Label-free terahertz metasurface based on bound state principle in quasi-continuous domain, preparation method and application

Abstract

The invention discloses a label-free terahertz metasurface based on a bound state principle in a quasi-continuous domain, a preparation method and application. The sensor comprises a substrate layer and a metal resonance layer arranged on the substrate layer, the metal layer is a unit structure array formed by connecting two semicircular opening resonance rings, and the unit structure array is arranged according to a square period; wherein the two connected semicircular split-ring resonators are asymmetrically provided with a right side gap and a left side gap by deleting two identical inferior arches symmetrically from a circle with a radius of R1, and the two connected semicircular split-ring resonators are asymmetrically provided with the right side gap and the left side gap; the bound state effect in the quasi-continuous domain is achieved by setting the position of the gap of the right semicircular opening resonant ring, namely the offset alpha of the distance from the center of the resonator. By breaking the in-plane symmetry, a bound state in a leakage-free continuous domain can be converted into a bound state mode in a controllable quasi-continuous domain, local field enhancement can be realized, and strong interaction between target cells and light is facilitated.

Description

Technical Field

[0001] The present invention belongs to the field of biosensors, and in particular relates to a label-free terahertz metasurface based on the principle of bound states in a quasi-continuous domain, a preparation method and an application thereof. Background Art

[0002] As a new and efficient method that is non-destructive, label-free, and supports long-term cell state monitoring, terahertz biosensors have great application prospects in early screening of diseases and cell drug sensitivity testing. There is a huge demand for high-performance sensors for biomedical detection in research and clinical practice. In order to detect small molecules and low-concentration target molecules, it is of great significance to improve the sensitivity and detection accuracy of sensors. In order to achieve reliable, non-destructive, and label-free detection, terahertz technology has entered our field of vision due to its good performance. However, due to the relatively long wavelength of terahertz waves, it is insensitive to tiny features, which hinders its further application in sensing. The bound state principle in the continuous domain breaks through the traditional wave binding mechanism. Its frequency exists within the continuous spectrum, but it has an infinitely high Q factor. By breaking the in-plane symmetry of the structure and transforming from an unobservable bound state to a bound state in a quasi-continuous domain with a high Q value, the interaction between light and matter can be enhanced, and local field enhancement can be achieved. It has opened up a feasible new path for ultra-sensitive biomedical detection. Summary of the invention

[0003] In view of the shortcomings of the prior art, the present invention provides a label-free terahertz metasurface based on the principle of bound states in a quasi-continuous domain, a preparation method, and an application.

[0004] In a first aspect, an embodiment of the present invention provides a label-free terahertz metasurface based on the principle of bound states in a quasi-continuous domain, wherein the sensor comprises:

[0005] Basal layer,

[0006] and a metal layer disposed on the base layer;

[0007] Basal layer,

[0008] and a metal layer disposed on the base layer;

[0009] The metal layer is a unit structure array composed of two connected semicircular open resonant rings, and the unit structure array is arranged in a square period; wherein the two connected semicircular open resonant rings symmetrically delete two identical inferior arcs in a circle with a radius of R1, and asymmetrically open a right gap and a left gap; the radius corresponding to the inferior arc is R2, and the central angle is Wherein, w is the width of the two semicircular open resonant rings, and w=R1-R2; the gap on the right is the same size as the gap on the left;

[0010] By setting the distance between the openings of the two semicircular open resonant rings, that is, the offset a from the center of the resonator, the bound state effect in the quasi-continuous domain is achieved.

[0011] In a second aspect, an embodiment of the present invention provides a method for preparing a label-free terahertz metasurface based on the principle of bound states in a quasi-continuous domain, the preparation method comprising:

[0012] A titanium film with a thickness of 10 nm is deposited on the substrate layer as a connecting layer, and then a gold film with a thickness of 200 nm is deposited;

[0013] Then the gold film is patterned according to two connected semicircular open resonant ring structures; wherein, the two connected semicircular open resonant rings are symmetrically deleted from a circle with a radius of R1, and a right gap and a left gap are asymmetrically opened; the radius corresponding to the inferior arc is R2, and the central angle is Wherein, w is the width of the two semicircular open resonant rings, and w=R1-R2; the gap on the right is the same size as the gap on the left.

[0014] In a third aspect, an embodiment of the present invention provides an application of a label-free terahertz metasurface based on the bound state principle in a quasi-continuous domain in biological detection.

[0015] Compared with the prior art, the present invention has the following beneficial effects:

[0016] The present invention provides a label-free terahertz metasurface based on the principle of bound states in a quasi-continuous domain. A unit structure array consisting of two connected semicircular open resonant rings is designed, and the unit structure array has a metal layer arranged in a square period; by introducing asymmetric parameters, the uncontrollable bound state in the continuous domain with infinite Q factor is converted into an adjustable bound state in the quasi-continuous domain with high Q factor, and the Q factor value can be flexibly customized by adjusting the parameters. The sensor is highly sensitive to environmental disturbances, significantly enhances the interaction between light and matter, and is conducive to the effective action and high-sensitivity detection of cancer cells. The designed biosensor has a detection sensitivity of up to 517GHz / RIU and a Q factor of up to 99.

[0017] The present invention provides an application of label-free terahertz metasurface in biological detection. By distinguishing different types of biological cells and detecting low-concentration biological cells, the excellent performance of the designed biosensor is verified, and the detection limit can reach 5×10 3 cells / mL, the actual sensitivity can reach up to 456.64kHz / (cell mL -1 ).

[0018] The terahertz metasurface provided by the present invention has the characteristic of being label-free, so that the metasurface does not need cumbersome labeling steps, greatly simplifies the detection process, and avoids the interference and influence that the markers may have on the biological samples, ensuring the accuracy and reliability of the detection results. As a new and efficient method that is non-destructive, label-free, and supports long-term cell state monitoring, the present invention has great application prospects in early screening of diseases and cell drug sensitivity detection. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings required for use in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings in the following description are only some embodiments of the present invention. For ordinary technicians in this field, other accompanying drawings can be obtained based on these accompanying drawings without paying creative labor.

[0020] Figure 1 (a) is a label-free terahertz metasurface based on bound states in a quasi-continuous domain provided by an embodiment of the present invention. Figure 1 (b) shows the structural morphology of the metasurface unit composed of a metal pattern and a substrate;

[0021] Figure 2 (a) is the simulated transmission spectra of five typical asymmetry degrees (α=0, 1, 2, 3, 4 μm) provided by the embodiment of the present invention, Figure 2 (b) is an electric field distribution diagram of the terahertz metasurface provided in an embodiment of the present invention;

[0022] Figure 3 The multipole decomposition results provided by the embodiments of the present invention; (a) is the result when α=0μm, which is in a bound state; (b) is the result when α=4μm, and the bound state in the quasi-continuous domain is mainly contributed by the electric dipole, in addition to the magnetic quadrupole and magnetic dipole;

[0023] Figure 4 A schematic diagram of the relationship between the Q factor and the asymmetry factor α of a metasurface obtained by simulation and experiment provided in an embodiment of the present invention;

[0024] Figure 5 (a) is a simulated transmission spectrum of an analyte with a refractive index n ranging from 1 to 2 placed in a terahertz biosensor. Figure 5 (b) is a graph showing the relationship between the peak-to-peak resonance frequency shift and the change in the refractive index of the analyte;

[0025] Figure 6 A schematic diagram of the relationship between the resonance intensity, quality factor and asymmetry provided in an embodiment of the present invention;

[0026] Figure 7(a) is the experimental transmission spectrum of 294T cells at different concentrations. Figure 7 (b) is the experimental transmission spectrum of HepG2 cells at different concentrations. Figure 7 (c) shows the peak-to-peak resonance frequency shift of 293T (red) at different concentrations. Figure 7 (d) in the figure shows the peak-to-peak resonance frequency shift of HepG2 (blue). DETAILED DESCRIPTION

[0027] Exemplary embodiments will be described in detail herein, examples of which are shown in the accompanying drawings. When the following description refers to the drawings, the same numbers in different drawings represent the same or similar elements unless otherwise indicated. The embodiments described in the following exemplary embodiments do not represent all embodiments consistent with the present invention. Instead, they are merely examples of devices and methods consistent with some aspects of the present invention as detailed in the appended claims.

[0028] The terms used in the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention. The singular forms "a", "the" and "the" used in the present invention and the appended claims are also intended to include plural forms unless the context clearly indicates other meanings. It should also be understood that the term "and / or" used herein refers to and includes any or all possible combinations of one or more associated listed items.

[0029] It should be understood that although the terms first, second, third, etc. may be used in the present invention to describe various information, these information should not be limited to these terms. These terms are only used to distinguish the same type of information from each other. For example, without departing from the scope of the present invention, the first information may also be referred to as the second information, and similarly, the second information may also be referred to as the first information. Depending on the context, the word "if" as used herein may be interpreted as "at the time of" or "when" or "in response to determining".

[0030] The present invention is described in detail below in conjunction with the accompanying drawings. In the absence of conflict, the features of the following embodiments and implementations can be combined with each other.

[0031] like Figure 1 (a) and Figure 1 As shown in (b), an embodiment of the present invention provides a label-free terahertz metasurface based on the bound state principle in a quasi-continuous domain, comprising:

[0032] Basal layer,

[0033] and a metal layer disposed on the base layer;

[0034] The metal layer is a unit structure array composed of two connected semicircular open resonant rings, and the unit structure array is arranged in a square period; wherein the two connected semicircular open resonant rings symmetrically delete two identical inferior arcs in a circle with a radius of R1, and asymmetrically open a right gap and a left gap; the radius corresponding to the inferior arc is R2, and the central angle is Wherein, w is the width of the two semicircular open resonant rings, and w=R1-R2; the gap on the right is the same size as the gap on the left;

[0035] By setting the gap position of the right semicircular open resonant ring structure, that is, the offset α from the center of the resonator, the bound state is broken and the resonance intensity is increased.

[0036] Furthermore, the base layer is made of polyimide (PI), and the metal layer is made of gold. Titanium metal is provided between the base layer and the metal layer as a connecting layer. The base layer has a thickness of 70 μm, the bonding layer has a thickness of 10 nm, and the metal layer has a thickness of 200 nm.

[0037] It should be noted that in this example, gold is selected as the metal resonator material and polyimide as the substrate material because gold has better stability than other metals and polyimide has good biocompatibility. Metamaterials are new electromagnetic materials designed artificially, generally composed of periodic array units of sub-wavelength size. The electromagnetic properties of metamaterials can be flexibly manipulated by designing metamaterial structural units, thereby achieving strong interaction between light and matter;

[0038] Specifically, since the bound state in the continuum domain breaks through the traditional wave binding mechanism, although the frequency exists within the continuous spectrum, it has an infinitely high Q factor and no radiation leakage. However, due to the inherent non-radiative characteristics and infinitely narrow resonance linewidth of the bound state in the continuum domain, the ideal bound state in the continuum domain cannot be observed in practice. By breaking the in-plane symmetry of the structure, the unobservable bound state is transformed into a quasi-continuum domain bound state with a high Q value, achieving local field enhancement, which is conducive to the strong interaction between the target cell and light.

[0039] Furthermore, the cross section of each unit in the metal layer is a square, and the side length p is 40 μm. The structure is two semicircular open resonant rings; the width w of the metal structure is 7 μm, and the super surface unit structure is as follows: Figure 1 As shown in (b);

[0040] The gap g of the semicircular open resonant ring in the metal structure is 7.5 μm; the gaps of the left open resonant ring and the right open resonant ring in the metal structure are the same in size;

[0041] The gap position of the right semicircular open resonant ring structure is set to an offset α from the center of the resonator to break the symmetry of the plane in the y direction.

[0042] Further, Figure 2 As shown in (a) in the figure, by changing the asymmetric parameter α of the metasurface, the change in the amplitude of the bound state transmission spectrum in the quasi-continuum domain is simulated. It can be seen that the proposed structure exhibits geometric dependence. When α = 0, the resonance line width disappears, indicating that it is a bound state without leakage. Figure 2 (b) shows the electric field distribution of the metasurface at 2.26 THz resonance when α = 4. It can be seen that the local electric field is mainly concentrated in the gaps of the pattern.

[0043] Specifically, by changing the asymmetry factor α, the transition from the bound state in the continuous domain to the bound state in the quasi-continuous domain is achieved. Figure 2 (a) shows the transmission spectra obtained by simulation under different asymmetry degrees α. It can be seen that the proposed structure exhibits geometric dependence characteristics, that is, the resonance amplitude can be adjusted by adjusting the asymmetry parameter α. By changing the asymmetry factor α, the bound state in the ideal continuous domain is transformed into the bound state in the observable quasi-continuous domain. The asymmetry parameter α varies from 0, 1, 2, 3, to 4μm. When α = 0μm, it is in a bound state and has an infinite Q factor under ideal conditions. When the offset α increases from 0 to 4μm, a typical Fano linear resonance peak appears, and its line width gradually increases. By adjusting the asymmetry factor α to control the asymmetry of the structure, the resonance line width and Q factor of the transmission spectrum can be controlled according to actual needs.

[0044] Furthermore, in this example, the optical response of the terahertz metasurface was analyzed by using CST Studio Suite 2020 software for simulation, with unite cell conditions set in the x and y directions and open (addspace) conditions set in the z direction. The unit cell of the metasurface was illuminated by a linear x-polarized plane wave at normal incidence.

[0045] Furthermore, in order to clarify the contribution of different electromagnetic modes to the resonance, this example performs a multipole decomposition of the metasurface in a Cartesian coordinate system. This example mainly considers the low-order terms of the multipole expansion, including electric dipole (ED), electric quadrupole (EQ), magnetic dipole (MD), magnetic quadrupole (MQ), and ring dipole (TD). The terahertz metasurfaces at α = 0 μm and α = 4 μm are selected for electromagnetic mode analysis. When α = 0 μm, the resonance peak and resonance line width disappear, proving that the bound state in the continuous domain at this time ( Figure 3 (a) in Figure 1). The electromagnetic mode observed at α = 4 μm is shown in Figure 3As shown in (b), the ED mode contributes mainly to the distribution of the energy. In addition, the MQ and MD modes also contribute.

[0046] Furthermore, the relationship between the offset from the center of the resonator and the Q factor is as follows: Figure 4 As shown. The Q factor is obtained by fitting the typical Fano formula:

[0047]

[0048] Where a1, a2 and b are real constant factors, j is an imaginary number, ω0 and γ are the resonant frequency and damping rate respectively, and Q = ω0 / 2γ. Figure 4 The relationship between the Q factor and the asymmetry parameter α is shown, and the maximum simulated Q factor can reach 99. In addition, the experimentally measured Q factor changes with the asymmetry parameter α in accordance with the simulation results, but the experimental Q factor value is generally lower than the Q factor value of the simulation and theoretical model, because both radiation and non-radiation losses affect the measured line width of the resonance. In addition, the inevitable scattering loss due to the rough surface and limited area of ​​the sample is also the reason for the reduction of the Q factor.

[0049] Furthermore, the resonance peak frequency of the transmission spectrum generated by the label-free terahertz metasurface is at 2.26 THz, and the sensitivity is 517 GHz / RIU.

[0050] Specifically, different refractive indices {n1, n2, ..., n n}, obtain its terahertz transmission spectrum, and calculate the peak values ​​of the resonance peak frequencies {f1,f2,…,f n};like Figure 5 As shown in (a) in .

[0051] Specifically, Figure 5 (b) shows the linear relationship between the refractive index change of the analyte and the frequency shift of the transmission spectrum and its fitting results. We define the sensitivity of the sensor as S = Δf / Δn, where Δf represents the peak-to-peak resonant frequency shift of the analyte on the metasurface, and Δn is the refractive index change of the analyte. According to the above formula, the sensitivity of the metasurface based on the bound state in the quasi-continuum domain of the electric dipole in this example is 517 GHz / RIU.

[0052] Furthermore, the present invention analyzes the resonance intensity and quality factor of the metasurface under different symmetry degrees.

[0053] Specifically, the parameter I = |T1-T2| is introduced to characterize the resonance intensity of the metasurface resonance, where T1 corresponds to the valley value of the resonance and T2 corresponds to the peak value of the resonance. The quality factor (FoM) is another important indicator to characterize the quality of the sensor, where FoM = I × Q. Figure 6As shown, it shows the change of FoM with the asymmetry parameter d. It is obvious that FoM gradually reaches saturation at α=2μm; the resonance intensity I increases with the increase of asymmetry and reaches the maximum value of I at α=4μm.

[0054] On the other hand, the present invention also provides a method for preparing a label-free terahertz metasurface based on the principle of bound states in a quasi-continuous domain, the preparation method comprising:

[0055] Step S100, depositing a titanium film with a thickness of 10 nm on the base layer as a connection layer, and then depositing a gold film with a thickness of 200 nm;

[0056] Step S200, the gold film is patterned according to two connected semicircular open resonant ring structures; wherein the two connected semicircular open resonant rings are symmetrically deleted from a circle with a radius of R1, and a right gap and a left gap are asymmetrically opened; the radius corresponding to the inferior arc is R2, and the central angle is Wherein, w is the width of the two semicircular open resonant rings, and w=R1-R2; the gap on the right is the same size as the gap on the left.

[0057] On the other hand, the present invention also provides an application of a label-free terahertz metasurface based on the bound state principle in a quasi-continuous domain in biological detection, the application comprising the following steps:

[0058] Step S1, select different refractive indices {n1, n2, ..., n n}, obtain its terahertz transmission spectrum, and calculate the peak values ​​of the resonance peak frequencies {f1,f2,…,f n};like Figure 5 As shown in (a) in .

[0059] Step S2, fitting the resonance peak frequency value pairs of the analytes with different refractive indices to calculate the sensitivity of the terahertz biosensor; and determining the concentration of the analyte to be measured according to the sensitivity of the analyte to be measured. Figure 5 As shown in (b) in .

[0060] On the other hand, the present invention also provides an application of a label-free terahertz metasurface based on the bound state principle in a quasi-continuous domain in cancer cell detection, the application comprising the following steps:

[0061] Step S1, the present invention uses two biological cell suspensions, 293T and HepG2, as examples for ultrasensitive sensing. Among them, 293T is normal human embryonic kidney cells, and HepG2 is liver cancer cells. Three concentration gradients (5×10 3 , 5×10 4 , 5×10 5The 293T and HepG2 cells with different concentrations of 10 cells / mL were detected by terahertz time-domain spectrometer to obtain the transmission spectra of different cells at different concentrations.

[0062] In step S2, the present invention analyzes the ability of the terahertz sensor to quantitatively detect the same type of cells at different concentrations. Figure 7 (a) and Figure 7 (b) shows the terahertz transmission spectra of the proposed biosensor covered with HepG2 solution or 293T solution of different concentrations. Figure 7 (c) shows the peak-to-peak resonance frequency shift of 293T (red) at different concentrations. Figure 7 (d) in the figure is the peak-to-peak resonance frequency shift of HepG2 (blue). The terahertz spectrum of the culture medium (Dulbecco Modified Eagle Medium) is also provided as a blank control. It can be seen that the biosensor we designed can accurately distinguish cancer cells and normal cells at different concentrations. We define the actual sensitivity in the experiment as S e =Δf / Δc, where Δc is the change in cell concentration. The experimental results show that the actual sensitivity of the metasurface resonance peak to 293T cell suspension and HepG2 cell suspension is 456.64kHz / cell mL -1 and 408.58kHz / cell mL -1 In addition, for 293T and HepG2 cell suspensions, the detection limit can reach 5×10 3 cells / mL.

[0063] Those skilled in the art will readily appreciate other embodiments of the present application after considering the description and practicing the contents disclosed herein. The present application is intended to cover any variations, uses or adaptations of the present application, which follow the general principles of the present application and include common knowledge or customary technical means in the art that are not disclosed in the present application. The description and examples are intended to be exemplary only.

[0064] It should be understood that the present application is not limited to the exact construction that has been described above and shown in the drawings, and that various modifications and changes may be made without departing from the scope thereof.

Claims

1. A label-free terahertz metasurface based on the principle of bound states in a quasi-continuous domain, characterized in that: The sensor comprises: Basal layer, and a metal layer disposed on the base layer; The metal layer is a unit structure array composed of two connected semicircular open resonant rings, and the unit structure array is arranged in a square period; wherein the two connected semicircular open resonant rings symmetrically delete two identical inferior arcs in a circle with a radius of R1, and asymmetrically open a right gap and a left gap; the radius corresponding to the inferior arc is R2, and the central angle is Wherein, w is the width of the two semicircular open resonant rings, and w=R1-R2; the gap on the right is the same size as the gap on the left; By setting the distance between the openings of the two semicircular open resonant rings, that is, the offset a from the center of the resonator, the bound state effect in the quasi-continuous domain is achieved.

2. A terahertz biosensor based on bound state effect in quasi-continuous domain according to claim 1, characterized in that: The base layer is made of polyimide, and the material of the metal layer is gold.

3. A terahertz biosensor based on bound state effect in quasi-continuous domain according to claim 1 or 2, characterized in that: Titanium metal is arranged between the base layer and the metal layer as a connecting layer.

4. A terahertz biosensor based on bound state effect in quasi-continuous domain according to claim 3, characterized in that: The thickness of the base layer is 70 μm, the thickness of the bonding layer is 10 nm, and the thickness of the metal layer is 200 nm; the cross section of each unit in the metal layer is a square with a side length of 40 μm.

5. The label-free terahertz metasurface based on the bound state principle in the quasi-continuous domain according to claim 1, characterized in that: The width w of the two semicircular open resonant rings is 7 μm, and R1 is 18 μm.

6. The label-free terahertz metasurface based on the bound state principle in the quasi-continuous domain according to claim 1, characterized in that: The gap g between the two semicircular open resonant rings is 7.5μm.

7. A label-free terahertz metasurface based on the bound state principle in a quasi-continuous domain according to claim 1 or 6, characterized in that: When the offset distance from the center of the resonator is a = 0 μm, the resonance peak and the resonance line width disappear; When the offset distance from the center of the resonator is a = 4 μm, the resonance peak frequency in the transmission spectrum generated by the terahertz metasurface is at 2.26 THz, and the sensitivity is 517 GHz / RIU.

8. A label-free terahertz metasurface based on the bound state principle in a quasi-continuous domain according to claim 1 or 7, characterized in that: In order to study the relationship between the offset from the center of the resonator and the Q factor, the typical Fano formula is used to fit the Q factor: Where a1, a2 and b are real constant factors, j is an imaginary number, ω0 and γ are the resonant frequency and damping rate respectively, and Q = ω0 / 2γ.

9. A method for preparing a label-free terahertz metasurface based on the principle of bound states in a quasi-continuous domain, characterized in that: The preparation method comprises: A titanium film with a thickness of 10 nm is deposited on the substrate layer as a connecting layer, and then a gold film with a thickness of 200 nm is deposited; Then the gold film is patterned according to two connected semicircular open resonant ring structures; wherein, the two connected semicircular open resonant rings are symmetrically deleted from a circle with a radius of R1, and a right gap and a left gap are asymmetrically opened; the radius corresponding to the inferior arc is R2, and the central angle is Wherein, w is the width of the two semicircular open resonant rings, and w=R1-R2; the gap on the right is the same size as the gap on the left.

10. Application of a label-free terahertz metasurface based on the bound state principle in a quasi-continuum domain in biological detection.

Images