A biological three-dimensional detection system, method and application based on terahertz-optical frequency domain sweep technology

Abstract

This invention provides a biological three-dimensional detection system, method, and application based on terahertz-optical frequency sweep technology, belonging to the field of biological sample detection technology. The invention utilizes a waveguide rotation device to deflect terahertz sweep light waves before illuminating the biological sample. The reflected beat-frequency interference light signals are then sequentially photoelectrically converted, acquired, and processed to obtain terahertz spectral information between different layers along the thickness direction of the biological sample. This invention employs a combination of frequency shifting and mixing techniques to construct a novel frequency-shifted terahertz light source, achieving a narrow-linewidth swept terahertz wave with a linewidth in the MHz range and a frequency modulation range of 5 terahertz. By using this light source in conjunction with a beam angle adjustment platform, the spatial resolution of three-dimensional biological cell detection can be improved from the centimeter level to the micrometer level, significantly enhancing detection accuracy and achieving high-resolution distributed detection of the three-dimensional spatial structure of cells.

Description

Technical Field

[0001] This invention belongs to the field of biological sample detection technology, and involves a detection technology that combines terahertz and optical frequency domain sweeping. Specifically, it relates to a biological three-dimensional detection system, method and application based on terahertz-optical frequency domain sweeping technology. Background Technology

[0002] High-precision detection technologies for biological cells have significant value in disease diagnosis, drug development, and basic medical research. Current mainstream detection methods face significant technical bottlenecks: traditional optical microscopy is limited by the optical diffraction limit, making it difficult to resolve subcellular structures; while electron microscopy offers nanometer-level resolution, it requires a vacuum environment and complex sample pretreatment, making in vivo detection impossible; flow cytometry relies on fluorescent labeling, which suffers from photobleaching effects and labeling interference with the state of native cells; and while Raman spectroscopy can provide molecular fingerprint information, its weak signal intensity limits detection sensitivity.

[0003] Terahertz waves (0.1-10 THz) exhibit significant advantages in the field of biodetection due to their unique non-ionizing properties and material fingerprinting capabilities: they can penetrate non-polar materials to detect living cells and specifically identify biomolecular characteristics, giving them a natural advantage in biological cell detection. Currently existing terahertz detection systems are based on the terahertz time-domain principle, allowing only two-dimensional planar scanning detection with long scan cycles. They cannot identify different cell types within the thickness direction and are limited to two-dimensional planar detection. In the transmission direction, they can only test the signal after the entire cell has absorbed the terahertz wave. Due to the superposition of absorbed signals, the received terahertz wave has a low signal-to-noise ratio, high noise, and is difficult to detect. Furthermore, point-by-point scanning in a two-dimensional plane is time-consuming.

[0004] Terahertz frequency domain detection systems can combine two-dimensional plane scanning and thickness detection information to perform three-dimensional detection, but currently the resolution depends on the step length of the sample loading platform (9) and the linewidth and sweep frequency range of the frequency-modulated light source (11). The difficulty in increasing the displacement step of the sample loading platform (9) results in its spatial resolution in two-dimensional plane movement measurement only reaching the millimeter level. At the same time, the mechanical displacement platform requires motor drive, which is slow, inaccurate, and takes a long time to complete the two-dimensional plane scan, resulting in inaccurate data. The frequency-modulated terahertz light source is generated by conventional frequency shifting, and its relatively wide linewidth makes coherent detection difficult. Therefore, the spatial resolution in the thickness direction can only reach the centimeter level, which is not suitable for the detection of small biological cells. Summary of the Invention

[0005] To address the shortcomings of existing technologies, the present invention aims to provide a biological three-dimensional detection system, method, and application based on terahertz-optical frequency domain sweep technology, thereby solving the technical problem that traditional terahertz detection technology cannot achieve high-resolution three-dimensional detection on small-sized biological samples.

[0006] To solve the above-mentioned technical problems, the present invention adopts the following technical solution: A biological three-dimensional detection method based on terahertz-optical frequency domain sweep technology, the method comprising the following steps: Step 1: Place the biological sample to be tested on the sample loading platform.

[0007] Step 2: The control and processing system issues a command to modulate the frequency of the frequency-modulated light source, so that the frequency of the light wave changes. The frequency of the light wave of the fixed light source remains unchanged. After the two beams of light enter the mixer at the same time, they generate terahertz frequency band mixed interference light. The terahertz frequency band mixed interference light is excited into terahertz waves by the transmitting antenna.

[0008] Step 3: After passing through the frequency shifter, the terahertz wave generates a terahertz swept light wave, whose frequency and wavelength change linearly.

[0009] Step 4: The terahertz swept light wave is split into two beams after passing through the beam splitter. One beam is the reference path, which is focused by the parabolic mirror and enters the receiving antenna. The other beam is the measurement path, which is first focused by the parabolic mirror onto the waveguide rotation device. Under the action of the waveguide rotation device, the light is deflected and then illuminates the biological sample to be tested on the sample loading platform. Then it returns to the waveguide rotation device along the original path, and is then focused by the parabolic mirror and enters the receiving antenna.

[0010] Step 5: The light waves from the reference path and the measurement path undergo beat frequency interference at the receiving antenna, generating a beat frequency interference light signal; the receiving antenna converts the beat frequency interference light signal into an electrical signal, which is transmitted to the control and processing system via the data acquisition module; after the control and processing system performs calculations on the electrical signal, it obtains the terahertz spectral information between different layers in the thickness direction of the biological sample under test.

[0011] Specifically, in step two, the frequency of the fixed light source is 193.5 THz, corresponding to a wavelength of 1550 nm; the frequency variation range of the frequency-modulated light source is 194.5 THz to 200.5 THz, corresponding to a wavelength of 1558 nm to 1602 nm.

[0012] Specifically, in step three, the process of generating terahertz swept light waves after the terahertz wave passes through the frequency shifter is as follows: the broadband terahertz light output from the mixer enters the wavelength screening grating through the wavelength screening grating, and at the same time, a voltage signal is applied to the piezoelectric ceramic plate, causing the piezoelectric ceramic plate to vibrate, which drives the wavelength screening grating to stretch and contract, thereby causing the center wavelength of the wavelength screening grating to shift periodically; after being screened by the wavelength screening grating, the above-mentioned broadband terahertz light becomes narrowband light of a single frequency, and its screening frequency changes periodically with the piezoelectric drive, forming a narrow-line frequency-shifting light source.

[0013] More specifically, in step three, the frequency shifter operates as follows: A triangular wave signal of -1mV to 1mV is applied to the piezoelectric ceramic plate, which then vibrates up and down at a frequency of 0.5Hz. The static screening frequency of the grating without vibration is 3.5THz. When the grating vibrates in sync with the piezoelectric ceramic, the screening frequency changes in a triangular wave range of 1THz to 6THz, with a frequency shift range of 5THz and a frequency shift speed of 500THz / s. Each vibration cycle is 20ms, and each vibration cycle includes two frequency sweeps: a linear increase in frequency is a forward frequency sweep, and a linear decrease in frequency is a reverse frequency sweep, with both results being consistent. One unidirectional frequency sweep takes 10ms, and the final terahertz frequency sweep light wave has a linewidth of 1.6kHz.

[0014] Specifically, in step four, the process of deflecting light under the action of the waveguide rotation device is as follows: voltages are applied to both ends of the X-axis and Y-axis of the waveguide rotation device, causing it to change its angle with respect to the X-axis and Y-axis, thereby causing the terahertz light to change the position of the terahertz light irradiating the surface of the biological sample to be tested by generating angle deflection in the X-axis and Y-axis directions.

[0015] Specifically, in step four, the process of returning to the waveguide rotation device via the original path is as follows: the terahertz wave of the measurement path reaches the bottom surface of the sample loading platform from the top surface of the biological sample to be tested. The bottom surface of the sample loading platform is a square reflector, which reflects the light back, so that the light returns from the bottom surface of the sample loading platform to the top surface of the biological sample to be tested. That is, the terahertz wave of the measurement path needs to penetrate the biological sample to be tested twice.

[0016] More specifically, in step four, when the waveguide rotating device deflects the angle with the X-axis and Y-axis as references, the step resolution of the angle deflection is 0.01°, the distance from the waveguide rotating device to the surface of the biological sample to be tested is 10cm, and the step distance of the terahertz wave of the measurement path irradiating the surface of the biological sample to be tested is (10×tan0.01°)cm.

[0017] More specifically, in step four, the voltage of the waveguide rotation device is controlled to ensure that the terahertz wave in the measurement path illuminates the biological sample in an S-shape, covering the entire sample surface. The size of the biological sample is 1cm × 1cm. The terahertz light is focused onto the sample loading platform to form a spot size of 0.005cm × 0.005cm, forming a 200×200 spot matrix. The frequency sweep time on each spot is 10ms, and the terahertz absorption information of all positions in the thickness direction of the spot is scanned within 10ms. The test is performed for a total of 400s. 40 measurement points are formed in the 1mm thickness direction, with a spatial resolution of 25um.

[0018] Specifically, in step five, the beat frequency interference light signals of the two light waves are acquired by equal frequency sampling.

[0019] Specifically, in step five, the control processing system performs the following calculations on the electrical signal: the electrical signal converted from the beat frequency interference light signal contains the beat frequency signal of terahertz light; the electrical signal is subjected to Fourier transform to obtain the time-domain reflection signal; the terahertz light information in the thickness direction is obtained from the time-domain reflection signal; the time-domain reflection signal is subjected to small-window inverse Fourier transform to obtain the terahertz spectral information between different layers in the thickness direction of the sample.

[0020] This invention also protects a biological three-dimensional detection system based on terahertz-optical frequency domain sweep technology, characterized in that it includes: a control and processing system, a terahertz light emitting module, a frequency shifter, a beam splitter, a parabolic mirror, a waveguide rotation device, a receiving antenna, a data acquisition module, and a sample loading platform.

[0021] Specifically, the terahertz light transmitting module consists of a fixed light source, a frequency-modulated light source, a mixer, and a transmitting antenna.

[0022] Specifically, the frequency shifter includes a fixed substrate on which a piezoelectric ceramic plate and a wavelength filtering grating are disposed; one end of the piezoelectric ceramic plate is electrically connected to a piezoelectric signal line, and the wavelength filtering grating is connected to a waveguide optical fiber.

[0023] This invention also protects the application of the biological three-dimensional detection method based on terahertz-optical frequency domain sweep technology, as described above, in cancer cell identification. Compared with the prior art, the present invention has the following technical effects: (I) This invention employs a combination of frequency shifting and mixing techniques to construct a novel frequency-shifting terahertz light source, achieving a narrow-linewidth swept terahertz wave with a linewidth in the megahertz (MHz) range and a frequency modulation range of 5 terahertz (THz). By using this light source in conjunction with a beam angle adjustment platform, the spatial resolution of three-dimensional biological cell detection can be improved from the original centimeter level to the micrometer level, significantly enhancing detection accuracy and thus enabling high-resolution distributed detection of the three-dimensional spatial structure of cells.

[0024] (II) This invention can be applied to the detection of biological cancer cells. By utilizing the difference in polarization state between diseased cancer cells and normal cells in the terahertz band, the cell state can be effectively identified; further, by combining terahertz optical frequency domain distributed detection technology with a waveguide rotation device, the planar information and thickness information of the biological sample to be tested are fused and reconstructed, thereby obtaining the accurate distribution result of the cell state in three-dimensional space. Attached Figure Description

[0025] Figure 1 This is a diagram of a biological detection system based on the terahertz-optical frequency domain sweep technology of the present invention.

[0026] Figure 2 This is a schematic diagram of the movement path of the terahertz light on the biological sample loading platform of the present invention.

[0027] Figure 3 This is a schematic diagram of the terahertz frequency signal of the present invention.

[0028] Figure 4 This is a schematic diagram of the wavelength frequency shifter structure of the present invention.

[0029] Figure 5 This is a schematic diagram illustrating the time-varying piezoelectric signal and terahertz frequency shift wavelength of the present invention.

[0030] Figure 6 This is a schematic diagram of the waveguide rotation device of the present invention.

[0031] The labels in the diagram represent the following: 1-Control and processing system, 2-Frequency shifter, 3-Beam splitter, 4-Front parabolic mirror, 5-Rear parabolic mirror, 6-Waveguide rotation device, 7-Receiving antenna, 8-Data acquisition module, 9-Sample loading platform, 10-Fixed light source, 11-Frequency tuned light source, 12-Mixer, 13-Transmitting antenna, 14-Waveguide fiber.

[0032] 201-Fixed substrate, 202-Piezoelectric ceramic plate, 203-Wavelength screening grating, 204-Piezoelectric signal line.

[0033] The specific content of the present invention will be further explained in detail below with reference to the embodiments. Detailed Implementation

[0034] It should be noted that, unless otherwise specified, all devices and software in this invention are conventional devices and software known in the art. For example, the control processing system (1) is a computer with terahertz optical module control software and data processing software. The data acquisition module (8) uses a conventional data acquisition card known in the prior art.

[0035] Following the above technical solutions, specific embodiments of the present invention are given below. It should be noted that the present invention is not limited to the following specific embodiments, and all equivalent modifications made based on the technical solutions of this application fall within the protection scope of the present invention.

[0036] Example 1 This embodiment presents a biological three-dimensional detection system based on terahertz-optical frequency domain sweep technology, such as... Figure 1As shown, it includes: a control and processing system (1) for controlling the terahertz light emission module and processing data; a terahertz light emission module for converting light into terahertz waves and emitting them; a frequency shifter (2) for changing the frequency of the terahertz waves and converting them into terahertz swept light waves; a beam splitter (3) for splitting the terahertz swept light waves into two paths; a front parabolic mirror (4) and a rear parabolic mirror (5) for changing the propagation path of the terahertz swept light waves; a waveguide rotation device (6) for changing the beam pointing direction to achieve mechanical scanning of a spatial region; a receiving antenna (7) for receiving reflected terahertz waves and converting them into electrical signals; a data acquisition module (8) for acquiring data; and a sample loading platform (9) for placing the biological samples to be tested.

[0037] As a specific embodiment of this invention, the terahertz light transmitting module consists of a fixed light source (10), a frequency-modulated light source (11), a mixer (12), and a transmitting antenna (13). The fixed light source (10) serves as a local oscillator signal source to provide a frequency-stable coherent reference light wave. The frequency-modulated light source (11) serves as a transmitting signal source to output a probe light wave whose frequency changes linearly with time. The mixer (12) is used to coherently mix the local oscillator signal with the echo signal to output a difference frequency signal carrying distance and speed information. Terahertz light is excited after passing through the transmitting antenna (13).

[0038] As one specific solution in this embodiment, such as Figure 4 As shown, the frequency shifter (2) includes a fixed substrate (201), on which a piezoelectric ceramic plate (202) and a wavelength screening grating (203) are disposed, and the two are glued together; one end of the piezoelectric ceramic plate (202) is electrically connected to a piezoelectric signal line (204), and the wavelength screening grating (203) is connected to a waveguide fiber (14).

[0039] Example 2 This embodiment presents a biological three-dimensional detection method based on terahertz-optical frequency domain sweep technology, which is implemented using the system described in Embodiment 1. The method includes the following steps: Step 1: Place the biological sample to be tested on the sample loading platform (9).

[0040] Step 2: The control processing system (1) issues a command to modulate the frequency of the frequency-modulated light source (11) so that the frequency of the light wave changes. The frequency of the light wave of the fixed light source (10) remains unchanged. After the two beams of light enter the mixer (12) at the same time, they generate terahertz frequency band mixed interference light. The terahertz frequency band mixed interference light is excited by the transmitting antenna (13) to generate terahertz waves.

[0041] Step 3: After passing through the frequency shifter (2), the terahertz wave generates a terahertz sweep wave, whose frequency and wavelength change linearly.

[0042] Step 4: The terahertz swept light wave is split into two beams after passing through the beam splitter (3). One beam is the reference path, which passes directly through the waveguide fiber (14) [i.e., the universal optical transmission medium] and is focused by the front parabolic mirror (4) and the rear parabolic mirror (5) in sequence before entering the receiving antenna (7). The other beam is the measurement path, which is transmitted through the waveguide fiber (14) and focused by the front parabolic mirror (4) and the rear parabolic mirror (5) onto the waveguide rotating device (6). Under the action of the waveguide rotating device (6), the light is deflected and then illuminates the biological sample to be tested on the sample loading platform (9). Then it returns to the waveguide rotating device (6) along the original path, and then passes through the waveguide fiber (14) and is focused by the rear parabolic mirror (5) before entering the receiving antenna (7).

[0043] Step 5: Since there is an optical path difference between the reference path and the measurement path, there is a frequency difference when the signals returned by the two paths reach the receiving antenna (7), resulting in beat frequency interference at the receiving antenna (7) and generating a beat frequency interference optical signal; the receiving antenna (7) converts the beat frequency interference optical signal into an electrical signal, which is transmitted to the control processing system (1) via the data acquisition module (8); after the control processing system (1) performs calculation processing on the electrical signal, the terahertz spectral information between different layers in the thickness direction of the biological sample to be tested is obtained.

[0044] As a specific solution in this embodiment, in step two, the frequency of the fixed light source (10) is 193.5THz (corresponding to a wavelength of 1550nm). The frequency-modulated light source (11) can make the light wave frequency vary in the range of 1T to 10T. In this embodiment, the frequency variation range of the frequency-modulated light source (11) is 194.5THz to 200.5THz (corresponding to a wavelength of 1558nm to 1602nm).

[0045] As a specific solution of this embodiment, in step three, the process of generating terahertz sweep light wave after the terahertz wave passes through the frequency shifter (2) is as follows: the broadband terahertz light output from the mixer (12) passes through the wavelength screening grating (201) and enters the wavelength screening grating (203). At the same time, a voltage signal is applied to the piezoelectric ceramic plate (202), causing the piezoelectric ceramic plate (202) to vibrate, which drives the wavelength screening grating (203) to stretch and contract, thereby causing the center wavelength of the wavelength screening grating (203) to move periodically. After being screened by the wavelength screening grating (203), the broadband terahertz light becomes a narrowband light of a single frequency, and its screening frequency changes periodically with the piezoelectric drive, forming a narrow-line frequency shift light source [i.e., terahertz sweep light wave].

[0046] As a specific scheme of this embodiment, in step three, the working process of the frequency shifter (2) is as follows: A triangular wave signal of -1mV to 1mV is applied to the piezoelectric ceramic plate, and the piezoelectric ceramic plate vibrates up and down at a frequency of 0.5Hz. The static screening frequency of the grating when there is no vibration is 3.5THz. When the grating vibrates in sync with the vibration of the piezoelectric ceramic, the screening frequency changes in a triangular wave range of 1THz to 6THz, the frequency shift range is 5THz, and the frequency shift speed is 500THz / s. Each vibration cycle is 20ms, and each vibration cycle includes two frequency sweeps: the frequency increases linearly for forward frequency sweep and the frequency decreases linearly for reverse frequency sweep. The results of the two are consistent. The time of one unidirectional frequency sweep is 10ms, and the linewidth of the terahertz frequency sweep light wave obtained is 1.6kHz (the schematic diagram of the piezoelectric signal and the terahertz frequency shift wavelength changing with time is shown in the figure). Figure 5 (As shown).

[0047] As a specific solution of this embodiment, in step four, the process of deflecting light under the action of waveguide rotation device (6) is as follows: voltage is applied to both ends of the X-axis and Y-axis of the waveguide rotation device (6) respectively, so that the angle changes with the X-axis and Y-axis as reference, thereby changing the position of the terahertz light irradiating the surface of the biological sample to be tested by generating angle deflection in the X-axis and Y-axis directions.

[0048] As one specific solution in this embodiment, such as Figure 6 As shown, in step four, the principle of the waveguide rotation device (6) is as follows: The Kerr effect is adopted, and the rotation core consists of two lanthanum zirconium titanate (PLZT) prisms. The first prism confines the terahertz light to a 30° direction for forward propagation. The second prism has electrodes along its X and Y axes. When a voltage is applied to the electrodes, their refractive index changes due to the Kerr effect. The beam originates from the reference prism (refractive index). Oblique incidence on electronically controlled prism (refractive index) When the light beam is emitted, refraction occurs at the interface, resulting in X-axis and Y-axis deflection angles. The calculation formulas are as follows: Equations 3 and 4: Formula 3.

[0049] Formula 4.

[0050] In Equations 3 and 4: Indicates the X-axis deflection angle. This represents the initial refractive index of the prism. This represents the change in refractive index along the X-axis after a voltage is applied across both ends. Indicates the Y-axis deflection angle. This represents the change in refractive index along the Y-axis after a voltage is applied across both ends.

[0051] According to the above principle, by controlling the magnitude of the voltage applied to the waveguide rotation device (6), the terahertz irradiation path is made to follow a sweeping pattern. This motion trajectory makes the terahertz light irradiation position cover the entire sample surface. By combining the terahertz spectral information between different layers in the thickness direction of each plane point, the terahertz spectral information of all points in the three-dimensional internal space of the entire test sample can be obtained.

[0052] As a specific solution in this embodiment, in step four, the process of returning to the waveguide rotating device (6) is as follows: the terahertz wave of the measurement path reaches the bottom surface of the sample loading platform (9) from the top surface of the biological sample to be tested. The bottom surface of the sample loading platform (9) is a square reflector, which reflects the light back, so that the light returns from the bottom surface of the sample loading platform (9) to the top surface of the biological sample to be tested. That is, the terahertz wave of the measurement path needs to penetrate the biological sample to be tested twice.

[0053] As a specific solution in this embodiment, in step five, the beat frequency interference light signal of the two light waves is acquired by equal frequency sampling.

[0054] As a specific embodiment, in step five, the electrical signal converted from the beat frequency interference optical signal is represented by the following equation 1: Formula 1.

[0055] In Equation 1: express The electrical signal converted from the beat frequency interference optical signal at that moment. express The main photoelectric field signal at that moment. Indicates photoelectric conversion efficiency. Represents the DC term coefficient. Indicates the beat frequency (angular frequency). Indicates the initial angular frequency. express Phase drift at any given moment.

[0056] The beat frequency angular frequency in Equation 1 is expressed as follows in Equation 2: Formula 2.

[0057] In Equation 2: This indicates the terahertz linear sweep frequency speed. To represent the periodic time, The beat frequency is represented by the extracted beat frequency signal, which is used to obtain the terahertz optical path length in the thickness direction (e.g., Figure 3 As shown in the figure, terahertz spectral information in each thickness direction is obtained to achieve distributed high-resolution detection in the thickness direction.

[0058] As a specific embodiment, the resolution of the biological sample to be tested in the thickness direction is: ΔH=c / 2nΔv=25um, where c is the speed of light, n≈3.05 is the refractive index of terahertz wave propagation in cells, and Δv=5THz is the frequency shift range of terahertz light, thereby achieving a detection resolution of 25um in the thickness direction.

[0059] As a specific solution in this embodiment, in step five, the control processing system (1) performs the following calculation process on the electrical signal: the electrical signal converted from the beat frequency interference light signal contains the beat frequency signal of terahertz light, the electrical signal is subjected to Fourier transform to obtain the time domain reflection signal, the terahertz light information in the thickness direction is obtained from the time domain reflection signal [distance domain along the terahertz propagation direction]; the time domain reflection signal is subjected to small window inverse Fourier transform [the small window signal at each position in the time domain corresponds to the terahertz light signal of each layer in the thickness direction], and the terahertz spectral information between different layers in the thickness direction of the sample can be obtained.

[0060] In this embodiment, when the waveguide rotating device (6) deflects the angle with the X-axis and Y-axis as references, the step resolution of the angle deflection is 0.01°. The distance from the waveguide rotating device (6) to the surface of the biological sample to be tested is 10cm. Therefore, the step distance of the terahertz wave of the measurement path irradiating the surface of the biological sample to be tested is about 10*tan0.01°=0.002cm.

[0061] By controlling the voltage in two directions, the terahertz wave in the measurement path irradiates the biological sample in an S-shape (e.g., ...). Figure 2 As shown), the motion path will cover the entire sample surface. The size of the plane of the biological sample to be tested is 1cm×1cm. Terahertz light is focused onto the surface of the sample loading platform (9) to form a spot size of 0.005cm×0.005cm, forming a 200×200 spot matrix. The frequency sweep time on each spot is 10ms. Within 10ms, the terahertz absorption information of all positions in the thickness direction of the spot is scanned. A total of 400s of testing is performed. 40 measurement points are formed in the 1mm thickness direction, with a spatial resolution of 25um.

[0062] according to Figure 2 The upward path movement allows the terahertz light irradiation position to cover the entire sample surface. By combining the terahertz spectral information of different layers in the thickness direction of each planar point, the terahertz spectral information of all points in the three-dimensional internal space of the entire test sample is obtained.

[0063] Example 3 This embodiment describes the application of the terahertz-optical frequency sweep technology-based biological three-dimensional detection method from Embodiment 2 in cancer cell identification. The application includes: firstly, sampling and identifying various cell types (including normal cells and cancer cells) using the method from Embodiment 2, extracting the characteristic polarization peak parameters of each cell type after the absorption sweep terahertz wave from the terahertz spectral information; then, using the characteristic polarization peak parameters of each cell type as a training set for neural network training; finally, sampling the cells to be detected using the method from Embodiment 2, extracting the characteristic polarization peak parameters of the cells to be detected after the absorption sweep terahertz wave, and using these as a test set to output to the trained neural network for cross-correlation calculation. Since the dielectric constant of cancer cells is typically more than twice that of normal cells, the absorption polarization peak of the terahertz wave after passing through cancer cells is more than twice that of normal cells. After calculation, the trained neural network can identify and distinguish between normal cells and cancer cells.

[0064] As a specific embodiment, the characteristic polarization peak parameters include: dielectric constant, absorption peak intensity, frequency position corresponding to the absorption peak, full width at half maximum (FWHM) of the absorption peak, and the variation law of the absorption peak under different polarization angles.

[0065] As a specific and optional solution in this embodiment, the neural network adopts the neural network described in the literature "Deep learning-assisted terahertz intelligent detection and identification of cancer tissue" (DOI: 10.1016 / j.fmre.2025.03.0130).

Claims

1. A biological three-dimensional detection method based on terahertz-optical frequency domain sweeping technology, characterized in that, The method comprises the following steps: Step one: placing the biological sample to be tested on the sample loading platform (9), and moving the sample loading platform (9) at a constant speed according to a set path; Step two: controlling the processing system (1) to issue an instruction to modulate the frequency of the frequency-modulated light source (11), so that the frequency of the light wave changes, while the frequency of the light wave of the fixed light source (10) remains unchanged, and the two light waves enter the frequency mixer (12) at the same time to generate a mixed interference light wave in the terahertz frequency band, which is excited into a terahertz wave by the transmitting antenna (13); Step three: the terahertz wave passes through the frequency shifter (2) to generate a terahertz sweep light wave, the frequency and wavelength of which change linearly; Step four: the terahertz sweep light wave passes through the beam splitter (3) to be divided into two beams, one of which is the reference path, focused by the parabolic mirror and then enters the receiving antenna (7); the other is the measurement path, which is first focused by the parabolic mirror to the waveguide rotating device (6), which deflects the light under the action of the waveguide rotating device (6) and then irradiates the biological sample to be tested on the sample loading platform (9), and then returns to the waveguide rotating device (6) via the original path, and then is focused by the parabolic mirror and enters the receiving antenna (7); Step five: the light waves of the reference path and the measurement path undergo beat interference at the receiving antenna (7) and generate a beat interference light signal; the receiving antenna (7) converts the beat interference light signal into an electrical signal, which is transmitted to the control processing system (1) via the data acquisition module (8); after the control processing system (1) calculates and processes the electrical signal, the terahertz spectral information between different levels in the thickness direction of the biological sample to be tested is obtained.

2. The biological three-dimensional detection method based on terahertz-optical frequency domain sweeping technology according to claim 1, wherein, In step two, the frequency of the fixed light source (10) is 193.5 THz, corresponding to a wavelength of 1550 nm; the frequency of the frequency-modulated light source (11) varies from 194.5 THz to 200.5 THz, corresponding to a wavelength of 1558 nm to 1602 nm.

3. The biological three-dimensional detection method based on terahertz-optical frequency domain sweeping technology according to claim 1, wherein, In step three, the process of generating a terahertz sweep light wave after the terahertz wave passes through the frequency shifter (2) is as follows: the broadband terahertz light output from the frequency mixer (12) enters the wavelength selection grating (203) through the wavelength selection grating (201), while a voltage signal is applied to the piezoelectric ceramic plate (202) to make the piezoelectric ceramic plate (202) vibrate and drive the wavelength selection grating (203) to stretch and contract, thereby causing the center wavelength of the wavelength selection grating (203) to move periodically; after being filtered by the wavelength selection grating (203), the above broadband terahertz light becomes a narrow-band light with a single frequency, and the filtered frequency changes periodically with the piezoelectric drive, forming a narrow-line frequency-shifted light source.

4. The biological three-dimensional detection method based on terahertz-optical frequency domain sweeping technology according to claim 3, characterized in that, In step three, the working process of frequency shifter (2) is as follows: A triangular wave signal of -1mV to 1mV is applied to the piezoelectric ceramic plate, and the piezoelectric ceramic plate vibrates up and down at a frequency of 0.5Hz. The static screening frequency of the grating when there is no vibration is 3.5THz. When the grating vibrates in sync with the vibration of the piezoelectric ceramic, the screening frequency changes in the range of 1THz to 6THz in a triangular wave. The frequency shift range is 5THz and the frequency shift speed is 500THz / s. Each vibration cycle is 20ms. Each vibration cycle includes two frequency sweeps: the frequency increases linearly for forward frequency sweep and the frequency decreases linearly for reverse frequency sweep. The results of the two are consistent. The time of one unidirectional frequency sweep is 10ms. The linewidth of the terahertz frequency sweep light wave obtained is 1.6kHz.

5. The biological three-dimensional detection method based on terahertz-optical frequency domain sweeping technology according to claim 1, wherein, In step four, the process of deflecting light under the action of waveguide rotation device (6) is as follows: voltages are applied to the X-axis and Y-axis ends of the waveguide rotation device (6) respectively, so that the angle changes with the X-axis and Y-axis as references, thereby causing the terahertz light to change the position of the terahertz light irradiating the surface of the biological sample to be tested by generating angle deflection in the X-axis and Y-axis directions.

6. The biological three-dimensional detection method based on terahertz-optical frequency domain sweeping technology according to claim 1, wherein, In step four, the process of returning to the waveguide rotating device (6) along the original path is as follows: the terahertz wave of the measurement path reaches the bottom surface of the sample loading platform (9) from the top surface of the biological sample to be tested. The bottom surface of the sample loading platform (9) is a square reflector, which reflects the light back, so that the light returns from the bottom surface of the sample loading platform (9) to the top surface of the biological sample to be tested. That is, the terahertz wave of the measurement path needs to penetrate the biological sample to be tested twice.

7. The biological three-dimensional detection method based on terahertz-optical frequency domain sweeping technology according to claim 1, wherein, In step five, beat frequency interference optical signals of the two optical waves are acquired by equal frequency sampling.

8. The biological three-dimensional detection method based on terahertz-optical frequency domain sweeping technology according to claim 1, wherein, In step five, the control processing system (1) performs the following calculation process on the electrical signal: the electrical signal converted from the beat frequency interference light signal contains the beat frequency signal of terahertz light, the electrical signal is subjected to Fourier transform to obtain the time domain reflection signal, and the terahertz light information in the thickness direction is obtained from the time domain reflection signal; the time domain reflection signal is subjected to small window inverse Fourier transform to obtain the terahertz spectral information between different layers in the thickness direction of the sample.

9. A biological three-dimensional detection system based on terahertz-optical frequency domain sweeping technology, characterized in that, include: Control and processing system (1), terahertz light emission module, frequency shifter (2), beam splitter (3), parabolic mirror, waveguide rotation device (6), receiving antenna (7), data acquisition module (8), sample loading platform (9); The terahertz light transmitting module consists of a fixed light source (10), a frequency-modulated light source (11), a mixer (12), and a transmitting antenna (13); The frequency shifter (2) includes a fixed substrate (201), on which a piezoelectric ceramic plate (202) and a wavelength filtering grating (203) are disposed; one end of the piezoelectric ceramic plate (202) is electrically connected to a piezoelectric signal line (204), and the wavelength filtering grating (203) is connected to a waveguide fiber (14).

10. The application of the biological three-dimensional detection method based on terahertz-optical frequency domain sweep technology as described in any one of claims 1 to 8 in cancer cell identification.

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