A terahertz metasurface sensor with parity-time symmetry structure and a biological detection method

Abstract

The present invention discloses a terahertz metasurface sensor with a parity-time symmetric structure and a biological detection method, comprising: a resonant layer and a substrate layer connected thereto; wherein, the resonant layer is an array of unit structures with a parity symmetric structure composed of cutting lines, first split ring resonators, and second split ring resonators, and the unit structure array is arranged in a square period; the cutting line is placed above the first split ring resonator and the second split ring resonator in a horizontal form; the angles of the openings of the first split ring resonator and the second split ring resonator with respect to the horizontal right direction are θ1 and θ2 respectively, θ1 is 0°, and θ1 is 90°. The method of the present invention introduces the frequency and amplitude information of the terahertz metasurface resonance peak, reduces the dimension of the transmission spectra of different types of biological cells by combining the principal component analysis method, and then realizes the highly specific detection of biological cells through a random forest model.

Description

Technical Field

[0001] The present invention belongs to the field of biomedical detection technology, and in particular relates to a terahertz metasurface sensor with a parity-time symmetric structure and a biological detection method. Background Art

[0002] Because terahertz waves have the characteristics of being label-free, non-ionizing, and having high temporal resolution, and can penetrate many non-metallic and non-water molecular materials, they show unique sensing capabilities for biological tissues and biomolecules, making them an ideal tool for sensing the internal structure and dynamic changes of biological cells. However, the current lack of sensitivity and frequency resolution is a key issue that needs to be addressed in the application of terahertz technology in biomedical testing. Insufficient sensitivity will affect the effective detection of low-concentration biomarkers, while the limitation of frequency resolution will hinder the specific detection of different types of cells.

[0003] Traditional terahertz metasurface biosensors can improve the sensitivity of biosensing to a certain extent, but their sensitivity to biological cells is limited, they cannot detect low-concentration biological cells, and they have no specificity for detecting biological cells.

[0004] Chinese patent CN108375556A proposes a double-layer metamaterial with two split rings whose opening polarization directions are perpendicular to each other, but this terahertz metamaterial biosensor is mainly aimed at high-sensitivity detection caused by changes in monolayer (10nm analyte thickness). However, this method cannot detect liquid analytes with micron-level thickness. In addition, the processing and manufacturing method of this double-layer metamaterial is relatively complicated and costly, which limits its widespread promotion in practical applications.

[0005] Chinese patent CN109557050 A proposes a terahertz metamaterial sensor with a complementary structure, which introduces complementarity into the asymmetric structure so that the substance to be tested can better contact with the sensing part of the sensor, thereby improving the sensitivity of the sensor. However, its sensitivity is only 66.5GHz / RIU, which is not enough to detect biological samples with lower concentrations. In addition, the metal resonance layer of the complementary structure has more consumables and higher manufacturing costs, and is not suitable for large-scale applications.

[0006] Chinese Patent CN116559116 A discloses a liquid detection sensor chip based on the dual-band electromagnetically induced transparency-like effect. This sensor utilizes the resonant characteristics of electromagnetically induced transparency-like (EIT-like) and its sensitivity to changes in the surrounding substances to detect the shift of the resonant point caused by the change in the refractive index of the liquid. It has the characteristics of simple structure, easy processing, multi-band, and high sensitivity. However, EIT-like belongs to a weak resonance mode, which limits the sensitivity of the device. The sensitivities of the two bands are only 150.0 GHz / RIU and 237.5 GHz / RIU.

[0007] Although the above methods have made certain progress in the field of terahertz biosensing, there are still problems such as limited detection thickness range, insufficient sensitivity, high manufacturing complexity, and high cost. Summary of the Invention

[0008] Aiming at the deficiencies of the prior art, the present invention provides a terahertz metasurface sensor with a parity-time symmetry structure and a biological detection method.

[0009] In a first aspect, an embodiment of the present invention provides a terahertz metasurface sensor with a parity-time symmetry structure, including: a resonant layer and a substrate layer connected thereto;

[0010] Wherein, the resonant layer is an array of unit structures with a parity-symmetric structure composed of a cutting line, a first split-ring resonator, and a second split-ring resonator, and the unit structure array is arranged in a square period;

[0011] The cutting line is placed above the first split-ring resonator and the second split-ring resonator in a horizontal form; the angles of the openings of the first split-ring resonator and the second split-ring resonator relative to the horizontal right direction are θ 1 and θ 2 , θ 1 is 0°, θ 1 is 90°.

[0012] In a second aspect, an embodiment of the present invention provides a biological detection method based on a terahertz metasurface sensor with a parity-time symmetry structure. The method includes the following steps:

[0013] Configure different types {t 1 , t 2 , …, t n} of different concentration gradients {c 1 , c 2 , …, c n}Biological cell suspension, incident terahertz wave, through the biological cell suspension and the terahertz metasurface sensor based on the parity-time symmetric structure, obtain the terahertz transmission spectrum of the biological cell suspension, so as to obtain the peak frequency points {{f 11 , f 12 , …, f 1m} of different concentrations of each type of biological cell, …, {f n1 , f n2 , …, f nm}} and the resonance peak amplitudes {{A 11 , A 12 , …, A 1m}, …, {A n1 , A n2 , …, A nm}};

[0014] Fit the peak frequency points of the resonance peaks of different concentrations of the same type of biological cells, and calculate the sensitivity of each type of biological cell.

[0015] For the peak frequency points {{f 11 , f 12 , …, f 1m} of different concentrations of each type of biological cell, …, {f n1 , f n2 , …, f nm}} and the resonance peak amplitudes {{A 11 , A 12 , …, A 1m}, …, {A n1 , A n2 , …, A nm} perform principal component analysis for dimensionality reduction;

[0016] Use the data after principal component analysis for dimensionality reduction to train a random forest model;

[0017] Obtain the peak frequency points and resonance peak amplitudes of the biological cells to be detected, and perform principal component analysis for dimensionality reduction;

[0018] Input the dimensionality-reduced data to be detected into the pre-trained random forest model to determine the type of biological cells;

[0019] Determine the concentration of the biological cells according to the sensitivity of the biological cells.

[0020] In a third aspect, an embodiment of the present invention provides an electronic device, including a memory and a processor, the memory is coupled to the processor; wherein, the memory is used to store program data, and the processor is used to execute the program data to implement the above-mentioned biological detection method of the terahertz metasurface sensor based on the parity-time symmetric structure.

[0021] Fourthly, an embodiment of the present invention provides a computer-readable storage medium, on which a computer program is stored. When the program is executed by a processor, the above-mentioned biological detection method of the terahertz metasurface sensor based on the parity-time symmetry structure is realized.

[0022] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0023] The present invention provides a parity-symmetric system for a terahertz metasurface sensor to achieve gain-loss balance based on a cutting line and a split-ring resonator structure. The high sensitivity of this balanced state to the perturbation of the analyte is used to realize ultrasensitive sensing of biological cells. At the same time, by adjusting the distance between the first split-ring resonator and the cutting line to reach the singular point of the parity-symmetric system, the high quality factor of this singular point is utilized, and combined with the principal component analysis method and the random forest classification model, specific detection of biological cells is realized. The present invention solves the problems of low sensitivity and high detection limit of terahertz for detecting liquid samples, and poor specificity in detecting biological cells due to the strong absorption of polar molecules. It can improve the detection sensitivity, reduce the detection limit, and realize qualitative detection and quantitative analysis of biological cells. Description of the Drawings

[0024] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the following will briefly introduce the drawings required for the description of the embodiments. Obviously, the following drawings are only some embodiments of the present invention. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without creative efforts.

[0025] Figure 1 It is a schematic structural diagram of the terahertz metasurface sensor with a parity-time symmetry structure provided by an embodiment of the present invention;

[0026] Figure 2 It is a front view of the unit structure provided by an embodiment of the present invention;

[0027] Figure 3 It is a relationship diagram between the singular point of the parity-time symmetry structure provided by an embodiment of the present invention and y 1 ;

[0028] Figure 4 It is a simulation diagram of the sensitivity of the singular point of the parity-time symmetry structure provided by an embodiment of the present invention;

[0029] Figure 5 It is a schematic flowchart of a biological detection method of a terahertz metasurface sensor based on a parity-time symmetry structure provided by an embodiment of the present invention;

[0030] Figure 6Experimental diagram of ultrasensitive sensing of biological cells provided by an embodiment of the present invention;

[0031] Figure 7 Input information for specific detection of biological cells provided by an embodiment of the present invention;

[0032] Figure 8 Effect diagram after dimensionality reduction by principal component analysis provided by an embodiment of the present invention;

[0033] Figure 9 Confusion matrix diagram of random forest classification provided by an embodiment of the present invention;

[0034] Figure 10 Schematic diagram of an electronic device provided by an embodiment of the present invention. Detailed implementation manners

[0035] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

[0036] It should be noted that, without conflict, the features in the following embodiments and implementation manners can be combined with each other.

[0037] As Figure 1 and Figure 2 shown, a terahertz metasurface sensor with a parity-time symmetric structure includes: a resonant layer and a substrate layer connected thereto;

[0038] Among them, the resonant layer is an array of unit structures with a parity-symmetric structure composed of a cutting line, a first split-ring resonator, and a second split-ring resonator, and the array of unit structures is arranged in a square period; in this example, the device is composed of 200×200 periodically arranged units.

[0039] The cutting line is placed above the first split-ring resonator and the second split-ring resonator in a horizontal form; the angles of the openings of the first split-ring resonator and the second split-ring resonator with respect to the horizontal right direction are θ 1 and θ 2 , θ 1 is 0°, and θ 1 is 90°. That is, the first split-ring resonator faces to the right, and the second split-ring resonator faces upward, forming a parity-symmetric structure.

[0040] Furthermore, the length L of the cutting line is 36 μm, and the width W is 4 μm; the radius R of the first split-ring resonator 1= 8 μm, the opening size is 4 μm; the radius R of the second split-ring resonator 2 = 6 μm, the opening size is 4 μm; the distance y1 from the center of the first split-ring resonator to the midline of the cutting line is 17 - 27 μm, and the distance y2 from the center of the second split-ring resonator to the midline of the cutting line is 12 μm.

[0041] Furthermore, the thickness of the resonant layer is 0.2 μm, and the material is gold; the thickness of the substrate layer is 75 μm, and the material is polyimide. A 10-nm titanium metal layer is provided between the resonant layer and the substrate layer as an adhesive.

[0042] Furthermore, the sensitivity of the terahertz metasurface sensor is 572.3 - 598.1 GHz / RIU; the resonance peak frequency point of the transmission spectrum generated by the terahertz metasurface sensor is at 2.51 THz. The terahertz metasurface biosensor generates a singularity at y 1 = 24 μm, and the quality factor at this singularity is 76.56. The relationship between the singularity of the parity symmetric structure and y 1 is as Figure 4 shown, and the sensitivity of the singularity of the parity-time symmetric structure is as Figure 5 shown.

[0043] Furthermore, the biological sample detected by the terahertz metasurface sensor is a biological cell suspension, and the detection thickness is less than or equal to 30 μm.

[0044] As Figure 5 shown, an embodiment of the present invention provides a biological detection method based on a terahertz metasurface sensor with a parity-time symmetric structure. The method includes the following steps:

[0045] Configure different types {t 1 , t 2 , …, t n} of different concentration gradients {c 1 , c 2 , …, c n} of biological cell suspensions, irradiate terahertz waves, and obtain the terahertz transmission spectrum of the biological cell suspension through the biological cell suspension and the terahertz metasurface sensor with a parity-time symmetric structure, so as to obtain the resonance peak frequency point peaks {{f 11 , f 12 , …, f 1m}, …, {f n1 , f n2 , …, f nm}} and resonance peak amplitudes {{A 11 , A 12 , …, A 1m}, …, {A n1 , An2 ,…,A nm}};

[0046] Fit the peak frequencies of the resonance peaks of different concentrations of the same type of biological cells, and calculate the sensitivity of each type of biological cell;

[0047] For the peak frequencies of the resonance peaks of different concentrations of each type of biological cell {{f 11 , f 12 ,…, f 1m},…,{f n1 , f n2 ,…, f nm}} and the resonance peak amplitudes {{A 11 , A 12 ,…, A 1m},…,{A n1 , A n2 ,…, A nm}, perform principal component analysis for dimensionality reduction; in this example, take the first two principal component feature data as the dimensionality reduction data;

[0048] Use the data after dimensionality reduction by principal component analysis to train a random forest model;

[0049] Obtain the peak frequency and resonance peak amplitude of the biological cell to be detected, and perform principal component analysis for dimensionality reduction; in this example, take the first two principal component feature data as the dimensionality reduction data;

[0050] Input the dimensionality reduction data of the biological cell to be detected into the pre-trained random forest model to determine the type of biological cell;

[0051] Determine the concentration of the biological cell according to the sensitivity of the biological cell.

[0052] Example 1

[0053] In this example, four biological cell suspensions of Hela, 293T, Miha, and HepG2 are used as examples for ultrasensitive sensing and highly specific detection. Among them, 293T and Miha are normal human cells, and Hela and HepG2 are cervical cancer and liver cancer tumor cells. The cell concentrations configured in this example are 5×10 3 cells / mL, 5×10 4 cells / mL, 5×10 5 cells / mL, and the measured transmission spectrum results are as shown in Figure 6 . Among them, DMEM is a blank medium without any biological cells. The experimental results show that the terahertz metasurface biosensor with parity symmetry structure has sensitivities to four biological cells of Hela, 293T, Miha, and HepG2 of 1030.51 kHz / (cell·mL-1 )、1011.42 kHz / (cell·mL -1 )、1000 kHz / (cell·mL -1 ) and 974.16 kHz / (cell·mL -1 ). Taking Hela cells as an example, the detection limit can reach 1.84 cells / mL.

[0054] The specific detection of the above four types of cells in this example uses the resonance peak frequencies and amplitude information of different types as the input for the random forest model. As Figure 7 shown, the transmission coefficients of the four biological cells in the figure have obvious overlaps in the frequency domain and cannot effectively distinguish cell types. The principal component analysis method is used to reduce the dimension of the input information. The visualized result after dimension reduction is as Figure 8 shown, which can effectively distinguish cell types. To obtain better consistency and accuracy, cells of different types and different concentration gradients are experimented multiple times. In this example, 625 groups of experiments are conducted for each type of biological cell, and a total of 2500 groups of transmission spectrum frequency domain data are obtained. 80% of the dataset is used as the training set, and 20% is used as the test set. The data is input into the random forest model, and an appropriate number of decision trees is selected. The cross-validation method is used to select the number of decision trees with the best detection and classification effect. The confusion matrix diagram of the random forest classification in the example is as Figure 9 shown. The finally selected number of decision trees is 50, and the detection and classification accuracy, recall rate, and precision rate after cross-validation all reach 99%.

[0055] Correspondingly, the present application also provides an electronic device, including: one or more processors; a memory for storing one or more programs; when the one or more programs are executed by the one or more processors, the one or more processors implement the biological detection method of the terahertz metasurface sensor based on the parity-time symmetry structure as described above. As Figure 10 shown, it is a hardware structure diagram of any device with data processing capabilities where the biological detection method of the terahertz metasurface sensor based on the parity-time symmetry structure provided by the embodiment of the present invention is located. In addition to Figure 10 the processors, memory, and network interfaces shown, any device with data processing capabilities where the device in the example is located usually includes other hardware according to the actual functions of the device with data processing capabilities, which will not be elaborated here.

[0056] Correspondingly, the present application further provides a computer-readable storage medium, on which computer instructions are stored. When the instructions are executed by a processor, the biological detection method of the terahertz metasurface sensor based on the parity-time symmetric structure as described above is implemented. The computer-readable storage medium may be an internal storage unit of any device with data processing capabilities described in any of the foregoing embodiments, such as a hard disk or memory. The computer-readable storage medium may also be an external storage device, such as a plug-in hard disk, a Smart Media Card (SMC), an SD card, a Flash Card, etc. equipped on the device. Further, the computer-readable storage medium may also include both an internal storage unit of any device with data processing capabilities and an external storage device. The computer-readable storage medium is used to store the computer program and other programs and data required by any device with data processing capabilities, and may also be used to temporarily store data that has been output or will be output.

[0057] The above embodiments are only used to illustrate the design ideas and features of the present invention, and the purpose is to enable those skilled in the art to understand the content of the present invention and implement it accordingly. The protection scope of the present invention is not limited to the above embodiments. Therefore, all equivalent changes or modifications made according to the principles and design ideas disclosed in the present invention are within the protection scope of the present invention.

Claims

1. A terahertz metasurface sensor with a parity-time symmetric structure, characterized in that: include: A resonant layer and a base layer connected thereto; Wherein, the resonant layer is a unit structure array having a parity symmetric structure composed of a cutting line, a first open resonant ring, and a second open resonant ring, and the unit structure array is arranged in a square period; The cutting line is placed horizontally above the first open resonant ring and the second open resonant ring; the angles of the openings of the first open resonant ring and the second open resonant ring relative to the horizontal right direction are respectively θ 1 and θ 2, θ 1 is 0°, θ 1 is 90°; Among them, the cutting line length L=36μm, width W=4μm; the radius of the first open resonant ring R1=8μm, the opening size is 4μm; the radius of the second open resonant ring R2=6μm, the opening size is 4μm; the distance from the center of the first open resonant ring to the center line of the cutting line y1=17~27μm, the distance from the center of the second open resonant ring to the center line of the cutting line y2=12μm.

2. The terahertz metasurface sensor with a parity-time symmetric structure according to claim 1, characterized in that: The sensitivity of the terahertz metasurface sensor is 572.3~598.1GHz / RIU; the resonance peak frequency of the transmission spectrum generated by the terahertz metasurface sensor is at 2.51THz.

3. The terahertz metasurface sensor with a parity-time symmetric structure according to claim 1, characterized in that: The terahertz metasurface biosensor produces a singular point at y1=24μm, and the quality factor at this singular point is 76.

56.

4. The terahertz metasurface sensor with a parity-time symmetric structure according to claim 1, characterized in that: A titanium metal layer is arranged between the resonance layer and the base layer as an adhesive.

5. The terahertz metasurface sensor with a parity-time symmetric structure according to claim 1, characterized in that: The thickness of the resonance layer is 0.2 μm, and the material selected is gold; the thickness of the base layer is 75 μm, and the material selected is polyimide.

6. A biological detection method based on the terahertz metasurface sensor with a parity-time symmetric structure according to claim 1, characterized in that: The method comprises the following steps: Configure different types t 1, t 2,…, t n Different concentration gradients of c 1, c 2,…, c n } Biological cell suspension, incident terahertz wave, through the biological cell suspension, the terahertz metasurface sensor based on the parity-time symmetric structure obtains the terahertz transmission spectrum of the biological cell suspension, thereby obtaining the peak value of the resonance peak frequency of each type of biological cells with different concentrations{{ f 11 , f 12 ,…, f 1m },…,{ f n1 , f n2 ,…, f nm }} and the resonance peak amplitude {{ A 11 , A 12 ,…, A 1m },…,{ A n1 , A n2 ,…, A nm }}; Fit the peak values ​​of the resonance peak frequencies of biological cells of the same type and different concentrations, and calculate the sensitivity of each type of biological cells; For each type of biological cell with different concentrations, the peak frequency of the resonance peak is f 11 , f 12 ,…, f 1m },…,{ f n1 , f n2 ,…, f nm }} and the resonance peak amplitude {{ A 11 , A 12 ,…, A 1m },…,{ A n1 , A n2 ,…, A nm }}Perform principal component analysis to reduce dimensionality; The random forest model is trained using the data after dimensionality reduction by principal component analysis; Obtain the peak value of the resonance peak frequency and the resonance peak amplitude of the biological cells to be detected, and perform principal component analysis and dimensionality reduction; Input the dimension-reduced data to be tested into the pre-trained random forest model to determine the biological cell type; The concentration of the biological cells is determined based on the sensitivity of the biological cells.

7. The biological detection method based on the terahertz metasurface sensor with parity-time symmetric structure according to claim 6 is characterized in that: The process of principal component analysis dimensionality reduction includes: taking the first two principal component feature data as dimensionality reduction data.

8. An electronic device, comprising a memory and a processor, characterized in that: The memory is coupled to the processor; wherein the memory is used to store program data, and the processor is used to execute the program data to implement the biological detection method based on the terahertz metasurface sensor with a parity-time symmetric structure as described in any one of claims 6-7.

9. A computer-readable storage medium having a computer program stored thereon, characterized in that: When the program is executed by a processor, the biological detection method based on the terahertz metasurface sensor with a parity-time symmetric structure as described in any one of claims 6 to 7 is implemented.

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