip, and the uric acid sensing element is a ruthenium dioxide thin film uric acid sensing element. A measurement system of a biomedical sensor for uric acid detection, which includes: a uric acid sensing element, which includes a substrate; several sensing electrodes, which are arranged on the substrate of the uric acid sensing element, and the Several sensing electrodes are used to measure a uric acid sample to obtain a uric acid measurement signal; at least one uric acid signal processing circuit is electrically connected to the uric acid sensing element; and at least one signal readout circuit , which is electrically connected to the uric acid signal processing circuit wherein the uric acid measurement signal is processed by the uric acid signal processing circuit to obtain a processed uric acid measurement signal, and then the processed uric acid measurement signal is amplified by the signal readout circuit to obtain a processed uric acid measurement signal The uric acid measurement signal is amplified, and the uric acid sensing element is a ruthenium dioxide thin film uric acid sensing element. According to the measurement system of the biomedical sensor for uric acid detection according to item 6 or 7 of the patent scope of the application, wherein the plurality of sensing electrodes form an electrode array, and the electrode array includes a plurality of sensing electrode groups . The measuring system of the biomedical sensor for uric acid detection according to item 6 or 7 of the patent application, wherein the uric acid signal processing circuit includes an extended gate sensing field effect transistor and a voltage dividing resistor , or the uric acid signal processing circuit includes an NMOS extended gate sensing field effect transistor and a voltage dividing resistor. According to the measurement system of the biomedical sensor for uric acid detection described in item 6 or 7 of the scope of application, the signal readout circuit includes a positive terminal voltage follower, a negative terminal voltage follower and a differential amplifier.

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