Sensing chip, biosensor and biological detection method

Abstract

The invention discloses a sensing chip, a biosensor and a biological detection method. The sensing chip comprises a substrate and a plurality of sensing units. And the plurality of sensing units are distributed in an array on one side of the substrate. The sensing unit comprises a detection element extending in a first direction and a correction element extending in a second direction, and the first direction and the second direction are perpendicular to the substrate and are perpendicular to each other. The detection element rotates 90 degrees around a set axis to coincide with the correction element, and the set axis is perpendicular to the substrate.

Description

Technical Field

[0001] The present application belongs to the field of biosensor technology, and specifically relates to a sensor chip, a biosensor and a biological detection method. Background Art

[0002] Biosensors are instruments that are sensitive to biological substances and convert their concentrations into electrical signals for detection. They have great potential to convert invisible bioanalytical responses into readable information, which can track and transmit biomedical information to support health monitoring and clinical decision-making.

[0003] In recent years, biosensors based on micro-nano optical sensors have been a hot topic of research. Micro-nano optical sensors have the advantages of real-time, ease of use, high integration, high sensitivity, and low cost, and are becoming a game changer in disease diagnosis. However, micro-nano optical sensors can be interfered by environmental factors such as temperature, humidity, pollutants, and noise, resulting in inaccurate detection results. Summary of the invention

[0004] The present application provides a sensor chip, a biosensor and a biodetection method, which aim to solve the problem of inaccurate sensor detection results to at least a certain extent.

[0005] In a first aspect of the present application, a sensor chip is provided, the sensor chip comprising: substrate; A plurality of sensing units are distributed in an array on one side of the substrate; the sensing units include a detection element extending along a first direction and a correction element extending along a second direction, the first direction and the second direction are perpendicular to the substrate and perpendicular to each other; the detection element is rotated 90° around a set axis to overlap with the correction element, and the set axis is perpendicular to the substrate.

[0006] In some embodiments, the detection element is rotated 180° around the setting axis to coincide with the detection element, and the correction element is rotated 180° around the setting axis to coincide with the correction element.

[0007] In some embodiments, the detection element and the correction element are mirror-symmetrical figures, and the symmetry plane of the detection element and the symmetry plane of the correction element intersect at the set axis.

[0008] In some embodiments, the detection element includes a first strip structure extending along the first direction, and the correction element includes a second strip structure extending along the second direction, and the first strip structure and the second strip structure intersect to form a cross shape.

[0009] In some embodiments, the detection element also includes a first columnar structure located at both ends of the first strip structure, and the correction element also includes a second columnar structure located at both ends of the second strip structure, and the axis of the first columnar structure and the axis of the second columnar structure are parallel to the setting axis.

[0010] In some embodiments, the detection element includes a plurality of first spherical structures sequentially arranged along the first direction, the plurality of first spherical structures are distributed on opposite sides of the setting axis, and the number of the first spherical structures on both sides of the setting axis is equal; The correction element includes a plurality of second spherical structures sequentially arranged along the second direction. The plurality of second spherical structures are distributed on opposite sides of the setting axis, and the number of the second spherical structures on both sides of the setting axis is equal.

[0011] In some embodiments, the sensor chip further comprises: A dielectric layer, located between the sensing unit and the substrate, wherein the dielectric layer is made of a light-transmitting material; The reflective layer is located between the dielectric layer and the substrate, and the material of the reflective layer is the same as that of the sensing unit.

[0012] In some embodiments, the reflective layer and the sensing unit are made of metal materials.

[0013] In some embodiments, the sensing unit is a micro-nano structure.

[0014] In a second aspect of the present application, a biosensor is provided, the biosensor comprising: The sensor chip provided in the first aspect; A deflection light source, used for emitting a first polarized light and a second polarized light to the sensor chip, wherein the polarization direction of the first polarized light is the first direction, and the polarization direction of the second polarized light is the second direction; The spectrometer is used for receiving the first polarized light reflected by the detection element and the second polarized light reflected by the correction element and performing a difference to obtain a detection result.

[0015] In a third aspect of the present application, a biological detection method is provided, which is applied to the biosensor provided in the second aspect, and the biological detection method comprises: Immobilizing a binding substance of the analyte on the detection element, so that the analyte binds to the binding substance on the detection element; Controlling the polarized light source to emit a first polarized light and a second polarized light to the sensor chip, wherein the polarization direction of the first polarized light is the first direction, and the polarization direction of the second polarized light is the second direction; The spectrometer receives the first polarized light reflected by the detection element and the second polarized light reflected by the correction element and performs a difference to obtain a detection result.

[0016] In some embodiments, the step of fixing the binding substance of the analyte on the detection element comprises: Coating photoresist on the sensor chip and patterning it to expose the detection element; Adsorbing a conjugate of the object to be detected on the detection element and the photoresist; The photoresist and the binding substance on the photoresist are removed, leaving the binding substance on the detection element.

[0017] According to the sensor chip, biosensor and biodetection method provided by one or more embodiments of the present application, a plurality of sensor units are distributed in an array on one side of the substrate, and the sensor unit includes a detection element extending in a first direction and a correction element extending in a second direction, and the first direction and the second direction are perpendicular to the substrate and perpendicular to each other, so that the first polarized light with a polarization direction in the first direction can excite surface plasma resonance on the surface of the detection element, so that the first polarized light reflected by the detection element changes, and the second polarized light with a polarization direction in the second direction can excite surface plasma resonance on the surface of the correction element, so that the second polarized light reflected by the correction element changes. The detection element is rotated 90° around a set axis to coincide with the correction element, and the set axis is perpendicular to the substrate. In addition, the detection element and the correction element are in the same environment, so the difference between the change of the first polarized light reflected by the detection element and the change of the second polarized light reflected by the correction element is only caused by the analyte and the conjugate on the detection element. The first polarized light reflected by the detection element and the second polarized light reflected by the correction element are differentiated to obtain the detection result, which can eliminate the interference of environmental factors such as temperature, humidity, pollutants, and noise, and improve the accuracy of the detection result. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the following briefly introduces the drawings required for use in the description of the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0019] Figure 1 A schematic structural diagram of a biosensor in related art is shown.

[0020] Figure 2 A schematic diagram of the structure of a sensor chip in one or more embodiments of the present application is shown.

[0021] Figure 3 The intrinsic reflectance spectrum of the sensing unit is shown.

[0022] Figure 4 The reflectance spectrum after the sensing unit is attached to the object to be measured is shown.

[0023] Figure 5 A schematic diagram of the structure of a sensor chip in another embodiment of the present application is shown.

[0024] Figure 6 A schematic structural diagram of a sensor chip in another embodiment of the present application is shown.

[0025] Figure 7 A schematic diagram of the structure of a biosensor in one or more embodiments of the present application is shown.

[0026] Figure 8 A schematic flow chart of a biological detection method in one or more embodiments of the present application is shown.

[0027] Fig. 9 Shows Figure 8 Schematic diagram of the flow chart of step S101.

[0028] Fig.10 Shows Fig. 9 Schematic diagram of a top view of the sensor chip during the execution of the steps.

[0029] Explanation of the reference numerals: 10': light source; 20': spectrometer; 30': substrate; 40': sensing unit; 41': block structure; 10: substrate; 20: sensing unit; 21: detection element; 211: first strip structure; 212: first columnar structure; 213: first spherical structure; 22: correction element; 221: second strip structure; 222: second columnar structure; 223: second spherical structure; 30: dielectric layer; 40: reflection layer; 51: sensor chip; 52: deflected light source; 53: spectrometer; 61: photoresist; 62: binder; 63: object to be measured; 100: setting axis; 200: symmetry plane; 300: axis line. DETAILED DESCRIPTION

[0030] In order to make the technical personnel in the technical field to which the present application belongs to understand the present application more clearly, the technical scheme in the embodiments of the present application will be clearly and completely described below in conjunction with the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in the field without creative work are within the scope of protection of the present application.

[0031] Figure 1 For a schematic diagram of the structure of a biosensor in the related art, please refer to Figure 1The biosensor includes a light source 10', a spectrometer 20' and a sensor chip. The sensor chip includes a substrate 30' and a plurality of sensor units 40' arranged in an array on one side of the substrate 30'. The sensor unit 40' includes a plurality of block structures 41' arranged at intervals. The object to be tested is distributed on the sensor unit 40", and the light source 10' emits light of a specific wavelength band to the sensor unit 40'. The light excites surface plasma resonance on the surface of the block structure 41'. The spectrometer 20' receives the light reflected by the block structure 41' for analysis to determine the change amount of the fingerprint peak.

[0032] The fingerprint peak is a characteristic absorption peak located in a specific range in the Raman spectrum, corresponding to a unique vibration mode in the molecule, and can accurately identify and distinguish different compounds. The object to be tested on the sensor unit will affect the surface plasma resonance excited by light on the surface of the sensor unit, causing the fingerprint peak of the light reflected by the sensor unit to change. Therefore, the detection result of the object to be tested on the sensor unit can be obtained by the change in the fingerprint peak.

[0033] However, the variation of the fingerprint peak will not only be affected by the object to be tested, but also by environmental factors such as temperature, humidity, pollutants, and noise, which will lead to inaccurate test results. If the calibration process is added, additional sample preparation and measurement steps will be introduced, which will not only be complicated and time-consuming, but may also increase measurement errors and weaken detection capabilities.

[0034] Figure 2 For a schematic diagram of the structure of the sensor chip in one or more embodiments of the present application, please refer to Figure 2 In a first aspect of the present application, a sensor chip is provided, which includes a substrate 10 and a plurality of sensor units 20. The plurality of sensor units 20 are distributed in an array on one side of the substrate 10. The sensor unit 20 includes a detection element 21 extending along a first direction and a correction element 22 extending along a second direction, and the first direction and the second direction are perpendicular to the substrate 10 and perpendicular to each other. The detection element 21 rotates 90° around a set axis 100 to coincide with the correction element 22, and the set axis 100 is perpendicular to the substrate 10, that is, the detection element 21 and the correction element 22 are rotationally symmetric.

[0035] Figure 3 is the intrinsic reflection spectrum of the sensing unit, see Figure 3 When there is no object to be measured on the sensing unit, there is a strong resonance absorption peak at the position of 6μm, and the amplitude reaches 98.1%, which is the fingerprint peak. Figure 4 For the reflection spectrum after the sensor unit is attached to the object to be measured, please refer to Figure 4 After the object to be tested is attached to the sensor unit, the position of the fingerprint peak moves, and the greater the concentration of the object to be tested on the sensor unit, the greater the change in the fingerprint peak.

[0036] The variation of the fingerprint peak depends not only on the object to be tested, but also on the environmental factors such as temperature, humidity, pollutants, and noise. Since the detection element 21 and the correction element 22 are in the same environment and are affected by the same environmental interference, if the reflection spectrum of the detection element 21 and the reflection spectrum of the correction element 22 are differentiated, the interference of environmental factors such as temperature, humidity, pollutants, and noise can be eliminated.

[0037] In practical applications, the object to be tested is fixed on the detection element 21, and there is no object to be tested on the correction element 22. The difference between the reflected light of the detection element 21 and the reflected light of the correction element 22 is only affected by the object to be tested. The reflected light of the correction element 22 is used as the correction data. The change in the fingerprint peak in the reflection spectrum of the detection element 21 is differentiated from the change in the fingerprint peak in the reflection spectrum of the correction element 22 to obtain the change in the fingerprint peak caused by the object to be tested. This fingerprint peak change is compared with the corresponding relationship between the fingerprint peak change and the concentration of the object to be tested preset in the database to obtain the concentration of the object to be tested.

[0038] The above-mentioned sensor chip includes a substrate 10 and a plurality of sensor units 20, and the plurality of sensor units 20 are distributed in an array on one side of the substrate 10. The sensor unit 20 includes a detection element 21 extending along a first direction and a correction element 22 extending along a second direction. The first direction and the second direction are perpendicular to the substrate 10 and perpendicular to each other, so that a first polarized light having a polarization direction in the first direction can excite surface plasmon resonance on the surface of the detection element 21, so that the first polarized light reflected by the detection element 21 changes, and a second polarized light having a polarization direction in the second direction can excite surface plasmon resonance on the surface of the correction element 22, so that the second polarized light reflected by the correction element 22 changes. The detection element 21 is rotated 90° around the setting axis 100 to coincide with the correction element 22. The setting axis 100 is perpendicular to the substrate 10. The detection element 21 and the correction element 22 are in the same environment. Therefore, the difference between the change in the first polarized light reflected by the detection element 21 and the change in the second polarized light reflected by the correction element 22 is only caused by the object to be detected and the conjugate on the detection element 21. The detection result is obtained by differentiating the first polarized light reflected by the detection element 21 and the second polarized light reflected by the correction element 22, which can eliminate the interference of environmental factors such as temperature, humidity, pollutants, and noise, thereby improving the accuracy of the detection result.

[0039] Moreover, it does not require a series of complex and time-consuming calibration processes, nor does it require the introduction of additional sample preparation and measurement steps. It can directly achieve data self-calibration, avoid errors caused by additional calibration, and improve detection capabilities and ease of use. In addition, biological detection can be achieved with simple or even integrated equipment, which has low requirements for experimental conditions, does not require large-scale and sophisticated detection equipment and its supporting experimental environment, has low detection costs, and is easy to use.

[0040] In some embodiments, the sensing unit 20 may be a micro-nano structure.

[0041] Exemplarily, in the first direction or the second direction, the length of the sensing unit 20 can be 0.1μm to 10μm, such as 0.1μm, 0.2μm, 0.3μm, 0.4μm, 0.5μm, 0.6μm, 0.7μm, 0.8μm, 0.9μm, 1μm, 2μm, 3μm, 4μm, 5μm, 6μm, 7μm, 8μm, 9μm, 10μm, etc.

[0042] In the direction perpendicular to the substrate 10, the thickness of the sensing unit 20 can be 0.01μm to 1μm, such as 0.01μm, 0.02μm, 0.03μm, 0.04μm, 0.05μm, 0.06μm, 0.07μm, 0.08μm, 0.09μm, 0.1μm, 0.2μm, 0.3μm, 0.4μm, 0.5μm, 0.6μm, 0.7μm, 0.8μm, 0.9μm, 1μm, etc.

[0043] In a direction parallel to the substrate 10 , the spacing of the sensing units 20 may be 1 μm to 10 μm, such as 1 μm, 2 μm, 3 μm, 4 μm, 5 μm, 6 μm, 7 μm, 8 μm, 9 μm, 10 μm, etc.

[0044] In some embodiments, the sensing unit 20 may be made of metal material.

[0045] Exemplarily, the material of the sensing unit 20 may be a metal material with high electrical conductivity, such as gold, silver, aluminum, copper, etc.

[0046] In some embodiments, the substrate 10 can be divided into cells corresponding to the sensing units 20, each sensing unit 20 is located in a corresponding cell, and one side of two adjacent cells overlaps. The shape of the cell can be rectangular, hexagonal, triangular, etc.

[0047] In some embodiments, see Figure 2 , the detection element 21 can be rotated 180° around the setting axis 100 to overlap with the detection element 21, and the correction element 22 can be rotated 180° around the setting axis 100 to overlap with the correction element 22. In this way, the sensor unit 20 is a rotationally symmetrical figure, and the whole can overlap with itself after rotating 90° around the setting axis 100 as an integer multiple.

[0048] In some embodiments, see Figure 2 The detection element 21 and the correction element 22 may be mirror-symmetrical figures, and the symmetry plane 200 of the detection element 21 and the symmetry plane 200 of the correction element 22 intersect at the setting axis 100 .

[0049] In one possible embodiment, see Figure 2 The detection element 21 may include a first strip structure 211 extending along a first direction, and the correction element 22 may include a second strip structure 221 extending along a second direction, and the first strip structure 211 and the second strip structure 221 intersect to form a cross. In this way, the sensor unit 20 is a mirror-symmetrical figure, and the whole can be overlapped with itself after rotating by an integer multiple of 90° around the set axis 100, which is simple and convenient to implement.

[0050] For example, in the first direction, the length of the first strip structure 211 may be 1 μm to 3 μm, such as 1 μm, 1.5 μm, 2 μm, 2.5 μm, 3 μm, etc. The width of the second strip structure 221 may be 0.2 μm to 0.6 μm, such as 0.2 μm, 0.3 μm, 0.4 μm, 0.5 μm, 0.6 μm, etc.

[0051] In the second direction, the width of the first strip structure 211 may be 0.2 μm to 0.6 μm, such as 0.2 μm, 0.3 μm, 0.4 μm, 0.5 μm, 0.6 μm, etc. The length of the second strip structure 221 may be 1 μm to 3 μm, such as 1 μm, 1.5 μm, 2 μm, 2.5 μm, 3 μm, etc.

[0052] In the direction perpendicular to the substrate 10 , the thickness of the first strip structure 211 may be 0.08 μm to 0.12 μm, such as 0.08 μm, 0.09 μm, 0.1 μm, 0.11 μm, 0.12 μm, etc. The thickness of the second strip structure 221 may be 0.08 μm to 0.12 μm, such as 0.08 μm, 0.09 μm, 0.1 μm, 0.11 μm, 0.12 μm, etc.

[0053] In a direction parallel to the substrate 10 , the spacing of the sensing units 20 may be 1 μm to 5 μm, such as 1 μm, 2 μm, 3 μm, 4 μm, 5 μm, etc.

[0054] Figure 5 For a schematic diagram of the structure of a sensor chip in another embodiment of the present application, please refer to Figure 5 In another possible embodiment, the detection element 21 may include a first strip structure 211 extending along the first direction and a first columnar structure 212 located at both ends of the first strip structure 211, and the correction element 22 may include a second strip structure 221 extending along the second direction and a second columnar structure 222 located at both ends of the second strip structure 221, the first strip structure 211 and the second strip structure 221 intersect in a cross shape, and the axis 300 of the first columnar structure 212 and the axis 300 of the second columnar structure 222 are parallel to the setting axis 100.

[0055] In the above embodiment, the detection element 21 and the correction element 22 are provided with columnar structures on both sides of the strip structure, and the columnar structure has an out-of-plane spatial degree of freedom. The adsorption surface of the object to be detected changes from two-dimensional to three-dimensional, and the sensor chip can adsorb more objects to be detected to affect the surface plasma resonance excited by the reflected light on the surface of the sensor chip, which can effectively improve the detection sensitivity of the sensor chip and reduce the minimum detection concentration. When the detection element 21 and the correction element 22 only include the strip structure, the sensitivity of the sensor chip is 450nm / RIU. When the detection element 21 and the correction element 22 include a strip structure and a columnar structure located on both sides of the strip structure, the sensitivity of the sensor chip can reach 4000nm / RIU, which can be applied to trace detection.

[0056] For example, in the first direction or the second direction, the length of the first columnar structure 212 may be 0.2 μm to 0.6 μm, such as 0.2 μm, 0.3 μm, 0.4 μm, 0.5 μm, 0.6 μm, etc. The length of the second columnar structure 222 may be 0.2 μm to 0.6 μm, such as 0.2 μm, 0.3 μm, 0.4 μm, 0.5 μm, 0.6 μm, etc.

[0057] In the direction perpendicular to the substrate 10 , the height of the first columnar structure 212 may be 0.2 μm to 0.6 μm, such as 0.2 μm, 0.3 μm, 0.4 μm, 0.5 μm, 0.6 μm, etc. The height of the second columnar structure 222 may be 0.2 μm to 0.6 μm, such as 0.2 μm, 0.3 μm, 0.4 μm, 0.5 μm, 0.6 μm, etc.

[0058] Figure 6 This is a schematic diagram of the structure of a sensor chip in another embodiment of the present application. Figure 6 In another possible embodiment, the detection element 21 may include a plurality of first spherical structures 213 sequentially arranged along the first direction, the plurality of first spherical structures 213 are distributed on opposite sides of the setting axis 100, and the number of the first spherical structures 213 on both sides of the setting axis 100 is equal. The correction element 22 may include a plurality of second spherical structures 223 sequentially arranged along the second direction, the plurality of second spherical structures 223 are distributed on opposite sides of the setting axis 100, and the number of the second spherical structures 223 on both sides of the setting axis 100 is equal. In this way, a resonant cavity can be formed inside the spherical structure, and polarized light can induce local plasma resonance of the spherical structure. According to the Smith-Purcell effect, the resonant cavity has a limiting effect on photons, which can improve the local light field state density, amplify the interaction between photons and molecules of the object to be detected, and realize the detection of small molecule drugs.

[0059] For example, in the direction perpendicular to the substrate 10 , the diameter of the first spherical structure 213 may be 0.2 μm to 0.6 μm, such as 0.2 μm, 0.3 μm, 0.4 μm, 0.5 μm, 0.6 μm, etc. The diameter of the second spherical structure 223 may be 0.2 μm to 0.6 μm, such as 0.2 μm, 0.3 μm, 0.4 μm, 0.5 μm, 0.6 μm, etc.

[0060] In the first direction, the interval between the first spherical structures 213 may be 0.3 μm to 0.7 μm, such as 0.3 μm, 0.4 μm, 0.5 μm, 0.6 μm, 0.7 μm, etc.

[0061] In the second direction, the interval between the second spherical structures 223 may be 0.3 μm to 0.7 μm, such as 0.3 μm, 0.4 μm, 0.5 μm, 0.6 μm, 0.7 μm, etc.

[0062] The above embodiments provide a variety of sensor unit design solutions, and the biological detection range can cover everything from small drug molecules to proteins and even cells.

[0063] In some embodiments, see Figure 2 , Figure 5 and Figure 6 The sensor chip may further include a dielectric layer 30 and a reflective layer 40. The dielectric layer 30 is located between the sensor unit 20 and the substrate 10, and the dielectric layer 30 is made of a light-transmitting material. The reflective layer 40 is located between the dielectric layer 30 and the substrate 10, and the material of the reflective layer 40 is the same as that of the sensor unit 20. In this way, the dielectric layer 30 forms a resonant cavity between the reflective layer 40 and the sensor unit 20, which can enhance the surface plasma resonance excited by light on the surface of the sensor unit 20, amplify the interaction between light and the molecules of the object to be detected, and realize the detection of a smaller volume of the object to be detected.

[0064] Exemplarily, the material of the dielectric layer 30 may be silicon dioxide, which has low light absorption and high transmittance.

[0065] In the direction perpendicular to the substrate 10 , the thickness of the dielectric layer 30 may be 0.1 μm to 0.3 μm, such as 0.1 μm, 0.15 μm, 0.2 μm, 0.25 μm, 0.3 μm, etc.

[0066] Exemplarily, the reflective layer 40 and the sensing unit 20 may be made of metal materials, such as gold, silver, aluminum, copper and other metal materials with high reflectivity.

[0067] In the direction perpendicular to the substrate 10 , the thickness of the reflective layer 40 may be 0.08 μm to 0.12 μm, such as 0.08 μm, 0.09 μm, 0.1 μm, 0.11 μm, 0.12 μm, etc.

[0068] Figure 7 For a schematic diagram of the structure of a biosensor in one or more embodiments of the present application, please refer to Figure 7 According to a second aspect of the present application, a biosensor is provided, which includes a sensor chip 51, a deflected light source 52, and a spectrometer 53. The sensor chip 51 is a sensor chip provided by any embodiment of the first aspect. The deflected light source 52 is used to emit a first polarized light and a second polarized light to the sensor chip 51, wherein the polarization direction of the first polarized light is a first direction, and the polarization direction of the second polarized light is a second direction. The spectrometer 53 is used to receive the first polarized light reflected by the detection element 21 and the second polarized light reflected by the correction element 22 and perform differential analysis to obtain a detection result.

[0069] For example, see Figure 7 The deflection light source 52 and the spectrometer 53 may be located on a side of the substrate 10 where the sensing unit 20 is disposed.

[0070] In practical applications, the spectrometer 53 can first obtain the reflection spectrum of the detection element 21 from the first polarized light reflected by the detection element 21, and obtain the reflection spectrum of the correction element 22 from the second polarized light reflected by the correction element 22. Then, the reflection spectrum of the detection element 21 is differentiated from the reflection spectrum of the correction element 22 to obtain the fingerprint peak change caused by the object to be tested. This fingerprint peak change is compared with the corresponding relationship between the fingerprint peak change and the concentration of the object to be tested preset in the database to obtain the concentration of the object to be tested.

[0071] Exemplarily, the spectrometer 53 may be a Raman spectrometer or an infrared spectrometer to detect small molecule drugs.

[0072] Figure 8 For a schematic diagram of the process of the biological detection method in one or more embodiments of the present application, please refer to Figure 8 The third aspect of the present application provides a biological detection method, which is applied to the biosensor provided in any embodiment of the second aspect. The biological detection method includes the following steps S101 to S103.

[0073] Step S101, fixing a binding substance of the analyte on a detection element, so that the analyte is combined with the binding substance on the detection element.

[0074] For example, the analyte may be an antigen protein, and the binding substance may be an antibody.

[0075] Step S102, controlling the polarized light source to emit a first polarized light and a second polarized light to the sensor chip, wherein the polarization direction of the first polarized light is a first direction, and the polarization direction of the second polarized light is a second direction.

[0076] Step S103, receiving the first polarized light reflected by the detection element and the second polarized light reflected by the correction element through a spectrometer and performing a difference to obtain a detection result.

[0077] Exemplarily, the reflection spectrum of the detection element can be obtained by the first polarized light reflected by the detection element through the spectrometer, and the reflection spectrum of the correction element can be obtained by the second polarized light reflected by the correction element. Then, the reflection spectrum of the detection element and the reflection spectrum of the correction element are differentiated to obtain the fingerprint peak change caused by the object to be tested. This fingerprint peak change is compared with the corresponding relationship between the fingerprint peak change and the concentration of the object to be tested preset in the database to obtain the concentration of the object to be tested, which is the detection result.

[0078] Fig. 9 for Figure 8 For a flow chart of step S101, please refer to Fig. 9 In some embodiments, the step S101 may include the following steps S201 to S203.

[0079] Step S201, coating photoresist on the sensor chip and patterning it to expose the detection element.

[0080] For example, patterning may include first exposing the photoresist by a photolithography machine, and then developing the photoresist by a developer, so that the photoresist on the detection element is dissolved in the developer to expose the detection element, while the photoresist on the correction element is retained and covers the correction element.

[0081] Step S202, adsorbing the combination of the object to be detected onto the detection element and the photoresist.

[0082] Step S203, removing the photoresist and the binding substance on the photoresist, leaving the binding substance on the detection element.

[0083] For example, the photoresist can be removed by stripping, and the bound substances on the photoresist are removed together with the photoresist, exposing the correction element, and only the bound substances on the detection element remain.

[0084] Fig.10 for Fig. 9 For a top view of the sensor chip during the execution of the steps in Fig.10The sensor chip includes a substrate 10 and a plurality of sensor units 20 arranged in an array on one side of the substrate 10, and each sensor unit 20 includes a detection element 21 and a correction element 22. A photoresist 61 is first coated on the sensor chip. Then the photoresist 61 is patterned to expose the detection element 21. Then a conjugate 62 of the object to be detected is adsorbed on the detection element 21 and the photoresist 61. Then the photoresist 61 and the conjugate 62 on the photoresist 61 are removed, leaving the conjugate 62 on the detection element 21. Finally, the object to be detected 63 is combined with the conjugate 62, so that the object to be detected 63 is attached to the detection element 21, but not to the correction element 22.

[0085] In the present application, unless otherwise clearly specified and limited, a first feature being "above" or "below" a second feature may include that the first and second features are in direct contact, or may include that the first and second features are not in direct contact but are in contact through another feature between them. Moreover, a first feature being "above", "above" and "above" a second feature includes that the first feature is directly above and obliquely above the second feature, or simply indicates that the first feature is higher in level than the second feature. A first feature being "below", "below" and "below" a second feature includes that the first feature is directly below and obliquely below the second feature, or simply indicates that the first feature is lower in level than the second feature.

[0086] In the description of the present application, it should be understood that the terms "center", "longitudinal", "lateral", "length", "width", "thickness", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside", "clockwise" and "counterclockwise" indicate orientations or positional relationships based on the orientations or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present application and simplifying the description, and do not indicate or imply that the referred device or element must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be understood as a limitation on the present application.

[0087] In this application, unless otherwise clearly specified and limited, the terms "connection", "fixation", etc. should be understood in a broad sense. For example, "fixation" can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium, it can be the internal connection of two elements or the interaction relationship between two elements. For ordinary technicians in this field, the specific meanings of the above terms in this application can be understood according to specific circumstances.

[0088] In addition, the descriptions of "first", "second", etc. in this application are only for descriptive purposes and cannot be understood as indicating or implying their relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined as "first" or "second" may explicitly or implicitly include one or more features. In the description of this application, the meaning of "plurality" is two or more, unless otherwise clearly and specifically defined.

[0089] Although the embodiments of the present application have been shown and described, those skilled in the art will appreciate that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present application, and that the scope of the present application is defined by the claims and their equivalents.

Claims

1. A sensor chip, characterized in that: The sensor chip comprises: A substrate (10); A plurality of sensing units (20) are distributed in an array on one side of the substrate (10); the sensing units (20) comprise a detection element (21) extending along a first direction and a correction element (22) extending along a second direction, the first direction and the second direction being perpendicular to the substrate (10) and perpendicular to each other; the detection element (21) is rotated 90 degrees around a set axis (100) to coincide with the correction element (22), the set axis (100) being perpendicular to the substrate (10).

2. The sensor chip according to claim 1, characterized in that: The detection element (21) is rotated 180° around the setting axis (100) to coincide with the detection element (21), and the correction element (22) is rotated 180° around the setting axis (100) to coincide with the correction element (22).

3. The sensor chip according to claim 1, characterized in that: The detection element (21) and the correction element (22) are mirror-symmetrical figures, and the symmetry plane (200) of the detection element (21) and the symmetry plane (200) of the correction element (22) intersect at the setting axis (100).

4. The sensor chip according to claim 2 or 3, characterized in that: The detection element (21) comprises a first strip structure (211) extending along the first direction, and the correction element (22) comprises a second strip structure (221) extending along the second direction, wherein the first strip structure (211) and the second strip structure (221) intersect to form a cross shape.

5. The sensor chip according to claim 4, characterized in that: The detection element (21) further includes a first columnar structure (212) located at both ends of the first strip structure (211), and the correction element (22) further includes a second columnar structure (222) located at both ends of the second strip structure (221), and the axis (300) of the first columnar structure (212) and the axis (300) of the second columnar structure (222) are parallel to the setting axis (100).

6. The sensor chip according to claim 2 or 3, characterized in that: The detection element (21) comprises a plurality of first spherical structures (213) arranged in sequence along the first direction, the plurality of first spherical structures (213) are distributed on opposite sides of the setting axis (100), and the number of the first spherical structures (213) on the two sides of the setting axis (100) is equal; The correction element (22) comprises a plurality of second spherical structures (223) arranged in sequence along the second direction, wherein the plurality of second spherical structures (223) are distributed on opposite sides of the setting axis (100), and the number of the second spherical structures (223) on both sides of the setting axis (100) is equal.

7. The sensor chip according to any one of claims 1 to 3, characterized in that: The sensor chip also includes: a dielectric layer (30), located between the sensing unit (20) and the substrate (10), the dielectric layer (30) being made of a light-transmitting material; A reflective layer (40) is located between the dielectric layer (30) and the substrate (10); the material of the reflective layer (40) is the same as that of the sensing unit (20).

8. The sensor chip according to claim 7, characterized in that: The reflective layer (40) and the sensing unit (20) are made of metal material.

9. The sensor chip according to any one of claims 1 to 3, characterized in that: The sensing unit (20) is a micro-nano structure.

10. A biosensor, characterized in that: The biosensor comprises: The sensor chip (51) as claimed in any one of claims 1 to 9; a deflection light source (52), used for emitting a first polarized light and a second polarized light to the sensor chip (51), wherein the polarization direction of the first polarized light is the first direction, and the polarization direction of the second polarized light is the second direction; The spectrometer (53) is used for receiving the first polarized light reflected by the detection element (21) and the second polarized light reflected by the correction element (22) and performing differential analysis to obtain a detection result.

11. A biological detection method, characterized in that: Applied to the biosensor as claimed in claim 10, the biological detection method comprises: Immobilizing a binding substance of the analyte on the detection element, so that the analyte binds to the binding substance on the detection element; Controlling the polarized light source to emit a first polarized light and a second polarized light to the sensor chip, wherein the polarization direction of the first polarized light is the first direction, and the polarization direction of the second polarized light is the second direction; The spectrometer receives the first polarized light reflected by the detection element and the second polarized light reflected by the correction element and performs a difference to obtain a detection result.

12. The detection method according to claim 11, characterized in that: The step of fixing the binding substance of the object to be detected on the detection element comprises: Coating photoresist on the sensor chip and patterning it to expose the detection element; Adsorbing a conjugate of the object to be detected on the detection element and the photoresist; The photoresist and the binding substance on the photoresist are removed, leaving the binding substance on the detection element.

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