A spin terahertz source and a terahertz high-flux biochip integrated with metamaterials, a preparation method and applications thereof

Abstract

The present application relates to the technical field of terahertz biosensing application, in particular to a terahertz high-throughput biochip integrated with a spin terahertz source and a metamaterial, a preparation method and application thereof, a heterojunction film is grown on one side of a dielectric layer as a spin terahertz emission source, a periodic metamaterial structure is designed and processed on the other side and a specific sensing film is coated thereon, when a to-be-detected substance is dropped on the surface of the sensor, the specific film can capture the to-be-detected substance, causing a change in the permittivity of the surface of the metamaterial, terahertz radiation is generated by using infrared light to be incident on the film, and the near-field interaction between the terahertz and the superstructure and the to-be-detected substance causes a shift in the terahertz resonance peak position, thereby achieving the purpose of detecting the to-be-detected substance, and through preparation of a large-area sensing array chip, different specific films are coated on different sensing chips, so that the function of high-throughput detection can be realized.

Description

Technical Field

[0001] This invention relates to the field of terahertz biosensing application technology, specifically to a high-throughput terahertz biochip integrating a spin terahertz source and metamaterials, its preparation method, and its application. Background Technology

[0002] Terahertz spectroscopy is an electromagnetic spectrum between microwaves and infrared radiation, with a frequency range of 0.1–10 THz and a wavelength range of 30 μm–3 mm. Due to the lack of effective radiation sources and sensitive detection technologies in the past, this band of electromagnetic waves has not been extensively studied and is therefore referred to as the "terahertz gap." The development of ultrafast optoelectronic technology and micro-semiconductor devices has provided more effective radiation sources and detection technologies for terahertz research, leading to its widespread and in-depth study. Because the terahertz band contains information about the physical, chemical, and structural properties of matter, it is widely used in materials science, biomedical science, food chemistry, communication radar, and other fields.

[0003] The key to terahertz applications lies in the need for high-performance, low-cost terahertz sources and highly sensitive detection technologies. Currently, common terahertz sources include photoconductive antennas and organic crystals. However, these sources suffer from high costs, difficulty in miniaturization and integration, challenges in balancing signal strength and spectral width, and the need for specific pump lasers, among other problems. Therefore, a low-cost, high-signal, wide-spectrum, and integrated terahertz emission source is needed. In recent years, the development of ultrafast spintronics has opened a new path for terahertz source research, enabling the realization of terahertz radiation through ultrafast demagnetization and spin-charge conversion.

[0004] Terahertz metamaterials are novel artificial materials that operate in the terahertz band, enabling the modulation of the amplitude and phase of terahertz waves. When the surface of a metamaterial is covered by other substances, the change in its local effective dielectric constant causes a change in capacitance, resulting in a shift in its resonant frequency. Therefore, the shift in the resonant frequency of terahertz metamaterials can be used to detect trace substances. Currently, commercially available miniaturized terahertz spectrometers are based on fiber lasers to excite antennas or crystals to generate terahertz light, which is then incident on the analyte in the far field, and the terahertz signal is detected through electro-optic sampling. This far-field detection method lacks the sensitivity to detect trace substances, limiting the commercial application of terahertz spectrometers in high-sensitivity detection fields.

[0005] In view of the above-mentioned defects, the inventors of this invention have finally obtained this invention after a long period of research and practice. Summary of the Invention

[0006] The purpose of this invention is to provide a solution to the problem that current commercial miniaturized terahertz spectrometers, which utilize far-field detection methods, cannot achieve the sensitivity required for the detection of trace substances, thus limiting the commercial application of terahertz spectrometers in the field of high-sensitivity detection. This invention provides a high-throughput terahertz biochip integrating a spin terahertz source and metamaterials, its preparation method, and its application.

[0007] To achieve the above objectives, this invention discloses a high-throughput terahertz biochip integrating a spin terahertz source and metamaterials, comprising a spin terahertz emission source, a dielectric layer, and a metamaterial structure. The spin terahertz emission source comprises a PtO2 / CoFeB / MgO three-layer thin film, and the metamaterial structure comprises an asymmetric open resonant ring and a short metal wire.

[0008] The surface of the metamaterial structure is provided with a specific sensing film, which is a binding reagent capable of specifically recognizing the analyte, including aptamers, antibodies or biological probes, and the medium layer is a quartz, polyimide or PDMS film.

[0009] The thickness of PtO2 in the PtO2 / CoFeB / MgO three-layer film is 1-6 nm, the thickness of CoFeB is 1-6 nm, and the thickness of MgO is 1-6 nm.

[0010] The oxygen concentration of PtO2 in the PtO2 / CoFeB / MgO three-layer film is 10% to 90% in the cavity during preparation.

[0011] The asymmetric open-ended resonant ring includes two openings located on the same side of the vertical diameter passing through the asymmetric open-ended resonant ring. The center lines of the two openings form an acute angle α with the vertical diameter, where α is 1 to 20° and the width g of the opening is 1 to 10 μm.

[0012] The period P1 of the metamaterial sensor is 80–120 μm, the period P2 is 80–120 μm, the outer diameter r of the asymmetric open resonant ring is 20–40 μm, and the linewidth w is 5–20 μm.

[0013] The short metal wire is located on one side of the asymmetric open-ring resonator and is arranged vertically. The width of the short metal wire is 2 to 10 μm, the length of the short metal wire is 30 to 80 μm, and the distance between the short metal wire and the asymmetric open-ring resonator is 5 to 20 μm.

[0014] The thickness of the asymmetric open resonant ring and the metal short wire is 100–300 nm.

[0015] This invention also discloses a method for fabricating the above-mentioned spin terahertz source and metamaterial integrated terahertz high-throughput biochip, comprising the following steps:

[0016] S1, the surface of the dielectric substrate is ultrasonically cleaned sequentially with acetone, alcohol and deionized water;

[0017] S2, a layer of photoresist is first spin-coated on one side of the dielectric substrate, then pre-baked, and then the designed pattern is processed onto the thin layer by exposure using a laser direct writing system. After soaking in the developer, it is cleaned with ultrapure water and dried with nitrogen. Finally, a 200nm thick layer of gold is deposited using a magnetron sputtering system and then stripped clean to obtain the metamaterial structure.

[0018] S3 uses magnetron sputtering to deposit three thin films of PtO2 / CoFeB / MgO sequentially on the other side of the dielectric substrate, wherein the sputtering of PtO2 is carried out in the cavity at an oxygen concentration of 30%.

[0019] In step S3, the sputtering vacuum degree is 10. -6 Pa, the sputtering gases are Ar and O2.

[0020] This invention also discloses the application of the above-mentioned spin terahertz source and metamaterial integrated terahertz high-throughput biochip in the detection of biomarkers, including the following steps:

[0021] (1) Fix the high-throughput biochip on a two-dimensional translation stage, and move the translation stage to make the infrared femtosecond laser incident on the back of the sensing area, i.e. the terahertz emitter.

[0022] (2) Drop the solution of the biomarker to be tested onto different sensor chips, incubate at room temperature for 2 hours, rinse 3 times with deionized water to remove non-specifically bound molecules, and then dry with nitrogen before detection;

[0023] (3) By moving the sensor chip in the xy direction through a two-dimensional translation stage, all sensor chip arrays can be scanned, which can realize high-throughput biomarker detection function.

[0024] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0025] 1. This invention provides a detection chip integrating a spin terahertz emission source and a sensor. It utilizes a PtO2 / CoFeB / MgO three-layer structure with extremely high terahertz emission power. Based on the inverse spin Hall effect, when an infrared femtosecond laser is incident on the sample surface, it can excite a spin-to-charge conversion from CoFeB to the heavy metal layer, thereby radiating terahertz light. Traditional heavy metals such as platinum have large spin Hall angles. The platinum oxide prepared in this invention at a 30% oxygen concentration has an even stronger spin Hall angle, and its interface effect further enhances the spin-to-charge conversion efficiency. The intensity of the radiated terahertz signal is 4-5 times stronger than that of the Pt / CoFeB structure. Furthermore, magnesium oxide primarily serves as an antioxidant protective layer. Compared to traditional open-ring resonators, this designed metamaterial structure can simultaneously generate Fano resonance and EIT resonance, giving the metamaterial three-band resonant frequencies in the terahertz band. The Fano resonance is a resonant mode with a high Q value. The advantage of this integrated structure is that it enables near-field detection. When an infrared laser is focused onto the emission source, all the radiated terahertz light directly interacts with a periodic unit structure of the metamaterial. This near-field detection method not only reduces losses but also greatly improves detection sensitivity.

[0026] 2. The specific sensing film on the surface of the metamaterial structure in this invention utilizes the principle of specific antibody binding to biomarkers. Specific antibodies are coated onto the surface of the metamaterial sensor, giving it the characteristic of specifically binding to the antigen to be tested. When the antigen solution is dropped onto the sensor surface, the antibody can capture the antigen, causing a change in the dielectric constant of the surrounding environment of the metamaterial surface, resulting in a shift in the position of the metamaterial's resonance peak, thereby achieving the purpose of detecting biomarkers. Furthermore, by fabricating a large-area sensor array chip and coating different arrays with different specific antibodies, high-throughput biomarker detection can be achieved. This invention features low cost, high sensitivity, specificity, and high-throughput biomarker detection, and has broad application prospects. Attached Figure Description

[0027] Figure 1 This is a schematic diagram of the integrated terahertz biochip in an embodiment of the present invention;

[0028] Figure 2 This is a schematic diagram of a spin terahertz emission source in an embodiment of the present invention;

[0029] Figure 3 The terahertz emission signals of PtO2 prepared under different oxygen concentrations in the embodiments of the present invention;

[0030] Figure 4 This is a schematic diagram of the metamaterial unit structure in an embodiment of the present invention;

[0031] Figure 5 These are simulation diagrams of different opening angles of the metamaterial structure in the embodiments of the present invention;

[0032] Figure 6 This is a simulation diagram of the sensing sensitivity in an embodiment of the present invention;

[0033] Figure 7 This is a schematic diagram of high-throughput detection using a terahertz biochip in an embodiment of the present invention;

[0034] Figure 8 This is a diagram showing the experimental results of specific detection of TGF-β1 samples in an embodiment of the present invention. Detailed Implementation

[0035] The above-mentioned and other technical features and advantages of the present invention will be described in more detail below with reference to the accompanying drawings.

[0036] like Figure 1 As shown, the spin terahertz emission source and metamaterial integrated biosensor chip of this invention includes a terahertz emission source, a dielectric layer, and a metamaterial sensor. Additionally, a specific sensing film is fixed to the surface of the metastructure, and the specific sensing film includes a binding reagent capable of specifically recognizing the analyte. The terahertz emission source comprises a three-layer structure: platinum oxide, cobalt iron boron, and magnesium oxide. The inventors have experimentally discovered that the strongest terahertz signal intensity is generated when the thicknesses of the three layers are 3 nm, 4 nm, and 2 nm, respectively. The dielectric layer can be made of quartz, polyimide, or PDMS to shield the mutual influence between the emission source and the metastructure. Each periodic structure includes an open-loop resonant ring and a short metal line, wherein the open-loop includes two openings located on the same side of the vertical diameter, indicating that the two openings are asymmetrical along the vertical diameter. The centerlines of both openings pass through the center of the asymmetrical open-loop resonant ring and form an acute angle α with the vertical diameter.

[0037] Through experimentation, the inventors discovered that higher detection sensitivity can be achieved when the opening angle is less than 30°, and the smaller the opening angle, the higher the sensitivity. The preferred opening angle is α = 1-20°. The opening is rectangular, and its width g is preferably 5-10 μm. Furthermore, the distance between the short metal wire and the opening ring is preferably 10-20 μm.

[0038] This embodiment provides a terahertz high-throughput sensor for detecting biomarkers TNF and TGF-β1, in order to solve the problem of rapid, low-cost, high-sensitivity, specific, and high-throughput detection of biomarkers.

[0039] 1. Fabrication of biosensors integrating spin terahertz sources and metamaterials

[0040] The integrated metamaterial sensor designed in this invention uses quartz as the dielectric layer, a three-layer structure grown by magnetron sputtering as the emission source, and gold as the periodic metamaterial structure. Its fabrication process includes:

[0041] (1) Cleaning of quartz substrate surface: In order to ensure the cleanliness of the quartz sheet surface and make the film firmly adhere to the quartz, the substrate surface must first be ultrasonically cleaned in sequence with acetone, alcohol and deionized water.

[0042] (2) Preparation of metamaterial structure: First, spin-coat a layer of photoresist S1813 (4000 rpm, 40 seconds) on one side of the dielectric substrate, then pre-bake (115℃, 1 minute), then use a laser direct writing system to expose and process the designed pattern onto the substrate, then soak in the developer for 40 seconds, then clean with ultrapure water and blow dry with nitrogen, finally use a magnetron sputtering system to deposit a 200 nm thick layer of gold, and then peel it off to obtain the metamaterial structure;

[0043] (3) Spin terahertz emission source preparation: First, place the corresponding Pt, CoFeB, and MgO targets and substrates, adjust their positions and angles, then start the mechanical pump. When the pressure inside the furnace drops to about 10 Pa, start the molecular pump and evacuate to a vacuum of 10 Pa. - 6 First, sputter Pt, selecting sputtering gases Ar and O2, setting the O2 content to 30%, and opening the gas control valves. Then, set the working gas pressure to 10. -4 With the operating power set at 50W, sputtering time at 40s, and sample stage rotation speed at 20 rpm, the substrate baffle was opened, and sputtering began. Next, CoFeB was sputtered using Ar gas for 60s, with all other conditions remaining the same. Finally, MgO was sputtered for 70s, with all other conditions identical. After sputtering, the nitrogen cylinder and valve were opened to fill the sputtering chamber with dry nitrogen, and the coated sample was removed from the sample stage.

[0044] A schematic diagram of the spin terahertz emission source according to an embodiment of the present invention is shown below. Figure 2 As shown, the terahertz emission source employs a three-layer structure of PtO2 / CoFeB / MgO, with each layer having thicknesses of 3 nm, 4 nm, and 2 nm, respectively. Notably, during the preparation of the PtO2 thin film, the terahertz signal emission intensity was maximized when the oxygen concentration within the cavity was 30%. Figure 3 The terahertz emission signal intensity of PtO2 prepared under different oxygen concentrations is shown. It can be seen that the terahertz emission signal is weak when the oxygen concentration is 10%, and the terahertz signal is strongest when the oxygen concentration is 30%. The terahertz signal gradually weakens as the oxygen concentration gradually increases.

[0045] The structural diagram of the periodic metamaterial unit of this invention is shown in the figure below. Figure 4 As shown, on the substrate is an open ring and a short line made of gold. The ring has two openings. The specific parameters are as follows: periodic side length P1 = 95 μm, P2 = 90 μm, outer diameter of the ring r = 30 μm, ring width w = 5 μm, opening width g = 5 μm, opening angle α = 10°, length of the metal short line l1 = 5 μm, height l2 = 50 μm, spacing d = 15 μm, and thickness of the periodic metal structure is 200 nm.

[0046] This is a structure consisting of an open-ended ring and short metal lines. This special asymmetric open-ended metal resonant ring structure has a unique resonance response compared to the traditional single-open-ended resonant ring structure. When the electric field of a terahertz wave is incident perpendicularly along the vertical direction (y-direction), this structure can simultaneously induce three resonance peaks: one Fano resonance and two EIT resonances. The Fano resonance is an asymmetric resonance generated by the interference of discrete spectral lines with very narrow linewidths and continuous spectral lines. This Fano resonance has a very narrow spectral width and a higher quality factor (Q value).

[0047] The metamaterial sensor was simulated using the frequency domain solver in CST software. Simulation results were obtained by setting different aperture angles, as shown below. Figure 5 As shown, when the aperture angle is symmetrical (a = 0), the transmission spectrum has two resonance peaks near 1.4 THz and 1.8 THz, which is a typical EIT resonance. When the aperture angle is asymmetrical, the transmission spectrum adds a resonance peak near 1 THz, which is a typical Fano resonance. It is worth noting that as the aperture angle increases, the spectral lines broaden and the Q value decreases. When the aperture angle is 10°, the corresponding Q value reaches a maximum of 22.

[0048] In addition, the sensitivity of the sensor was simulated. When the refractive index of the analyte on the sensor surface changes, the corresponding resonance peak redshifts. The simulation results are as follows: Figure 6 As shown, the shift of the EIT resonance peak can reach up to 370 GHz / RIU. In an embodiment of the present invention, this optimized metamaterial structure is used as a biosensor to detect acetamiprid pesticide.

[0049] 2. Preparation of specific sensing films

[0050] TNF and TGF-β1 antibodies were diluted to the required concentrations with buffer solution. 100 μL of each diluted antibody solution was dropped onto the surface of two metamaterial sensors. After incubation at room temperature for 2 hours, the sensors were rinsed three times with deionized water to remove uncoated antibody molecules. After drying with nitrogen, a specific sensing film was obtained.

[0051] 3. High-throughput detection of biomarkers

[0052] The schematic diagram of the integrated terahertz biochip detection principle is as follows: Figure 7 As shown, this chip is an array-type high-throughput sensor chip, in which each small sensing area is coated with a different specific thin film. The biochip is fixed on a two-dimensional translation stage. By moving the stage, an infrared femtosecond laser is incident on the back side of the sensing area, i.e., the terahertz emitter, thereby exciting terahertz radiation. Terahertz radiation can directly interact with the metamaterial structure and the analyte. The presence of analyte molecules alters the dielectric constant of the environment surrounding the sensor surface, causing a redshift of the resonance peak. Furthermore, since different concentrations of the analyte solution have different dielectric constants, the dielectric constant of the analyte solution increases with increasing concentration, resulting in a linear increase in the resonance peak shift. In the experiment, 100 μL of TNF and TGF-β1 solutions of different concentrations were prepared and dropped onto different sensor chips. After incubation at room temperature for 2 hours, the chips were rinsed three times with deionized water to remove non-specifically bound molecules, and then dried with nitrogen before detection. By moving the sensor chips in the xy direction using a two-dimensional translation stage and scanning the entire sensor chip array, high-throughput biomarker detection can be achieved. For example... Figure 8 The figure shows the experimental results for the specific detection of TGF-β1 samples. The reference signal is the transmission spectrum of a blank chip coated with the corresponding antibody. The far-field signal is measured using a traditional terahertz time-domain spectroscopy system based on a photoconductive antenna, with a resonance peak shift of 40 GHz. The near-field signal is measured using the detection chip of this invention, with a resonance peak shift of 110 GHz. It can be seen that the detection chip of this invention has a larger resonance peak shift and higher detection sensitivity. This embodiment of the invention, by coating the surface of a metamaterial biosensor with specific antibodies, possesses the ability to specifically detect biomarkers, enabling the sensor to achieve low-cost, high-sensitivity, specific, and high-throughput detection.

[0053] The above description is merely a preferred embodiment of the present invention and is illustrative rather than restrictive. Those skilled in the art will understand that many changes, modifications, and even equivalents can be made within the spirit and scope defined by the claims of the present invention, all of which will fall within the protection scope of the present invention.

Claims

1. A terahertz high-throughput biochip integrating a spin terahertz source and metamaterials, characterized in that, It includes a spin terahertz emission source, a dielectric layer, and a metamaterial structure. The spin terahertz emission source includes a PtO2 / CoFeB / MgO three-layer thin film, and the metamaterial structure includes an asymmetric open resonant ring and a short metal wire. The PtO2 in the PtO2 / CoFeB / MgO three-layer thin film has an oxygen concentration of 30% in the cavity during preparation.

2. The terahertz high-throughput biochip integrating a spin terahertz source and metamaterials as described in claim 1, characterized in that, The surface of the metamaterial structure is provided with a specific sensing film, which is a binding reagent capable of specifically recognizing the analyte, including aptamers, antibodies or biological probes, and the medium layer is a quartz, polyimide or PDMS film.

3. The terahertz high-throughput biochip integrating a spin terahertz source and metamaterials as described in claim 1, characterized in that, The thickness of PtO2 in the PtO2 / CoFeB / MgO three-layer film is 1-6 nm, the thickness of CoFeB is 1-6 nm, and the thickness of MgO is 1-6 nm.

4. The terahertz high-throughput biochip integrating a spin terahertz source and metamaterials as described in claim 1, characterized in that, The asymmetric open-ended resonant ring includes two openings located on the same side of the vertical diameter passing through the asymmetric open-ended resonant ring. The center lines of the two openings form an acute angle α with the vertical diameter, where α is 1~20° and the width g of the opening is 1~10μm.

5. The terahertz high-throughput biochip integrating a spin terahertz source and metamaterials as described in claim 1, characterized in that, The period P1 of the metamaterial structure is 80~120μm, the period P2 is 80~120μm, the outer diameter r of the asymmetric open resonant ring is 20~40μm, and the linewidth w is 5~20μm.

6. The terahertz high-throughput biochip integrating a spin terahertz source and metamaterials as described in claim 1, characterized in that, The short metal wire is located on one side of the asymmetric open-ring resonator and is arranged vertically. The width of the short metal wire is 2~10μm, the length of the short metal wire is 30~80μm, and the distance between the short metal wire and the asymmetric open-ring resonator is 5~20μm.

7. The terahertz high-throughput biochip integrating a spin terahertz source and metamaterials as described in claim 1, characterized in that, The thickness of the asymmetric open resonant ring and the metal short wire is 100~300nm.

8. A method for fabricating a terahertz high-throughput biochip integrating a spin terahertz source and metamaterials as described in any one of claims 1 to 7, characterized in that, Includes the following steps: S1, the surface of the dielectric substrate is ultrasonically cleaned sequentially with acetone, alcohol and deionized water; S2, a layer of photoresist is first spin-coated on one side of the dielectric substrate, then pre-baked, and then the designed pattern is processed onto the dielectric layer + photoresist layer by exposure using a laser direct writing system. After soaking in the developer, it is cleaned with ultrapure water and dried with nitrogen. Finally, a 200nm thick layer of gold is deposited using a magnetron sputtering system and then stripped clean to obtain the metamaterial structure. S3 uses magnetron sputtering to deposit three thin films of PtO2 / CoFeB / MgO sequentially on the other side of the dielectric substrate, wherein the sputtering of PtO2 is carried out in the cavity at an oxygen concentration of 30%.

9. The application of a high-throughput terahertz biochip integrating a spin terahertz source and metamaterials as described in any one of claims 1 to 7 in the detection of biomarkers, characterized in that, Includes the following steps: (1) Fix the high-throughput biochip on a two-dimensional translation stage, and move the translation stage to make the infrared femtosecond laser incident on the back of the sensing area, i.e. the terahertz emitter. (2) Drop the solution of the biomarker to be tested onto different sensor chips, incubate at room temperature for 2 hours, rinse with deionized water 3 times to remove non-specifically bound molecules, and then dry with nitrogen before detection; (3) By moving the sensor chip in the xy direction through a two-dimensional translation stage, all sensor chip arrays can be scanned, which can realize high-throughput biomarker detection function.

Images