High-precision protein concentration detection method and device

Abstract

The invention discloses a high-precision protein concentration detection method and device, and belongs to the technical field of protein sensing. The detection method is a novel two-parameter sensing theory capable of simultaneously detecting the protein concentration and the temperature, changes of the protein concentration and the temperature can be simultaneously calculated through the two-parameter sensing theory by measuring the refractive index sensitivity, the temperature sensitivity and the frequency shift of double resonance, and finally the protein concentration is calculated. The device is a double-BIC terahertz all-dielectric metasurface sensor, and a periodic unit is sequentially composed of a dielectric layer 1 and a dielectric layer 2 from top to bottom. The dielectric layer 1 is made of silicon; the dielectric layer 2 is composed of silicon dioxide. The invention provides a high-precision protein concentration detection method and a high-precision protein concentration detection device, which realize simultaneous detection of protein concentration and temperature, and can effectively eliminate interference of temperature change on protein concentration detection, thereby realizing high-precision detection of protein concentration. Wide application prospects are realized in the fields of clinical diagnosis and biological pharmacy.

Description

Technical Field

[0001] The present invention relates to the field of protein sensing technology, and in particular to a detection method and a device capable of simultaneously detecting protein concentration and temperature. Background Art

[0002] Protein concentration detection can be used to detect changes in disease markers, help detect diseases early, determine disease types, and evaluate treatment effects, and plays an important role in clinical diagnosis and biopharmaceuticals. In the field of protein concentration detection, terahertz detection technology has the advantages of low photon energy and the vibration frequency of proteins within the terahertz frequency range, and has received widespread attention from researchers in this field. However, terahertz spectroscopy technology has the disadvantages of requiring sample pretreatment, low sensitivity, and large sample demand. In order to solve these problems, researchers have proposed terahertz sensors based on metasurfaces. Metasurfaces are artificial materials composed of periodically arranged subwavelength structures with strange electromagnetic responses that do not exist in nature. Compared with traditional detection methods, metasurface sensors have the advantages of being label-free, highly sensitive, and easy to operate.

[0003] In actual detection, the refractive index of a protein solution is not only related to its protein concentration, but also to its temperature. In recent years, researchers have proposed many terahertz metasurface refractive index sensors for protein concentration detection. However, these studies based on single-parameter theory ignore the interference of temperature changes on protein concentration detection, and only use the change in the refractive index of the protein solution to calculate the protein concentration, resulting in low accuracy of the detection results. In order to achieve high-precision detection of protein concentration, a new sensing theory that takes temperature changes into account must be proposed. To this end, the present invention proposes a dual-parameter sensing theory that can simultaneously detect protein concentration and temperature, and constructs a dual-BIC terahertz all-medium metasurface sensor. By measuring the sensitivity coefficient and the frequency shift of the dual resonance, the changes in protein concentration and temperature can be simultaneously calculated through the dual-parameter sensing theory, thereby completing high-precision detection of protein concentration. Summary of the invention

[0004] The present invention aims to solve the problem that temperature changes in existing protein concentration detection technologies interfere with protein concentration. To this end, in view of the above problems, the purpose of the present invention is to propose a new sensing theory that can simultaneously detect protein concentration and temperature, and to design a dual BIC terahertz all-dielectric metasurface sensor that can simultaneously detect protein concentration and temperature, so as to achieve high-precision detection of protein concentration.

[0005] In order to achieve the above-mentioned invention object, the technical solution adopted by the present invention is:

[0006] In a first aspect, the present invention provides a dual-parameter sensing theory capable of simultaneously detecting protein concentration and temperature.

[0007] The dual-parameter sensing theory of the present invention is characterized in that dual-parameter sensing of protein concentration and temperature is achieved by analyzing the frequency shift of the dual resonance. The dual-parameter sensing theory formula can be expressed as: where n is the refractive index of the protein solution, c is the protein concentration, T is the temperature, and f i (i=1, 2) is the frequency of double resonance.

[0008] The dual-parameter sensing theory of the present invention is characterized in that: the dual-parameter sensing theory formula (1) can be further expressed in matrix form: Where Δc is the change in protein concentration, ΔT is the change in temperature, and S n and S T are the refractive index sensitivity and temperature sensitivity, Δf i (i=1, 2) is the frequency shift of the double resonance.

[0009] The dual-parameter sensing theory of the present invention is characterized by: firstly, calculating the refractive index sensitivity, temperature sensitivity and frequency shift of the double resonance of the device; secondly, calculating the changes in protein concentration and temperature through the dual-parameter sensing theory formula (2); and finally calculating the protein concentration, thereby eliminating the interference of temperature on protein concentration and achieving high-precision measurement of protein concentration.

[0010] In the second aspect, the present invention provides a dual BIC terahertz all-dielectric metasurface sensor.

[0011] The dual BIC terahertz all-dielectric metasurface sensor of the present invention is characterized in that the metasurface structure is composed of a dielectric layer 1 and a dielectric layer 2 in sequence from top to bottom.

[0012] The dual BIC terahertz all-dielectric metasurface sensor described in the present invention is characterized in that the material used for the dielectric layer 1 is silicon, and the unit structure is composed of two asymmetric rectangular blocks, the widths of the two rectangular blocks are w1=57μm and w2=61μm, the length is l=70μm, and the height is H=45μm.

[0013] The dual BIC terahertz all-dielectric metasurface sensor of the present invention is characterized in that: the material used for the dielectric layer 2 is silicon dioxide, and the periods of each unit structure on the x-axis and y-axis are P and x =166μm and P y =140μm.

[0014] The dual BIC terahertz all-dielectric metasurface sensor of the present invention is characterized in that the operating frequency of the dual BIC terahertz all-dielectric metasurface sensor is 1.05-1.20 THz, the applicable temperature range is 0-60°C, and the applicable refractive index range is 1.3-1.4.

[0015] Compared with the existing technology, the present invention has the following advantages:

[0016] 1. The present invention proposes a new dual-parameter sensing theory that can simultaneously detect protein concentration and temperature. The theory is used to achieve simultaneous detection of protein concentration and temperature, and can effectively eliminate the interference of temperature changes on protein concentration detection, thereby achieving high-precision detection of protein concentration. It has broad application prospects in clinical diagnosis and biopharmaceutical fields.

[0017] 2. The present invention proposes a new dual-BIC terahertz all-dielectric metasurface sensor, which realizes the simultaneous detection of protein concentration and temperature. Compared with traditional protein detection methods, the sensor has the advantages of label-free detection, high sensitivity and low sample requirement.

[0018] 3. The dual BIC terahertz all-dielectric metasurface sensor proposed in the present invention can change the position of the resonant frequency by changing the structural parameters of the metasurface, so the working frequency band of the sensor is almost unrestricted and has wide applicability. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 It is a schematic diagram of a periodic unit of a dual-BIC terahertz all-dielectric metasurface sensor provided by the present invention.

[0020] Figure 2 yes Figure 1 Top view of the periodic unit of the dual-BIC terahertz all-dielectric metasurface sensor.

[0021] Figure 3 It is the terahertz transmission spectrum of the dual-BIC terahertz all-dielectric metasurface sensor in the frequency range of 1.05-1.20THz.

[0022] Figure 4 is the terahertz transmission spectrum of the dual-BIC terahertz all-dielectric metasurface sensor under different asymmetric parameters.

[0023] Figure 5 is the terahertz transmission spectrum of the dual-BIC terahertz all-dielectric metasurface sensor at different unit periods.

[0024] Figure 6 It is the fitting curve of the resonance frequency shift of the dual-BIC terahertz all-dielectric metasurface sensor as the refractive index of the protein solution changes.

[0025] Figure 7 It is the fitting curve of the resonance frequency shift of the dual BIC terahertz all-dielectric metasurface sensor changing with temperature. DETAILED DESCRIPTION

[0026] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention:

[0027] Reference Figure 1 , Figure 2 The present invention discloses a dual BIC terahertz all-dielectric metasurface sensor. The structure of the metasurface is composed of a dielectric layer 1 and a dielectric layer 2 from top to bottom. The dielectric layer 1 is made of silicon, and the unit structure is composed of two asymmetric cuboids. The dielectric layer 2 is made of silicon dioxide.

[0028] We then studied the sensing properties of the metasurface to further illustrate the application value of the present invention in the field of protein concentration detection.

[0029] Reference Figure 3 , the transmission spectrum of the metasurface in the frequency range of 1.05-1.20THz is given. As can be seen from the figure, the device structure has two high-Q resonances in the range of 1.05-1.20THz. The Q factor is an important indicator of sensing performance. The higher the Q factor of the device resonance, the stronger the sensing ability. This shows that the present invention has successfully realized a highly sensitive terahertz sensor.

[0030] Reference Figure 4 , the transmission spectrum of the device changes when the asymmetry parameter α is changed. As can be seen from the figure, when α = 0μm, the resonance disappears. When α ≠ 0μm, two sharp resonances appear in the transmission spectrum. The calculation shows that the Q value is inversely proportional to α, indicating that both resonances are excited by quasi-BIC, so the device has double BIC resonance in the terahertz band.

[0031] Reference Figure 5 , given by changing the unit period P x The transmission spectrum of the device changes with the change of P. x As the value of the double BIC resonance increases, the Q value decreases, and both appear red-shifted. This shows that the frequency band and Q value of the resonance can be adjusted by changing the structural parameters of the device.

[0032] Reference Figure 6, the resonant frequency shift of the device is shown when the refractive index of the protein solution is changed. As can be seen from the figure, as the refractive index n of the protein solution increases, there is a linear relationship between the resonant frequency shift and the refractive index. The calculated refractive index sensitivity of the double resonance is 159GHz / RIU and 316GHz / RIU. Therefore, the proposed device is a highly sensitive refractive index sensor.

[0033] Reference Figure 7 , the resonant frequency shift of the device is shown when the ambient temperature changes. As can be seen from the figure, as the ambient temperature T increases, there is a linear relationship between the resonant frequency shift and the ambient temperature. The temperature sensitivity of the double resonance is calculated to be 41.2KHz / ℃ and 24.4KHz / ℃. Therefore, the proposed device is a highly sensitive temperature sensor.

[0034] Substituting the refractive index sensitivity and temperature sensitivity calculated above into the dual-parameter sensing theoretical formula (2), we obtain: First, the frequency shift of the double resonance is obtained by measuring, and then the changes in protein concentration and temperature are simultaneously calculated through dual-parameter sensing theory, thereby completing high-precision measurement of protein concentration.

[0035] Five sets of concentration and temperature combination data were selected, as shown in Table 1. set and T set is the set value of the ambient temperature, C cal and T cal is the protein concentration and temperature calculated based on the two-parameter formula (3), δ c is the relative error of protein concentration. From the table, we can see that the relative error of protein concentration obtained by this method is less than 1%. Table 1 Calculation results of protein concentration detection using dual-parameter sensing theory

Claims

1. The present invention discloses a high-precision protein concentration detection method and device, wherein the device refers to a dual BIC terahertz all-dielectric metasurface sensor.

2. The protein concentration detection method according to claim 1, characterized in that: Theoretical formula for dual-parameter sensing of protein concentration and temperature simultaneously: Where Δc is the change in protein concentration, ΔT is the change in temperature, and Δf i (i=1, 2) are the frequency shifts of the two resonances, dn / dc and dn / dT are the coefficients of variation of the refractive index of the protein solution with respect to protein concentration and temperature.

3. The protein concentration detection method according to claim 1, characterized in that: The dual-parameter sensing theoretical formula (1) for simultaneous detection of protein concentration and temperature has the following two items: the first item on the left is the transmission spectrum frequency shift caused by changes in protein concentration, where dn / dc is the coefficient of change of the refractive index of the protein solution with respect to concentration; the second item is the transmission spectrum frequency shift caused by changes in the temperature of the protein solution, where dn / dT is the coefficient of change of the refractive index of the protein solution with respect to temperature; and the third item is the transmission spectrum frequency shift caused by changes in the temperature of the metasurface material.

4. The protein concentration detection method according to claim 1, characterized in that: The dual-parameter sensing theory formula (1) for simultaneous detection of protein concentration and temperature can be written in dual-parameter matrix form: Among them, S n，i (i=1, 2) is the refractive index sensitivity, S T,i (i=1, 2) is the temperature sensitivity, Δf i (i=1, 2) is the frequency shift of the double resonance.

5. The protein concentration detection method according to claim 1, characterized in that: First, the refractive index sensitivity, temperature sensitivity and frequency shift of the double resonance of the device are calculated. Then, the changes in protein concentration and temperature are calculated using the dual-parameter sensing theory formula (2). Finally, the protein concentration is calculated to eliminate the interference of temperature on protein concentration and achieve high-precision measurement of protein concentration.

6. The dual-BIC terahertz all-dielectric metasurface sensor according to claim 1, characterized in that: The structure of the metasurface is composed of dielectric layer 1 and dielectric layer 2 from top to bottom. Dielectric layer 1 is composed of a periodic arrangement of two asymmetric silicon cuboids, and dielectric layer 2 is composed of a rectangular silicon dioxide substrate layer.

7. The dual-BIC terahertz all-dielectric metasurface sensor according to claim 1, characterized in that: The dielectric layer 1 is made of silicon, and the unit structure is composed of two asymmetric cuboids. The widths of the two cuboids are w1=57 μm and w2=61 μm, respectively, the length is l=70 μm, and the height is H=45 μm.

8. The dual-BIC terahertz all-dielectric metasurface sensor according to claim 1, characterized in that: The dielectric layer 2 is made of silicon dioxide, and the periods of each unit structure on the x-axis and y-axis are P and x =166μm and P y =140μm.

9. The dual-BIC terahertz all-dielectric metasurface sensor according to claim 1, characterized in that: The operating frequency of the dual-BIC terahertz all-dielectric metasurface sensor is 1.05-1.20 THz, the applicable temperature range is 0-60° C., and the applicable refractive index range is 1.3-1.4.

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