Terahertz metamaterial sensing device and blood glucose concentration detection method

Abstract

The invention discloses a terahertz metamaterial sensing device and a blood glucose concentration detection method, and belongs to the field of terahertz science and technology. The terahertz metamaterial sensing device comprises an upper-layer asymmetric arc-shaped silicon column array and a lower-layer silicon substrate; the asymmetric arc-shaped silicon column array is composed of a plurality of arc-shaped silicon column unit structures with one long arc-shaped silicon column unit structure and one short arc-shaped silicon column unit structure. The long arc-shaped silicon column and the short arc-shaped silicon column have the same circle center and radius, and the arc length of the long arc-shaped silicon column is longer than that of the short arc-shaped silicon column; 3-aminopropyltriethoxysilane and glucose oxidase are used for carrying out surface functional modification on the asymmetric arc-shaped silicon column array and the silicon substrate. The device can be used for sensing and detecting blood glucose in a clinical serum sample, the concentration information of the blood glucose in the sample is obtained through the frequency shift of the resonance peak of the device, and the real-time, label-free and nondestructive detection of the sample is realized while the detection sensitivity is improved.

Description

Technical Field

[0001] The present invention relates to a terahertz metamaterial sensor device and a blood sugar concentration detection method, belonging to the field of terahertz science and technology. Background Art

[0002] Terahertz (THz) waves usually refer to frequencies between 0.1 and 10 THz (1 THz = 10 12 Electromagnetic waves in the THz (100 Hz) range have attracted widespread attention in the detection of biochemical substances due to their low photon energy, non-invasive, and non-ionizing properties. Their applications have already expanded to the detection of biomolecules such as proteins, amino acids, cells, and nucleic acids. Traditional THz bioassays are primarily based on time-domain spectroscopy (TDS) systems, which characterize samples using their transmission or absorption spectra. Although TDS systems can achieve broadband spectral measurements, this method typically requires tableting the sample powder, which can compromise the activity of biological samples and is incapable of detecting physiologically active samples (especially aqueous solutions). Furthermore, spectral detection suffers from low precision, making trace detection difficult. These drawbacks significantly reduce its applicability.

[0003] As core components in sensing and detection systems, THz metamaterial biosensors have attracted considerable research attention. Currently, THz sensor research primarily focuses on the application of planar structures such as metasurfaces. Metasurfaces are artificial electromagnetic structures composed of subwavelength planar units arranged in a certain pattern. By rationally designing their components, the amplitude, phase, and polarization of electromagnetic waves can be manipulated in both time and space. The strong localized resonance effect of metasurfaces can enhance the optical response of samples, significantly improving the sensitivity of sensors. For example, a THz metasurface chip composed of nanoslit arrays can effectively increase the absorption cross-section of carbohydrate molecules, achieving a detection limit of 10 mg / dL (Scientific Reports, 2015, 5:15459). Furthermore, the chiral enhancement mechanism of all-dielectric metamaterials can significantly enhance the chiral spectra of amino acids (Sensors Actuator A-Physics, 2023, 348:114001). While numerous studies have been conducted on metasurface biochemical detection in recent years, few reports have used THz all-dielectric metamaterials as sensors for the specific detection of blood glucose in serum samples.

[0004] Currently, most research on THz metamaterial biochemical sensing struggles to address specific sensing and chiral recognition. This is because metamaterial-based biosensing essentially relies on the sensor's response to changes in the surrounding dielectric environment. This allows it to only macroscopically reflect changes in the refractive index caused by the substance being tested, and the sensor itself cannot specifically identify target biomolecules. Furthermore, because THz waves are highly absorbed by water, metamaterial-based biosensing typically involves drying biological samples, making it impossible to directly test samples in physiologically active environments. Therefore, achieving specific detection of blood glucose in serum samples is crucial for THz metamaterial biochemical testing.

[0005] In summary, the rapid development of terahertz spectroscopy technology and the urgent demands of fields such as materials science and biology have placed higher performance requirements on THz biochemical detection. On the other hand, existing traditional THz metamaterial biochemical detection has drawbacks such as difficulty achieving specificity, difficulty detecting clinical samples, and unavoidable water absorption losses. Therefore, research on liquid samples, clinical samples, and specific detection has important scientific value and significance. Summary of the Invention

[0006] To address or partially address the problems in related technologies, the present invention provides a terahertz metamaterial sensor device and a method for detecting blood glucose concentration. This sensor device can detect blood glucose in clinical serum samples and obtain blood glucose concentration information in the sample through the frequency shift of the device's resonant peak. This improves detection sensitivity while enabling real-time, label-free, and nondestructive testing of samples.

[0007] The present invention provides a terahertz metamaterial sensor device, comprising an upper asymmetric arc-shaped silicon pillar array and a lower silicon substrate; the asymmetric arc-shaped silicon pillar array is composed of a plurality of arc-shaped silicon pillar unit structures, one long and one short; the long arc-shaped silicon pillar and the short arc-shaped silicon pillar have the same center and radius, and the arc length of the long arc-shaped silicon pillar is longer than the arc length of the short arc-shaped silicon pillar;

[0008] The asymmetric arc-shaped silicon pillar array and silicon substrate were surface functionalized using 3-aminopropyltriethoxysilane and glucose oxidase.

[0009] The present invention immobilizes a macromolecular protease on the surface of a silicon-based micro-nanostructure. The APTES molecular film exposes a layer of polar amino groups (-NH2), which facilitates cross-linking of linker molecules. Without this modified APTES molecular film, glucose oxidase cannot stably attach to the sensor surface, making it impossible for the terahertz metamaterial sensor to detect glucose concentration.

[0010] The upper unit structure of the terahertz metamaterial sensor device of the present invention consists of two arc-shaped silicon pillars, one long and one short, breaking the mirror symmetry of the overall structure. Due to the rich electromagnetic response and low loss of THz waves in silicon materials, whether excited by Y- or X-polarized incident THz waves, a significant local electromagnetic field enhancement is generated at the arc break. Simultaneously, the central region surrounded by the two arcs can also excite an extremely high local electric field, resulting in a transmission spectrum with a high Q value and high transmittance, which can significantly enhance the interaction between THz waves and the sample being tested. Compared to terahertz metamaterial sensors with a symmetrical upper layer of arc-shaped silicon pillar arrays, the asymmetry of the silicon pillars of the present invention can generate more hot spots, enhance the local field, and thus enhance the signal changes caused by the detected object. Therefore, the asymmetric structure can lead to more significant changes in the resonant frequency. When biomolecules bind to the sensor surface, the change in refractive index causes a larger frequency shift or other changes in the optical response, thereby improving detection sensitivity. In addition, asymmetric structures can support multiple frequency bands or a wider tuning range, so that they can operate at multiple frequencies or be more easily adjusted to a specific resonant frequency to meet different biomolecule detection needs, while symmetric structures may only have strong resonance at specific frequencies. Finally, asymmetric structures can more easily introduce specific functionalization during the manufacturing process, such as modifying biomolecule recognition elements (such as antibodies, DNA probes, etc.) at specific locations, because the asymmetry of the structure can provide more distinguishable areas, facilitating directional modification, which is conducive to enhancing selectivity or reducing nonspecific binding.

[0011] Preferably, the thickness of the silicon substrate is 250 μm-350 μm, the height of the asymmetric arc-shaped silicon pillar array is 150 μm-250 μm; the central angle of the short arc-shaped silicon pillar is 30°-60°, the central angle of the long arc-shaped silicon pillar is 100°-150°, and the arc line width of the long arc-shaped silicon pillar and the short arc-shaped silicon pillar is both 40 μm-60 μm; and the period of two adjacent unit structures along the X direction and the Y direction is 500 μm.

[0012] Preferably, the surface functionalization modification specifically includes the following steps:

[0013] (1) placing a terahertz metamaterial sensor device that has not undergone surface functionalization modification in a Piranha solution and heating it, taking it out and storing it in water to obtain a cleaned sensor device;

[0014] (2) The sensor device is rinsed with ethanol, and then added to a solution of ethanol and 3-aminopropyltriethoxysilane for oscillation reaction to obtain a sensor device with an APTES film layer formed on the surface;

[0015] (3) Cleaning the sensor device with the APTES film layer formed on the surface with anhydrous ethanol, then washing with water, and then rinsing with PBS buffer. Finally, the sensor device is added to a mixture of glutaraldehyde and PBS buffer and oscillated at room temperature;

[0016] (4) Dissolve glucose oxidase in PBS buffer, stir evenly, and then place the sensor device obtained in step (3) into the solution. Oscillating reaction is carried out at room temperature to complete the surface functionalization modification.

[0017] The present invention also protects the use of the terahertz metamaterial sensor device in blood glucose concentration detection, comprising the following steps:

[0018] (1) installing a terahertz metamaterial sensor device in a microfluidic device, and injecting sample solutions with known blood glucose concentrations into the cavity of the microfluidic device and flowing through the terahertz metamaterial sensor device;

[0019] (2) The microfluidic device is then placed in a linearly polarized transmission THz time-domain spectroscopy system to obtain the transmission signals E of different sample solutions with known blood glucose concentrations. s (t);

[0020] (3) A set of air signals Er(t) without adding sample solution was measured using a transmission THz time-domain spectroscopy system as a reference. s (t) and Er(t) are Fourier transformed to obtain amplitude spectrum information As(ω) and Ar(ω), respectively. The linear polarization transmission spectrum T(ω) of sample solutions with different known blood glucose concentrations is obtained by calculation. The calculation formula is as follows: T(ω)=A s (ω) / A r (ω);

[0021] (4) Obtain the resonance peak at the highest frequency position of the sensor device through the linear polarization transmission spectrum T(ω) obtained in step (3), and then obtain the frequency shift of the resonance peak, wherein the frequency shift of the resonance peak = the position of the highest frequency resonance peak of the sensor device - the initial highest frequency position of the resonance peak of the linear polarization transmission spectrum when no sample solution is added, and based on the known concentration of the sample solution of blood glucose concentration, the sensing sensitivity of the terahertz metamaterial sensor device is obtained as: S f =Δf / Δc, where Δf represents the frequency shift of the resonance peak, and Δc represents the blood glucose concentration of the blood glucose concentration sample solution;

[0022] (5) Obtain the linear polarization transmission spectrum T(ω) of the sample solution of unknown blood glucose concentration through steps (1) to (3), and then obtain the blood glucose concentration of the sample solution of unknown blood glucose concentration based on the sensing sensitivity formula obtained in step (4).

[0023] To reduce the impact of THz wave absorption by water in a sample solution, the present invention integrates a metasurface sensor chip into a self-made microfluidic device. A micropump is used to inject the sample solution into the microfluidic device and flow it through the sensor chip. This effectively reduces the impact of THz wave absorption by water in the sample and improves the detection signal-to-noise ratio. The microfluidic device comprises a housing and a terahertz metamaterial sensor device. The housing has a cavity within it, a sample injection port on its upper surface, connected to the cavity, and a sample outflow port on its side, connected to the cavity. A sensor chip slot is provided below the cavity, and the terahertz metamaterial sensor device is secured within the slot, connecting the terahertz metamaterial sensor device to the cavity.

[0024] Preferably, after the terahertz metamaterial sensor device is inserted into the sensor chip slot, the sensor chip slot opening is covered with ultraviolet glue or waterproof sticker.

[0025] Preferably, the height of the cavity is 10-30 μm, and the length and width are both 7-9 mm; the pore radius of the sample injection hole and the sample outflow hole is 10-20 μm; the length and width of the sensor chip slot are both 1-1.1 cm, and the height is 500-530 μm. The size of the sensor chip slot is consistent with the size of the terahertz metamaterial sensor device.

[0026] The basic operating principle of a terahertz metamaterial sensor for blood glucose concentration detection is as follows: When a linearly polarized THz wave is incident on an asymmetric circular arc-shaped silicon pillar metamaterial, a significant localized electromagnetic field enhancement is generated at the arc's break. Furthermore, an extremely high localized electric field is generated in the central region surrounded by the two arcs. This significantly enhances the interaction between the THz wave and the sample being tested, thereby improving the detection sensitivity of biomolecules. Using THz time-domain spectroscopy, a high-Q value, high transmittance transmission spectrum and resonance peak are detected. The frequency shift of the resonance peak can be used to characterize the concentration of the target biomolecule. To achieve specific detection of glucose, the sensor chip surface is functionalized with glucose oxidase, which specifically binds to glucose. When modified with glucose, the sensor can specifically recognize glucose in the sample solution without binding to other substances in the sample, reducing interference from non-target biomolecules. The reaction between the sensor chip and glucose produces gluconic acid and hydrogen peroxide, which causes a change in the effective refractive index and a shift in the resonance peak. Glucose concentration can be detected by detecting the resonance peak shift. Furthermore, the terahertz metamaterial sensor device is inserted into the slot of the microfluidic device. The flow rate of liquid injection can be controlled through the sample injection port, and biological molecules that cannot specifically bind to the sensor can be discharged through the sample outflow port. This not only reduces the impact of the solution sample water absorbing THz waves, but also effectively reduces the interference of non-target substances on the detection results, thereby improving the detection signal-to-noise ratio.

[0027] The technical solution provided by the present invention can have the following beneficial effects:

[0028] (1) In order to overcome the shortcomings of existing non-invasive blood glucose detection technologies (such as near-infrared spectroscopy or sweat sensors) that may be affected by factors such as skin condition and environmental humidity, and have insufficient sensitivity and stability, the terahertz metamaterial sensor device proposed in the present invention significantly amplifies the interaction between terahertz waves and glucose molecules through the local field enhancement effect, and can detect trace concentration changes (theoretically up to the order of <1mmol / L), which is particularly suitable for early blood glucose fluctuation monitoring.

[0029] (2) Existing terahertz metasurface biochemical sensors are difficult to achieve specific detection of glucose in serum. The present invention can achieve specific detection of glucose in serum through bio-modified functionalized metasurfaces and microfluidic devices.

[0030] (3) The microfluidic device of the present invention has fast response (single signal acquisition time can reach milliseconds) and portability (metamaterial sensors can be miniaturized), and may provide more comfortable and continuous blood glucose monitoring solutions for diabetic patients in the future. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] The above and other objects, features and advantages of the present invention will become more apparent through a more detailed description of exemplary embodiments of the present invention with reference to the accompanying drawings, wherein like reference numerals generally represent like components throughout the exemplary embodiments of the present invention.

[0032] Figure 1 Top view and side view of the terahertz metamaterial sensor device.

[0033] Figure 2 Diagram of the external and internal structure of the microfluidic device.

[0034] Figure 3 These are the linearly polarized transmission spectra of glucose solutions of different concentrations in Example 2.

[0035] Figure 4 3 is a graph showing how the resonance peak frequency shift at the highest frequency position of the terahertz metamaterial sensor in Example 2 changes with the concentration of the glucose solution.

[0036] Figure 5 These are the linear polarization transmission spectra of serum samples with different glucose concentrations in Example 3.

[0037] Figure 6 3 is a graph showing the change in the resonance peak frequency shift at the highest frequency position of the terahertz metamaterial sensor in Example 3 as a function of the glucose concentration in the serum sample.

[0038] In the figure, 1. Asymmetric arc-shaped silicon pillar array, 2. Silicon substrate, 3. Sample injection hole, 4. Cavity, 5. Sample outflow hole, 6. Sensor chip slot. DETAILED DESCRIPTION

[0039] The present invention is further described in detail below with reference to the accompanying drawings and specific embodiments, but the protection scope of the present invention is not limited to the contents described above.

[0040] Example 1

[0041] like Figure 1 A terahertz metamaterial sensor device includes an upper asymmetric arc-shaped silicon pillar array and a lower silicon substrate; the asymmetric arc-shaped silicon pillar array is composed of a plurality of arc-shaped silicon pillar unit structures, one long and one short; the long arc-shaped silicon pillar and the short arc-shaped silicon pillar have the same center, radius and height, and the arc length of the long arc-shaped silicon pillar is longer than the arc length of the short arc-shaped silicon pillar.

[0042] In this embodiment, the thickness of the silicon substrate is 300 μm, the height of the asymmetric arc-shaped silicon pillar array is 200 μm; the central angle of the short arc-shaped silicon pillar is 60°, the central angle of the long arc-shaped silicon pillar is 140°, and the arc line width of the long arc-shaped silicon pillar and the short arc-shaped silicon pillar is 50 μm; the period of two adjacent unit structures along the X direction and the Y direction is 500 μm.

[0043] 3-aminopropyltriethoxysilane and glucose oxidase are used to perform surface functionalization modification of the asymmetric arc-shaped silicon pillar array and the silicon substrate, specifically including:

[0044] (1) The terahertz metamaterial sensor device is cleaned and then placed in a Piranha solution, heated in a water bath for 2 hours, taken out and stored in deionized water. The Piranha solution is a mixture of concentrated sulfuric acid and hydrogen peroxide, which can remove organic matter on the surface of the structure and hydroxylate the surface of the structure.

[0045] (2) The sensor device obtained in step (1) was placed in a beaker, rinsed twice with anhydrous ethanol, and then 15 ml of anhydrous ethanol and 1 ml of APTES solution were added. The mixture was shaken for 2 hours to form an APTES film layer on the surface of the sensor device.

[0046] (3) Rinse the sensor obtained in step (2) repeatedly with anhydrous ethanol to remove any remaining APTES molecules on the surface, then rinse the sensor with deionized water to remove the anhydrous ethanol. Rinse the chip 3-5 times with PBS buffer to create a PBS environment on the sensor surface. Add a mixture of glutaraldehyde and PBS buffer, and shake the reaction on a shaker at room temperature for 1 hour.

[0047] (4) Using an electronic scale, 5 ml of glucose oxidase was weighed and dissolved in 5 ml of PBS buffer. After stirring evenly, the sensor device obtained in step (3) was placed in the prepared solution. The reaction was shaken on a shaker at room temperature for 4 h to complete the connection of glucose oxidase to the surface of the sensor device.

[0048] A microfluidic device comprises a housing and a terahertz metamaterial sensor device prepared in Example 1; a cavity is provided inside the housing, a sample injection hole is provided on the upper surface of the housing and is connected to the cavity; a sample outflow hole is provided on the side surface of the housing and is connected to the cavity; a sensor chip slot is provided below the cavity of the housing, the terahertz metamaterial sensor device is fixed in the sensor chip slot, the terahertz metamaterial sensor device is connected to the cavity, and after the terahertz metamaterial sensor device is inserted into the sensor chip slot, the sensor chip slot opening is covered with ultraviolet glue or waterproof tape to ensure that the sample solution does not flow out.

[0049] In this embodiment, the cavity has a height of 20 μm and a length and width of 8 mm. The sample injection and discharge holes have a radius of 20 μm. The sensor chip slot has a length and width of 1 cm and a height of 500 μm. The terahertz metamaterial sensor and the sensor chip slot have the same dimensions.

[0050] In this embodiment, the housing of the microfluidic device is manufactured by 3D printing technology, and the printing material is polylactic acid (PLA), which has a high THz transmittance when the thickness is small.

[0051] Example 2

[0052] The application of terahertz metamaterial sensor devices in glucose concentration detection includes the following steps:

[0053] (1) After completing the surface modification of the terahertz metamaterial sensor device, rinse the surface of the sensor device with deionized water, blow dry it with a nitrogen gun, and then place the sensor device in the sensor chip slot 6 of the microfluidic device. Cover the sensor chip slot with UV glue or waterproof stickers to ensure that the sample solution does not flow out. Connect capillary glass tubes to the sample injection hole 3 and the sample outflow hole 5 respectively, and place the entire microfluidic device into the THz time-domain spectroscopy system. Use a micropump to inject the sample solution to be tested into the cavity 4 through the sample injection hole 3. During measurement, the sample solution to be tested is in a flowing state and flows out from the sample outflow hole 5. The sample solutions to be tested are glucose solutions containing 1, 2, 4, and 8 mmol / L glucose concentrations, respectively.

[0054] (2) The microfluidic device is placed in a linearly polarized transmission THz time-domain spectroscopy system. After the THz wave directly penetrates the sample to be tested, the transmission signal E of the sample to be tested can be obtained at the detection end of the THz time-domain spectroscopy system. s(t), and at the same time measure a set of air signals Er(t) without adding samples as a reference. Perform Fourier transform on these two signals respectively to obtain the amplitude spectrum information As(ω) and Ar(ω). Through further calculation, the linear polarization transmission spectrum of the sample can be obtained as follows: Figure 3 The calculation process is shown in the following formula:

[0055] T(ω)=A s (ω) / A r (ω) (1).

[0056] like Figure 3 Under the stimulation of the incident wave, the surface of the terahertz metamaterial sensor device can produce a significant surface electric field enhancement and generate different resonance peaks near 0.45THz, 0.82THz and 1.02THz. The movement of each resonance peak can be observed as the sample concentration increases, and the different resonance peaks have undergone a significant red shift. When the sample concentration is 8mmol / L, it can be observed that compared with the resonance peak of the transmission spectrum of the terahertz metamaterial sensor without any sample, the resonance peak frequency shift at the highest frequency position of the sample reaches 87GHz. Figure 4 The linear fitting result of the experimental results shows that the change of the resonance peak frequency shift at the highest frequency position of the terahertz metamaterial sensor of the sample and the concentration change meet a very high linear relationship y = -0.217 + 10.993x, y is the resonance peak frequency shift, x is the concentration, (R 2 =0.997), where the change in the resonant peak frequency shift is the difference between the resonant peak of the sample at a certain concentration and the resonant peak of the terahertz metamaterial sensor transmission spectrum without any sample, and the concentration change is the sample concentration. Since the change in the resonant peak frequency shift of the terahertz metamaterial sensor is linearly related to the concentration change, taking a sample concentration of 8 mmol / L as an example, the detection sensitivity of the terahertz metamaterial sensor device can be calculated using formulas (2) and (3) to be 10.875 GHz·L / mmol, and the detection accuracy is 0.09 mmol / L.

[0057] The sensing sensitivity and sensing accuracy of terahertz metamaterial sensor devices are:

[0058] S f =Δf / Δc (2);

[0059] M f =Δ / S f (3);

[0060] Where Δf represents the frequency shift of the resonance, Δc represents the change in sample concentration, and Δ = 1 GHz represents the frequency resolution of the terahertz time-domain spectroscopy system. Terahertz metamaterial sensors operate in the 0.1-1.5 THz frequency range, and all devices operate normally at room temperature.

[0061] (3) The linear polarization transmission spectrum T(ω) of the glucose solution of unknown concentration to be measured is obtained through steps (1)-(2), and then the glucose concentration of the glucose solution of unknown concentration is obtained based on the linear relationship between the change in the resonant peak frequency shift at the highest frequency position of the terahertz metamaterial sensor of the sample and the concentration change obtained based on formula (2).

[0062] Example 3

[0063] The application of terahertz metamaterial sensor devices in blood glucose concentration detection includes the following steps:

[0064] (1) After completing the surface modification of the terahertz metamaterial sensor device, rinse the sensor device surface with deionized water, blow dry with a nitrogen gun, and place the sensor device in the sensor chip slot 6 of the microfluidic device. Cover the sensor chip slot with UV glue or waterproof stickers to ensure that the sample solution does not flow out. Connect capillary glass tubes to the sample injection hole 3 and the sample outflow hole 5, respectively, and place the entire microfluidic device into the THz time-domain spectroscopy system. Use a micropump to inject the sample solution to be tested into the cavity 4 through the sample injection hole 3. During measurement, the sample solution to be tested is in a flowing state and flows out from the sample outflow hole 5. The sample solutions to be tested are serum samples containing 1, 2, 4, and 8 mmol / L glucose concentrations, respectively.

[0065] (2) Place the microfluidic device in a linearly polarized THz wave atmosphere. After the THz wave directly penetrates the sample to be tested, the transmission signal E of the sample to be tested can be obtained at the detection end. s (t), and at the same time measure a set of air signals Er(t) without adding samples as a reference. Perform Fourier transform on these two signals respectively to obtain the amplitude spectrum information As(ω) and Ar(ω). Through further calculation, the linear polarization transmission spectrum of the sample can be obtained as follows: Figure 5 The calculation process is shown in the following formula:

[0066] T(ω)=A s (ω) / A r (ω) (1).

[0067] like Figure 5 The shift of the various resonance peaks can be observed as the glucose concentration in the serum sample increases, with distinct red shifts observed across the different resonance peaks. Unlike the detection of pure samples (glucose solutions), the shifts in the resonance peaks caused by different glucose concentrations are not as significant: when the sample concentration is 8 mmol / L, the resonance peak at the highest frequency position of the sample is observed to shift by 65 GHz compared to the resonance peak of the terahertz metamaterial sensor without any sample solution. Figure 6is the linear fitting result of the experimental results. It can be seen that the change of the resonance peak frequency shift at the highest frequency position of the sample terahertz metamaterial sensor still satisfies the linear relationship with the concentration change. The change of the resonance peak frequency shift at the highest frequency position of the sample terahertz metamaterial sensor still satisfies the linear relationship with the concentration change. y=-0.217+8.1913x, y is the resonance peak frequency shift, x is the concentration, (R 2 =0.998), where the change in the resonant peak frequency shift is the difference between the resonant peak of the sample at a certain concentration and the resonant peak of the terahertz metamaterial sensor transmission spectrum without any sample, and the concentration change is the sample concentration. Furthermore, even when the glucose concentration in the serum sample is as low as 1 mmol / L, there is still a frequency shift response of approximately 7 GHz. Similarly, using a sample concentration of 8 mmol / L as an example, the sensor's detection sensitivity is calculated to be 8.125 GHz·L / mmol using equations (2) and (3), and the detection accuracy for the glucose concentration in the serum sample is 0.123 mmol / L.

[0068] (3) The linear polarization transmission spectrum T(ω) of the sample solution with unknown blood glucose concentration to be measured is obtained through steps (1)-(2), and then the blood glucose concentration of the sample solution with unknown blood glucose concentration is obtained based on the linear relationship between the change in the resonant peak frequency shift at the highest frequency position of the terahertz metamaterial sensor of the sample obtained by formula (2) and the concentration change.

[0069] Compared to previous terahertz metamaterial biosensor devices, the advantages of this invention lie in its ability to generate multiple resonance peaks to characterize samples, improving detection reliability. The metamaterial device is modified using a biomodification method, enabling it to specifically detect glucose molecules. The integration of a microfluidic device with a sensor chip significantly reduces interference from non-target biomolecules and water absorption on the detection signal, improving the sensor's sensitivity and accuracy. The device has no special operating temperature requirements and can operate normally at room temperature. Its operating frequency range is 0.1 THz to 1.5 THz, generating strong resonance within the operating band. Clear resonance peaks are observed when the incident wave is polarized in both the X and Y directions. It can be used to sense samples of varying concentrations, achieving detection accuracy below 1 mmol / L. This device has significant application value in the field of terahertz biosensing, particularly in the development of highly sensitive and high-precision biosensors, particularly for the detection of sugars.

[0070] While various embodiments of the present invention have been described above, the foregoing description is intended to be illustrative, non-exhaustive, and not limited to the disclosed embodiments. Many modifications and variations will be apparent to those skilled in the art without departing from the scope and spirit of the described embodiments. The terminology used herein is selected to best explain the principles of the embodiments, their practical applications, or improvements to existing technologies, or to enable others skilled in the art to understand the embodiments disclosed herein.

Claims

1. A terahertz metamaterial sensor device, characterized in that: The invention comprises an upper asymmetric arc-shaped silicon pillar array and a lower silicon substrate; the asymmetric arc-shaped silicon pillar array is composed of a plurality of arc-shaped silicon pillar unit structures, one long and one short; the long arc-shaped silicon pillar and the short arc-shaped silicon pillar have the same center and radius, and the arc length of the long arc-shaped silicon pillar is longer than the arc length of the short arc-shaped silicon pillar; The asymmetric arc-shaped silicon pillar array and silicon substrate were surface functionalized using 3-aminopropyltriethoxysilane and glucose oxidase.

2. The terahertz metamaterial sensor device according to claim 1, characterized in that: The thickness of the silicon substrate is 250 μm-350 μm, the height of the asymmetric arc-shaped silicon pillar array is 150 μm-250 μm; the central angle of the short arc-shaped silicon pillar is 30°-60°, the central angle of the long arc-shaped silicon pillar is 180°-240°, and the arc line width of the long arc-shaped silicon pillar and the short arc-shaped silicon pillar are both 40 μm-60 μm; and the period of two adjacent unit structures along the X direction and the Y direction is 500 μm.

3. The terahertz metamaterial sensor device according to claim 1, characterized in that: The surface functionalization modification specifically comprises the following steps: (1) placing a terahertz metamaterial sensor device that has not undergone surface functionalization modification into a Piranha solution and heating it, then taking it out and storing it in water to obtain a cleaned sensor device; (2) The cleaned sensor device is rinsed with ethanol, and then added to a mixed solution of ethanol and 3-aminopropyltriethoxysilane for oscillation reaction to obtain a sensor device with an APTES film layer formed on the surface; (3) The sensor device with the APTES film layer formed on the surface was cleaned with anhydrous ethanol, then washed with water, and then rinsed with PBS buffer. Finally, the sensor device was added to a mixture of glutaraldehyde and PBS buffer and oscillated at room temperature. (4) Dissolve glucose oxidase in PBS buffer, stir evenly, and then place the sensor device obtained in step (3) into the solution. Oscillate the reaction at room temperature to complete the surface functionalization modification.

4. The terahertz metamaterial sensor device according to claim 3, characterized in that: In step (2), the volume ratio of ethanol to 3-aminopropyltriethoxysilane is 15:

1.

5. The terahertz metamaterial sensor device according to claim 3, characterized in that: In step (4), the volume ratio of glucose oxidase to PBS buffer is 1:1-1:

9.

6. Application of the terahertz metamaterial sensor device according to any one of claims 1 to 5 in blood glucose concentration detection, characterized in that: The steps include: (1) The terahertz metamaterial sensor device is installed in a microfluidic device, and sample solutions with known blood glucose concentrations are injected into the cavity of the microfluidic device and flow through the terahertz metamaterial sensor device; (2) The microfluidic device is then placed in a linearly polarized transmission THz time-domain spectroscopy system to obtain transmission signals of different sample solutions with known blood glucose concentrations. E s (t); (3) Using a transmission THz time-domain spectroscopy system to measure a set of air signals without adding sample solution Er (t) For reference, E s (t) and Er (t) Perform Fourier transform to obtain amplitude spectrum information As (ω) and Ar (ω), the linear polarization transmission spectra of sample solutions with different known blood glucose concentrations were obtained by calculation , the calculation formula is as follows: ; (4) The linear polarization transmission spectrum obtained by step (3) The resonance peak at the highest frequency position of the sensor device is obtained, and then the frequency shift of the resonance peak is obtained, where the frequency shift of the resonance peak = the position of the highest frequency resonance peak of the sensor device - the highest frequency position of the initial resonance peak of the linear polarization transmission spectrum when no sample solution is added. Based on the known concentration of the sample solution with blood glucose concentration, the sensing sensitivity of the terahertz metamaterial sensor device is obtained as: ,in ∆f represents the frequency shift of the resonance peak, ∆c Indicates the blood glucose concentration of the blood glucose concentration sample solution; (5) Obtain the linear polarization transmission spectrum of the sample solution with unknown blood glucose concentration through steps (1)-(3) , and then the blood glucose concentration of the unknown blood glucose concentration sample solution is obtained based on the sensor sensitivity formula obtained in step (4).

7. The use according to claim 6, characterized in that: The microfluidic device includes a housing and a terahertz metamaterial sensor device; a cavity is provided inside the housing, a sample injection hole is provided on the upper surface of the housing and is connected to the cavity; a sample outflow hole is provided on the side surface of the housing and is connected to the cavity; a sensor chip slot is provided below the cavity of the housing, and the terahertz metamaterial sensor device is connected to the cavity.

8. The application according to claim 6, characterized in that: After the terahertz metamaterial sensor device is inserted into the sensor chip slot, the sensor chip slot opening is covered with ultraviolet glue or waterproof sticker.

9. The application according to claim 6, characterized in that: The height of the cavity is 10-30 μm, and the length and width are both 7-9 mm; the pore radius of the sample injection hole and the sample outflow hole is 10-20 μm; the length and width of the sensor chip slot are both 1-1.1 cm, and the height is 500-530 μm. The size of the sensor chip slot is consistent with the size of the terahertz metamaterial sensor device.

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