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

Abstract

The present invention discloses a label-free terahertz metasurface based on the principle of bound states in a quasi-continuous domain, a preparation method, and an application. The sensor comprises: a substrate layer, and a metal resonant layer disposed on the substrate layer; the metal layer is a unit structure array formed by connecting two semicircular open resonant rings, and the unit structure array is arranged in a square period; wherein the two connected semicircular open resonant rings are formed by symmetrically deleting two identical inferior arcs in a circle with a radius of R1, and asymmetrically opening a right-side gap and a left-side gap; by setting the position of the gap of the right semicircular open resonant ring, that is, the offset α from the center of the resonator, the bound state effect in the quasi-continuous domain is achieved. By breaking the in-plane symmetry, the bound state in the continuous domain without leakage can be converted into a bound state mode in the controllable quasi-continuous domain, which can achieve local field enhancement and facilitate the strong interaction between the target cell and light.

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 applications. Background Art

[0002] As a novel, highly efficient, non-destructive, label-free method for long-term cell state monitoring, terahertz biosensors hold great promise for early disease screening and cell-based drug sensitivity testing. High-performance sensors for biomedical applications are in great demand in both research and clinical settings. Improving sensor sensitivity and accuracy is crucial for detecting small molecules and low concentrations of target molecules. Terahertz technology has emerged as a promising approach for reliable, non-destructive, label-free detection. However, the relatively long wavelength of terahertz waves makes them insensitive to minute features, hindering their further application in sensing. The principle of bound states in the continuum domain breaks through traditional wave binding mechanisms. Its frequency resides within the continuum spectrum, yet it possesses an infinitely high Q factor. By breaking the in-plane symmetry of the structure, the bound state is transformed from an unobservable bound state to a high-Q bound state in the quasi-continuum domain, enhancing the interaction between light and matter and achieving local field enhancement. This opens a new and viable avenue for ultrasensitive 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, characterized in that the label-free terahertz metasurface comprises:

[0005] basal layer,

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

[0007] 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 are formed by symmetrically deleting two identical inferior arcs in a circle with a radius of R1, and asymmetrically opening 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;

[0008] By setting a height difference a between the bottom surface of the right gap and the bottom surface of the left gap, the bound state effect in the quasi-continuous domain is achieved.

[0009] In a second aspect, an embodiment of the present invention provides a method for preparing the above-mentioned label-free terahertz metasurface based on the principle of bound states in a quasi-continuous domain, characterized in that the preparation method comprises:

[0010] A titanium film with a thickness of 10 nm was deposited on the substrate as a connecting layer, and then a gold film with a thickness of 200 nm was deposited;

[0011] The gold film is then patterned according to the structure of two connected semicircular open resonant rings; wherein the two connected semicircular open resonant rings are formed by symmetrically deleting two identical inferior arcs in a circle with a radius of R1, and asymmetrically opening 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.

[0012] In a third aspect, an embodiment of the present invention provides an application of the above-mentioned label-free terahertz metasurface based on the bound state principle in the quasi-continuous domain in biological detection.

[0013] Compared with the prior art, the present invention has the following beneficial effects:

[0014] This invention provides a label-free terahertz metasurface based on the principle of bound states in a quasi-continuous domain. It designs a unit structure array consisting of two connected semicircular open resonant rings, each with a metal layer arranged in a square period. By introducing an asymmetric parameter, the uncontrollable bound state in the continuous domain with an infinite Q factor is converted into a tunable bound state in the quasi-continuous domain with a high Q factor. The Q factor value can be flexibly customized by adjusting the parameter. The sensor is highly sensitive to environmental perturbations and significantly enhances the interaction between light and matter, facilitating effective action and high-sensitivity detection of cancer cells. The designed biosensor has a detection sensitivity of up to 517 GHz / RIU and a Q factor of up to 99.

[0015] 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 / (cellmL -1 ).

[0016] The terahertz metasurface provided by this invention features label-free properties, eliminating the need for cumbersome labeling steps. This greatly simplifies the detection process while avoiding potential interference and impact of labeling on biological samples, ensuring the accuracy and reliability of test results. As a novel, non-destructive, label-free, and highly efficient method for long-term cell status monitoring, this invention holds great promise for early disease screening and cell drug sensitivity testing. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the following briefly introduces the drawings required for use in the description of the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0018] Figure 1 (a) is a label-free terahertz metasurface based on bound states in a quasi-continuous domain proposed in 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;

[0019] 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 by an embodiment of the present invention;

[0020] Figure 3 Multipole decomposition results provided by an embodiment of the present invention; (a) is the result when α = 0 μm, which is in a bound state; (b) is the result when α = 4 μm, where the bound state in the quasi-continuous domain is mainly contributed by electric dipoles, in addition to magnetic quadrupoles and magnetic dipoles;

[0021] Figure 4 Schematic diagram of the relationship between the Q factor and the asymmetry factor α of the metasurface obtained by simulation and experiment according to an embodiment of the present invention;

[0022] 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) shows the relationship between the peak-to-peak resonance frequency shift and the change in the refractive index of the analyte;

[0023] Figure 6 A schematic diagram showing the relationship between resonance intensity, quality factor, and asymmetry provided by an embodiment of the present invention;

[0024] 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) in the figure 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

[0025] Exemplary embodiments will be described in detail herein, examples of which are illustrated in the accompanying drawings. In the following description, when referring to the drawings, like numbers in different figures represent like or similar elements unless otherwise indicated. The embodiments described in the following exemplary embodiments are not intended to represent all possible embodiments consistent with the present invention. Rather, they are merely examples of apparatus and methods consistent with certain aspects of the present invention, as detailed in the appended claims.

[0026] The terms used in this invention are for the purpose of describing specific embodiments only and are not intended to limit the invention. The singular forms "a," "the," and "the" used in this invention and the appended claims are also intended to include plural forms unless the context clearly indicates otherwise. It should also be understood that the term "and / or" as used herein refers to and includes any or all possible combinations of one or more of the associated listed items.

[0027] It should be understood that although the terms "first," "second," "third," etc. may be used in the present invention to describe various information, such information should not be limited to these terms. These terms are merely used to distinguish information of the same type from one another. For example, first information may also be referred to as second information, and similarly, second information may also be referred to as first information, without departing from the scope of the present invention. Depending on the context, the term "if" as used herein may be interpreted as "when," "when," or "in response to determining."

[0028] The present invention will be described in detail below with reference to the accompanying drawings. Unless there is any conflict, the features of the following embodiments and implementations may be combined with each other.

[0029] like Figure 1 (a) and Figure 1 As shown in (b) of FIG. , an embodiment of the present invention provides a label-free terahertz metasurface based on the bound state principle in a quasi-continuous domain, comprising:

[0030] basal layer,

[0031] and a metal layer disposed on the base layer;

[0032] 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 are formed by symmetrically deleting two identical inferior arcs in a circle with a radius of R1, and asymmetrically opening 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;

[0033] By setting a height difference α between the bottom surface of the right gap and the bottom surface of the left gap, the restrained state is broken and the resonance intensity is increased.

[0034] Furthermore, the base layer is made of polyimide (PI), and the metal layer is made of gold. Titanium is provided as a connecting layer between the base layer and the metal layer. The base layer has a thickness of 70 μm, the connecting layer has a thickness of 10 nm, and the metal layer has a thickness of 200 nm.

[0035] It should be noted that in this example, gold was chosen as the metal resonator material and polyimide as the substrate material due to its superior stability compared to other metals and its good biocompatibility. Metamaterials are artificially designed new electromagnetic materials, generally composed of subwavelength periodic array units. By designing metamaterial structural units, their electromagnetic properties can be flexibly manipulated, thereby achieving strong interactions between light and matter.

[0036] Specifically, because 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 properties 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.

[0037] Furthermore, the cross section of each unit in the metal layer is a square with a side length p of 40 μm. The structure is two semicircular open resonant rings; the width w of the metal structure is 7 μm, and the metasurface unit structure is as follows: Figure 1 As shown in (b);

[0038] 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;

[0039] The symmetry of the surface in the y direction is broken by setting a height difference α between the bottom surface of the right gap and the bottom surface of the left gap.

[0040] Further, Figure 2 As shown in Figure (a), by varying the height difference α between the bottom surfaces of the right and left gaps (i.e., the metasurface's asymmetry parameter α), 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 resonant linewidth disappears, indicating a leak-free bound-state state. Figure 2 (b) shows the electric field distribution of the metasurface at the 2.26 THz resonance when α = 4. It can be seen that the local electric field is mainly concentrated in the gaps between the patterns.

[0041] Specifically, by changing the height difference α between the bottom surface of the right gap and the bottom surface of the left gap, 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 height difference α between the bottom surface of the right gap and the bottom surface of the left gap 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.

[0042] Furthermore, this example uses CST Studio Suite 2020 software for simulation to analyze the optical response of the terahertz metasurface. Unite cell conditions are set in the x and y directions, and open (addspace) conditions are set in the z direction. The unit cell of the metasurface is illuminated by a linear x-polarized plane wave at normal incidence.

[0043] 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 electromagnetic mode analysis of the terahertz metasurface is performed when α = 0 μm and α = 4 μm. The resonance peak and resonance linewidth disappear when α = 0 μm, proving that the bound state ( Figure 3(a) in Figure 1). The electromagnetic mode observed at α = 4 μm is as follows: Figure 3 As shown in (b), the ED mode mainly contributes to the distribution of the energy, and the MQ and MD modes also contribute.

[0044] Furthermore, the relationship between the height difference between the bottom surface of the right gap and the bottom surface of the left gap and the Q factor is as follows: Figure 4 As shown. The Q factor is obtained by fitting the typical Fano formula:

[0045]

[0046] 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 demonstrated, and the simulated Q factor reaches a maximum of 99. Furthermore, the experimentally measured Q factor varies in accordance with the asymmetry parameter α, consistent with the simulation results. However, the experimental Q factor is generally lower than that obtained from the simulation and theoretical model. This is because both radiative and non-radiative losses affect the measured linewidth of the resonance. Furthermore, scattering losses, unavoidable due to the rough surface and limited area of the sample, also contribute to the reduced Q factor.

[0047] 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.

[0048] Specifically, different refractive indices {n1, n2, ..., n n}, obtain its terahertz transmission spectrum, calculate the peak values of the resonance peak frequencies {f1, f2, …, f n};like Figure 5 As shown in (a) in .

[0049] Specifically, Figure 5 Panel (b) shows the linear relationship between the analyte's refractive index change and the transmission spectrum frequency shift, along with the fitting results. We define the sensor sensitivity as S = Δf / Δn, where Δf represents the peak-to-peak resonant frequency shift of the analyte on the metasurface, and Δn is the analyte's refractive index change. Calculated from the above formula, the sensitivity of this example's bound-state metasurface in the quasi-continuum domain of electric dipoles is 517 GHz / RIU.

[0050] Furthermore, the present invention analyzes the resonance intensity and quality factor of the metasurface under different symmetry degrees.

[0051] 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 6 As shown in Figure 3, the variation of FoM with the asymmetry parameter d is demonstrated. It is obvious that FoM gradually reaches saturation at α = 2 μm. The resonance intensity I increases with the increase of asymmetry and reaches the maximum value of I at α = 4 μm.

[0052] 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:

[0053] Step S100 , depositing a titanium film with a thickness of 10 nm as a connection layer on the base layer, and then depositing a gold film with a thickness of 200 nm;

[0054] 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 formed by symmetrically deleting two identical inferior arcs in a circle with a radius of R1, and asymmetrically opening 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.

[0055] On the other hand, the present invention also provides an application of a label-free terahertz metasurface based on the principle of bound states in a quasi-continuous domain in biological detection, the application comprising the following steps:

[0056] Step S1, select different refractive indices {n1, n2, ..., n n}, obtain its terahertz transmission spectrum, calculate the peak values of the resonance peak frequencies {f1, f2, …, f n};like Figure 5 As shown in (a) in .

[0057] 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 .

[0058] 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:

[0059] Step S1, the present invention uses 293T and HepG2 two biological cell suspensions as examples for ultrasensitive sensing. Among them, 293T is normal human embryonic kidney cell, and HepG2 is liver cancer cell. Three concentration gradients (5×10 3 , 5×10 4 , 5×10 5 The 293T and HepG2 cells at different concentrations of 10 cells / mL were detected using a terahertz time-domain spectrometer to obtain the transmission spectra at different cell concentrations.

[0060] 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 with different concentrations. Figure 7 (c) in the figure 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 resonant 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 for 293T cell suspension and HepG2 cell suspension is 456.64kHz / cell mL, respectively. -1 and 408.58kHz / cell mL -1 In addition, for both 293T and HepG2 cell suspensions, the detection limit can reach 5×10 3 cells / mL.

[0061] Those skilled in the art will readily appreciate other embodiments of the present application after considering the specification and practicing the contents disclosed herein. This application is intended to cover any variations, uses, or adaptations of the present application that follow the general principles of this application and include common knowledge or customary techniques in the art not disclosed herein. The description and examples are to be considered as exemplary only.

[0062] It will 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 bound state principle in a quasi-continuous domain, characterized in that: The label-free terahertz metasurface 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 are formed by symmetrically deleting two identical inferior arcs in a circle with a radius of R1, and asymmetrically opening 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 a height difference a between the bottom surface of the right gap and the bottom surface of the left gap, the bound state effect in the quasi-continuous domain is achieved.

2. The label-free terahertz metasurface based on the bound state principle in the quasi-continuous domain according to claim 1, characterized in that: The base layer is made of polyimide, and the metal layer is made of gold.

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

4. The label-free terahertz metasurface based on the bound state principle in the quasi-continuous domain according to claim 3, characterized in that: The thickness of the base layer is 70 μm, the thickness of the connection 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 resonant ring 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 of the resonant ring is 7.5 μm.

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 height difference between the bottom surface of the right gap and the bottom surface of the left gap is a = 0 μm, the resonance peak and the resonance line width disappear; When the height difference between the bottom surface of the right gap and the bottom surface of the left gap is a=4μm, the resonance peak frequency in the transmission spectrum generated by the terahertz metasurface is at 2.26THz, and the sensitivity is 517GHz / RIU.

8. The label-free terahertz metasurface based on the bound state principle in a quasi-continuous domain according to claim 1 or 7, characterized in that: To study the relationship between the height difference a between the bottom surfaces of the right and left gaps and the Q factor, the typical Fano formula is used to obtain 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 bound state principle in a quasi-continuous domain according to any one of claims 1 to 8, characterized in that: The preparation method comprises: A titanium film with a thickness of 10 nm was deposited on the substrate as a connecting layer, and then a gold film with a thickness of 200 nm was deposited; The gold film is then patterned according to the structure of two connected semicircular open resonant rings; wherein the two connected semicircular open resonant rings are formed by symmetrically deleting two identical inferior arcs in a circle with a radius of R1, and asymmetrically opening 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.

10. Application of the label-free terahertz metasurface based on the bound state principle in a quasi-continuous domain according to any one of claims 1 to 8 in biological detection.

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