SPR (Surface Plasmon Resonance) angle sensor for detecting low-concentration substances

Abstract

The utility model discloses an SPR (Surface Plasmon Resonance) angle sensor for detecting low-concentration substances, and relates to the technical field of sensors. Comprising a first metal layer, a sensitization layer and a second metal layer which are sequentially arranged on the prism; wherein the sensitization layer is made of gallium nitride. According to the utility model, the first metal layer, the gallium nitride layer and the second metal layer are sequentially arranged on the prism to form the double-metal-layer sandwich sensitization layer structure, so that the electric field intensity between the film layer and the object to be detected is increased, the detection sensitivity is improved, and the quality factor of the sensor is improved.

Description

Technical Field

[0001] The utility model relates to the technical field of sensors, in particular to an SPR angle sensor for detecting low-concentration substances. Background Art

[0002] Angle-Modulated Surface Plasmon Resonance sensor, referred to as SPR angle sensor in this application, is a new type of high-sensitivity optical sensor that excites the collective oscillation of free electrons on the metal surface by adjusting the angle of incident light. When light is incident at a specific angle, the intensity of reflected light is significantly reduced, forming a resonance angle, and its change is closely related to the change of refractive index on the metal surface. This sensor is widely used in the fields of biomolecule detection, chemical analysis and environmental monitoring. It has the advantages of high sensitivity, real-time detection and label-free detection. It can monitor biological or chemical reaction processes in real time and has a high detection capability for extremely low concentrations of analytes.

[0003] In the field of low-concentration molecular detection, literature and market research have found that the existing detection methods include colorimetry (BCD method, Lowry method), immunoassay (ELISA method), electrophoresis (SDS-PAGE), mass spectrometry (MS), etc. The current detection market lacks a low-concentration molecular detection tool that takes into account sensitivity, specificity, economy, and simple operation. On the other hand, these chemical reagent methods cannot avoid safety hazards and environmental problems during the detection process. The SPR angle sensor spawned by non-toxic and pollution-free optical sensing technology has great advantages in these aspects.

[0004] Traditional angle-modulated SPR sensors have good detection effects for substances with high concentrations (above 1 nmol / L), but the detection effect will be greatly reduced for low-concentration molecules (such as thyroglobulin Tg in human blood, with a concentration of about 90 pmol / L). On the other hand, factors such as the film thickness and structural design of traditional SPR angle sensors do not significantly enhance the surface coupling electric field strength, and the stability is poor, which also leads to limited detection effects of existing SPR angle sensors. The sensitivity of existing traditional gold film sensors based on angle modulation is only 69.7° / RIU, so there are higher requirements for improving the detectability of the sensor. Utility Model Content

[0005] The utility model at least solves one of the technical problems existing in the prior art or related technology.

[0006] The utility model provides an SPR angle sensor for detecting low-concentration substances, comprising: a first metal layer, a sensitization layer and a second metal layer which are sequentially arranged on a prism; wherein the sensitization layer material is a gallium nitride layer.

[0007] Furthermore, the light source of the SPR angle sensor is near infrared light.

[0008] Furthermore, the material of the prism is sapphire, and the shape of the prism is semi-cylindrical.

[0009] Furthermore, the material of the first metal layer is gold, silver or copper.

[0010] Furthermore, the material of the second metal layer is gold, silver or copper.

[0011] Furthermore, the thickness of the first metal layer is 50 nm to 70 nm.

[0012] Furthermore, the particle size of the gallium nitride is not greater than 7 μm.

[0013] Furthermore, the thickness of the second metal layer is 10 nm to 20 nm.

[0014] Furthermore, the concentration of the low-concentration substance is 1 pmol / L~1 μmol / L.

[0015] Furthermore, the material of the first metal layer is copper, and the thickness of the first metal layer is 60 nm to 70 nm; the material of the second metal layer is copper, and the thickness of the second metal layer is 15 nm to 20 nm.

[0016] Compared with the prior art, the present invention has at least the following beneficial effects:

[0017] The utility model provides an SPR angle sensor for detecting low-concentration substances. By sequentially arranging a double metal layer sandwich sensitivity enhancement layer structure of a first metal layer, a gallium nitride layer, and a second metal layer on a prism, the electric field strength between the film layer and the object to be detected is increased, and the detection sensitivity is improved. This coupling structure comprehensively improves the quality factor of the sensor. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] In the accompanying drawings, the following are given by way of example and not limitation:

[0019] Figure 1 The utility model shows an overall structural schematic diagram of an SPR angle sensor for detecting low-concentration substances.

[0020] In the figure: 1. prism; 2. first metal layer; 3. sensitization layer; 4. second metal layer. DETAILED DESCRIPTION

[0021] In the following detailed disclosure, these embodiments are fully described with reference to the drawings. In order to make the technical scheme of the utility model more clear and specific to those skilled in the art, the implementation methods described below are not limited to this. The utility model is further described in detail below in combination with the embodiments and drawings.

[0022] In the present invention, the terms "first", "second", and "third" are used for descriptive purposes only and should not be understood as indicating or implying relative importance; the term "plurality" refers to two or more, unless otherwise clearly defined. The terms "installed", "connected", "connected", "fixed" and the like should be understood in a broad sense. For example, "connected" can be a fixed connection, a detachable connection, or an integral connection; "connected" can be a direct connection or an indirect connection through an intermediate medium. For those of ordinary skill in the art, the specific meanings of the above terms in the present invention can be understood according to the specific circumstances.

[0023] In the description of the present invention, it is necessary to understand that the directions or positional relationships indicated by terms such as "up", "down", "left", "right", "front" and "back" are based on the directions or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or unit referred to must have a specific direction, be constructed and operated in a specific orientation, and therefore, cannot be understood as a limitation on the present invention.

[0024] like Figure 1 As shown, an embodiment of the utility model provides an SPR angle sensor for detecting low-concentration substances, comprising: a first metal layer 2, a sensitization layer 3 and a second metal layer 4 sequentially arranged on a prism 1; wherein the material of the sensitization layer 3 is gallium nitride.

[0025] The SPR angle sensor for low-concentration substance detection provided by the embodiment of the utility model increases the electric field strength between the film layer (the film layer includes the first metal layer, the gallium nitride layer and the second metal layer) and the object to be detected by coating a double metal layer sandwich sensitivity enhancement layer structure on the prism substrate, that is, coating a first metal layer, a sensitivity enhancement layer and a second metal layer structure on the prism substrate, thereby improving the detection sensitivity. This coupling structure comprehensively improves the quality factor of the sensor.

[0026] Specifically, gallium nitride (GaN) is a material with high electron mobility and low absorption coefficient, which can enhance the intensity of surface plasmon polaritons (SPP) excited by metal films. This double metal layer sandwich structure can increase the electric field strength between the film layer and the object to be measured, thereby improving the sensitivity and quality factor of the sensor.

[0027] In some embodiments, the light source of the SPR angle sensor is near infrared light.

[0028] Specifically, the light source uses near-infrared light to increase the surface plasmon polaritons of the SPR angle sensor and improve sensitivity.

[0029] In some embodiments, the material of the prism 1 is sapphire, and the shape of the prism 1 is semi-cylindrical.

[0030] It is understandable that sapphire prisms are used to transmit light. Sapphire (Sapphire) compresses the resonance valley to a smaller angle due to its high refractive index (n=1.770) and stability, which can obtain a better half-maximum full width; however, sapphire prisms lose detection sensitivity, resulting in a lower quality factor. By coating a double metal layer sandwich sensitization layer structure on the sapphire substrate, the electric field strength between the film layer and the object to be tested is increased, the detection sensitivity is improved, and the quality factor of the sensor is improved. The semi-cylindrical prism can ensure that during the test, no matter which angle the turntable rotates to, the propagation path length of the light in the prism remains consistent.

[0031] Optionally, the first metal layer 2 is metal gold, silver or copper, preferably metal copper. Using Cu to replace traditional precious metals Au or Ag saves costs to a great extent.

[0032] Optionally, the second metal layer 4 is metal gold, silver or copper, preferably metal copper. Using Cu to replace traditional precious metals Au or Ag saves costs to a great extent.

[0033] Specifically, gold and silver have strong SPR responses in the visible light and near-infrared bands, which can effectively enhance the resonance effect of the surface plasma, thereby improving the sensitivity of the sensor. When copper is used as the first metal layer 2 and the second metal layer 4, the results of the COMSOL simulation software show that the sensor can produce an SPR effect similar to that of gold when the thickness is appropriate, and even more obvious than that of gold.

[0034] In some embodiments, the thickness of the first metal layer 2 is 50 nm to 70 nm.

[0035] Specifically, the thickness of the first metal layer 2 is parametrically scanned using COMSOL simulation software, and it is found that the resonance valley effect is best when the thickness is between 50 nm and 70 nm, which can take into account both accuracy and sensitivity. If the thickness is too high, the resonance valley will become shallower and wider, and the accuracy will decrease; if the thickness is too low, it will be difficult to stimulate the SPR effect.

[0036] In some embodiments, the particle size of the gallium nitride is no greater than 7 μm.

[0037] Specifically, GaN is a material with high electron mobility and low absorption coefficient, which can enhance the SPP intensity excited by the metal film. We used COMSOL simulation software to perform a parametric scan on the thickness of the GaN layer and found that the electric field intensity excited was the strongest when the thickness was between 1.5nm and 2.5nm, reaching 2.2×10 5 V / m, the resonance valley effect is the best, so the smaller the particle size of the GaN powder, the better. Large particle size will cause uneven surface distribution after coating, which will affect the detection effect. This application uses 5 μm~7 μm GaN powder to prepare the SPR angle sensor sensitization layer, which can effectively enhance the SPP intensity excited by the metal film. Therefore, the particle size of GaN is not greater than 7 μm.

[0038] In some embodiments, the thickness of the second metal layer 4 is 10 nm to 20 nm.

[0039] Specifically, the thickness of the second metal layer 4 is parametrically scanned using COMSOL simulation software, and the thickness of the second metal layer 4 is found to be 10 nm to 20 nm. The second metal layer 4 is used to stimulate the electric field again on the basis of the first metal layer 2. If the thickness is too high, the resonance valley will become shallower and wider, and the accuracy will decrease; if the thickness is too low, it will be difficult to stimulate the SPR effect.

[0040] Preferably, the material of the first metal layer 2 is copper, and the thickness of the first metal layer 2 is 60 nm to 70 nm, and the material of the second metal layer 4 is copper, and the thickness of the second metal layer 4 is 15 nm to 20 nm. More preferably, the material of the first metal layer 2 is copper, and the thickness of the first metal layer 2 is 64 nm to 66 nm, and the material of the second metal layer 4 is copper, and the thickness of the second metal layer 4 is 16 nm to 18 nm. Most preferably, the material of the first metal layer 2 is copper, and the thickness of the first metal layer 2 is 65 nm, and the material of the second metal layer 4 is copper, and the thickness of the second metal layer 4 is 17 nm.

[0041] In summary, the SPR angle sensor for low-concentration substance detection of the utility model, especially the SPR angle sensor with sapphire-Cu-GaN-Cu coupling structure, is a low-concentration molecule detection tool that takes into account sensitivity, quality factor, economy, simple operation, and environmental friendliness. When the prism of the SPR angle sensor is a semi-cylindrical sapphire prism, the first metal layer is a 65nm copper film, the sensitization layer is a gallium nitride layer, the second metal layer is a 17nm copper film, and the light source is near-infrared light, the quality factor of the SPR angle sensor is 83.33, which is 154.9% higher than that of the traditional SPR sensor, and the detection accuracy is 1.11 degree -1, which is 5.56 times that of traditional SPR sensors, and the sensitivity can reach 75° / RIU, which is 7% higher than that of traditional SPR sensors, and the detection concentration of low-concentration substances can reach 1 pmol / L~1 μmol / L. When using this SPR angle sensor, the analyte can be labeled by neutral protein-functionalized gold nanoparticles (N-AuNPs), which increases the local refractive index of the dielectric layer on the sensor surface, and dramatically improves the sensitivity.

[0042] The following further introduces the preparation method and detection method of the SPR angle sensor for low-concentration substance detection of the utility model, and the specific steps are as follows:

[0043] Step 1: Adjust the discharge current of the small ion sputtering instrument (SBC-12) to 8 mA, sputter the copper film on the semi-cylindrical sapphire prism for 150 s, and then slowly clean it with anhydrous ethanol after sputtering.

[0044] Step 2: Take 200 mg of chitosan powder, add it to 50 mL of 4% glacial acetic acid aqueous solution, stir it with a magnetic stirrer, and heat it for 40 min to completely dissolve it.

[0045] Step 3: Take 60 mg of gallium nitride powder (6 μm~7 μm), add it to the chitosan acetic acid solution, and use a magnetic stirrer to stir at 1500 r / min for 1 h to fully disperse the gallium nitride in the chitosan solution.

[0046] Step 4: Transfer the mixed solution to an ultrasonic dispersion instrument, set the power to 300 W, the frequency to 20 kHz~25 kHz, and perform ultrasonic treatment for 1 h to further disperse the gallium nitride particles.

[0047] Step 5: Transfer the mixed solution after ultrasonic treatment to a centrifuge at a centrifugal speed of 5000 r / min for 15 minutes to allow the particles to settle to the bottom. Then take out the supernatant, which is the gallium nitride dispersion.

[0048] Step 6: The surface of the semi-cylindrical sapphire prism is treated with a polyacrylic acid (PAA) solution to make it negatively charged.

[0049] Step 7: Take 0.05 mL of the dispersion for coating each time and let it stand for 5 hours. Use the characteristics of positive and negative charge adsorption to allow GaN to evenly adhere to the copper film.

[0050] Step 8: Plate another layer of copper film according to the method in step 1, control the discharge time to 17 s, and the double metal layer sandwich structure is completed.

[0051] Step 9: Incubate the sensor surface in methanol for 30 min and in hexane for 2 min. Rinse the sensor disk with ultrapure water, immerse in 1 mM 11-MUA methanol solution, and store at room temperature for 24 h. After 11-MUA is formed on the sensor disk surface, rinse the sensor disk with methanol and UHQ water, and dry.

[0052] Step 10: The sensor surface was exposed to 10 mM NaAc buffer for 200 s, and then 0.4 M EDC and 0.1 M NHS were mixed at a ratio of 1:1 for 10 min. After washing the EDC / NHS mixture with 10 mM NaAc buffer, the sensor surface was exposed to the analyte antibody solution in 10 mM NaAc buffer for 30 min.

[0053] Step 11: Wash the surface with 10 mM NaAc buffer (pH 4.5) to remove unbound antibody.

[0054] Step 12: The sensor surface was exposed to 10 mM PBS buffer for 200 s, and then the analyte at an appropriate concentration in PBS was injected into the SPR channel for 10 min.

[0055] Step 13: Start the measurement, prepare solutions of different concentrations (refractive index), and introduce them into the surface of the SPR angle sensor through the microfluidic device. After the solution covers the detection area, start the prism turntable to perform angle scanning and draw a curve of the light intensity received by the SPR angle sensor as the angle changes.

[0056] In the description of this specification, the description of the terms "one embodiment", "some embodiments", "specific embodiments", etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the utility model. In this specification, the schematic representation of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner.

[0057] The above are only preferred embodiments of the present invention and are not intended to limit the present invention. For those skilled in the art, the present invention may be subject to various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

[0058] In view of the above detailed description, these and other changes can be made to these embodiments, and this written description includes the best mode embodiments to disclose the utility model. The scope of the patent obtained by the utility model is defined by the claims, and the claims are not limited by the content of the present disclosure. The protection scope of the utility model is not limited thereto. Any technician familiar with the technical field within the scope disclosed by the utility model, according to the technical solution and its concept of the utility model, makes equivalent replacement or change, which is within the protection scope of the utility model.

Claims

1. A SPR angle sensor for detecting low-concentration substances, characterized in that: include: A first metal layer (2), a sensitivity enhancement layer (3) and a second metal layer (4) are sequentially arranged on a prism (1); wherein the material of the sensitivity enhancement layer (3) is gallium nitride.

2. The SPR angle sensor for low-concentration substance detection according to claim 1, characterized in that: The light source of the SPR angle sensor is near infrared light.

3. The SPR angle sensor for low concentration substance detection according to claim 2, characterized in that: The material of the prism (1) is sapphire, and the shape of the prism (1) is semi-cylindrical.

4. The SPR angle sensor for low-concentration substance detection according to claim 3, characterized in that: The material of the first metal layer (2) is gold, silver or copper.

5. The SPR angle sensor for low-concentration substance detection according to claim 3 or 4, characterized in that: The material of the second metal layer (4) is gold, silver or copper.

6. The SPR angle sensor for low-concentration substance detection according to claim 5, characterized in that: The thickness of the first metal layer (2) is 50 nm to 70 nm.

7. The SPR angle sensor for low-concentration substance detection according to claim 6, characterized in that: The particle size of the gallium nitride is not greater than 7 μm.

8. The SPR angle sensor for low-concentration substance detection according to claim 7, characterized in that: The thickness of the second metal layer (4) is 10 nm to 20 nm.

9. The SPR angle sensor for low-concentration substance detection according to claim 8, characterized in that: The concentration of the low-concentration substance is 1 pmol / L~1 μmol / L.

10. The SPR angle sensor for low-concentration substance detection according to claim 9, characterized in that: The material of the first metal layer (2) is copper, and the thickness of the first metal layer (2) is 60 nm to 70 nm; the material of the second metal layer (4) is copper, and the thickness of the second metal layer (4) is 15 nm to 20 nm.

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