Ultrasensitive terahertz biosensor based on quasi-continuum bound states

Abstract

The present invention relates to an ultra-sensitive terahertz biosensor based on quasi-continuum bound state, which can induce quasi-continuum bound state (Q-BIC) in the frequency domain by changing the overall configuration of the resonator and the size and relative position of its local opening in the resonator unit in the sensor, thereby introducing asymmetric perturbations, thereby achieving a Q-BIC resonance peak with a quality factor (Q value) higher than 1000 in the terahertz frequency band, and this highly sensitive resonance peak has better sensing performance for nanomolar (nmol) or even picomolar (pmol) biological sample molecules, and can generate obvious response signals in the terahertz spectrum, thereby achieving ultra-sensitive detection of trace substances, greatly improving detection efficiency and accuracy. The processing technology is more mature, the production cost is lower, and it is suitable for commercial applications; the present invention has good reusability, is compatible with various terahertz detection systems, and has the expansibility of secondary development such as surface functionalization treatment.

Description

Technical Field

[0001] The invention relates to a terahertz biomedical detection technology, and in particular to an ultra-sensitive terahertz biosensor based on a quasi-continuum bound state. Background Art

[0002] Terahertz waves are electromagnetic waves with a frequency range of 0.1-10.0THz. They have the advantages of high signal-to-noise ratio, strong penetration, low energy, wide spectrum, good coherence, etc. They have great application value in security or non-destructive testing, terahertz communication, military radar, astronomical observation and even biomedical fields. Especially in the biomedical field, a large number of weak interactions between biomolecules (hydrogen bonds, van der Waals forces), biomolecular skeleton vibrations and biomolecular rotation frequencies are all within the terahertz frequency band, so the application of terahertz technology can realize the "fingerprint" identification and structural characterization of samples, and its photon energy is relatively small, and non-destructive testing of the detected substances can also be realized. Therefore, terahertz technology is a beneficial supplement to traditional high-performance liquid chromatography, mass spectrometry, and kit methods in the biomedical field.

[0003] In actual detection, the concentration of many samples is small or the samples themselves are trace substances, which makes it difficult to accurately identify their spectral signals and characteristics by relying solely on traditional terahertz detection technology. Therefore, in recent years, some scholars have used metal or graphene-based metasurface biosensors as terahertz signal enhancement carriers to enhance detection capabilities, and achieve more sensitive and accurate detection based on parameters such as the frequency shift of the resonance peak in the spectrum caused by the presence of the sample. The resonance peak quality factor (Q value) is a key parameter to measure the detection capability of the sensor. The larger the Q value, the higher the detection accuracy of the sensor. However, the research on metasurface biosensors is still limited to the excitation of low-frequency inductive-capacitive coupled resonance or high-frequency plasma resonance, and its Q value is very low and is often limited to tens to hundreds. This leads to low detection accuracy, poor anti-interference ability and poor experimental repeatability of traditional THz metasurface biosensors for nanomolar (nmol) or even femtomolar (fmol) biological samples. Therefore, how to achieve an ultra-high Q value of the resonance peak has become the key to the promotion and application of terahertz technology in the field of biomedical detection. Bound states in the continuum (BIC) are a method that can theoretically achieve ultra-high Q values ​​and even infinite quality factors. In this state, the energy in the metasurface resonator will be trapped and will not leak into the continuum, so the BIC in the ideal case has infinite lifetime and Q value. However, ideal conditions are impossible, but by introducing external perturbations, BICs can be made to produce finite leakage in the spectrum and visible as quasi-continuum bound states (Q-BICs), whose characteristics include extremely narrow linewidths that lead to ultra-high Q values. The more common type of BIC is symmetry-protected BIC. The corresponding Q-BIC can be excited by introducing micro-perturbations, that is, changing the key parameter size of the metasurface resonator to destroy its structural symmetry. The resulting leakage resonance mode will be coupled to the free space and can be observed in the far field. The Q value of its Q-BIC resonance peak can easily reach hundreds or more, which has great application potential in the detection of extremely low concentration biological samples.

[0004] On the one hand, the Q values ​​of existing sensors in the THz frequency band are generally low, ranging from tens to hundreds, based on the traditional resonance mechanism, and it is difficult to further increase the Q value; on the other hand, in order to pursue a higher Q value, existing sensors often limit the processing accuracy to the nanometer level, and the processing technology is more difficult and the cost is higher, which greatly limits their commercial application. The present invention achieves a Q value of more than 1000 based on a new quasi-continuum bound state induction mechanism, which is about 2 orders of magnitude higher than that of traditional sensors. At the same time, the processing accuracy only needs to be at the micron level, the process is mature, and the cost is low, which is very suitable for commercial applications. Summary of the invention

[0005] In order to solve the problem of low sensitivity of terahertz detection technology for trace sample molecules, an ultra-sensitive terahertz biosensor based on quasi-continuum bound state is proposed. By introducing asymmetric perturbations by changing the overall configuration of the resonator and the size and relative position of its local opening in the resonator unit in the sensor, a quasi-continuum bound state (Q-BIC) can be induced in the frequency domain, thereby realizing a Q-BIC resonance peak with a quality factor (Q value) higher than 1000 in the terahertz frequency band. This highly sensitive resonance peak has better sensing performance for nanomolar (nmol) or even picomolar (pmol) biological sample molecules, and can generate obvious response signals in the terahertz spectrum, thereby realizing ultra-sensitive detection of trace substances and greatly improving detection efficiency and accuracy.

[0006] The technical solution of the present invention is: an ultra-sensitive terahertz biosensor based on a quasi-continuum bound state, which is composed of a metasurface unit array constructed on a dielectric substrate, wherein the metasurface unit array is composed of a plurality of identical metasurface units arranged in a horizontal and vertical array at the same interval, and the metasurface unit includes a rectangular dielectric substrate and a pair of capacitor-inductor coupling resonators attached to the dielectric substrate, and the capacitor-inductor coupling resonator is an open photoelectric response ring, and the two open photoelectric response rings opposite to each other only differ in the size of the gap, and the other structures are completely the same, and the two openings as the capacitor part constitute an asymmetric opening, and the asymmetric opening is located at the center of the metasurface unit, and the asymmetric opening introduces an asymmetric disturbance and induces a terahertz wave to form a quasi-continuum bound state resonance peak with an ultra-high Q value thereon, which is used for ultra-sensitive detection of samples.

[0007] Preferably, the open photoelectric response rings in the same row of the metasurface unit array are connected end to end in sequence, and the asymmetric openings on a pair of capacitor-inductor coupled resonators are set with different configurations and opening widths. By introducing asymmetric perturbations, the emergence of quasi-continuum bound states is additionally induced, thereby achieving a Q-BIC resonance peak with an ultra-high Q value of more than 1000 in the frequency domain of the metasurface unit array.

[0008] Preferably, the asymmetry of the asymmetric openings of a pair of capacitor-inductor coupling resonators in the metasurface unit is formed by the different sizes and relative positions of the openings.

[0009] Preferably, the dielectric substrate material in the metasurface unit is selected from silicon, quartz or polyimide dielectric material.

[0010] Preferably, the open photoelectric response ring material is selected from gold, silver, copper, platinum or graphene materials with photoelectric response.

[0011] A method for detecting the content of each component of a sample using the ultra-sensitive terahertz biosensor based on a quasi-continuum bound state comprises: a terahertz source module, a terahertz biosensor, a terahertz detection module and a data processing and display module are sequentially placed on the same optical axis, wherein the spectrum range of the terahertz source should include and be greater than the sensor working frequency band; firstly, the terahertz biosensor is fixed on a sample rack and aligned with the polarization direction of the terahertz wave sent by the terahertz source module, the terahertz detection module detects and records the intrinsic resonance peak spectrum of the terahertz biosensor and sends it to the data processing and display module, and the data processing and display module obtains the capacitance-inductance coupling resonance peak and the Q-BIC resonance peak after processing; then, the sample solution is dripped and dried to form a film on the array structure on the surface of the terahertz biosensor, and the sensing spectrum change of the terahertz biosensor is detected and recorded; finally, the two transmission spectra are compared, the frequency offset and amplitude change before and after the Q-BIC resonance peak are read, and the content of each component in the biological sample can be obtained through data processing and comparison.

[0012] The beneficial effects of the present invention are as follows: the present invention is an ultra-sensitive terahertz biosensor based on a quasi-continuum bound state, and based on a quasi-continuum bound state (Q-BIC) induction mechanism, a Q-BIC resonance peak with a Q value of more than 1000 can be achieved, which is far superior to the existing sensors developed by traditional resonance mechanisms with Q values ​​of only tens to hundreds. The detection accuracy and detection limit are greatly improved, and the problem of the difficulty of traditional sensors in detecting nmol and below biological molecules can be effectively solved; the processing technology used in the present invention is at the micron level, the processing technology is more mature, the production cost is lower, and it is suitable for commercial applications; the present invention has good reusability, is compatible with various terahertz detection systems, and has the expansibility of secondary development such as surface functionalization treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 This is a schematic diagram of the unit structure of the ultrasensitive terahertz biosensor based on quasi-continuum bound state of the present invention;

[0014] Figure 2 Schematic diagram of an ultra-sensitive terahertz biosensor array based on quasi-continuum bound state of the present invention;

[0015] Figure 3 This is a real sample diagram of the ultra-sensitive terahertz biosensor based on the quasi-continuum bound state of the present invention;

[0016] Figure 4 It is a schematic diagram of the detection system designed based on the sensor of the present invention;

[0017] Figure 5 It is the transmission spectrum of the sensor in the present invention, and the corresponding transmission spectrum of detecting different samples. DETAILED DESCRIPTION

[0018] The present invention is described in detail below in conjunction with the accompanying drawings and specific embodiments. This embodiment is implemented based on the technical solution of the present invention, and provides a detailed implementation method and specific operation process, but the protection scope of the present invention is not limited to the following embodiments.

[0019] like Figure 1 , 2 The figure shows the unit structure and array schematic diagram in the sensor. The sensor is composed of a metasurface unit array constructed on a dielectric substrate. The metasurface unit array is composed of a plurality of identical metasurface units arranged in a horizontal and vertical array with the same interval. The metasurface unit includes a rectangular dielectric substrate 201, a pair of capacitor-inductor coupling resonators attached to the dielectric substrate, a toroidal inductor 202 and a capacitor 203 formed by the opening of the toroidal inductor 202 form a first capacitor-inductor coupling resonator, and a toroidal inductor 205 and a capacitor 204 formed by the opening of the toroidal inductor 205 form a second capacitor-inductor coupling resonator. The two openings 203 and 204 as the capacitor part are opposite to each other. The toroidal inductor 202 and the toroidal inductor 205 only differ in the size of the notch, and the other structures are exactly the same. The toroidal inductors in the same row are connected end to end in sequence. The resonant frequencies of the two capacitor-inductor coupling resonators both reach the terahertz wave frequency. The two openings 203 and 204 as the capacitor part constitute an asymmetric opening, and the asymmetric opening is located at the center of the metasurface unit. When the two capacitor-inductor coupling resonators are resonantly coupled, due to the size difference of the two openings, an asymmetric disturbance will be introduced, thereby inducing the terahertz wave to form a quasi-continuum bound state (Q-BIC) resonance peak with an ultra-high Q value thereon.

[0020] For example, if the width of one opening is 2um and remains unchanged, and the width of the other opening can be larger or smaller than 2um, thus forming an asymmetric state. The larger the width ratio is, the greater the asymmetric disturbance introduced is.

[0021] like Figure 3 As shown in the figure, multiple identical metasurface units are aligned horizontally and vertically on a dielectric substrate, and the rings are connected to form a complete metasurface unit array structure, i.e., a terahertz biosensor. Due to the combination of asymmetric openings and capacitive-inductive coupling resonators, a quasi-continuum bound state (Q-BIC) can be induced, thereby realizing a Q-BIC resonance peak with an ultra-high Q value in the frequency domain to achieve ultra-sensitive detection of the sample.

[0022] like Figure 4 The schematic diagram of the detection system based on sensor design shown in the figure includes a terahertz source module 1, a terahertz biosensor 2, a terahertz detection module 3 and a data processing and display module 4 placed sequentially on the same optical axis. The spectrum range of the terahertz source should include and be greater than the sensor working frequency band.

[0023] First, the terahertz biosensor is fixed on the sample holder and aligned with the polarization direction of the terahertz wave sent by the terahertz source module 1, and the intrinsic resonance peak spectrum of the terahertz biosensor is detected and recorded. The capacitance-inductance coupling resonance peak and the Q-BIC resonance peak will appear on the display screen of the detection system (data processing and display module 4). Then the sample solution is dripped and dried to form a film on the array structure on the surface of the terahertz biosensor, and the sensing spectrum changes of the terahertz biosensor, that is, the frequency shift of the Q-BIC resonance peak and other information are detected and recorded. The terahertz wave is generated by the terahertz source module 1, vertically incident and produces a strong light-matter interaction with the terahertz biosensor and the sample to be tested, and is finally received by the detection module 3 after passing through the sample film and the terahertz biosensor. Since the microstructure array in the terahertz biosensor has a selective transmission characteristic for terahertz waves of different frequency bands, when different samples are dripped on its surface, the spectrum response of the terahertz biosensor will change differently, and it can be used to detect different substances. After being collected by the terahertz detection module 3 and processed by the data processing and display module 4, the terahertz biosensor transmission spectrum containing the sample will be displayed on the display screen. The sample characteristics are mainly reflected in the changes in the Q-BIC resonance peak. Finally, the two transmission spectra are compared, and the frequency offset and amplitude change before and after the Q-BIC resonance peak are read. After data processing and comparison, the content of each component in the sample can be obtained. Figure 5 The transmission spectra of different samples after being dropped onto the sensor are different, especially the difference in frequency shift directly reflects the difference in sample type and concentration.

[0024] The Q-BIC peak of this terahertz biosensor has a quality factor (Q value) of more than hundreds, and has high detection accuracy even for sample molecules with concentrations below nmol.

[0025] In the following embodiments, the dielectric substrate of the terahertz biosensor is quartz with a thickness of 500 μm, the metal array structure is made of gold with a thickness of 200 nm, and the array structure is prepared by photolithography. Each super surface unit is a rectangle with a side length of 70×30 μm. The overall side length of the terahertz biosensor is 10 mm, and the number of units contained is 20,000. The dielectric substrate and the metal array can be replaced with other dielectric and metal materials, and the number of array units is variable, which has a high potential for secondary development. All the above parameters can be designed and processed according to the characteristics of the sample to be tested; in this embodiment, the sample to be tested is a homocysteine ​​solution, and other terahertz biomolecule sample detection implementation methods are consistent with this implementation method.

[0026] The terahertz source module 1 outputs a terahertz time domain signal with a frequency of 0.1-7.0 THz; the first step is to take a piece of terahertz biosensor and clean it. Figure 4As shown, the device is aligned and fixed on the sample holder according to the polarization direction of the terahertz wave, ensuring that the device surface is perpendicular to the incident direction of the terahertz wave, and the terahertz detection module 3 is used to measure its Q-BIC resonance peak transmission spectrum and record it; the second step is to drip the sample solution to be tested on the device and quickly dry it to form a film, remove the free water molecules contained in the sample, use the terahertz detection module 3 to obtain the transmission spectrum, and use the data processing and display module 4 to complete data acquisition and processing; the third step is to compare the two spectrum graphs, compare and analyze the frequency shift and other parameters of the Q-BIC resonance peak, so as to obtain a better frequency shift result and calculate the sample component concentration. The present invention only needs to drip the sample solution to be detected directly on the biosensor to greatly improve the terahertz detection accuracy, and the operation is simple.

[0027] The above-mentioned embodiments only express several implementation methods of the present invention, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the invention patent. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. An ultrasensitive terahertz biosensor based on quasi-continuum bound states, characterized in that: The invention is composed of a metasurface unit array constructed on a dielectric substrate, wherein the metasurface unit array is composed of a plurality of identical metasurface units arranged at the same intervals in the horizontal and vertical arrays, wherein the metasurface unit comprises a rectangular dielectric substrate and a pair of capacitor-inductor coupling resonators attached to the dielectric substrate, wherein the capacitor-inductor coupling resonator is an open photoelectric response ring, wherein the two open photoelectric response rings opposite to each other differ only in the size of the gaps, and the other structures are exactly the same, and the two openings as the capacitor part constitute an asymmetric opening, which is located at the center of the metasurface unit, and the asymmetric opening introduces an asymmetric disturbance and induces the terahertz wave to form a quasi-continuum bound state resonance peak with an ultra-high Q value thereon, which is used for ultra-sensitive detection of samples.

2. The ultrasensitive terahertz biosensor based on quasi-continuum bound state according to claim 1, characterized in that: The open photoelectric response rings in the same row of the metasurface unit array are connected end to end in sequence, and the asymmetric openings on a pair of capacitor-inductor coupled resonators are set with different configurations and opening widths. By introducing asymmetric perturbations, the emergence of quasi-continuum bound states is additionally induced, thereby achieving a Q-BIC resonance peak with an ultra-high Q value of more than 1000 in the frequency domain of the metasurface unit array.

3. The ultrasensitive terahertz biosensor based on quasi-continuum bound state according to claim 2, characterized in that: The asymmetry of the asymmetric openings of a pair of capacitive-inductive coupling resonators in the metasurface unit is formed by the different sizes and relative positions of the openings.

4. The ultrasensitive terahertz biosensor based on quasi-continuum bound states according to any one of claims 1 to 3, characterized in that: The dielectric substrate material in the metasurface unit is selected from silicon, quartz or polyimide dielectric material.

5. The ultrasensitive terahertz biosensor based on quasi-continuum bound state according to claim 1, characterized in that: The material of the open photoelectric response ring is selected from gold, silver, copper, platinum or graphene with photoelectric response.

6. A method for detecting the content of each component of a biological sample using the ultrasensitive terahertz biosensor based on quasi-continuum bound state according to any one of claims 1 to 5, characterized in that: A terahertz source module, a terahertz biosensor, a terahertz detection module and a data processing and display module are placed on the same optical axis in sequence, wherein the spectrum range of the terahertz source should include and be greater than the working frequency band of the sensor; firstly, the terahertz biosensor is fixed on the sample holder and aligned with the polarization direction of the terahertz wave sent by the terahertz source module, the terahertz detection module detects and records the intrinsic resonance peak spectrum of the terahertz biosensor and sends it to the data processing and display module, and the data processing and display module obtains the capacitance-inductance coupling resonance peak and the Q-BIC resonance peak after processing; then, the sample solution is dripped and dried to form a film on the array structure on the surface of the terahertz biosensor, and the sensing spectrum change of the terahertz biosensor is detected and recorded; finally, the two transmission spectra are compared, the frequency offset and amplitude change before and after the Q-BIC resonance peak are read, and the content of each component in the biological sample can be obtained through data processing and comparison.

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