Biochip Detection Device, Its Biosensor Platform, Manufacturing Method and Application

By optimizing the thickness of gold thin film electrodes and streptavidin biological mediators of semiconductor manufacturing technology, the reproducibility and stability of biosensors are improved, and the accuracy of label-free affinity electrochemical biosensors is insufficient, and rapid and accurate detection of virus and microbial infections is achieved.

CN114460149BActive Publication Date: 2025-08-05AGRITALK TECH INC
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Patent Information

Application Number
CN202011238422.4
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2020-11-09
Publication Date
2025-08-05
Estimated Expiration
2040-11-09

AI Technical Summary

Technical Problem

Existing label-free affinity electrochemical biosensors have shortcomings in reproducibility, accuracy and stability, especially in electrode assembly and biological receptor fixation, affecting the accuracy and stability of the detection results.

Method used

By optimizing the thickness of the gold thin film electrode made by semiconductor manufacturing technology and combining streptavidin biological mediators, the immobility of the biological receptor is improved, a self-assembled monolayer structure is formed, and the reproducibility and stability of the biosensor is improved.

Benefits of technology

It has achieved high accuracy, stability and reproducibility of label-free affinity electrochemical biosensors. It is suitable for real-time medical products, can quickly screen virus and microbial infections, and is widely used in biotechnology, medical diagnosis and drug quarantine and other fields.

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Abstract

The present invention provides a biochip detection device and its biosensor platform, as well as its manufacturing method and application. The biosensor platform comprises a chip manufactured using semiconductor manufacturing technology; the chip is provided with a gold thin-film electrode, the surface of which is fixed with a biotinylated linker and a bioreceptor connected to the biotinylated linker, and the gold thin-film electrode has a thickness of at least a single gold atom. A biological sample to be tested is placed on the biosensor platform, where it reacts with the bioreceptor to form an impedance signal, thereby detecting whether the biological sample is infected. This improves the immobilization of the bioreceptor, thereby producing a label-free affinity electrochemical biosensor with excellent accuracy and stability, achieving the purpose of rapidly detecting viral and / or microbial infections.
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Description

Technical Field

[0001] The present invention relates to an electrochemical biosensor; in particular, to a biochip detection device manufactured using semiconductor manufacturing technology and formed by self-assembly of immunoglobulins bonded to a gold thin film electrode, as well as its biosensor platform, manufacturing method and application. Background Art

[0002] A biochip is broadly defined as a reaction zone on a solid phase (glass, silicon wafer, plastic, nylon membrane, etc.) created using methods such as microlithography or micro-immobilization. Biological samples react with molecules on the solid phase for applications in biological testing and chemical analysis. Due to their low sample volume, fast reaction speed, and parallel detection, they can detect a large number of molecules in a short period of time, allowing people to quickly obtain information from the sample. Among all biochips, biosensors are devices that combine biological and physical and chemical detection elements to detect analytes. They have great market potential due to their advantages, such as the ability to significantly reduce testing costs through the development of simple test strips, their high recognition of target objects, their industrial mass production, their ease of operation, their high sensitivity, low sample volume requirements, and their ability to quickly analyze data, allowing for real-time on-site detection.

[0003] Currently, the most suitable candidate for development as a point-of-care (POC) product is a label-free affinity electrochemical biosensor. The sensor comprises electrodes produced using semiconductor manufacturing technology and a biosynthesized streptavidin mediator. Semiconductor manufacturing technology enhances the consistency of electrode assemblies, thereby improving the reproducibility of the biosensor. Label-free affinity detection simplifies production and allows for direct interaction with a wide range of targets, expanding potential applications and improving the accuracy of the biosensor. Furthermore, streptavidin exhibits strong binding affinity for biotin-linked bioreceptors and stabilizes bioreceptor modifications, thereby improving the stability of the biosensor. Consequently, the label-free affinity electrochemical biosensor exhibits higher reproducibility, accuracy, and stability than biosensors produced by other methods.

[0004] It is worth noting that although the aforementioned label-free affinity electrochemical biosensors have improved in terms of performance in reproducibility, accuracy, and stability, the aforementioned three indicators are important indicators for POC products, and it is currently known that many factors will seriously affect the reproducibility, accuracy, and stability of biosensors. For example, in terms of electrode assembly, semiconductor manufacturing technology is adjusted to adapt to label-free affinity detection; this detection method directly measures the changes in electrical signals on the chip surface, so the accuracy depends largely on the electrode manufacturing method; among them, the thickness of the metal film is one of the important factors affecting accuracy, and it will seriously affect the conductivity (conductivity), which ultimately affects the detection results. Therefore, adjustments to semiconductor manufacturing technology can effectively improve accuracy. At the same time, although the use of streptavidin biomediators can improve stability, directly fixing the bioreceptor on the mediator will restrict its direction and interfere with its function, thereby limiting accuracy, and further improvement is needed.

[0005] In summary, it is necessary to further improve existing biosensors, especially the important components that determine the reproducibility, accuracy and stability of electrochemical biosensors: electrodes and biological mediators. Summary of the Invention

[0006] The first objective of the present invention is to provide a biosensor platform and a method for manufacturing the same. By optimizing semiconductor technology processes, the thickness of the gold thin film electrodes on the biosensor platform can be adjusted, and a streptavidin biomediator is used as a linker to improve the immobilization of bioreceptors. This results in a label-free affinity electrochemical biosensor suitable for real-time medical products with excellent accuracy and stability, thereby optimizing the reproducibility of label-free affinity detection.

[0007] Another object of the present invention is to provide a biochip detection device. By placing the aforementioned biosensor platform on a portable and disposable chip module and using it in conjunction with a detection host, rapid screening of biological samples can be performed based on the principle of biological receptor detection methods using immunoglobulins, nucleic acid probes, chemical molecules, functional proteins, or a combination thereof, thereby significantly reducing screening time.

[0008] Another object of the present invention is to provide an application of a biochip detection device. According to the object to be screened (infection of viral and / or microbial types), by fixing biological receptors selected from immunoglobulins, nucleic acid probes, chemical molecules, functional proteins or their combinations on the biochip of the chip module of the device, it can be quickly applied to screen different infection targets. It can be widely used in biotechnology, medical diagnosis, drugs and quarantine and other fields, and has great market competitive advantages.

[0009] To achieve the above objectives, the present invention provides a biosensor platform comprising a chip manufactured using semiconductor manufacturing technology; wherein: a gold thin film electrode is provided on the chip, a biotinylated linker and a bioreceptor connected to the biotinylated linker are fixed to the surface of the gold thin film electrode, and the gold thin film electrode has a thickness of at least a single gold atom; a biological sample to be tested is placed on the biosensor platform, where it reacts with the bioreceptor to form an impedance signal, thereby detecting whether the biological sample to be tested is infected.

[0010] The present invention further provides a method for manufacturing a biosensor platform, wherein the biosensor platform includes a chip produced using semiconductor manufacturing technology, and a gold thin film electrode is provided on the chip. The steps of the method include:

[0011] Step 1: activating the gold thin film electrode to form a self-assembled monolayer (SAM) structure on the surface of the gold thin film electrode;

[0012] Step 2: performing biotin bonding on the gold thin film electrode to add the biotinylated bioreceptor to the surface of the gold thin film electrode modified with the biomediator;

[0013] Step 3: Cleaning and drying the gold thin film electrode to prepare a biosensor platform with the gold thin film electrode.

[0014] The present invention further provides a biochip detection device, comprising: a detection host; a chip module having a biochip disposed therein, the biochip comprising a substrate, a biosensor platform disposed at opposite ends of the substrate, and a conductive electrode; wherein the biochip substrate is provided with a gold thin film electrode, a biotinylated linker and a bioreceptor connected to the biotinylated linker being fixed to the surface of the gold thin film electrode, and the gold thin film electrode having a thickness of at least a single gold atom; a conductive wire connecting the conductive electrode to the gold thin film electrode of the biosensor platform; the chip module is connected to the detection host, a biological sample to be tested is placed on the biosensor platform to react with the bioreceptor to form an impedance signal, and the detection host receives and processes the impedance signal to determine whether the biological sample to be tested is infected.

[0015] The present invention further provides an application of the biosensor platform, wherein the biosensor platform is used to detect biological receptors of immunoglobulins, nucleic acid probes, chemical molecules, functional proteins or a combination thereof.

[0016] The present invention further provides an application of the biochip detection device, wherein the biochip detection device is used to detect biological receptors of immunoglobulins, nucleic acid probes, chemical molecules, functional proteins or a combination thereof. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 Schematic diagram of the manufacturing process of the gold thin film electrode on the biosensor platform of the present invention;

[0018] Figure 2 Schematic diagram of the manufacturing process of the biosensor platform of the present invention;

[0019] Figure 3 Schematic diagram of the overall structure of the biochip detection device of the present invention;

[0020] Figure 4 This is a schematic diagram of the three-dimensional appearance of the detection main body of the biochip detection device of the present invention with the cover closed;

[0021] Figure 5 This is a schematic diagram of the three-dimensional appearance of the detection main body of the biochip detection device of the present invention with its cover opened;

[0022] Figure 6A 、 Figure 6B Schematic diagram of the display content of the human-machine interface of the biochip detection device of the present invention.

[0023] Description of symbols in the accompanying drawings:

[0024] 100: Biosensor Platform

[0025] 10: Chip

[0026] 11: Ceramic substrate

[0027] 12: Copper plating

[0028] 13: Resistive coating

[0029] 14: Light source device

[0030] 15: Gold thin film electrode

[0031] 16: Biotinylated linker

[0032] 17: Gelatin

[0033] 18: Biological receptors

[0034] 200: Biochip detection device

[0035] 20: Detect host

[0036] 21: Circuit Board

[0037] 22: Cable

[0038] 23: First pump

[0039] 231: First gas pipeline

[0040] 232: First pipeline interface

[0041] 24: Second pump

[0042] 241: Second gas pipeline

[0043] 242: Second pipeline interface

[0044] 25: Power supply

[0045] 26: Chip socket

[0046] 27: Human-Machine Interface

[0047] 28: Start button

[0048] 29: Integrated shell

[0049] 291: Main housing

[0050] 292: Flip

[0051] 293: Charging jack

[0052] 30: Chip module

[0053] 31: Biochip

[0054] 310: Electrode connector

[0055] 311: Substrate

[0056] 312: Conductive Electrode

[0057] 313: Conductive thread

[0058] 32: Integrated shell

[0059] 33: Cleaning fluid container

[0060] 331: First air pressure line

[0061] 332: First air inlet plug

[0062] 333: First infusion line

[0063] 34: Detection liquid container

[0064] 341: Second air pressure line

[0065] 342: Second air inlet plug

[0066] 343: Second infusion line

[0067] 35: Liquid recovery box

[0068] 351: Recovery pipeline DETAILED DESCRIPTION

[0069] The following is a clear and complete description of the technical solution of the present invention. Obviously, the embodiments described are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making any creative efforts are within the scope of protection of the present invention.

[0070] The biosensor platform provided by this invention is a semiconductor-based electrochemical biosensor platform. It optimizes the thickness of electrodes manufactured using semiconductor manufacturing technology and then combines them with a streptavidin biomediator to prepare for subsequent binding to various bioreceptors, thereby providing a label-free affinity electrochemical biosensor suitable for point-of-care (POC) medical applications. The biosensor platform comprises a chip and thin-film electrodes mounted thereon. By adjusting the thickness of the electrodes, the reproducibility and stability of the biosensor in label-free affinity detection are optimized. Furthermore, by adding a unique linker with ideal flexibility to the streptavidin biomediator, the biosensor's detection accuracy is enhanced.

[0071] like Figure 1 and Figure 2 , showing the semiconductor manufacturing process steps of the biosensor platform 100 of the present invention and the process for immobilizing bioreceptors 18 on a gold thin film electrode 15. The biosensor platform 100 of the present invention is formed by immobilizing bioreceptors 18 on the surface of a gold thin film electrode 15 of a semiconductor chip 10. The present invention adjusts the thickness of the gold thin film electrode 15 to a thickness of at least a single gold atom. This adjustment results in a more uniform thickness distribution within the thin film electrode, reducing the measured impedance value and enabling a more uniformly distributed impedance. This ensures a more stable and consistent impedance signal output by the biosensor platform 100.

[0072] like Figure 1 As shown, the biosensor platform 100 of the present invention includes a chip 10 produced using semiconductor manufacturing technology. A gold thin film electrode 15 is provided on the chip 10. A biotinylated linker 16 and a bioreceptor 18 connected to the biotinylated linker 16 are fixed to the surface of the gold thin film electrode 15, and the gold thin film electrode 15 has a thickness of at least a single gold atom.

[0073] like Figure 1, showing the manufacturing process of the gold thin film electrode 15 on the biosensor platform 100 of the present invention, the steps of which include (a) providing a ceramic substrate 11 → (b) copper plating: forming a copper plating layer 12 on the surface of the ceramic substrate 11 → (c) resistive coating: forming a resistive coating 13 on the surface of the copper plating layer 12 → (d) exposure / development: using a light source device 14 to irradiate the resistive coating 13 to perform exposure and development procedures → (e) electroplating gold: electroplating gold in the space formed after the resistive coating 13 is removed to form a gold thin film electrode 15 → (f) etching / film removal: removing the remaining resistive coating 13 → (g) making a chip 10 with a gold thin film electrode 15 on the surface. Among them, the present invention produces the gold thin film electrode 15 through direct copper plating (DPC) technology, sputtering and etching processes, which has the same manufacturing process as the electrodes produced by semiconductor manufacturing technology. In addition, as Figure 1 As shown in the small figure (f), the gold thin film electrode 15 is formed by coating with a thickness of at least a single gold atom; in the embodiment of the present invention, the maximum thickness of the gold thin film electrode 15 can be increased to a reasonable range according to actual needs.

[0074] like Figure 2 , showing that the steps of the method for preparing the biosensor platform of the present invention include:

[0075] Step 1: The gold thin film electrode 15 on the surface of the chip 10 is immersed in an activator for activation reaction to form a self-assembled monolayer (SAM) structure on the surface of the gold thin film electrode 15, and then sealed with gelatin 17;

[0076] Step 2: In order to immobilize the bioreceptor (immunoglobulin, nucleic acid probe, chemical molecule, functional protein or a combination thereof) on the gold thin film electrode 15, biotin bonding is performed, and the biotinylated bioreceptor 18 is added to the gold thin film electrode 15 modified with the biomediator (biotinylated linker 16), so that the bioreceptor 18 is bonded to the biotinylated linker 16;

[0077] Step 3: Finally, the modified electrode is cleaned and dried to obtain a semiconductor-fabricated electrochemical biosensor platform in which the gold thin film electrode 15 has a thickness of at least a single gold atom.

[0078] The biological receptors 18 are binding molecules. Specifically, the biological receptors 18 can be selected from immunoglobulins, nucleic acid probes, chemical molecules, functional proteins, or a combination thereof, and are used to screen different targets.

[0079] The biotinylated linker 16 is a streptavidin biomediator. Specifically, the biomediator used in the biosensor platform of the present invention is a linker independently constructed from the streptavidin sequence.

[0080] like Figures 3 to 5 and Figures 6A to 6B , showing the overall architecture, appearance structure and detection display results of the biochip detection device 200 of the present invention.

[0081] like Figure 3 A schematic diagram of an embodiment of the biochip detection device 200 of the present invention is shown. The embodiment is not used to limit the biochip detection device 200 of the present invention. The biochip detection device 200 of the present invention can adjust the number, setting method and position of components and parts according to actual detection requirements.

[0082] like Figure 3 As shown, the biochip detection device 200 of the present invention includes a detection host 20 and a chip module 30. A biochip 31 is disposed within the chip module 30. The biochip 31 includes a substrate 311, a biosensor platform 100 disposed at opposite ends of the substrate 311, and conductive electrodes 312. The substrate 311 of the biochip 31 includes the aforementioned gold thin film electrodes 15. A biotinylated linker 16 and a bioreceptor 18 connected to the biotinylated linker 16 are fixed to the surface of the gold thin film electrodes 15. The gold thin film electrodes 15 have a thickness of at least a single gold atom. Conductive wires 313 connect the conductive electrodes 312 to the gold thin film electrodes 15 of the biosensor platform 100. Thus, the chip module 30 is connected to the detection host 20. A biological sample to be tested is placed on the biosensor platform 100, where it reacts with the bioreceptors 18 to generate an impedance signal. The detection host 20 receives and processes the impedance signal to determine whether the biological sample to be tested is infected.

[0083] In a preferred embodiment of the biochip detection device 200 of the present invention, a circuit board 21 is provided inside the detection host 20, and the circuit board 21 is respectively connected to the propeller and power supply 25 provided inside the detection host 20, as well as the chip socket 26, human-machine interface 27 and start button 28 exposed on the external surface of the detection host 20; a biochip 31 and a test liquid container are provided inside the chip module 30; the biochip 31 has an electrode connector 310 formed on the external surface of the chip module 30; the chip module 30 is connected to the detection host 20, the electrode connector 310 is plugged into the chip socket 26, the propeller is connected to the test liquid container, and the test liquid is pushed by the propeller to be output to the biochip 31.

[0084] In an embodiment of the biochip detection device 200 of the present invention, a propeller within the detection host 20 is used to connect to the test liquid container of the chip module 30 to propel the test liquid to be output to the biochip 31 for reaction to form an impedance signal; in an embodiment of the present invention, the propeller can be a micropump or other power source capable of outputting the test liquid from its container. The type of test liquid in the chip module 30 and the number of its containers can be adjusted according to actual detection requirements. The number of test liquid types in the chip module 30 is preferably one to three, but not limited to this; the test liquids are respectively contained in containers corresponding to the number of test liquid types.

[0085] like Figure 3 As shown, a specific embodiment of the propeller and test liquid container of the biochip detection device 200 of the present invention is shown. The propeller of the biochip detection device 200 includes a first pump 23 and a second pump 24 electrically connected to the circuit board 21. Two test liquids, cleaning liquid and detection liquid, are provided inside the chip module 30 and are respectively contained in the cleaning liquid container 33 and the detection liquid container 34; wherein, the first pump 23 and the second pump 24 are micro pumps for outputting gas to the pipeline to form air pressure, so as to push the liquid in the cleaning liquid container 33 and the detection liquid container 34 to flow to the biochip 31 for cleaning and detection.

[0086] Specifically, the first pump 23 is connected to the first pipeline interface 232 provided on the outer surface of the detection host 20 through the first air supply pipeline 231, and the second pump 24 is connected to the second pipeline interface 242 provided on the outer surface of the detection host 20 through the second air supply pipeline 241; the biochip 31 is connected to the cleaning liquid container 33 by a first infusion pipeline 333, and the biochip 31 is connected to the detection liquid container 34 by a second infusion pipeline 343; the surface of the chip module 30 is provided with a first air inlet plug 332 and a second air inlet plug 342, and the first air inlet plug 332 is connected to the cleaning liquid container 33 by a first air pressure pipeline 331, and the second air pressure pipeline 343 is connected to the cleaning liquid container 34. A second air pressure line 341 is connected between the air inlet plug 342 and the detection liquid container 34; thereby, the chip module 30 is connected to the detection host 20, and the first air inlet plug 332 and the second air inlet plug 342 are respectively engaged and sealed with the first pipeline interface 232 and the second pipeline interface 242, so that the first air supply pipeline 231 is connected to the first air pressure pipeline 331 to form a sealed flow channel, and the second air supply pipeline 241 is connected to the second air pressure pipeline 341 to form a sealed flow channel; the liquid inside the cleaning liquid container 33 and the detection liquid container 34 is respectively subjected to the pressure generated in the sealed flow channel by the first pump 23 and the second pump 24, so that it flows toward the biochip 31.

[0087] like Figure 3In the embodiment of the present invention, the first pump 23 and the second pump 24 of the detection host 20 are micro pumps for outputting gas to the pipeline to form air pressure, so as to push the liquid in the cleaning liquid container 33 and the detection liquid container 34 to flow to the biochip 31 for cleaning and detection. The first pipeline interface 232 and the second pipeline interface 242 of the detection host 20 are preferably female interfaces, and the first air inlet plug 332 and the second air inlet plug 342 of the chip module 30 are preferably male connectors, but are not limited to this, and the male and female connectors are interchangeable. Therefore, when the detection host 20 and the chip module 30 are plugged in, the air supply pipeline (231, 241) of the detection host 20 and the air pressure pipeline (331, 341) of the chip module 30 are tightly connected through the female interface and the male connector to form a complete flow channel, so that when the first pump 23 and the second pump 24 output gas, pressure is generated in the flow channel to force the liquid in the cleaning liquid container 33 and the detection liquid container 34 to flow to the biochip 31.

[0088] Furthermore, to confirm that the biochip 31 can fully contact and react with the test liquid, Figure 3 As shown, the chip module 30 of the biochip detection device 200 of the present invention is further provided with a liquid recovery box 35 for recovering excess test liquid output to the biochip 31; a recovery pipeline 351 is provided between the biochip 31 and the liquid recovery box 35. Therefore, when the test liquid output to the biochip 31 is greater than the absorption amount or reaction amount of the biochip 31, the pressure formed in the aforementioned sealed flow channel can be utilized to flow into the liquid recovery box 35 through the recovery pipeline 351 for concentration.

[0089] In addition, if Figure 3 As shown in the biochip detection device 200, the detection host 20 also includes an integrated shell 29, the integrated shell 29 has a relative operation end and a display end, the surface of the operation end is provided with a chip socket 26 and a connection structure of the propeller; the surface of the display end is provided with a human-machine interface 27, a start button 28 and a charging socket 293 electrically connected to the circuit board 21; the chip module 30 also includes an integrated shell 32, one end of the substrate 311 of the biochip 31 and the conductive electrode 312 together form the electrode connector 310 of the biochip 31, and the electrode connector 310 protrudes from the outside of the integrated shell 32; the test liquid container connection structure of the chip module 30 is provided on the surface of the integrated shell 32.

[0090] In the embodiment of the biochip detection device 200 of the present invention, Figure 3 、 Figure 4 、 Figure 5 As shown, the integrated housing 29 of the detection host 20 may include a main housing 291 and a flip cover 292 pivotally mounted on the operating end of the main housing 291. The flip cover 292 is used to close or expose the connection structure provided at the operating end of the integrated housing 29, such as the chip socket 26, the first pipeline interface 232, and the second pipeline interface 242. Figure 3 As shown, the surface of the integrated housing 32 of the chip module 30 is provided with a test liquid container connection structure, such as: a first air inlet plug 332, a second air inlet plug 342. Among them, the flip cover 292 of the integrated housing 29 is an optional component; specifically, the overall structure of the integrated housing 29 can be set according to actual needs and the arrangement of component installation positions is not limited to Figure 4 、 Figure 5 form.

[0091] In the embodiment of the biochip detection device of the present invention, the circuit board 21 of the detection host 20 is a microcontroller (MCU) circuit board. The circuit board 21 is electrically connected to the first pump 23, the second pump 24, the power supply 25, the chip socket 26, the human-machine interface 27, and the start button 28 via a cable 22. The power supply 25 of the detection host 20 is a rechargeable battery.

[0092] In the embodiment of the biochip detection device of the present invention, the conductive electrodes 312 and conductive lines 313 of the chip module 30 are electrode patterns fabricated using semiconductor technology. The integrated housing 32 of the chip module 30 has injection ports (not shown) corresponding to the positions of the cleaning fluid container 33 and the detection fluid container 34 for injecting cleaning fluid and detection fluid into the cleaning fluid container 33 and the detection fluid container 34. Furthermore, the integrated housing 32 has a window (not shown) corresponding to the position of the biosensor platform 100 of the biochip 31 for adding a biological sample to the biosensor platform 100.

[0093] In the embodiment of the present invention, the chip module 30 is an object in which all components are integrated into a whole. The entire chip module 30 is taken out during use and is discarded after use. It is a disposable item.

[0094] The above describes the structure of the biochip detection device of the present invention. The following describes its operation method. The detection operation steps of the biochip detection device of the present invention include:

[0095] Step 1: Insert the electrode connector of the chip module 30 into the chip socket 26 of the detection host 20;

[0096] Step 2: Add the biological sample to be tested to the reaction area of the biochip 31 (i.e., the biosensor platform 100);

[0097] Step 3: Drive the first pump 23 to allow the cleaning buffer in the cleaning liquid container 33 to flow to the reaction area of the biochip 31 until it flows into the liquid recovery box 35. After completion, the reaction area of the biochip 31 is dried.

[0098] Step 4, waiting for the detection host 20 to respond;

[0099] Step 5: Drive the first pump 23 again to allow the cleaning buffer in the cleaning liquid container 33 to flow to the reaction area of the biochip 31 until it flows into the liquid recovery box 35. After completion, the reaction area of the biochip 31 is dried.

[0100] Step 6: Drive the second pump 24 to allow the detection buffer in the detection liquid container 34 to flow to the reaction area of the biochip 31 until it flows into the liquid recovery box 35. After completion, the reaction area of the biochip 31 is dried.

[0101] Step 7: Press the start button 28 of the detection host 20 to start detecting the biological sample to be tested;

[0102] Step 8, wait for detection;

[0103] Step 9: The human-machine interface 27 of the detection host 20 displays the detection result ( Figure 6A 、 Figure 6B ).

[0104] like Figure 6A 、 Figure 6B , showing the display content of the human-machine interface 27 of the biochip detection device 200 of the present invention. Figure 6A A screen is displayed indicating that the detection host 20 has determined that the biological sample is "not detected" (ND), i.e., no virus and / or microbial infection is detected in the biological sample; Figure 6B The screen displays that the detection host 20 has detected and determined that the biological sample is "infected", that is, a virus or microorganism type infection is detected in the biological sample.

[0105] In an embodiment of the biochip detection device of the present invention, the biochip detection device 200 can be used to detect viral and / or microbial infections. The bioreceptors 18 on the biochip 31 are binding molecules with detectable labels. Preferably, the binding molecules for antigens / antibodies suitable for detecting viral and / or microbial infections are IgG and IgM antibodies. Thus, when a biological sample to be tested (e.g., a blood sample) is infected with a virus and / or microorganism, the binding molecules on the biochip 31 bind to immunoglobulins produced by the virus and / or microorganism in the biological sample to be tested, generating a biochemical reaction, thereby causing a change in the measured impedance value. This impedance change is converted into a corresponding electrical signal and output to the circuit board 21 of the detection host 20. After matching and signal amplification by the sensing circuit of the circuit board 21, a readable response signal is generated, which is ultimately output to the human-machine interface 27 to display the test result.

[0106] In summary, the present invention establishes a biosensor platform that can be further developed into a portable biochip detection device. By optimizing the thickness of the electrodes fabricated using semiconductor manufacturing techniques to at least the thickness of a single gold atom, and by using a streptavidin biomediator to provide ideal flexibility for the immobilized bioreceptors, the biosensor platform performs better than previously used linkers, significantly improving biosensor performance and ensuring reproducibility, accuracy, and stability that meet POC standards. Overall, the biosensor platform provided by the present invention achieves reproducibility, accuracy, and stability, making it suitable for integration into a variety of POC products.

[0107] In summary, the above embodiments are merely preferred embodiments of the present invention and are not intended to limit the scope of protection of the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A biosensor platform, characterized in that: It includes chips manufactured using semiconductor manufacturing technology; in which: The chip is provided with a gold thin film electrode, the surface of which is fixed with a biotinylated linker and a bioreceptor connected to the biotinylated linker, the biotinylated linker being a streptavidin biomediator, and the gold thin film electrode having a thickness of at least a single gold atom; The biological sample to be tested is placed on the biosensor platform to react with the biological receptor to form an impedance signal, so as to detect whether the biological sample to be tested is infected.

2. The biosensor platform according to claim 1, characterized in that The bioreceptors are chemical molecules.

3. The biosensor platform according to claim 2, characterized in that The chemical molecule is selected from nucleic acid probes or functional proteins.

4. The biosensor platform according to claim 3, characterized in that The functional protein is immunoglobulin.

5. A method for preparing a biosensor platform, characterized in that: The biosensor platform includes a chip manufactured using semiconductor manufacturing technology, on which a gold thin film electrode is provided, wherein the gold thin film electrode has a thickness of at least a single gold atom; wherein the steps of the manufacturing method include: Step 1: subjecting the gold thin film electrode to an activation reaction to form a self-assembled monolayer (SAM) structure on the surface of the gold thin film electrode; Step 2: biotin-bonding the gold thin film electrode to add a bioreceptor connected to a biotinylated linker to the surface of the gold thin film electrode modified with a biomediator; the biotinylated linker is a streptavidin biomediator; Step 3: Cleaning and drying the gold thin film electrode to prepare a biosensor platform with the gold thin film electrode.

6. The method for preparing the biosensor platform according to claim 5, wherein: The bioreceptors are chemical molecules.

7. The method for preparing the biosensor platform according to claim 6, wherein: The chemical molecule is selected from nucleic acid probes or functional proteins.

8. The method for preparing the biosensor platform according to claim 7, wherein: The functional protein is immunoglobulin.

9. A biochip detection device, characterized in that: include: Detect host; A chip module, wherein a biochip manufactured using semiconductor manufacturing technology is installed inside the chip module. The biochip comprises a substrate, a biosensor platform disposed at opposite ends of the substrate, and conductive electrodes. The substrate of the biochip is provided with a gold thin film electrode, the surface of which is fixed with a biotinylated linker and a bioreceptor connected to the biotinylated linker, wherein the biotinylated linker is a streptavidin biomediator, and the gold thin film electrode has a thickness of at least a single gold atom. A conductive wire connects the conductive electrode to the gold thin film electrode of the biosensor platform. The chip module is connected to the detection host, and the biological sample to be tested is placed on the biosensor platform to react with the biological receptor to form an impedance signal. The detection host receives and processes the impedance signal to determine whether the biological sample to be tested is infected.

10. The biochip detection device according to claim 9, characterized in that: A circuit board is provided inside the detection host, and the circuit board is respectively connected to the propeller and power supply provided inside the detection host, as well as the chip socket, human-machine interface and start button exposed on the external surface of the detection host; The chip module is provided with a biochip and a test liquid container; the biochip has an electrode connector formed on the outer surface of the chip module; The chip module is connected to the detection host, the electrode connector is plugged into the chip socket, the pusher is connected to the test liquid container, and the test liquid is output to the biochip by forming a propulsion pressure through the pusher.

11. The biochip detection device according to claim 10, characterized in that: The detection host further includes an integrated housing having an operating end and a display end opposite to each other, the surface of the operating end being provided with the chip socket and the connection structure of the pusher; the surface of the display end being provided with the human-machine interface, the start button, and a charging jack electrically connected to the circuit board; The chip module also includes an integrated shell, one end of the substrate of the biochip and the conductive electrode together form the electrode connector of the biochip, and the electrode connector protrudes from the outside of the integrated shell; the test liquid container connection structure of the chip module is arranged on the surface of the integrated shell.

12. The biochip detection device according to any one of claims 9 to 11, characterized in that: The bioreceptors are chemical molecules.

13. The biochip detection device according to claim 12, characterized in that: The chemical molecule is selected from nucleic acid probes or functional proteins.

14. The biochip detection device according to claim 13, characterized in that: The functional protein is immunoglobulin.

15. A use of the biosensor platform according to claim 1, characterized in that: The biosensor platform is used to detect infection by microorganisms, and the biological receptor is an immunoglobulin.

16. A use of the biosensor platform according to claim 1, characterized in that: The biosensor platform is used to detect viral infections, and the biological receptor is immunoglobulin.

17. An application of the biochip detection device according to claim 9, characterized in that: The biochip detection device is used to detect infection by microorganisms, and the biological receptor is immunoglobulin.

18. An application of the biochip detection device according to claim 9, characterized in that: The biochip detection device is used to detect viral infection, and the biological receptor is immunoglobulin.

Citation Information

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