A resonant chip and a manufacturing method thereof

Abstract

The present invention relates to the field of semiconductors and relates to a resonant chip and a manufacturing method thereof. The resonant chip includes: a dielectric layer. A resonant channel is provided on the dielectric layer; the dielectric layer includes a resonator and a transition dielectric layer; the resonator is formed on the surface of the transition dielectric layer; the resonant channel sequentially penetrates through the resonator and the transition dielectric layer; the resonator is used to form a resonance response with the excitation light and confine the electric field energy within the resonant channel; the transition dielectric layer is used to isolate the passage of biomolecules and enable the biological reaction to occur only within the resonant channel. Compared with the metal coating layer, the present application uses a dielectric layer to avoid the problems of energy loss of electromagnetic waves and fluorescence quenching. By placing the resonator with the resonant channel, the electromagnetic field is confined within the resonant channel, realizing the enhancement of the single-molecule fluorescence process within the resonant channel. The biological reaction occurs only within the resonant channel, thereby controlling and increasing the capture probability of the reactants.

Description

Technical Field

[0001] The present invention relates to the field of semiconductors, and more particularly, to a resonant chip and a manufacturing method thereof. Background Art

[0002] The combination of solid-state electronics technology and biological research applications has achieved many important progress, including valuable sensing technologies such as molecular array technology, microfluidic chip technology, chemically sensitive field effect transistors, and zero-mode waveguides.

[0003] Molecular array technology, namely DNA array (U.S. Patent 6261776), microfluidic chip technology (U.S. Patent 5976336), chemically sensitive field effect transistors, zero-mode waveguides (Chinese Patent CN101467082B), and other valuable sensing technologies.

[0004] Zero-mode waveguide (ZMW) arrays have further extended semiconductor manufacturing technology to research and diagnostics and have been used in a series of biochemical analyses, especially in the field of gene analysis. A typical ZMW includes an opening, a well, or a core at the nanoscale in an opaque coating layer on a transparent substrate. The narrow scale of the core always prevents electromagnetic radiation with a frequency higher than a specific cut-off frequency from propagating through the core. Therefore, by irradiating a very small volume, a very small amount of reactants can be accessed, including single-molecule reactions.

[0005] By monitoring reactions at the single-molecule level, a given reaction can be accurately identified and / or monitored, which is the basis of the field of single-molecule DNA sequencing technology - monitoring molecules by the molecular synthesis of DNA strands by a single DNA polymerase in a template-dependent manner.

[0006] However, when existing array chips perform biochemical fluorescence analysis, there are often problems such as low accuracy of fluorescence sequencing and low signal-to-noise ratio of fluorescence signals.

[0007] Currently, the relative intensity of the excitation field strength in the core of a metal ZMW array is usually low, but this requires high input power to meet the signal-to-noise ratio for single-molecule detection. High input power will increase the error rate of DNA polymerase and is more likely to cause photochemical processes such as photobleaching of biofluorescent molecules, introducing unnecessary optical interference and errors.

[0008] During the process of preventing the propagation of electromagnetic wave radiation, ZMW will generate a large amount of electromagnetic wave energy loss. Under the premise of high input power, these energy losses will be propagated into the system in the form of heat, thus affecting the biochemical stability of the substrate and the activity and error rate of DNA polymerase.

[0009] Since the ZMW is mainly an opening or a well on a metal thin film with high optical loss, there is a problem of optical quenching during the radiation of the fluorescence signal, that is, the relative distance between the enzyme reaction site that emits fluorescence and the metal core will seriously affect the intensity of single-molecule fluorescence radiation.

[0010] Most of the above problems are determined by the material system selected for the substrate. The biochemical stability of the substrate can be coated or modified by a monolayer surface coating. However, the conventional change in the structural design does not fundamentally solve the problems of high input power, temperature rise, and optical quenching, that is, there is no effective solution to the increase in interference and errors introduced into the enzyme process. Summary of the Invention

[0011] The purpose of the embodiments of the present application is to provide a resonant chip and a manufacturing method thereof.

[0012] In a first aspect, the present application provides a resonant chip, including:

[0013] A dielectric layer, on which a resonant channel is provided, and the resonant channel penetrates through the dielectric layer;

[0014] The dielectric layer includes a resonator and a transition dielectric layer;

[0015] The resonator is formed on the surface of the transition dielectric layer;

[0016] The resonant channel sequentially penetrates through the resonator and the transition dielectric layer; the resonator is used to form a resonance response with the excitation light and confine the electric field energy in the resonant channel; the transition dielectric layer is used to isolate the passage of biomolecules so that the biological reaction occurs only in the resonant channel.

[0017] First of all, the resonant chip of the present application is provided with a dielectric layer with low optical loss and high refractive index. Compared with the metal cladding layer of the existing ZMW, the problems of electromagnetic wave energy loss and optical quenching are avoided.

[0018] Secondly, the present application proposes and designs a resonator with a resonant channel. The design principle is different from that of the ZMW, which blocks the propagation of electromagnetic radiation with a frequency higher than a specific cut-off frequency through the core. Instead, the optical field energy is confined in the resonant channel through the interaction of the electromagnetic modes of the resonator, realizing the enhancement of the single-molecule fluorescence process in the resonant channel.

[0019] Most importantly, the design of the two-layer dielectric layer of this chip, where the resonator is used to identify and / or monitor a given reaction; form a resonance response with the excitation light and confine the electric field energy in the resonant channel; the transition dielectric layer is used to isolate the passage of biomolecules so that the biological reaction occurs only in the resonant channel, thereby controlling and increasing the capture probability of the reactants.

[0020] In other embodiments of the present application, the above-mentioned resonator is island-shaped.

[0021] In other embodiments of the present application, the edge of the resonator forms a regular shape or a topological shape.

[0022] In other embodiments of the present application, the resonant channel is slit-shaped, a regular hole, or an irregular hole.

[0023] In other embodiments of the present application, the maximum value of the narrowest width of the resonant channel is 20 nm.

[0024] In other embodiments of the present application, the total volume of the resonant channel is controlled at the single-molecule detection level.

[0025] In other embodiments of the present application, the dielectric layer is made of a non-metallic material.

[0026] In other embodiments of the present application, the materials of the resonator and the transition dielectric layer may be the same or different.

[0027] In other embodiments of the present application, the resonant chip further includes:

[0028] a substrate;

[0029] a conductive layer formed on the surface of the substrate.

[0030] In other embodiments of the present application, the conductive layer is made of an electrode material and is used for external connection of voltage.

[0031] In other embodiments of the present application, the resonant chip further includes: an adhesion layer formed on the surface of the conductive layer; the dielectric layer is formed on the surface of the adhesion layer.

[0032] In other embodiments of the present application, the adhesion layer is made of a porous material.

[0033] In other embodiments of the present application, the resonant chip includes water seepage holes; the water seepage holes penetrate through the substrate and the conductive layer and are in contact with the adhesion layer.

[0034] The present application provides a resonant chip, which includes:

[0035] a substrate;

[0036] a conductive layer located on one side of the substrate;

[0037] an adhesion layer located on one side of the conductive layer;

[0038] a dielectric layer located on one side of the adhesion layer, wherein a resonant slit is provided on the dielectric layer and the resonant slit penetrates through the dielectric layer.

[0039] In other embodiments of the present application, the dielectric layer includes a resonator and a transition dielectric layer;

[0040] The transition dielectric layer is located on one side of the adhesion layer, and the resonator is located on one side of the transition dielectric layer;

[0041] The resonant slit penetrates through the resonator and the transition dielectric layer in sequence.

[0042] In other embodiments of the present application, the above-mentioned resonator has a regular or irregular shape such as circular or square, the shape of the resonant slit is a strip-shaped rectangle, and the resonant slit is arranged at the center of the resonator.

[0043] In other embodiments of the present application, the materials for fabricating the resonator and the transition dielectric layer include non-metallic materials such as gallium phosphide and gallium nitride.

[0044] In other embodiments of the present application, the above-mentioned dielectric layer further includes a dielectric waveguide, and the dielectric waveguide is located on the transition dielectric layer.

[0045] In other embodiments of the present application, the light beam emitted by the above-mentioned dielectric waveguide is incident on the resonator horizontally.

[0046] In other embodiments of the present application, the light beam emitted by the above-mentioned dielectric waveguide is parallel to the resonator.

[0047] In other embodiments of the present application, water seepage holes are further provided on the conductive layer and the substrate, and the positions of the water seepage holes correspond to the resonant slits.

[0048] In a second aspect, the present application provides a method for fabricating a resonant chip, and the method includes:

[0049] A resonant channel is provided on the dielectric layer to penetrate through the dielectric layer;

[0050] The dielectric layer includes a resonator and a transition dielectric layer. The resonator is formed on the surface of the transition dielectric layer; the resonant channel penetrates through the resonator and the transition dielectric layer in sequence; the resonator is used to form a resonance response with the excitation light and confine the electric field energy in the resonant channel; the transition dielectric layer is used to isolate the passage of biomolecules and make the biological reaction occur only in the resonant channel.

[0051] In other embodiments of the present application, the present application provides a method for fabricating a resonant chip, and the method includes:

[0052] Provide a substrate;

[0053] Generate a conductive layer along one side of the substrate;

[0054] Generate an adhesion layer along one side of the conductive layer;

[0055] Fabricate a dielectric layer along one side of the adhesion layer, wherein a resonant slit is provided on the dielectric layer and the resonant slit penetrates through the dielectric layer. Description of the Drawings

[0056] To more clearly illustrate the technical solutions of the embodiments of the present application, the accompanying drawings required for the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of the present application and should not be regarded as limiting the scope. For those of ordinary skill in the art, other related drawings can be obtained based on these drawings without creative efforts.

[0057] Figure 1 One of the cross-sectional schematic diagrams of the resonant chip provided by the embodiment of the present application;

[0058] Figure 2 Another cross-sectional schematic diagram of the resonant chip provided by the embodiment of the present application;

[0059] Figure 3 One of the structural schematic diagrams of the resonant chip provided by the embodiment of the present application;

[0060] Figure 4 The third cross-sectional schematic diagram of the resonant chip provided by the embodiment of the present application;

[0061] Figure 5 The perspective view of the resonant chip provided by the embodiment of the present application;

[0062] Figure 6 Another structural schematic diagram of the resonant chip provided by the embodiment of the present application;

[0063] Figure 7 The third structural schematic diagram of the resonant chip provided by the embodiment of the present application;

[0064] Figure 8 The flowchart of the manufacturing method of the resonant chip provided by the embodiment of the present application;

[0065] Figure 9 Another flowchart of the manufacturing method of the resonant chip provided by the embodiment of the present application;

[0066] Figure 10 The gallium phosphide resonator chip provided by the embodiment of the present application; wherein, Figure 10 In it, (a) top view of the scanning electron microscope, (b) near-field focusing distribution of electromagnetic waves under the excitation condition of 459 nm wavelength light, (c) near-field focusing distribution of electromagnetic waves under the excitation condition of 584 nm wavelength light;

[0067] Figure 11 The preliminary calculation and processing diagram of the gallium phosphide resonator chip provided by the embodiment of the present application, (a) scattering spectrum, (b) absorption spectrum, (c) electromagnetic field enhancement performance at different slit lengths of the resonator; (d) processed gallium phosphide resonator chips with different slit sizes;

[0068] Figure 12 Preliminary verification of the chips provided by the embodiments and comparative examples of the present application; (a) Comparison of the absorption and scattering spectra of gallium phosphide resonators and ZMWs; (b) Electromagnetic field enhancement performance inside the slits of gallium phosphide resonators and inside the holes of ZMWs.

[0069] Figure 13 Calculation verification of the dielectric resonator chips provided by the embodiments and comparative examples of the present application; (a) Comparison of the enhanced fluorescence quantum yields of ZMWs and gallium phosphide resonator chips; (b) Comparison of the enhanced fluorescence radiation of ZMWs and gallium phosphide resonator chips.

[0070] Figure 14 Calculation verification of the enhanced fluorescence of the chips provided by the embodiments and comparative examples of the present application; (a) Distribution of the fluorescence radiation inside the holes of ZMWs; (b) Distribution of the fluorescence radiation inside the slits of gallium phosphide resonators; (c) Distribution of the fluorescence radiation inside the slits of gallium nitride resonators.

[0071] Figure 15 Preliminary verification of the enhanced excitation of the dielectric waveguide resonator chips provided by the embodiments of the present application; (a) Schematic diagrams of four excitation methods; (b) Electric field enhancement spectra corresponding to the excitation methods; (c) Electric field distribution diagrams corresponding to the excitation methods.

[0072] Figure 16 Preliminary calculation verification of the enhanced quantum yield of the dielectric waveguide resonator chips provided by the embodiments of the present application; (a) Schematic diagrams of different units on the waveguide resonator chips, and (b) Fluorescence quantum yield enhancement maps when the initial quantum yield is 0.3 and (c) when the initial quantum yield is 0.003. (d) Schematic diagram of on-chip collection and radiation directivity.

[0073] Icons: 101 - Dielectric layer; 102 - Adhesion layer; 103 - Conductive layer; 104 - Substrate; 1011 - Resonator; 1012 - Transition dielectric layer; 1013 - Dielectric waveguide. Detailed implementation manners

[0074] To make the objectives, technical solutions and advantages of the embodiments of the present application clearer, the technical solutions in the embodiments of the present application will be clearly and completely described below. Apparently, the described embodiments are some, but not all, of the embodiments of the present application.

[0075] Therefore, the following detailed description of the embodiments of the present application is not intended to limit the scope of the claimed present application, but merely represents selected embodiments of the present application. All other embodiments obtained by those of ordinary skill in the art based on the embodiments in the present application without creative efforts shall fall within the scope of protection of the present application.

[0076] As described in the background art, currently, the combination of solid-state electronics technology and biological research applications has achieved many important progress, including valuable sensing technologies such as molecular array technology, microfluidic chip technology, chemically sensitive field effect transistors, and zero-mode waveguides.

[0077] However, when the existing array chips perform biochemical fluorescence analysis, there are often problems of low accuracy of fluorescence sequencing and low signal-to-noise ratio of fluorescence signals.

[0078] Regarding the problems existing in the prior art, they are all the results obtained by the inventors through practice and careful research. Therefore, the process of discovering the above problems and the solutions proposed by the embodiments of the present invention below for the above problems should all be the contributions made by the inventors during the invention process.

[0079] In view of this, in order to solve the above problems, the present application provides a resonant chip. By setting a resonant channel, the fluorescence enhancement effect of biomolecules in the channel is greatly improved, thereby effectively improving the accuracy of fluorescence sequencing and the signal-to-noise ratio of fluorescence signals.

[0080] Referring to Figures 1 - 7 , some embodiments of the present application provide a resonant chip, including: a dielectric layer 101. A resonant channel is provided on the dielectric layer 101, and the resonant channel penetrates the dielectric layer 101.

[0081] The above-mentioned resonant channel is the Figure 1 resonant slit in. When the resonator forms a resonance response with the excitation light, the electric field energy can be confined within the resonant channel. And Figure 1 the resonant slit in is also called a resonant channel, that is, the electric field energy can also be confined within the Figure 1 resonant slit.

[0082] Further, the above-mentioned dielectric layer 101 includes a resonator 1011 and a transition dielectric layer 1012.

[0083] Further, the resonator 1011 is formed on the surface of the transition dielectric layer 1012.

[0084] Further, the resonant channel penetrates the resonator 1011 and the transition dielectric layer 1012 in sequence; the resonator 1011 is used to form a resonance response with the excitation light and confine the electric field energy within the resonant channel; the transition dielectric layer 1012 is used to isolate the passage of biomolecules and make the biological reaction occur only within the resonant channel.

[0085] The resonant chip of the present application utilizes a dielectric resonator 1011 with a high refractive index and a resonant channel structure, which has rich electromagnetic mode characteristics in the visible light band. At a specific wavelength, the interaction between the electric dipole and the toroidal dipole modes confines the near-field energy within the resonant channel of the resonator 1011, and the far-field scattering shows a non-dipole mode. At this time, the electric field is all concentrated in the resonant channel, improving the local electric field strength. At the same time, this structure assists in enhancing the quantum yield of fluorescent molecules during the fluorescence radiation process and achieves directional radiation, which is beneficial to the collection of fluorescence signals.

[0086] Further, in some embodiments of the present application, the resonator 1011 is island-shaped.

[0087] The above-mentioned island-shaped resonator 1011 corresponds to Figure 3 the disk-shaped resonator 1011 in Figure 3 In other words, the disk-shaped resonator 1011 in

[0088] can also be referred to as an island-shaped resonator 1011. That is, any resonator protruding from the transition dielectric layer 1012 can be used to form a resonance response with the excitation light.

[0089] Further, in some embodiments of the present application, the edge of the resonator 1011 forms a regular shape or a topological shape. In other words, the overall shape of the resonator 1011 of the present application is not limited. For example, in some specific embodiments, the above-mentioned island-shaped resonator 1011 can be disk-shaped; it can have a disk-shaped bottom edge, but there are protrusions on the surface of the disk-shaped bottom surface, forming an island shape. It can also have a quadrilateral or other irregular shape, such as a topological shape, as the bottom edge, but there are protrusions on the upper surface of the quadrilateral or other irregular-shaped bottom surface, forming an island shape.

[0090] Further, in some embodiments of the present application, the maximum value of the width of the narrowest part of the resonant channel is 20 nm. Within this range, the local electric field strength inside the resonant channel can be greatly improved, and at the same time, the quantum yield of fluorescent molecules can be assisted to increase during the fluorescence radiation process.

[0091] Further optionally, in some embodiments of the present application, the width of the resonant channel is 0.1 nm to 19.8 nm. Further optionally, in some embodiments of the present application, the width of the resonant channel is 1 nm to 19 nm. Exemplarily, the width of the resonant channel is 1 nm, 2 nm, 3 nm, 4 nm, 5 nm, 6 nm, 7 nm, 8 nm, 9 nm, 10 nm, 11 nm, 12 nm, 13 nm, 14 nm, 15 nm, 16 nm, 17 nm, 18 nm or 19 nm.

[0092] Furthermore, in some embodiments of the present application, the total volume of the resonant channel is controlled at the single-molecule detection level. By controlling the total volume of the resonant channel at the single-molecule detection level, it is possible to ensure that single molecules enter the resonant channel, thereby improving the quantum yield of fluorescent molecules during the fluorescence radiation process.

[0093] Exemplarily, the above single-molecule detection level is achieved by using a slit channel to enable the detection volume of the biological solution to reach the order of 10 - 21 L.

[0094] Furthermore, in some embodiments of the present application, the dielectric layer 101 is made of a dielectric material.

[0095] Further optionally, in some embodiments of the present application, the above dielectric layer 101 is made of dielectric materials such as gallium phosphide and gallium nitride.

[0096] In other alternative embodiments of the present application, the above dielectric layer 101 can also be selected to be made of other common dielectric materials in the art.

[0097] Furthermore, in some embodiments of the present application, the materials of the resonator 1011 and the transition dielectric layer 1012 can be the same or different.

[0098] Exemplarily, in some embodiments of the present application, the materials of both the resonator 1011 and the transition dielectric layer 1012 are gallium phosphide; that is, both the resonator 1011 and the transition dielectric layer 1012 are made of gallium phosphide.

[0099] In other alternative embodiments of the present application, the materials of the resonator 1011 and the transition dielectric layer 1012 are different. Exemplarily, the materials of the resonator 1011 and the transition dielectric layer 1012 are gallium phosphide and gallium nitride, respectively. That is, the resonator 1011 is made of gallium phosphide; the transition dielectric layer 1012 is made of gallium nitride.

[0100] Furthermore, in some embodiments of the present application, the resonant chip includes: a dielectric layer 101, a substrate 104, a conductive layer 103 formed on the surface of the substrate, and an adhesion layer 102 formed on the surface of the conductive layer 103; the dielectric layer 101 is formed on the surface of the adhesion layer 102.

[0101] The dielectric layer 101 here can adopt the dielectric layer 101 provided in any of the foregoing embodiments.

[0102] This chip adopts a design with at least two layers of coating layers. One layer is the dielectric layer 101, a continuous dielectric resonator array, which is used to identify and / or monitor a given reaction; the other layer is the adhesion layer 102, a porous transport structure, which can control and improve the capture probability of reactants by means of DC electrophoresis or dielectrophoresis.

[0103] Further, in some embodiments of the present application, the conductive layer 103 is made of an electrode material and is used to externally connect a voltage.

[0104] Further optionally, in some embodiments of the present application, the conductive layer 103 may be made of a dielectric thin film (silicon nitride) or a conductive thin film (indium tin oxide, ITO).

[0105] In other alternative embodiments of the present application, the above-mentioned conductive layer 103 may also be made of other common conductive materials in the art.

[0106] Further, in some embodiments of the present application, the attachment layer 102 is made of a porous material, which is used to attach biomolecules to the surface of this layer, and at the same time is also used to ensure the water permeability for biomolecule testing in a liquid environment, enhance the entry and exit of the liquid, and improve the fluidity of the liquid.

[0107] Further optionally, in some embodiments of the present application, the attachment layer 102 is made of a porous alumina or titanium oxide thin film.

[0108] In some embodiments of the present application, the material of the above-mentioned attachment layer 102 can be selected from other common pore materials in the art.

[0109] Further, in some embodiments of the present application, the resonant chip includes water seepage holes; the water seepage holes penetrate through the substrate 104 and the conductive layer 103 and are in contact with the attachment layer 102.

[0110] The above-mentioned water seepage holes correspond to Figure 4 the water seepage holes in. By providing the water seepage holes, the liquid in the resonant slit can pass through the attachment layer 102 and immerse into the water seepage holes, thereby improving the fluidity of the liquid.

[0111] Some embodiments of the present application provide a method for manufacturing a resonant chip, and the method includes:

[0112] Providing a resonant channel on the dielectric layer, such that the resonant channel penetrates through the dielectric layer;

[0113] The dielectric layer includes a resonator and a transition dielectric layer, such that the resonator is formed on the surface of the transition dielectric layer; the resonant channel sequentially penetrates through the resonator and the transition dielectric layer; the resonator is used to form a resonance response with the excitation light and confines the electric field energy within the resonant channel; the transition dielectric layer is used to isolate the passage of biomolecules, such that the biological reaction occurs only within the resonant channel.

[0114] Further, in some specific embodiments of the present application, the above-mentioned resonant chip is prepared according to the following steps:

[0115] High-quality group III-V material thin films and nitride material thin films can be grown on lattice-matched substrates by epitaxial deposition. The typical processing technology is as Figure 9 shown (the arrow direction is the direction of the preparation steps). First, the adhesion layer 102 (for example, a porous alumina or titanium oxide thin film) can be deposited on the surface of the sandwich substrate (for example, the AlGap sandwiched in the Gap substrate in the figure) by atomic layer deposition; second, the conductive layer 103 (a dielectric thin film (for example, silicon nitride) or a conductive thin film (for example, indium tin oxide, ITO)) can be formed on another substrate 104 (a substrate, such as silicon dioxide) by physical deposition or chemical deposition; third, the two substrates are assembled together by bonding, and the sacrificial layer (for example, the sandwiched AlGaP or AlGaN in the figure) is selectively removed by chemical etching. Then, a dielectric layer 101 is deposited on the surface of the adhesion layer 102, and a resonator 1011 is formed. The group III-V or nitride single crystal substrate can be reused. After bonding, the group III-V or nitride thin film is patterned and a via hole is formed by two-step exposure and etching. Finally, the support layer of the substrate can be optionally opened by long-time etching to obtain a reaction solution inlet, and Figure 9 .

[0116] In other alternative embodiments of the present application, other high refractive index thin films (such as titanium dioxide TiO2, chalcogenide glass Sb2S3, etc.) can also be selected for the porous dielectric resonator. These materials have lower quality requirements and can usually be processed by evaporation and sputtering, etc., so they can be directly formed on a substrate containing porous alumina or titanium oxide. The subsequent photolithography (or nanoimprinting) and etching processes are the same as those of the aforementioned group III-V and nitride systems.

[0117] Further optionally, in other alternative embodiments of the present application, the processed device can be assembled after being cleaned by plasma oxygen to form a fluid chamber for the solution to interact with the porous dielectric resonator. The device with fluid can be placed on an inverted microscope or a CMOS camera for imaging to detect single molecule fluorescence signals. At the same time, the electrodes and fluid channels carried by the chip can be connected to an electrical control and detector to control the process of charged biological single molecules entering and exiting the slit.

[0118] Compared with the conventional ZMW, the present application proposes and uses a dielectric material with no light loss and a high refractive index as the cladding layer of the substrate, completely avoiding the use of a metal cladding layer, thereby avoiding the problems of energy loss of electromagnetic waves and fluorescence quenching.

[0119] This application proposes and designs a resonator with a resonant channel. The design principle is different from that of ZMW, which blocks the propagation of electromagnetic radiation with a frequency higher than a specific cut-off frequency through the core. Instead, the electromagnetic field is confined in the slit by the resonator to enhance the single-molecule fluorescence process in the slit.

[0120] Some embodiments of this application provide a resonant chip.

[0121] Please refer to Figure 1 , as an optional embodiment, the resonant chip includes a substrate 104, a conductive layer 103, an adhesion layer 102, and a dielectric layer 101; wherein, the conductive layer 103 is located on one side of the substrate 104, the adhesion layer 102 is located on one side of the conductive layer 103, and the dielectric layer 101 is located on one side of the adhesion layer 102, that is, the substrate 104, the conductive layer 103, the adhesion layer 102, and the dielectric layer 101 are connected layer by layer. Among them, a resonant slit is provided on the dielectric layer 101, and the resonant slit penetrates the dielectric layer 101.

[0122] In this embodiment, the substrate 104 serves as the support layer of the chip to fix the conductive layer 103 and ensure the structural stability of the hierarchical units above it; an appropriate voltage can be applied to the conductive layer 103 through an external device to accelerate the biospecific reaction of the sample to be tested at the resonant slit; the adhesion layer 102 is also called the bioadhesion water-permeable layer, which is used to attach biomolecules to the surface of this layer, and at the same time is used to ensure the water permeability for biomolecule testing in a liquid environment, strengthen the entry and exit of the liquid, and improve the fluidity of the liquid; the dielectric layer 101 is made of all-dielectric nanomaterials, and a through resonant slit is provided on the dielectric layer 101, thus forming a resonant unit. When light with a specific wavelength is incident, the dielectric layer 101 can confine the light field energy within the dielectric layer 101. Due to the existence of the resonant slit, the original polarization mode is broken, so that the light field energy is all concentrated inside the resonant slit, realizing the enhancement of the local field, which is beneficial to improving the luminescence efficiency of fluorescent molecules inside the resonant slit, that is, fluorescence enhancement, and thus effectively improving the accuracy of fluorescence sequencing and the signal-to-noise ratio of the fluorescence signal.

[0123] Taking the biomolecule fluorescence test as an example, the resonant chip provided in this embodiment will be specifically described below.

[0124] When using this resonant chip to perform fluorescence tests on biomolecules, the resonant chip needs to be immersed in a liquid environment. There are corresponding biomolecules in the liquid environment. The biomolecules will slowly move into the resonant slit and adhere to the surface of the adhesion layer 102. At this time, by irradiating a light beam with a corresponding wavelength, due to the existence of the resonant slit, the light field energy will be concentrated inside the resonant slit, thereby achieving the purpose of fluorescence enhancement, improving the accuracy of fluorescence sequencing, and the signal-to-noise ratio of the fluorescence signal. At the same time, due to the certain permeability of the adhesion layer 102 itself, it can also improve the fluidity of the liquid environment. When it is necessary to observe the specific reaction of biomolecules, it can be achieved by applying an appropriate voltage to the conductive layer 103.

[0125] Please refer to Figure 2 , as another alternative implementation, the dielectric layer 101 includes a resonator 1011 and a transition dielectric layer 1012.

[0126] The transition dielectric layer 1012 is located on one side of the adhesion layer 102, and the resonator 1011 is located on one side of the transition dielectric layer 1012, that is, the adhesion layer 102, the transition dielectric layer 1012, and the resonator 1011 are arranged layer by layer.

[0127] The resonant slit penetrates through the resonator 1011 and the transition dielectric layer 1012 in sequence.

[0128] In this embodiment, the resonator 1011 and the transition dielectric layer 1012 are made of the same dielectric material and are essentially integrally formed. The main function of the transition dielectric layer 1012 is to isolate the adhesion layer 102 from the liquid environment, so that biomolecules adhere to the adhesion layer 102 through the resonant slit, while the main function of the resonator 1011 is to absorb the light field energy.

[0129] It should be noted that when the dielectric layer 101 is a planar structure, the resonator 1011 and the transition dielectric layer 1012 are located on the same plane and are integrated into one to form the dielectric layer 101. When the dielectric layer is a convex structure and the dielectric layer 101 is divided into the resonator 1011 and the transition dielectric layer 1012, its essence is just another structure of the dielectric layer 101.

[0130] Please refer to Figure 3 , in another possible implementation, the resonator 1011 is circular, the shape of the resonant slit is a strip rectangle, and the resonant slit is arranged at the center of the resonator 1011.

[0131] It should be noted that specifically, the resonator 1011 is in the shape of a disc, the resonant slit is a narrow long rectangle, the center point of the resonant slit is vertically aligned with the center of the resonator 1011, and the resonant slit sequentially penetrates the resonator 1011 and the transition dielectric layer 1012. The long strip-shaped resonant slit can better improve the fluorescence enhancement effect.

[0132] In another possible embodiment, the materials for fabricating the resonator 1011 and the transition dielectric layer 1012 include gallium phosphide.

[0133] It should be noted that the materials of the above-mentioned resonator 1011 and the transition dielectric layer 1012 are only one of the implementation manners, including but not limited to gallium phosphide, and can also be other dielectric materials without optical loss and with a high refractive index, so as to avoid the loss of optical field energy and the problem of optical quenching.

[0134] In another optional implementation manner, the refractive index of the dielectric layer 101 is higher than that of the adhesion layer 102. That is to say, the material of the dielectric layer 101 should be selected as a dielectric material with a refractive index higher than that of the material of the adhesion layer 102.

[0135] Since the biological sample is in a liquid environment, in order to improve the fluidity of the liquid environment, in another optional implementation manner, please refer to Figure 4 and Figure 5 , water seepage holes are also provided on the conductive layer 103 and the substrate 104, and the positions of the water seepage holes correspond to the resonant slits.

[0136] The position of the water seepage hole corresponding to the resonant slit means that the water seepage hole should be arranged directly below the resonant slit, and the center point of the water seepage hole and the center point of the resonant slit are located on the same vertical axis.

[0137] By providing the water seepage holes, the liquid in the resonant slit can pass through the adhesion layer 102 and immerse into the water seepage holes, thereby improving the fluidity of the liquid.

[0138] Generally speaking, when spatially polarized light is incident perpendicularly to the surface of the resonant chip, the polarization mode will affect the spatial distribution of its electric field. The optical field energy at a specific wavelength is confined inside the slit, realizing the enhancement of the fluorescence of the molecules inside the slit. However, it is difficult to achieve optical excitation on the chip with this vertical excitation system, which is not conducive to the construction of an integrated optical system.

[0139] In view of this, please refer to Figure 6 , in another possible implementation manner, the dielectric layer 101 further includes a dielectric waveguide 1013, and the dielectric waveguide 1013 is located on the transition dielectric layer 1012.

[0140] It should be noted that, in this embodiment, the dielectric waveguide is located on the transition dielectric layer. The dielectric waveguide should be in the same plane as the resonator 1011 and have the same thickness as the resonator 1011. By setting the dielectric waveguide, it is possible to achieve parallel incidence of the excitation light on the resonator 1011, thereby achieving higher-energy light field localization in the resonant slit, greatly improving the molecular fluorescence enhancement effect in the resonant slit, and realizing the construction of a portable integrated optical system.

[0141] In an alternative embodiment, please continue to refer to Figure 6 , the light beam emitted by the dielectric waveguide 1013 is incident horizontally on the resonator 1011 (as shown by the arrow in the figure, which is the emission direction of the light beam), thereby achieving horizontal incidence of the excitation light.

[0142] It should be noted that the horizontal incidence in this embodiment means that when the dielectric waveguide 1013 and the resonator 1011 are in the same plane, the light beam emitted by the dielectric waveguide 1013 is incident on the resonator 1011 through the side surface of the resonator 1011 (i.e., the side perpendicular to the transition dielectric layer 1012).

[0143] It should be noted that in actual applications, the position of the dielectric waveguide 1013 can be adjusted as needed, thereby adjusting the direction of the light beam it emits.

[0144] In another alternative embodiment, please refer to Figure 7 , the light beam emitted by the dielectric waveguide 1013 is parallel to the resonator 1011 (as shown by the arrow in the figure, which is the emission direction of the light beam).

[0145] In this embodiment, although the dielectric waveguide 1013 is still in the same plane as the resonator 1011, the light beam emitted by the dielectric waveguide 1013 does not enter the resonator 1011 through the side surface of the resonator 1011, but is parallel to the entire resonator 1011. The form of total internal reflection transmission of the light beam in the dielectric waveguide 1013 causes an evanescent wave to be generated at the waveguide surface. When the resonator 1011 is close to the side surface of the dielectric waveguide 1013, the energy of the evanescent wave at the waveguide surface can be coupled into the resonator 1011. Due to the existence of the resonant slit, the electric field is confined in the resonant slit, and it is possible to achieve enhanced molecular fluorescence in the resonant slit. By setting the distance between the side surface of the dielectric waveguide 1013 and the resonator 1011, the coupling efficiency can be improved.

[0146] It should be noted that in this embodiment, the length of the dielectric waveguide 1013 can be set arbitrarily. In this embodiment, it is preferably extended to the edge of the chip.

[0147] Please refer to Figure 8 , this embodiment of the present application also provides a method for manufacturing a resonant chip. The method includes the following steps:

[0148] Step 201: Provide a substrate 104;

[0149] Step 202: Generate a conductive layer 103 along one side of the substrate 104;

[0150] Step 203: Generate an adhesion layer 102 along one side of the conductive layer 103;

[0151] Step 204: Fabricate a dielectric layer 101 along one side of the adhesion layer 102, wherein a resonant slit is provided on the dielectric layer 101 and penetrates through the dielectric layer 101.

[0152] In another alternative embodiment, after the above step 204, the method further includes:

[0153] Step 205: Divide the dielectric layer 101 into a resonator 1011 and a transition dielectric layer 1012, the transition dielectric layer 1012 is located on one side of the adhesion layer 102, the resonator 1011 is located on one side of the transition dielectric layer 1012, and the resonant slit sequentially penetrates through the resonator 1011 and the transition dielectric layer 1012.

[0154] Optionally, in the above step 205, the resonator 1011 is circular, the shape of the resonant slit is strip-shaped rectangular, and the resonant slit is provided at the center of the resonator 1011.

[0155] The features and performance of the present application will be further described in detail below in conjunction with embodiments:

[0156] Embodiment 1

[0157] Provide a gallium phosphide resonator chip, and the structure is as Figure 1 .

[0158] An indium tin oxide conductive layer 103 is formed on the surface of a silicon dioxide substrate 104, a porous aluminum oxide adhesion layer 102 is formed on the surface of the conductive layer 103, a transition dielectric layer 1012 is formed on the surface of the adhesion layer 102, and a disk-shaped resonator 1011 is formed on the surface of the transition dielectric layer 1012. The resonant channel is slit-shaped. Both the transition dielectric layer 1012 and the resonator 1011 are formed of gallium phosphide.

[0159] Comparative Example 1

[0160] Provide a common chip in the prior art: ZMW.

[0161] The performance of the chips in Embodiment 1 and Comparative Example 1 is detected below, and the results ( Figures 10 - 16 ) are calculated for relevant excitation, radiation, etc. using the finite-difference time-domain method, which is applicable to the liquid environment for biological detection:

[0162] Experimental Example

[0163] 1. Electromagnetic wave near-field focusing detection of the chip in Example 1.

[0164] Figure 10 The gallium phosphide resonator chip provided by the embodiment of the present application. Among them, Figure 10 In (a), top view of scanning electron microscope, (b) electromagnetic wave near-field focusing distribution under the excitation condition of 459 nm wavelength light, (c) electromagnetic wave near-field focusing distribution under the excitation condition of 584 nm wavelength light.

[0165] Figure 10 (a) shows that electron beam lithography and reactive ion etching can achieve slits less than 30 nanometers wide in a semiconductor disk. From the preliminary simulation calculations, as Figure 10 (b) and 10(c) show, placing the slit at the center of the disk in the non-polariton mode (excitation wavelengths of 459 nm and 584 nm) can effectively converge the electromagnetic field, and its highest value can reach 120.

[0166] 2. Electric field strength detection of the chip in Example 1.

[0167] Figure 11 It is the preliminary calculation and processing diagram of the gallium phosphide resonator chip provided by the embodiment of the present application, (a) scattering spectrum, (b) absorption spectrum, (c) electromagnetic field enhancement performance of the resonator under different slit lengths. (d) Processed gallium phosphide resonator chips with different slit sizes.

[0168] Figure 11 (a) and Figure 11 (b) show the changing trends of the scattering and absorption spectra of the resonator under different slit lengths in the preliminary simulation calculations. It can be seen that two scattering valleys appear in the resonant chip at the excitation wavelength, which correspond to the non-polariton states in the resonance mode. At the same time, from Figure 11 (c) the enhancement of the electric field strength, it can be seen that the electric field strength in the resonant channel under the non-polariton state is generally enhanced, and "double resonance enhancement" also appears at the excitation wavelength. Figure 11 (d) shows the processed semiconductor resonant chips with different slit sizes.

[0169] 3. Detect the electromagnetic field enhancement performance of the chips in Example 1 and Comparative Example 1. The results are as Figure 12 .

[0170] Figure 12 It is the preliminary verification of the gallium phosphide resonant chip provided by the embodiment of the present application. (a) Comparison of the absorption and scattering spectra of the gallium phosphide resonator and ZMW. (b) Electromagnetic field enhancement performance inside the slit of the gallium phosphide resonator and inside the hole of ZMW.

[0171] Figure 12(a) shows the comparison of the absorption and scattering cross-sections of the gallium phosphide resonant chip and the ZMW. It can be seen that the gallium phosphide resonator chip has lower absorption compared to the ZMW. The gallium phosphide resonator has two obvious scattering valleys in the visible band, and these two valleys correspond to the resonance modes of the resonator. At the same time, according to Figure 12 (b)'s electromagnetic field enhancement performance, the gallium phosphide resonant chip has strong electric field energy in the resonance mode, and the electric field energy in the hole of the gallium phosphide resonant chip is also one order of magnitude higher than that of the ZMW.

[0172] 4. Detect the enhanced fluorescence quantum yield of the chips in Example 1 and Comparative Example 1. The results are as Figure 13 .

[0173] Figure 13 Calculation verification of the dielectric resonant chips provided in the embodiments and comparative examples of this application. (a) Comparison of the enhanced fluorescence quantum yield of the ZMW and the gallium phosphide resonant chip. (b) Comparison of the enhanced fluorescence radiation of the ZMW and the gallium phosphide resonant chip.

[0174] Figure 13 (a) shows the comparison of the enhanced fluorescence quantum yield of the ZMW and the gallium phosphide resonant chip. The gallium phosphide resonator can produce a higher fluorescence quantum yield in the visible band. Among them, the information of 4 fluorescence wavelengths is extracted from the two spectra on the left and summarized in the enhanced fluorescence quantum yield spectrum line on the right (the solid line represents the gallium phosphide resonant chip, and the dotted line represents the ZMW). The gallium phosphide resonant chip can produce a fluorescence quantum yield that is one order of magnitude higher than that of the ZMW. Figure 13 (b) shows the comparison of the enhanced fluorescence radiation of the ZMW and the gallium phosphide resonant chip. The gallium phosphide resonator can produce higher fluorescence radiation in the non-polariton mode. Among them, the information of 4 fluorescence wavelengths is extracted from the two spectra on the left and summarized in the enhanced fluorescence radiation spectrum line on the right (the solid line represents the gallium phosphide resonant chip, and the dotted line represents the ZMW). The gallium phosphide resonant chip can produce an enhanced fluorescence radiation that is one order of magnitude higher than that of the ZMW.

[0175] 5. Carry out calculation verification on the enhanced fluorescence of the chips in Example 1 and Comparative Example 1. The results are as Figure 14 .

[0176] Figure 14 Calculation verification of the enhanced fluorescence of the dielectric resonant chips provided in the embodiments and comparative examples of this application. (a) In-hole distribution of the ZMW fluorescence radiation. (b) In-slit distribution of the fluorescence radiation of the gallium phosphide resonator. (c) In-slit distribution of the fluorescence radiation of the gallium nitride resonator.

[0177] Figure 14 (a) shows the in-hole distribution of the fluorescence radiation. The fluorescence intensity at the radiation wavelengths of 555 nm / 568 nm is higher than that at the radiation wavelengths of 647 nm / 660 nm;Figure 14 (b), Figure 14 (c) respectively show the distribution of fluorescence radiation within the slits of gallium phosphide and gallium nitride resonators. It is obvious that the dielectric resonator chip has a better fluorescence enhancement effect than the ZMW structure.

[0178] 6. Preliminary verification of the enhanced excitation of the chips in Example 1 and Comparative Example 1. The results are as Figure 15 .

[0179] Figure 15 This is the preliminary verification of the enhanced excitation of the dielectric waveguide resonator chip provided by the embodiment of the present application. (a) Schematic diagrams of four excitation methods. (b) Electric field enhancement spectra corresponding to the excitation methods. (c) Electric field distribution diagrams corresponding to the excitation methods.

[0180] Figure 15 (a) shows the ways of exciting the resonator chip by the waveguide, including waveguide end-face coupling, embedded coupling, and side coupling (different slit orientations). According to Figure 15 the electric field enhancement results in (b), the end-face coupling method can generate a higher electric field enhancement at the excitation wavelength of 500 nm - 700 nm. From Figure 15 the analysis of the electric field distribution in (c), end-face coupling, embedded coupling, and side coupling (the long axis of the slit is parallel to the waveguide) can better confine the energy in the slit channel of the resonator, which is beneficial to realizing on-chip excitation of the resonator chip.

[0181] 7. Preliminary calculation verification of the enhanced quantum yield of the chips in Example 1 and Comparative Example 1. The results are as Figure 16 .

[0182] Figure 16 This is the preliminary calculation verification of the enhanced quantum yield of the dielectric waveguide resonator chip provided by the embodiment of the present application. (a) Schematic diagrams of different units on the waveguide resonator chip, and (b) fluorescence quantum yield enhancement spectra when the initial quantum yield is 0.3 and (c) when the initial quantum yield is 0.003. (d) Schematic diagram of on-chip collection and radiation directivity.

[0183] Figure 16 (a) shows the placement of the fluorescence source in different units of the waveguide resonator chip, including placement on a single chip substrate, placement in the resonant channel of the resonator, placement on the resonator with a substrate, and placement in the waveguide resonator chip. According to Figure 16 (b) and 16(c), from the quantum yield enhancement results, the presence of the resonator plays a key role in enhancing the quantum yield. The waveguide resonator chip can produce a higher fluorescence enhancement for a fluorescence source with a low quantum yield. From Figure 16(d) Radiation directivity analysis. Due to the design of the on-chip waveguide, the waveguide resonance chip can couple more fluorescence radiation energy into the waveguide, further realizing on-chip collection of fluorescence signals.

[0184] The foregoing are only preferred embodiments of the present application and are not intended to limit the present application. For those skilled in the art, the present application may have various changes and modifications. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included within the protection scope of the present application.

Claims

1. A resonant chip, characterized in that, Comprising: A dielectric layer, on which a resonant channel is provided, and the resonant channel penetrates through the dielectric layer; The dielectric layer includes a resonator and a transition dielectric layer; The resonator is formed on the surface of the transition dielectric layer; The resonant channel sequentially penetrates through the resonator and the transition dielectric layer; the resonator is used to form a resonance response with the excitation light and confine the electric field energy within the resonant channel; The transition dielectric layer is used to isolate the passage of biomolecules so that the biological reaction occurs only within the resonant channel; The resonant chip further includes: A substrate; A conductive layer formed on the surface of the substrate; The resonant chip further includes: An adhesion layer formed on the surface of the conductive layer; the dielectric layer is formed on the surface of the adhesion layer; The resonant chip includes a water seepage hole; the water seepage hole penetrates through the substrate and the conductive layer and contacts the adhesion layer.

2. The resonant chip according to claim 1, wherein The resonator is island-shaped.

3. The resonant chip according to claim 2, characterized in that, The edge of the resonator forms a regular shape or a topological shape.

4. The resonant chip according to claim 1, wherein The resonant channel is in the shape of a slit, a regular hole, or an irregular hole.

5. The resonant chip according to claim 4, wherein The maximum width of the narrowest part of the resonant channel is 20 nm.

6. The resonant chip according to claim 4, wherein The total volume of the resonant channel is controlled at the single-molecule detection level.

7. The resonant chip according to any one of claims 1-6, characterized in that, The dielectric layer is made of a non-metallic material.

8. The resonant chip according to claim 7, characterized in that, The materials of the resonator and the transition dielectric layer are the same or different.

9. The resonant chip according to claim 8, wherein The conductive layer is made of an electrode material and is used for external connection of voltage.

10. The resonant chip according to claim 1, wherein The adhesion layer is made of a porous material.

11. The resonant chip according to claim 4, characterized in that, The resonator is circular, the shape of the resonant channel is a strip rectangle, and the resonant channel is disposed at the center of the resonator.

12. The resonant chip according to claim 1, characterized in that The materials for fabricating the resonator and the transition dielectric layer include gallium phosphide.

13. The resonant chip according to claim 1, characterized in that, The dielectric layer further includes a dielectric waveguide, and the dielectric waveguide is located on the transition dielectric layer.

14. The resonant chip according to claim 13, wherein The light beam emitted by the dielectric waveguide is incident on the resonator horizontally.

15. The resonant chip according to claim 13, characterized in that, The light beam emitted by the dielectric waveguide is parallel to the resonator.

16. The resonant chip according to claim 1, characterized in that, The position of the water seepage hole corresponds to the resonant channel.

17. The manufacturing method of the resonant chip according to any one of claims 1-16, characterized in that, The method includes: Providing a substrate; Generating a conductive layer along one side of the substrate; Generating an adhesion layer along one side of the conductive layer; Fabricating a dielectric layer along one side of the adhesion layer, wherein a resonant slit is provided on the dielectric layer, and the resonant slit penetrates through the dielectric layer.

18. The manufacturing method of the resonant chip according to claim 17, characterized in that, The method includes: Providing a resonant channel on the dielectric layer to make the resonant channel penetrate through the dielectric layer; The dielectric layer includes a resonator and a transition dielectric layer, making the resonator formed on the surface of the transition dielectric layer; making the resonant channel sequentially penetrate through the resonator and the transition dielectric layer; the resonator is used to form a resonance response with the excitation light and confine the electric field energy within the resonant channel; the transition dielectric layer is used to isolate the passage of biomolecules so that the biological reaction occurs only within the resonant channel.

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