A light-controlled terahertz biosensor and its preparation method and detection spectrum system

Abstract

The present invention provides a light-controlled terahertz biosensor and a preparation method thereof and a detection spectrum system, which relate to the field of biomedical detection, including: a substrate and a dielectric material and a supersurface structure integrated on the substrate; wherein the substrate is a terahertz wave high-transmittance material, the dielectric material is a semiconductor material, and the supersurface structure is an array structure composed of multiple metal resonators and cutting wires; a lattice resonance structure is formed between multiple metal resonators, a Lorentz resonance structure is formed between multiple cutting wires, and the lattice resonance structure and the Lorentz resonance structure are coupled to form a Lorentz-lattice resonance mode; the dielectric material is integrated between the cutting wires to connect the paired cutting wires, so as to rely on the ultrafast carrier excitation and relaxation process of the dielectric material, and realize the switching of the Lorentz-lattice mode to the EIT mode within the picosecond range. The present invention realizes highly sensitive quantitative and qualitative detection of tiny biological substances, and has the advantages of portability and high integration.

Description

Technical Field

[0001] The present invention relates to the field of biomedical detection, and in particular to a light-controlled terahertz biosensor, a preparation method of the light-controlled terahertz biosensor, and a terahertz detection spectrum system. Background Art

[0002] Terahertz waves are located between the millimeter wave band and the infrared band, and have both photonic and electronic properties. Because of its non-ionizing, non-destructive, high penetration, high resolution and spectral fingerprint characteristics, terahertz waves have become a potential tool in the biomedical field. With its rapid development in the field of biological material detection, terahertz sensing has become a promising technology in biomedical research and material detection. However, due to the lack of terahertz sources with high radiation intensity and the mismatch between the wavelength of terahertz waves and the size of analytes, terahertz waves have not been widely used in material detection.

[0003] Micro-nano photonics hopes to break this limitation by utilizing the strong near-field enhancement effect of subwavelength resonant structures. Subwavelength resonant structures can control the polarization, phase, and amplitude of light, and can be used for light emission, detection, modulation, control, and amplification at the micro-nano scale. The near-field enhancement of the light field in the microstructure can promote the interaction between light and matter. Therefore, terahertz spectroscopy technology based on metasurface micro-nano structures has become a promising method for detecting biochemical substances. However, conventionally designed metasurface micro-nano structures can only provide a single-mode state with a fixed resonance peak position, which is difficult to meet the ultra-high sensitivity requirements in the detection and identification of trace biological substances.

[0004] At present, there are still the following defects in biological qualitative detection using the above technology:

[0005] First, qualitative detection is achieved by designing a single microstructure so that its resonance peak overlaps with the single fingerprint of the analyte. The response of the designed microstructure needs to be based on a known characteristic fingerprint spectrum of the analyte, and a single peak can only be used to detect a single target. If more substances are to be detected, the structural parameters of the sensor can only be changed, and more sensors can be processed according to these structural parameters. This is far from meeting the development requirements of fast, convenient, small-sized, and highly integrated sensor devices, which seriously limits the widespread application of sensors in practice.

[0006] Second, design a single-mode microstructure for quantitative detection of trace biological substances. The resonant response of the microstructure is highly dependent on the refractive index change of the surrounding medium, so the thickness and density of the analyte will directly affect the response of the microstructure. Therefore, it is very difficult to detect the frequency shift and amplitude difference of the resonance peak position of trace substances of different doses in experimental operation.

[0007] Third, metamaterials combined with ultrafast optics are used in biomedical detection applications. Metamaterials provide strong local fields for the detection of tiny or trace substances, enhancing the full interaction between light and matter; the application of ultrafast optics in the optical field is developing rapidly, but the research and application in the biomedical field is almost blank.

[0008] Fourth, the data processing of the single-mode resonant structure for biological detection is cumbersome, and the measured information needs to be processed by Fourier transform. The conventional application of the prior art is to first transform the material detection information from the time domain signal through Fourier transform, and then go through cumbersome data processing to obtain the ideal data. The complex processing process greatly limits the application of biosensors to the detection of batch substances.

[0009] Therefore, how to further improve the existing terahertz detection system to achieve ultra-sensitive detection of tiny biological substances has become a technical problem that needs to be solved. Summary of the invention

[0010] The present invention aims to solve at least one of the technical problems existing in the above-mentioned prior art or related technology, and provides a light-controlled terahertz biosensor and its preparation method and detection spectrum system, which combines ultrafast optics with metamaterials as carriers and is applied to ultra-sensitive detection of biological substances such as cells and macromolecules by terahertz waves, providing an exploration idea of ​​multidisciplinary cross-collaboration in the application of material detection in the biomedical field.

[0011] The first aspect of the present invention provides a light-controlled terahertz biosensor, comprising: a substrate and a dielectric material and a supersurface structure integrated on the substrate; wherein the substrate is a terahertz wave highly transparent material, the dielectric material is a semiconductor material, and the supersurface structure is an array structure composed of a plurality of metal resonators and cutting wires; a lattice resonance structure is formed between the plurality of metal resonators, a Lorentz resonance structure is formed between the plurality of cutting wires, and the lattice resonance structure and the Lorentz resonance structure are coupled to form a Lorentz-lattice resonance mode; the dielectric material is arranged between the cutting wires to connect the paired cutting wires, so as to rely on the ultrafast carrier excitation and relaxation process of the dielectric material to realize the switching of the Lorentz-lattice mode to the EIT (Electromagnetic Induced Transparency) mode within the picosecond range.

[0012] According to the light-controlled terahertz biosensor provided by the present invention, preferably, the metasurface structure is a plurality of unit structures arranged periodically, each unit structure includes two pairs of metal resonators and a pair of cutting wires; the metal resonators are square opening resonators; the openings of the two metal resonators are arranged opposite to each other to form a pair of metal resonators; the two pairs of metal resonators arranged up and down in the same plane are separated by a pair of cutting wires.

[0013] According to the light-controlled terahertz biosensor provided by the present invention, preferably, the cut wires are connected by silicon bridges.

[0014] According to the light-controlled terahertz biosensor provided by the present invention, preferably, the metal resonator is made of any one of gold, silver or aluminum.

[0015] According to the light-controlled terahertz biosensor provided by the present invention, preferably, the dielectric material is silicon or germanium.

[0016] The second aspect of the present invention provides a method for preparing a light-controlled terahertz biosensor, comprising: cleaning sapphire substrate silicon with acetone and isopropanol; preparing a metal supersurface structure; constructing a silicon pattern using an alignment photolithography technique combined with a silicon deep etching technique to complete a secondary pattern transfer; wherein the metal supersurface structure is a plurality of unit structures arranged periodically, and each unit structure comprises: two pairs of open square resonators, and two cutting wires connected by semiconductor material.

[0017] In this technical solution, the specific layout of the metal metasurface structure includes: each unit structure includes two pairs of metal resonators and a pair of cutting wires; the metal resonators are square open resonators; the openings of the two metal resonators are arranged opposite to each other to form a pair of metal resonators; the two pairs of metal resonators arranged up and down in the same plane are separated by a pair of cutting wires; the semiconductor material is integrated between the two cutting wires to form a pair of cutting wires.

[0018] According to the method for preparing the light-controlled terahertz biosensor provided by the present invention, preferably, the sapphire substrate silicon specifically includes an epitaxial silicon layer with a thickness of 600 nm and a sapphire substrate with a thickness of 460 nm.

[0019] According to the method for preparing the light-controlled terahertz biosensor provided by the present invention, preferably, step photolithography and ion beam etching are used to prepare the metal super surface structure on the titanium and gold films. Specifically, the thickness of the titanium is 10 nm and the thickness of the gold film is 160 nm.

[0020] The third aspect of the present invention provides a terahertz detection spectrum system, comprising: a femtosecond laser, a beam splitter, and a light-controlled terahertz biosensor as disclosed in any of the above technical solutions; wherein the femtosecond laser is used to generate femtosecond laser; the beam splitter is used to split the femtosecond laser to form terahertz light, terahertz detection light and pump light; the pump light is used to achieve the excitation of optical carriers; the terahertz detection light is used to test and record the transmission spectrum of the pump light before and after it enters the metasurface.

[0021] The beneficial effects achieved by the present invention include at least: the application of ultrafast optics can provide the possibility for the ultra-surface micro-nano structure to complete the rapid switching of the resonance peak position in an ultra-fast time to realize dual-mode or even multi-mode detection, thereby greatly improving the sensitivity of detection. Specifically, when the detected substance moves to the ultra-surface interface and causes a slight change in the dielectric constant of the dielectric layer, the coupling state of the resonance changes according to the different sensitivities of the two resonance structures. During the experiment, obvious changes can be discovered and recorded through the terahertz time domain signal. Compared with the method in the prior art that requires tedious and complex data processing such as Fourier transform to obtain the final result, the light-controlled terahertz sensor has a more sensitive detection result, is more convenient and simple to use, and eliminates the subsequent tedious data processing such as Fourier transform, providing a new method for high-sensitivity detection. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 A schematic structural diagram of a light-controlled terahertz biosensor according to an embodiment of the present invention is shown.

[0023] Figure 2 The transmission spectra of the light-controlled terahertz biosensor according to an embodiment of the present invention at different pump energies are shown.

[0024] Figure 3 The transmission spectra of the light-controlled terahertz biosensor according to an embodiment of the present invention are shown when the silicon conductivity is different.

[0025] Figure 4 The transmission spectrum of the light-controlled terahertz biosensor according to an embodiment of the present invention is shown when the pump light detection time delay is between -2ps and 32ps.

[0026] Figure 5 The transmission spectrum of the light-controlled terahertz biosensor according to an embodiment of the present invention is shown when the pump light detection time delay is between 32 ps and 162 ps.

[0027] Figure 6 A schematic diagram of the optical path of a terahertz detection spectroscopy system according to an embodiment of the present invention is shown.

[0028] Figure 7 A schematic diagram of a unit structure of a supersurface structure according to an embodiment of the present invention is shown. DETAILED DESCRIPTION

[0029] In order to be able to more clearly understand the above-mentioned objects, features and advantages of the present invention, the present invention is further described in detail below in conjunction with the accompanying drawings and specific embodiments. In order to simplify the disclosure of the present invention, the components and settings of specific examples are described below. In addition, the present invention can repeat reference numbers and / or letters in different examples. This repetition is for the purpose of simplification and clarity, and does not itself indicate the relationship between the various embodiments and / or settings discussed. It should be noted that the components illustrated in the accompanying drawings are not necessarily drawn to scale. The present invention omits the description of known components and processing techniques and processes to avoid unnecessary limitation of the present invention.

[0030] like Figure 1 As shown, according to one embodiment of the present invention, a light-controlled terahertz biosensor is disclosed, comprising: a substrate 1, a dielectric material 2 and a supersurface structure integrated on the substrate; wherein the substrate is a terahertz wave high-transmittance material, the dielectric material is a semiconductor material, and the supersurface structure is an array structure composed of a plurality of metal resonators 3 and cutting wires 4; a lattice resonance structure is formed between the plurality of metal resonators, a Lorentz resonance structure is formed between the plurality of cutting wires, and the lattice resonance structure and the Lorentz resonance structure are coupled to form a Lorentz-lattice resonance mode; the dielectric material is integrated between the cutting wires to connect the paired cutting wires, so as to rely on the ultrafast carrier excitation and relaxation process of the dielectric material to realize the switching of the Lorentz-lattice mode to the EIT mode within the picosecond range.

[0031] In this embodiment, when the pump light is injected into the optically controlled terahertz biosensor, the physical interval between the two cutting wires is opened due to the ultrafast carrier excitation and relaxation process of the dielectric material, so that the resonance mode of the metasurface switches from the Lorentz-lattice mode to the Electromagnetic Induced Transparency (EIT) mode within the picosecond range, realizing the detection application of two tunable modes based on the same structure under optical control conditions, breaking the single mode microstructure of the traditional metasurface design, and having the advantages of high sensitivity, strong portability and high integration. The rapid switching of sensing modes and functions realizes the ultra-sensitive and rapid detection of the dual-mode state of biological substances. The spectral positions of the two modes are mainly related to the sizes of the two pairs of open square resonators, the two cutting wires and the dielectric materials, the distance between the three, and the distance between the unit array structures; and the conversion time of the two modes depends on the characteristics of the ultrafast carrier excitation and relaxation of the dielectric material itself. The ultrafast carrier excitation and relaxation characteristics of dielectric materials provide a basis for ultrafast switching under light-controlled conditions, and greatly promote the miniaturization of light-controlled terahertz biosensors. After the pump light is injected, with the excitation of ultrafast carriers in the dielectric material, the physical gap between the two dividing lines connected by the dielectric material is opened, causing the resonant mode of the metasurface structure to switch rapidly within the picosecond range. At the same time, the rapid switching of two tunable modes under light-controlled conditions is completed on the basis of the same structure. The dual-mode detection greatly improves the detection efficiency and provides a new idea for the miniaturization and integrated design of metasurface micro-nano structures.

[0032] According to the above embodiments, preferably, the metasurface structure is a plurality of unit structures arranged periodically, each unit structure includes two pairs of metal resonators and a pair of cutting wires; the metal resonators are square opening resonators; the openings of the two metal resonators are arranged opposite to each other to form a pair of metal resonators; the two pairs of metal resonators arranged up and down in the same plane are separated by a pair of cutting wires.

[0033] In this embodiment, the Lorentz mode composed of multiple two-splitting wire (cut wire) array structures and the lattice mode composed of multiple two pairs of open square resonator array structures are coupled to realize the Lorentz-lattice resonance mode. When the detected material moves to the metasurface interface and causes a slight change in the dielectric constant of the dielectric layer, the coupling state of the resonance changes according to the different sensitivities of the two resonance structures. During the experiment, the obvious changes can be found and recorded through the terahertz time domain signal, eliminating the subsequent tedious data processing such as Fourier transform, providing a new method for high-sensitivity detection.

[0034] According to the above embodiment, preferably, the cutting wires are connected by silicon bridges.

[0035] According to the above embodiment, preferably, the metal resonator is made of any one of gold, silver or aluminum.

[0036] According to the above embodiment, preferably, the dielectric material is silicon or germanium.

[0037] According to the above embodiment, preferably, Figure 7 An implementation method of the specific parameters of each unit structure in the metasurface structure is shown as: a=10μm, b=18μm, c=26μm, d=32.5μm, e=9μm, P=83μm. The above parameters are the optimal solution that can meet the rapid switching of the Lorentz-lattice resonance mode and the Electromagnetic Induced Transparency (EIT) resonance mode after repeated simulation and measurement.

[0038] According to another embodiment of the present invention, a preparation method of the light-controlled terahertz biosensor corresponding to the above embodiment is disclosed:

[0039] 1) Clean the sapphire substrate silicon with acetone and isopropanol to remove surface dust. The sapphire substrate silicon includes: a 600nm epitaxial silicon layer and a 460nm sapphire substrate.

[0040] 2) Prepare a metal superstructure (metal supersurface structure). The superstructure is a periodically arranged multiple unit structures (such as Figure 1 The unit structure includes: two pairs of open square resonators, the openings of the square resonators are opposite to each other, and two cutting wires connected by semiconductor materials. The cutting wires are connected by silicon bridges (dielectric materials).

[0041] In this step, a metal superstructure is prepared on the titanium and gold films by using step photolithography and ion beam etching. The thickness of the titanium metal is 10 nm; the thickness of the gold film is 160 nm.

[0042] 3) Use alignment photolithography technology combined with silicon deep etching technology to construct silicon patterns and complete secondary pattern transfer. According to microscope observation results, the lateral etching accuracy is ±0.5μm and the longitudinal etching accuracy is +10%.

[0043] According to another embodiment of the present invention, a terahertz detection spectrum system using the above-mentioned light-controlled terahertz biosensor for detection is also disclosed. The terahertz detection spectrum system includes: a femtosecond laser, a beam splitter and a light-controlled terahertz biosensor. The femtosecond laser is used to generate femtosecond laser; the beam splitter is used to split the above-mentioned femtosecond laser to form terahertz light, terahertz detection light and pump light; wherein the pump light is used to achieve the excitation of optical carriers; the terahertz detection light is used to test and record the transmission spectrum of the pump light before and after it enters the metasurface.

[0044] like Figure 6 As shown, the terahertz detection spectrum system specifically includes: a reflector (M), a beam splitter 1 (BS1), a beam splitter 2 (BS2), a half-wave plate (HWP), a thin film polarizer (TFP), an indium tin oxide transparent conductive film glass (ITO), an off-axis parabolic mirror (OPM1, OPM2, OPM3, OPM4), a high-resistance silicon wafer (HR Si), a quarter-wave plate (QW), a Wollaston prism (WP), a balanced diode (BPD), and a zinc telluride crystal (ZnTe). The process of using the terahertz detection spectrum system to detect biological substances includes the following steps:

[0045] First, a beam splitter is used to split the laser light (800nm, 100fs) emitted by a femtosecond laser into three paths. One path is used to generate terahertz waves, one path is used for terahertz detection light, and one path is used for pump light to achieve the excitation of silicon carriers. The terahertz generation and detection light tests are used, and the transmission spectrum of the metasurface structure before and after the pump light is injected is recorded;

[0046] Secondly, the biological substances to be tested, such as cells or macromolecular biological substances of different types and concentrations, are processed and samples are taken out. After that, the samples are moved to the surface of the metasurface structure, and the transmission spectra before and after the pump light is injected are tested again, and the frequency shift and amplitude change spectra of each test are recorded.

[0047] Since the electric and magnetic field energies of the resonant metal structure are mainly localized at the metal / dielectric interface, it is beneficial to enhance the interaction between light and matter in the near field. Therefore, after the cells or macromolecular biological substances of different types and concentrations are transplanted, the resonant structure will shift in frequency or amplitude due to the difference in cell dielectric constant and conductivity or the coupling between the vibration of biomacromolecules and the enhanced magnetic field around the resonator.

[0048] Finally, by comparing the changes in spectrum information (such as frequency shift and amplitude shift) of cells or macromolecular biological substances of different types and concentrations before and after placement and before and after the pump light is injected, the substances can be qualitatively or quantitatively analyzed.

[0049] Furthermore, the biosensor can qualitatively analyze the resonant coupling between a characteristic peak of a biomacromolecule and a resonance peak in one mode, and verify it by ultrafast conversion to another mode. It optimizes the scheme that may cause false positives by identifying substances through a single characteristic absorption spectrum. The application of two or even multiple modes can also realize the accurate detection of multiple characteristic spectra of a single substance or multiple mixed substances. At the same time, quantitative analysis can also be performed based on the changes in frequency shift and amplitude shift of biomacromolecules at different doses.

[0050] Figure 2 to Figure 5 That is, the transmission spectrum under different conditions. Among them, Figure 2Shown are the transmission spectra of the light-controlled terahertz biosensor of the present invention at different pump energies; Figure 3 Shown are transmission spectra of the light-controlled terahertz biosensor of the present invention when it has different silicon conductivities; Figure 4 Shown is the transmission spectrum of the light-controlled terahertz biosensor of the present invention when the pump light detection time delay is between -2ps and 32ps; Figure 5 Shown is the transmission spectrum of the light-controlled terahertz biosensor of the present invention when the pump light detection time delay is between 32 ps and 162 ps.

[0051] In order to achieve the best detection effect, the above-mentioned spectral system needs to first use the light-controlled terahertz biosensor for which protection is requested by the present invention. In order to prepare a high-precision biosensor, first, it is necessary to calculate and simulate and adjust the parameters of the supersurface micro-nanostructure, and simulate the resonant mode conversion before and after the pump light is injected. Make the design structure conform to the coupling state of the Lorentz and lattice modes before the pump light is injected, and the sensing mode is converted to the EIT mode after the pump light is injected. The coupling mode provides ultra-sensitive characteristics for the detection of biological substances. In order to improve the simulation accuracy, preferably, FDTD software can be used for calculation and simulation. Afterwards, according to the supersurface structure parameters, the silicon material and the superstructure are integrated onto the substrate to produce a light-controlled terahertz biosensor with ultrafast switching sensing function.

[0052] By designing and adjusting the structural parameters, the present invention can realize the rapid switching of the resonance mode under the conditions of pump light injection and non-pump light injection, thereby completing the rapid detection of biological substances in a dual-mode state, and ultimately achieving more accurate, sensitive and portable qualitative and quantitative detection of the object to be detected.

[0053] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have 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.

Claims

1. A light-controlled terahertz biosensor, characterized in that: include: A substrate and a dielectric material and a supersurface structure integrated on the substrate; wherein the substrate is a terahertz wave high-transmittance material, the dielectric material is a semiconductor material, and the supersurface structure is an array structure composed of multiple metal resonators and cut wires; A plurality of the metal resonators form a lattice resonance structure, a plurality of the cut wires form a Lorentz resonance structure, and the lattice resonance structure and the Lorentz resonance structure are coupled to form a Lorentz-lattice resonance mode; The dielectric material is integrated between the cutting wires to connect the pairs of cutting wires, so as to switch the Lorentz-lattice mode to the EIT mode within the picosecond range by relying on the ultrafast carrier excitation and relaxation process of the dielectric material; The metasurface structure is a plurality of unit structures arranged periodically, each unit structure includes two pairs of metal resonators and a pair of cutting wires; the metal resonators are square opening resonators; the openings of the two metal resonators are arranged opposite to each other to form a pair of metal resonators; the two pairs of metal resonators arranged up and down in the same plane are separated by a pair of cutting wires.

2. The light-controlled terahertz biosensor according to claim 1, characterized in that: The cutting wires are connected by silicon bridges.

3. The light-controlled terahertz biosensor according to claim 1 or 2, characterized in that: The metal resonator is made of any one of gold, silver or aluminum.

4. The light-controlled terahertz biosensor according to claim 1 or 2, characterized in that: The dielectric material is silicon or germanium.

5. A method for preparing a light-controlled terahertz biosensor, for preparing the light-controlled terahertz biosensor according to any one of claims 1 to 4, characterized in that: include: The sapphire substrate silicon was cleaned with acetone and isopropyl alcohol; Preparation of metal super surface structures; The silicon pattern is constructed by combining the alignment photolithography technology with the silicon deep etching technology to complete the secondary pattern transfer; The metal supersurface structure is a plurality of unit structures arranged periodically, and each unit structure includes: two pairs of open square resonators and two cut wires connected by semiconductor materials.

6. The method for preparing the light-controlled terahertz biosensor according to claim 5, characterized in that: The sapphire substrate silicon specifically includes an epitaxial silicon layer with a thickness of 600 nm and a sapphire substrate with a thickness of 460 nm.

7. The method for preparing the light-controlled terahertz biosensor according to claim 5, characterized in that: The metal super surface structure is prepared on titanium and gold films by using step photolithography and ion beam etching.

8. The method for preparing the light-controlled terahertz biosensor according to claim 7, characterized in that: The thickness of the titanium film is 10 nm, and the thickness of the gold film is 160 nm.

9. A terahertz detection spectrum system, characterized in that: include: A femtosecond laser, a beam splitter, and a light-controlled terahertz biosensor as claimed in any one of claims 1 to 4; in The femtosecond laser is used to generate femtosecond laser; The beam splitter is used to split the femtosecond laser into terahertz light, terahertz detection light and pump light; The pump light is used to achieve excitation of optical carriers; The terahertz detection light is used to test and record the transmission spectrum of the pump light after it enters the front and rear metasurfaces.

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