Biochemical sensor based on nanosheet stacking structure and its manufacturing method

Abstract

The present invention discloses a biochemical sensor based on a nanosheet stacking structure and a method for manufacturing the same. The biochemical sensor comprises: an SOI substrate, a multi-layer suspended stacking structure comprising a sensitive material formed by selectively etching multiple stacking layers composed of a sacrificial layer / sensitive material layer, an anode electrode and a cathode electrode formed on the multi-layer suspended stacking structure, and an active film terminated with an active group attached to the surface of the multi-layer suspended stacking structure. When the biochemical sensor is in operation, the anode electrode and the cathode electrode are respectively connected to the positive electrode of an adjustable voltage source and the negative electrode of an ammeter, and the negative electrode of the adjustable voltage source is connected to the positive electrode of the ammeter. The manufacturing method comprises: cleaning the silicon wafer; growing multiple stacking layers of sacrificial layers / sensitive material layers; patterning the multiple stacking layers; manufacturing electrodes; selectively etching the sacrificial layer portion of the multiple stacking layers; and modifying with an active reagent. The biochemical sensor of the present invention has low cost, high sensitivity, and high precision. The present invention can mass-produce biochemical sensors efficiently and at low cost.

Description

Technical Field

[0001] The present invention relates to a biochemical sensor based on a nanosheet stacking structure and a manufacturing method thereof, belonging to the technical field of biochemical sensors. Background Art

[0002] Biological and chemical sensors (biochemical sensors) have widespread and important applications in many fields, including biomedicine, chemical engineering, environmental monitoring, and food hygiene. The ever-expanding application demands place increasingly stringent performance requirements on biochemical sensors, requiring not only excellent selectivity, high sensitivity, fast analysis speed, and low cost, but also miniaturization, integration, automation, and the ability to perform continuous online monitoring in complex systems. Biochemical sensors can be broadly categorized as resistive, capacitive, diode, bipolar transistor, and field-effect transistor types. Resistive biochemical sensors have been the most extensively studied and intensively researched due to their simple structure, high accuracy, wide measurement range, long lifespan, and ease of miniaturization. The basic principle of resistive biochemical sensors is to convert changes in the measured physical quantity into changes in resistance, which are then displayed or recorded via a corresponding measurement circuit.

[0003] Until now, the fabrication of biochemical sensors typically requires the creation of additional microfluidic channels to provide a support environment for the analyte. Fabricating these channels requires a complex series of processes, including photolithography, molding, and bonding, significantly increasing the complexity of device design and fabrication, and increasing production costs. To reduce device fabrication costs while meeting the requirements for sensor miniaturization and integration, researchers have turned their attention to three-dimensional (3D) devices. They exploit the internal stress generated by SU-8 photoresist, which adheres well to graphene, under incomplete exposure to drive the self-assembly of graphene films into 3D devices with specific shapes. This 3D structure significantly increases the contact and reaction area between graphene and the analyte per unit chip area, providing more attachment points for adsorption and doping of analyte molecules, thereby improving the overall performance of the sensor. This microtubular 3D graphene sensor, based on the SU-8 stress layer, features a natural microfluidic channel, eliminating the need for additional microfluidic channel fabrication, sealing, and other components, reducing the complexity of device design and fabrication. However, the device's manufacturing difficulty, poor operability, and reliability limit its application in the field of biochemical sensors. Summary of the Invention

[0004] The purpose of the present invention is to provide a biochemical sensor based on a nanosheet stacking structure to overcome the problems of high cost, low sensitivity and precision of traditional planar two-dimensional (2D) biochemical sensors.

[0005] Another object of the present invention is to provide a method for manufacturing the biochemical sensor, which can efficiently and cost-effectively batch-produce micro-stacked three-dimensional (3D) biochemical sensors.

[0006] To achieve the above object, the present invention adopts the following technical solutions:

[0007] A biochemical sensor based on a nanosheet stacking structure comprises: an SOI substrate, a multi-layer suspended stacking structure comprising sensitive materials formed by selectively etching multiple stacking layers consisting of sacrificial layers / sensitive material layers, an anode electrode and a cathode electrode formed on the multi-layer suspended stacking structure, and an active film terminated with active groups attached to the surface of the multi-layer suspended stacking structure. When the biochemical sensor is in operation, the anode electrode and the cathode electrode are respectively connected to the positive electrode of an adjustable voltage source and the negative electrode of an ammeter, and the negative electrode of the adjustable voltage source is connected to the positive electrode of the ammeter.

[0008] The sacrificial layer is made of a thin film material such as germanium (Ge) or silicon germanium (SiGe). The selection criteria are that the etching solution for the sacrificial layer will not affect the sensitive material layer, the anode electrode, and the cathode electrode. The sensitive material layer is made of a conductive thin film material such as silicon (Si) or silver (Ag). Multilayer refers to two or more layers. The thickness of each sacrificial layer and sensitive material layer is 10nm-100μm, respectively.

[0009] The anode and cathode electrodes are made of commonly used electrode materials such as chromium / gold (Cr / Au), titanium / gold (Ti / Au), palladium / gold (Pd / Au), and titanium / platinum (Ti / Pt). The thickness of the adhesion layer materials such as chromium (Cr), titanium (Ti), and palladium (Pd) is 5nm-30nm, and the thickness of the conductive layer such as gold (Au) and platinum (Pt) is 10nm-1μm.

[0010] The active film includes 3-(2,3-epoxypropoxy)propyltrimethoxysilane, 3-aminopropyltriethoxysilane and glutaraldehyde, and the active groups formed are amino, carboxyl or aldehyde groups.

[0011] A method for manufacturing the biochemical sensor based on the nanosheet stacking structure comprises the following steps:

[0012] Step 1: Clean the silicon wafer. Place the SOI substrate in a mixture of hydrogen peroxide and sulfuric acid at a ratio of 1:4. Boil the wafer at 85°C for 15 minutes to remove surface stains. Then clean it with diluted hydrofluoric acid for 3 minutes to remove the natural oxide layer on the surface. Finally, rinse with deionized water and dry it with nitrogen or spin dryer.

[0013] Step 2: Growth of multiple stacks of sacrificial layers / sensitive material layers. Multiple stacks of sacrificial layers / sensitive material layers are grown on the SOI substrate using thin film deposition techniques such as chemical vapor deposition (CVD) or reduced pressure chemical vapor deposition (RPCVD).

[0014] Step 3: Patterning the multi-stacked layer. Using photolithography technology, with photoresist as a barrier layer, RIE is used to etch the multi-stacked layer without photoresist covering it, and then the photoresist on the surface of the multi-stacked layer is cleaned with acetone.

[0015] Step 4: Make electrodes. Use photolithography, sputtering or electron beam evaporation, and lift-off techniques to prepare the anode and cathode electrodes. First, photoresist openings are formed in the anode and cathode regions by photolithography. Then, metal material is deposited using thermal evaporation or electron beam evaporation. Finally, a lift-off process is used to remove the photoresist and the metal material attached to the photoresist, leaving the electrode pattern, completing the preparation of the anode electrode 3 and the cathode electrode 4.

[0016] Step 5: Selectively etch the sacrificial layer in the multi-stacked layer. Immerse the chip with the electrode fabricated in an etching solution, which selectively etches the sacrificial layer, forming a three-dimensional (3D) structure with multiple suspended stacks of sensitive materials. Remove the etched sample and immediately rinse it with deionized water for 5 minutes, then blow dry it with high-pressure nitrogen.

[0017] Step 6: Active reagent modification. Immerse the chip after etching the sacrificial layer in a mixed solution of concentrated sulfuric acid and hydrogen peroxide at 70°C for 1-5 hours for hydroxylation treatment; then immediately wash and dry it, immerse it in a mixture of concentrated hydrochloric acid and anhydrous ethanol with a volume ratio of 1:1 for acid treatment for 1-24 hours; after washing and drying, immerse it in the active reagent solution for 0.5-7 days; then rinse it with ethanol and deionized water for 5 minutes in sequence, put it in an oven to dry, and complete the active reagent modification;

[0018] Step 7: Connect the anode electrode and cathode electrode to the positive electrode of the adjustable voltage source and the negative electrode of the ammeter respectively, and connect the negative electrode of the adjustable voltage source to the positive electrode of the ammeter; thus completing the fabrication of the biochemical sensor based on the nanosheet stacking structure.

[0019] Compared with the prior art, the present invention has the following advantages:

[0020] (1) Compared with two-dimensional planar sensors, this three-dimensional (3D) biochemical sensor based on a stacked nanosheet structure significantly reduces the chip footprint while maintaining or even increasing the area where the sensitive material contacts and reacts with the substance to be measured (gas or liquid), thereby improving the sensor's responsiveness and sensitivity. This is consistent with the development trend of miniaturization and integration of biochemical sensors.

[0021] (2) The stacking structure reduces the complexity of biochemical sensor design and production, and improves its reliability. The biochemical sensor based on the nanosheet stacking structure is formed by selective etching into a three-dimensional stacking structure, and its spacing is adjustable within the range of tens of nanometers to tens of micrometers, thereby having a strong capillary effect on the liquid test substance. During operation, a very small amount of the test solution can be automatically sucked into the conductive channel area of the sensitive material to complete the detection. This self-assembled sensor does not require additional auxiliary components such as microfluidics and sealing devices, thereby reducing the difficulty and cost of the manufacturing process and improving reliability. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 Schematic diagram of the structure of the biochemical sensor based on the nanosheet stacking structure of the present invention.

[0023] Figure 2 This is a flow chart for the production of a biochemical sensor based on a nanosheet stacking structure according to the present invention. DETAILED DESCRIPTION

[0024] The present invention will be described in detail below with reference to the accompanying drawings, but this does not limit the scope of protection of the present invention.

[0025] like Figure 1 As shown, the biochemical sensor based on the nanosheet stacking structure of the present invention includes: an SOI substrate 1, a multi-layer suspended stacking structure 8 with sensitive materials formed by selectively etching multiple stacking layers composed of sacrificial layers / sensitive material layers, an anode electrode 3 and a cathode electrode 4 formed on the multi-layer suspended stacking structure, and an active film 7 terminated with active groups attached to the surface of the multi-layer suspended stacking structure; when the biochemical sensor is in operation, the anode electrode 3 and the cathode electrode 4 are respectively connected to the positive electrode of the adjustable voltage source 5 and the negative electrode of the ammeter 6, and the negative electrode of the adjustable voltage source 5 is connected to the positive electrode of the ammeter 6.

[0026] like Figure 2 As shown in (a)-(g), the method for making a biochemical sensor based on a nanosheet stacking structure of the present invention comprises the following steps:

[0027] Step 1: Clean the silicon wafer. Place the SOI substrate in a mixture of hydrogen peroxide and sulfuric acid at a ratio of 1:4. Boil the wafer at 85°C for 15 minutes to remove surface stains. Then clean it with diluted hydrofluoric acid for 3 minutes to remove the natural oxide layer on the surface. Finally, rinse with deionized water and dry it with nitrogen or spin dryer.

[0028] Step 2: Growing a multi-stack of sacrificial layers / sensitive material layers 2. A thin film deposition technique, such as chemical vapor deposition (CVD) or reduced pressure chemical vapor deposition (RPCVD), is used to grow the multi-stack of sacrificial layers / sensitive material layers 2 on an SOI substrate 1. The thickness of the sacrificial layers and sensitive material layers ranges from 10 nm to 10 μm.

[0029] Step 3: Patterning the multi-stacked layer 2 of the sacrificial layer / sensitive material layer. Using photolithography technology, with photoresist as a barrier layer, RIE is used to etch the multi-stacked layer 2 of the sacrificial layer / sensitive material layer not covered by the photoresist. The photoresist on the surface of the multi-stacked layer 2 of the sacrificial layer / sensitive material layer is then cleaned with acetone.

[0030] Step 4: Electrode Fabrication. Anode electrode 3 and cathode electrode 4 are fabricated using photolithography, sputtering or electron beam evaporation, and lift-off techniques. First, photoresist openings are formed in the anode and cathode regions using photolithography. Metal is then deposited using thermal evaporation or electron beam evaporation. Finally, a lift-off process removes the photoresist and any metal attached to it, leaving the electrode patterns. This completes the fabrication of anode electrode 3 and cathode electrode 4.

[0031] Step 5: Selectively etch the sacrificial layer portion of the multi-stack of sacrificial layer / sensitive material layer 2. The chip with the electrodes fabricated is immersed in an etchant, which selectively etches the sacrificial layer, forming a three-dimensional (3D) structure with multiple suspended stacks of sensitive materials. The etched sample is removed and immediately rinsed with deionized water for 5 minutes, then blown dry with high-pressure nitrogen.

[0032] Step 6: Active agent modification. After etching the sacrificial layer, immerse the chip in a mixture of concentrated sulfuric acid and hydrogen peroxide at 70°C for 1-5 hours for hydroxylation. Immediately rinse, dry, and immerse in a mixture of concentrated hydrochloric acid and anhydrous ethanol at a volume ratio of 1:1 for acid treatment for 1-24 hours. After rinsing and drying, immerse in an active agent solution for 0.5-7 days. Rinse with ethanol and deionized water for 5 minutes each, then dry in an oven to complete the active agent modification.

[0033] Step 7: Connect the anode electrode 3 and the cathode electrode 4 to the positive electrode of the adjustable voltage source 5 and the negative electrode of the ammeter 6 respectively, and connect the negative electrode of the adjustable voltage source 10 to the positive electrode of the ammeter 6; thus completing the fabrication of the biochemical sensor based on the nanosheet stacking structure.

[0034] The detection method using the above-mentioned biochemical sensor based on the nanosheet stacking structure is as follows:

[0035] First, the sensor is placed in a detection environment (liquid medium or gas medium); the biochemical substance particles to be detected form surface adsorption with the active film 7, and the surface of the multi-layer suspended stack structure 8 containing sensitive materials generates an electric field or potential change, thereby changing the resistivity of the multi-layer stack 2 of the sacrificial layer / sensitive material layer; the change in the resistivity of the multi-layer suspended stack structure 8 containing sensitive materials can be detected by detecting the change in its current (current I between the anode electrode 3 and the cathode electrode 4) under a certain anode voltage (voltage V between the anode electrode 3 and the cathode electrode 4). Therefore, the doping level of the surface of the multi-layer suspended stack structure 8 containing sensitive materials (corresponding to the type and concentration of the biochemical substance to be detected) can be detected. That is, the type (Type) and concentration (Concentration) of the substance to be detected are functions of I, which can be obtained through analytical calculation.

Claims

1. A biochemical sensor based on a nanosheet stacking structure, characterized in that: include: An SOI substrate, a multi-layer suspended stack structure having a sensitive material formed by selectively etching multiple stacked layers composed of a sacrificial layer / sensitive material layer, an anode electrode and a cathode electrode formed on the multi-layer suspended stack structure, and an active film terminated with an active group attached to the surface of the multi-layer suspended stack structure, wherein the thickness of each sacrificial layer and the sensitive material layer are 10 nm to 10 μm, respectively; the sensitive material layer is a silver conductive film material; the active film is 3-(2,3-epoxypropyloxy)propyltrimethoxysilane, 3-aminopropyltriethoxysilane, or glutaraldehyde, and the active group formed is an amino group, a carboxyl group, or an aldehyde group; when the biochemical sensor is in operation, the anode electrode and the cathode electrode are connected to the positive electrode of an adjustable voltage source and the negative electrode of an ammeter, respectively, and the negative electrode of the adjustable voltage source is connected to the positive electrode of the ammeter; The anode and cathode electrodes are made of chromium / gold, titanium / gold, palladium / gold or titanium / platinum electrode materials, wherein the thickness of the chromium, titanium and palladium adhesion layer materials is 5nm-30nm, and the thickness of the gold and platinum conductive layers is 10nm-1μm.

2. The biochemical sensor according to claim 1, characterized in that The sacrificial layer is made of germanium or germanium silicon thin film material; the multilayer is more than two layers.

3. A method for manufacturing a biochemical sensor based on a nanosheet stacking structure according to claim 1, characterized in that: The steps include: Step 1: Cleaning the SOI substrate; Step 2: Using thin film deposition technology to grow multiple stacked layers of sacrificial layer / sensitive material layer on the SOI substrate; Step 3: Using photolithography technology, with photoresist as a barrier layer, RIE is used to etch the multi-stacked layer without photoresist covering it, and then the photoresist on the surface of the multi-stacked layer is cleaned with acetone; Step 4: Prepare the anode and cathode electrodes using photolithography, sputtering or electron beam evaporation, or lift-off technology. Step 5: Immerse the chip with the electrodes fabricated in an etching solution to selectively etch the sacrificial layer portion of the multi-stacked layer to form a three-dimensional (3D) structure with a multi-layer suspended stacked structure of sensitive materials; Step 6: After the sacrificial layer is etched, the chip is cleaned and dried, and then immersed in an active reagent solution for active reagent modification; Step 7: Connect the anode electrode and cathode electrode to the positive electrode of the adjustable voltage source and the negative electrode of the ammeter respectively, and connect the negative electrode of the adjustable voltage source to the positive electrode of the ammeter; thus completing the fabrication of the biochemical sensor based on the nanosheet stacking structure.

4. The production method according to claim 3, characterized in that: The thin film deposition technology is a reduced pressure chemical vapor deposition technology.

5. The production method according to claim 3, characterized in that: The cleaning process of the SOI substrate is as follows: the SOI substrate is placed in a mixture of hydrogen peroxide and sulfuric acid in a ratio of 1:4, the silicon wafer is boiled at 85°C for 15 minutes to remove surface stains, and then cleaned with diluted hydrofluoric acid for 3 minutes to remove the natural oxide layer on the surface. Finally, it is rinsed with deionized water and dried with nitrogen or a spin dryer.

6. The production method according to claim 3, characterized in that: After etching the sacrificial layer, the chip is immersed in a mixed solution of concentrated sulfuric acid and hydrogen peroxide at 70°C and kept at a constant temperature for 1-5 hours for hydroxylation treatment; then it is immediately washed, dried, and immersed in a mixture of concentrated hydrochloric acid and anhydrous ethanol with a volume ratio of 1:1 for acid treatment for 1-24 hours; after washing and drying, it is immersed in an active reagent solution for 0.5-7 days; then it is washed with ethanol and deionized water for 5 minutes in sequence, and placed in an oven for drying to complete the active reagent modification.

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