CN115128045A

CN115128045A - Integrated near-field enhanced terahertz biosensor

Info

Publication number: CN115128045A
Application number: CN202210829185.1A
Authority: CN
Inventors: 殷明; 王建林; 黄浩亮
Original assignee: Lutonic Technology Wuxi Co ltd
Current assignee: Lutonic Technology Wuxi Co ltd
Priority date: 2022-07-15
Filing date: 2022-07-15
Publication date: 2022-09-30

Abstract

The invention discloses a near-field biosensor integrating a terahertz source structure and a metamaterial structure and a preparation method thereof. The terahertz source structure is grown on the substrate, a dielectric layer is coated in a spinning mode, and then a periodic metamaterial structure with Fano and EIT resonance is designed and processed on the terahertz source structure, so that the terahertz wave band has the sensing characteristics of high Q value and high sensitivity; and in addition, a layer of specific sensing film is solidified on the superstructure, so that the superstructure has the characteristic of specific combination with the object to be detected. When an object to be detected is dripped on the surface of the sensor, the specific film can capture the object to be detected, the change of the surface dielectric constant of the metamaterial is caused, the terahertz resonance peak is obviously shifted by utilizing the interaction of near fields, and the purpose of detecting the trace object to be detected is realized. The terahertz biosensor is utilized, trace biomolecule detection with low cost, high sensitivity and specificity can be realized based on the obvious near field enhancement effect, and the terahertz biosensor has a wide application prospect in the field of terahertz detection.

Description

Integrated near-field enhanced terahertz biosensor

Technical Field

The invention relates to the field of terahertz biosensor application, in particular to a biosensor technology with low cost, high sensitivity and specific detection in a terahertz waveband, and specifically relates to an integrated terahertz biosensor integrating a terahertz emission source structure and a metamaterial structure and a preparation method thereof.

Background

The terahertz spectrum is an electromagnetic wave between microwave and infrared, the frequency range of the terahertz spectrum is 0.1-10 THz, the wavelength range of the terahertz spectrum is 30 mu m-3 mm, and the terahertz spectrum is in the transition stage from macroscopic electronics to microscopic photonics. This segment of electromagnetic waves has not been studied intensively due to the lack of effective radiation sources and sensitive detection techniques in the past, and is therefore also referred to as a "terahertz gap". With the development of the ultrafast photoelectric technology and the miniature semiconductor device, a more effective radiation source and detection technology are provided for terahertz research, so that the terahertz technology is widely and deeply researched. The terahertz wave band contains physical, chemical and structural information of related substances, so that the terahertz wave band is widely applied to the fields of material science, biomedical science, food chemistry, communication radar and the like.

The key to terahertz application is the need for a high-performance, low-cost terahertz source, and a high-sensitivity detection technology. Currently, common terahertz sources include photoconductive antennas, organic crystals. However, the terahertz source has many problems that the cost is high, the miniaturization and integration are difficult, the signal intensity and the spectrum width are difficult to be compatible, and a specific pump laser is required. Therefore, a terahertz emission source with low cost, strong signal, wide spectrum and integration is needed. In recent years, the development of ultrafast spintronics opens up a new path for the development of terahertz sources, and terahertz radiation can be realized by utilizing ultrafast demagnetization and spin-charge conversion.

The terahertz metamaterial is a novel artificial material acting on a terahertz waveband, and can be used for adjusting the amplitude and the phase of terahertz waves. When the surface of the metamaterial is covered by other substances, the change of the local effective dielectric constant of the metamaterial can cause the change of capacitance, thereby causing the shift of the resonant frequency of the metamaterial. Therefore, the detection of the trace substance can be realized through the shift of the resonance frequency of the terahertz metamaterial. At present, commercial miniaturized terahertz spectrometers excite antennas or crystals to generate terahertz light based on fiber lasers, then the terahertz light is incident on a far field to be detected, and terahertz signals are detected through electro-optical sampling. The method for detecting the substances in the far field has the advantages that the detection of trace or ultra-trace substances is difficult to realize due to the sensitivity, and the commercial application of a terahertz spectrometer in the field of high-sensitivity detection is limited.

Disclosure of Invention

In view of this, the invention provides an integrated near-field enhanced terahertz biosensor, which can realize trace biomolecule detection with low cost, high sensitivity and specificity.

In order to achieve the above object, in one aspect, the present invention provides a biosensor monolithically integrating a terahertz source structure and a metamaterial structure, including a terahertz source structure, a dielectric layer, and a periodically arranged metamaterial structure, where the terahertz source includes a nonlinear electro-optic crystal (ZnTe, GaP, LiNO) ₃ And organic crystals, etc.), photoconductive antennas (based on GaAs, InGaAs, etc.), and spin terahertz sources (ferromagnetic/nonmagnetic structures, antiferromagnetic layers, etc.). The metamaterial structure comprises an asymmetric open-ended resonant ring and a metal stub, wherein the asymmetric open-ended resonant ring comprises two openings, the two openings are positioned on the same side of the vertical diameter passing through the asymmetric open-ended resonant ring, and included angles between the two openings and a straight line are the same acute angle alpha (hereinafter referred to as an opening angle); the metal short wire is positioned on the right side of the split ring and is vertical in direction.

A functionalized specific film is fixed on the surface of the integrated near-field enhanced terahertz biosensor, and the functionalized specific film comprises a binding reagent capable of specifically recognizing an object to be detected.

In some embodiments, the substrate material of the biosensor is quartz or silicon, and the thickness of the substrate is 1-5 mm (e.g., 2 mm, 3 mm, or 4 mm)

In some embodiments, the ferromagnetic layer of the spin terahertz source is cofeb, the nonmagnetic layer comprises platinum or tungsten.

In some embodiments, the ferromagnetic layer of the spin terahertz source has a thickness of 1-6 nanometers (e.g., 2 nanometers, 3 nanometers, 4 nanometers, or 5 nanometers)

In some embodiments, the nonmagnetic layer of the spin terahertz source has a thickness of 1-6 nanometers (e.g., 2 nanometers, 3 nanometers, 4 nanometers, or 5 nanometers)

In some embodiments, the dielectric layer is a polyimide or PDMS film.

In some embodiments, the dielectric layer has a thickness of 1-10 microns (e.g., 2 microns, 3 microns, 4 microns, 5 microns, 6 microns, 7 microns, 8 microns, or 9 microns)

In some embodiments, the asymmetric open resonator ring has an opening angle α =1-20 ° (e.g., 2 °, 3 °, 4 °, 5 °, 6 °, 7 °, 8 °, 9 °, 10 °, 11 °, 12 °, 13 °, 14 °, 15 °, 16 °, 17 °, 18 °, or 19 °).

In some embodiments, the asymmetric open resonator ring has an opening width g =5-10 microns (e.g., 6 microns, 7 microns, 8 microns, or 9 microns).

In some embodiments, the asymmetric open resonator ring has a period P1=80-120 microns (e.g., 90 microns, 100 microns, or 110 microns), a period P2=80-120 microns (e.g., 90 microns, 100 microns, or 110 microns), an outer diameter r =20-40 microns (e.g., 22 microns, 25 microns, 28 microns, 30 microns, 32 microns, 35 microns, or 38 microns), and a line width w =5-20 microns (e.g., 6 microns, 7 microns, 8 microns, 9 microns, 10 microns, 11 microns, 12 microns, 13 microns, 14 microns, 15 microns, 16 microns, 17 microns, 18 microns, or 19 microns).

In some embodiments, the metal stubs have a width of 2-10 microns (e.g., 3 microns, 4 microns, 5 microns, 6 microns, 7 microns, 8 microns, or 9 microns) and a height of 30-80 microns (e.g., 35 microns, 40 microns, 45 microns, 50 microns, 55 microns, 60 microns, 65 microns, 70 microns, or 75 microns).

In some embodiments, the asymmetric open resonator ring and the metal stub have a thickness of 100 nm-300 nm (e.g., 120 nm, 150 nm, 180 nm, 200 nm, 220 nm, 250 nm, or 280 nm).

In some embodiments, the metamaterial structure is made of gold, silver or aluminum.

In some embodiments, the binding agent is selected from an aptamer, an antibody, or a biological probe.

On the other hand, the invention provides an application of the terahertz metamaterial biosensor in detecting pesticide residues,

compared with the prior art, the terahertz metamaterial biosensor has the following beneficial effects:

the invention provides a terahertz source structure and metamaterial structure integrated terahertz biosensor, wherein a W/CoFeB/Pt three-layer structure with strong terahertz emission performance is selected, and according to the reverse spin Hall effect principle, when infrared femtosecond laser is incident to the surface of a sample, the conversion of spin current-charge current of CoFeB can be excited, so that terahertz light is radiated. In addition, compared with a traditional open-loop resonant ring structure, the designed metamaterial structure can generate Fano resonance and EIT resonance at the same time, so that the metamaterial has a three-band resonance frequency in a terahertz band, wherein the Fano resonance is a resonance mode with a high Q value. The integrated structure has the advantages that near-field detection can be realized, when infrared laser light is focused and incident on the emission source, all terahertz light radiated directly interacts with one periodic unit structure of the metamaterial, and the near-field detection method not only reduces loss, but also greatly improves detection sensitivity.

The embodiment of the invention prepares the specific sensing film, and the acetamiprid aptamer is fixed on the surface of the metamaterial sensor by utilizing the specific binding principle of the aptamer and pesticide molecules, so that the acetamiprid aptamer has the characteristic of specific binding with the acetamiprid pesticide molecules. The metamaterial biosensor has the capability of specifically detecting substances to be detected by curing the specific aptamer on the surface of the metamaterial biosensor, so that the metamaterial biosensor has the functions of low cost, high sensitivity and specific detection.

Drawings

Fig. 1 is a schematic structural diagram of an integrated terahertz sensor chip in an embodiment of the present invention.

Fig. 2 is a schematic structural diagram of a terahertz radiation source in an embodiment of the present invention.

FIG. 3 is a schematic diagram of a metamaterial unit structure in an embodiment of the invention.

Fig. 4 is a simulation diagram of different opening angles of the metamaterial structure in the embodiment of the present invention.

Fig. 5 is a sensor sensitivity simulation diagram in the embodiment of the present invention.

FIG. 6 is a schematic diagram of integrated biosensor near field detection in an embodiment of the present invention.

Detailed Description

In the description of the present invention, reference to "one embodiment" means that a particular feature, structure, or parameter, step, or the like described in the embodiment is included in at least one embodiment according to the present invention. Thus, appearances of the phrases such as "in one embodiment," "in one embodiment," and the like in this specification are not necessarily all referring to the same embodiment, nor are other phrases such as "in another embodiment," "in a different embodiment," and the like. Those of skill in the art will understand that the particular features, structures or parameters, steps, etc., disclosed in one or more embodiments of the present description may be combined in any suitable manner.

As shown in fig. 1, the biosensor integrating the spin terahertz source structure and the metamaterial structure according to the embodiment of the present invention includes a substrate, a terahertz emission source, a dielectric layer, and a periodic superstructure. In addition, a specific sensing film is fixed on the surface of the superstructure, and the specific sensing film comprises a binding reagent capable of specifically identifying the object to be detected. The terahertz emission source comprises a spinning terahertz emission source, ZnTe crystals, photoconductive antennas, organic crystals and the like. The dielectric layer can be polyimide or PDMS to shield the mutual influence of the emission source and the superstructure. Each periodic structure comprises an open resonant ring and a metal stub, wherein the open ring comprises two openings which are positioned on the same side of the vertical diameter. It can be seen that the two openings are asymmetric along the vertical diameter. The central lines of the two openings pass through the centers of the asymmetric opening resonance rings and form acute angles alpha with the vertical diameter at the same angle.

The inventors have found through experiments that a higher detection sensitivity can be achieved when the opening angle is less than 30 °, and the smaller the opening angle, the higher the sensitivity, and the preferred opening angle is α =1-20 °. The opening is rectangular and preferably has a width g of 5-10 microns. In addition, the spacing between the metal stub and the split ring is preferably 10-20 microns.

The following description is given with reference to specific examples:

the embodiment provides a terahertz near field sensor for detecting acetamiprid pesticide, and aims to solve the problem of quickly detecting pesticide residues with low cost, high sensitivity and specificity.

1. Preparation of spin terahertz source structure and metamaterial structure integrated biosensor

The integrated metamaterial sensor designed by the invention adopts quartz as a substrate, a three-layer structure is grown by magnetron sputtering of an emission source, a periodic metamaterial structure is made of gold, and the preparation process comprises the following steps:

(1) cleaning the surface of the quartz substrate: in order to ensure that the surface of the quartz plate is clean and the film is firmly attached to the quartz, the surface of the substrate is first cleaned by ultrasonic cleaning with acetone, alcohol and deionized water.

(2) Preparing a spinning terahertz emission source structure: firstly, putting corresponding W, CoFeB, Pt targets and a substrate, and adjusting the position and the angle; then starting the mechanical pump, when the pressure in the cavity is reduced to about 10 Pa, starting the molecular pump, and pumping to a vacuum degree of 10 ^-4 Pa; setting working air pressure, working power, sputtering time and the rotating speed of the sample stage, opening a substrate baffle, and starting sputtering coating; and opening a nitrogen gas cylinder and a valve after sputtering is finished, filling dry nitrogen into the sputtering chamber, and taking out the plated sample from the sample table.

(3) Spin coating of polyimide solution: a polyimide film was coated on the sample using a spin coating method. In order to evaporate all the water in the polyimide solution and solidify the solution and attach the solution to the sample, the spin-coated polyimide solution is placed in a vacuum drying oven for solidification.

(4) Preparing a periodic structure: firstly, a layer of photoresist is spin-coated on a prepared polyimide film, and then a designed mask pattern is processed on the thin layer by adopting a photoetching process. Finally, a layer of gold is plated by magnetron sputtering and is stripped cleanly.

The structure diagram of the spinning terahertz emission source in the embodiment of the invention is shown in fig. 2, wherein the terahertz emission source adopts a W/CoFeB/Pt three-layer structure, and the thickness of each layer in the three-layer structure is 2 nanometers, 4 nanometers and 4 nanometers respectively.

The structure of the periodic metamaterial unit of the embodiment of the invention is shown in fig. 3, wherein a split ring and a short line made of gold are arranged on a substrate, and the ring has two openings. Specific parameters are periodic side length P1=95 micrometers, P2=90 micrometers, circular ring outer diameter r =30 micrometers, circular ring width w =5 micrometers, opening width g =5 micrometers, opening angle α =10 °, length l1=5 micrometers, height l2=50 micrometers, spacing d =15 micrometers of a metal short line, and thickness of the periodic metal structure is 200 nanometers.

The terahertz wave resonant structure is a periodic structure consisting of split rings and metal short wires, and compared with a traditional single-split resonant ring structure, the special asymmetric split metal resonant ring structure has unique resonance response, and when the electric field direction of terahertz waves is vertically incident along the vertical direction (y direction), the structure can simultaneously induce three resonance peaks, one is Fano resonance, and the other two are EIT resonance. The Fano resonance is an asymmetric resonance generated by interference of discrete spectral lines and continuous spectral lines with narrow line widths, and has a narrow line width and a higher quality factor (Q value).

The metamaterial sensor is simulated, different opening angles are set, and the simulation result is shown in fig. 4, and it can be seen that when an open ring is a symmetrical angle (α =0 °), a transmission spectrum has two resonance peaks near 1.4 THz and 1.8 THz, which are typical EIT resonances; when the opening angle is asymmetric, the transmission spectrum increases by one resonance peak around 1THz, which is a typical Fano resonance. It is noted that as the opening angle increases, the spectral line becomes wider and the Q value becomes smaller. When the opening angle is 10 °, the corresponding Q value is up to 22. In addition, the sensitivity of the sensor is simulated in an analog mode, when the refractive index of a substance to be measured on the surface of the sensor changes, the corresponding resonance peak can be subjected to red shift, and the simulation result is shown in fig. 5, so that the offset of the EIT resonance peak can reach 370 GHz/RIU at most. In the embodiment of the invention, the optimized metamaterial structure is used as a biosensor for detecting acetamiprid pesticide residues.

2. And preparing the specific sensing film.

Diluting acetamiprid aptamer with buffer solution to required concentration, mixing 5 mu L of diluted aptamer solution with 2 mu L of 1 mM TCEP solution, incubating the mixed solution at room temperature for 30 minutes, dripping 5 mu L of activated solution onto the surface of the metamaterial sensor, incubating at room temperature for 2 hours, washing with deionized water for 3 times, removing the acetamiprid aptamer which is not coupled with the gold electrode, and drying with nitrogen to obtain the specific sensing film.

3. Detecting the acetamiprid pesticide residue by a terahertz near field.

An integrated terahertz sensor chip near-field detection schematic diagram is shown in fig. 6, exciting light is focused through a lens and then enters the surface of a terahertz source structure, and a focusing light spot can be smaller than 10 micrometers, so that the size of a radiated terahertz light spot can be smaller than the size of a unit structure. Terahertz radiation can directly interact with a periodic unit structure, and then emitted terahertz light enters a detector after passing through a terahertz lens. In the experiment, 5 mu l of prepared acetamiprid solution with the concentration is dripped onto a sensor chip, the sample solution to be detected is specifically combined by an aptamer attached to the surface of the metamaterial structure, and then the sample is subjected to spectrum collection by using the optical path, and the frequency domain signal of the sample is analyzed. Because acetamiprid molecules of a sample to be detected change the dielectric constant of the surrounding environment of the surface of the sensor, the position of a resonance peak is caused to generate red shift, and because virus solutions with different concentrations have different dielectric constants, the dielectric constant of the sample solution to be detected is increased along with the increase of the concentration, and then the offset of the resonance peak is linearly increased. Therefore, the metamaterial biosensor has the capability of specifically detecting the substance to be detected by curing the specific aptamer on the surface of the metamaterial biosensor, so that the metamaterial biosensor has the functions of low cost, high sensitivity and specific detection.

It should be understood by those skilled in the art that the integrated terahertz sensor chip of the present invention is not limited to detecting acetamiprid pesticides, and the integrated terahertz biosensor of the present invention can be used to detect various corresponding substances by using other suitable aptamers or other types of binding reagents (e.g., antibodies, biological probes, etc.).

The above-mentioned embodiments are intended to illustrate the objects, technical solutions and advantages of the present invention in further detail, and it should be understood that the above-mentioned embodiments are merely exemplary embodiments of the present invention, and are not intended to limit the scope of the present invention, and any modifications, equivalent substitutions, improvements and the like made within the spirit and principle of the present invention should be included in the scope of the present invention.

Claims

1. An integrated near-field enhanced terahertz biosensor is characterized by comprising a terahertz source structure and a metamaterial structure, wherein the terahertz source structure comprises a spinning terahertz emission source (a ferromagnetic/nonmagnetic structure, an antiferromagnetic/nonmagnetic structure or an antiferromagnetic), a nonlinear electro-optic crystal (ZnTe, GaP, LiNO) ₃ Or organic crystals), photoconductive antennas (based on GaAs or InGaAs); the metamaterial structure is a periodic unit structure consisting of asymmetric open resonant rings and metal short wires.

2. An integrated near-field enhanced terahertz biosensor is characterized in that a specific sensing film is fixed on the surface of the sensor.

3. An integrated near-field enhanced terahertz biosensor is characterized in that a dielectric layer is arranged between a terahertz source structure and a metamaterial structure, and the dielectric layer is a polyimide or PDMS film and is 1-10 microns thick.

4. The integrated near-field enhanced terahertz biosensor as claimed in claim 1, wherein: the asymmetric open resonator ring of the metamaterial structure comprises two openings which are positioned on the same side of a vertical diameter passing through the asymmetric open resonator ring, and the central lines of the two openings form acute angles alpha with the vertical diameter, wherein the acute angles alpha are the same, and the central lines of the two openings are =1-20 degrees, and the width of the openings is g =1-10 micrometers.

5. The integrated near-field enhanced terahertz biosensor as claimed in claim 1, wherein: the period P1=80-120 microns, the period P2=80-120 microns, the outer diameter r =20-40 microns and the line width w =5-20 microns of the asymmetric open resonant ring of the metamaterial structure.

6. The integrated near-field enhanced terahertz biosensor as claimed in claim 1, wherein: the metal short wire of the metamaterial structure is positioned on the right side of the split ring, is vertical in direction and has the width of 2-10 micrometers; the height of the metal short line is 30-80 microns; the distance between the metal short line and the split ring is 5-20 microns.

7. The integrated near-field enhanced terahertz biosensor as claimed in claim 1, wherein: the thicknesses of the asymmetric open-ended resonant ring and the metal short line of the metamaterial structure are 100-300 nanometers.

8. The integrated near-field enhanced terahertz biosensor as claimed in claim 1, wherein: the asymmetric open-ended resonant ring and the metal short wire are made of gold, silver or aluminum.

9. The integrated near-field enhanced terahertz biosensor as claimed in claim 2, wherein: the specific sensing film comprises a binding agent capable of specifically recognizing the analyte.