Plasmonic optical enhancement chip system and applications thereof

Abstract

The application provides a plasmonic optical enhancement chip system and application thereof, which comprises a nanopore chip, an optical chip set and an image sensor chip, the nanopore chip comprises a substrate layer, an excitation light introduction layer, a microcavity layer and a metal film, at least one reaction unit is arranged in the microcavity layer, the reaction unit comprises a Bragg mirror and a microcavity, and the bottom surface of the microcavity is provided with a nanopore opening; the optical chip set comprises a relay optical chip and an integrated optical chip to form at least one optical unit, which is used for receiving the optical signal excited at the nanopore opening and sequentially collimating, converging, collecting, processing and outputting; and the image sensor chip comprises at least one photoelectric conversion unit. The plasmonic optical enhancement chip system of the application utilizes the amplification effect of the plasmonic enhanced electric field, efficiently excites the molecules at the nanopore opening of the microcavity, has super-high sensitive detection capability, can realize super-high sensitive optical detection of the lowest single molecule, and can be applied to the fields of single molecule detection and DNA / RNA sequencing.

Description

Technical Field

[0001] This invention belongs to the field of biochip technology and relates to a plasmonic optical enhancement chip system and its application. Background Technology

[0002] Biochips have a wide range of applications, finding broad use in life science research and practice, medical research and clinical practice, drug design, environmental protection, agriculture, military and other fields, and have broad economic, social and scientific prospects. Improving the detection sensitivity of biochips has become an important technical problem that urgently needs to be solved by those skilled in the art. Summary of the Invention

[0003] In view of the shortcomings of the prior art described above, the purpose of this invention is to provide a plasmonic optical enhancement chip system and its application, which solves the problem of low detection sensitivity of biochips in the prior art.

[0004] To achieve the above and other related objectives, the present invention provides a plasmonic optical enhancement chip system, comprising:

[0005] A nanoporous chip includes a substrate, an excitation light guiding layer, a microcavity layer, and a metal film. The excitation light guiding layer is located between the substrate and the microcavity layer. The microcavity layer has at least one reaction unit, which includes a Bragg mirror and a microcavity. The microcavity opens from the top surface of the microcavity layer and extends to the bottom surface of the microcavity layer to form a nano-opening. The Bragg mirror is distributed on both sides of the microcavity and is spaced at a predetermined distance from the microcavity. The excitation light guiding layer has a through-hole communicating with the microcavity through the nano-opening. The metal film is located on the upper surface of the microcavity layer and covers the surface of the Bragg mirror and the surface of the microcavity.

[0006] An optical chip assembly is located above the nanopore chip. The optical chip assembly includes relay optical chips and integrated optical chips stacked sequentially from bottom to top to form at least one optical unit, which is used to receive the optical signals excited at the nanopore opening and collimate and converge them sequentially, collect the converged optical signals, process them and output them.

[0007] An image sensor chip is located above the optical chipset. The image sensor chip includes at least one photoelectric conversion unit for receiving optical signals output by the optical chipset and converting them into electrical signals.

[0008] Optionally, the optical unit includes a lens group located in the relay optical chip. The lens group includes a first lens and a second lens spaced apart in the vertical direction. The first lens is used to collimate the optical signal excited at the nano-aperture, and the second lens is used to converge the optical signal collimated by the first lens to the integrated optical chip.

[0009] Optionally, the first lens includes a microlens or a Fresnel lens, and the second lens includes a microlens or a Fresnel lens.

[0010] Optionally, the excitation light guiding layer includes a single-mode waveguide.

[0011] Optionally, the substrate layer is made of silicon dioxide; the excitation light guiding layer is made of silicon nitride; and the microcavity layer is made of silicon.

[0012] Optionally, the opening area of ​​the microcavity gradually decreases from top to bottom.

[0013] Optionally, the shape of the nano-opening includes one of rectangle, square and circle.

[0014] Optionally, the optical unit includes a collection grating coupler, a planar waveguide, a multimode waveguide, and a static interferometer located in the integrated optical chip. The collection grating coupler is used to collect the optical signals converged by the relay optical chip and transmit them sequentially through the planar waveguide and the multimode waveguide to the static interferometer. The static interferometer is used to generate interference signals and project them into the image sensor chip.

[0015] Optionally, the optical unit further includes a microring resonator structure located in the integrated optical chip, the microring resonator structure being disposed next to the multimode waveguide to filter out excitation light.

[0016] Optionally, the microring resonator structure includes a ring waveguide, a strip waveguide, and a metal block, wherein the ring waveguide is located between the multimode waveguide and the strip waveguide, and the metal block is connected to the output end of the strip waveguide.

[0017] Optionally, the plasmonic optical enhancement chip system further includes a laser and an optical fiber, with the nanopore chip connected to the laser via the optical fiber.

[0018] Optionally, the excitation light generated by the laser enters the nanopore chip through the optical fiber in an end-face coupling or grating coupling manner.

[0019] Optionally, the plasmonic optical enhancement chip system includes multiple reaction units, multiple optical units, and multiple photoelectric conversion units to form multiple detection units, and one detection unit includes one reaction unit, one optical unit, and one photoelectric conversion unit.

[0020] Optionally, the nanopore chip further includes a multi-level multimode interference coupler connected to the excitation light guiding layer, the multi-level multimode interference coupler being used to split the excitation light in the nanopore chip into multiple beams for input into different reaction units.

[0021] The present invention also provides an application of a plasmonic optical enhancement chip system, which utilizes the plasmonic optical enhancement chip system described in any of the above claims to detect the optical signals of molecules.

[0022] Optionally, an optical signal with single-molecule sensitivity can be obtained.

[0023] Optionally, the optical signal includes at least one of a spectral signal and a fluorescence signal.

[0024] Optionally, the plasmonic optical enhancement chip system can be used for DNA sequencing or RNA sequencing.

[0025] As described above, the plasmonic optical enhancement chip system of the present invention possesses ultra-high sensitivity detection capability, enabling ultra-high sensitivity optical detection down to the lowest single molecule level. The principle is based on utilizing the amplification effect of the plasmonic enhanced electric field to efficiently excite molecules within the optical enhancement antenna structure, thereby obtaining an optical signal with single-molecule sensitivity. This optical signal includes spectral signals and / or fluorescence. The plasmonic optical enhancement chip system of the present invention can be applied to single-molecule detection and DNA / RNA sequencing fields. Attached Figure Description

[0026] Figure 1a The diagram shows an architecture and schematic of the plasmonic optical enhancement chip system of the present invention.

[0027] Figure 1b This diagram shows another architecture and schematic of the plasmonic optical enhancement chip system of the present invention.

[0028] Figure 2 This is a partial top view of the nanopore chip.

[0029] Figure 3 This is another partial top view of the nanoporous chip.

[0030] Figure 4 The diagram shown illustrates the working principle of the nanopore chip.

[0031] Figure 5This is a schematic diagram of an end-face coupling method.

[0032] Figure 6 This is a schematic diagram of a grating coupling method.

[0033] Figure 7 The diagram shows a rectangular grating structure used in the coupling grating.

[0034] Figure 8 The diagram shows a fan-shaped grating used in the grating structure of a coupled grating.

[0035] Figure 9 The diagram shows a subwavelength grating used in the coupling grating structure.

[0036] Figure 10 The diagram shows the semi-elliptical shape of the collecting grating coupler.

[0037] Figure 11 The diagram shows the semi-circular shape of the collecting grating coupler.

[0038] Figure 12 The diagram shown is a schematic of a micro-ring resonator structure.

[0039] Figure 13 The diagram shows a chip-type spectrometer formed by packaging a static interferometer and an image sensor chip.

[0040] Figure 14 The diagram shows a multi-array configuration of the plasmonic optical enhancement chip system.

[0041] Figure 15 The diagram shown is a schematic of a multimode interference coupler structure.

[0042] Figure 16 The diagram shown is a schematic of a multi-stage multimode interference coupler structure.

[0043] Figure 17 The diagram shows the structure of the second type of static interferometer.

[0044] Figure 18 The diagram shown is a structural schematic of the third type of static interferometer.

[0045] Figure 19 The diagram shown is a structural schematic of the fourth type of static interferometer.

[0046] Figure 20 The diagram shown is a structural schematic of the fifth type of static interferometer.

[0047] Component designation explanation

[0048] 1 Nanopore chip

[0049] 101 microcavity layer

[0050] 102 metal film

[0051] 103 Bragg reflector

[0052] 104 microcavities

[0053] 105 nanometer opening

[0054] 106 Excitation Light Guide Layer

[0055] 107 Through Hole

[0056] 108-stage multimode interference coupler

[0057] 109 Substrate

[0058] 110 Optical Waveguide

[0059] 111 Grating Structure

[0060] 112 Waveguide

[0061] 112a Planar Waveguide

[0062] 112b single-mode waveguide

[0063] 2a Relay Optical Chip

[0064] 2b Integrated optical chip

[0065] 201 Collection grating coupler

[0066] 202 Planar waveguide

[0067] 203 Multimode Waveguide

[0068] 204 Static Interferometer

[0069] 204a Multimode Interference Coupler Structure

[0070] 204b grating structure

[0071] 204c Multi-stage Multimode Interference Coupler Structure

[0072] 204d interferometer unit structure

[0073] 204e multimode waveguide

[0074] 204F reflector

[0075] 204g multimode interference coupler

[0076] 204h loop waveguide

[0077] 204i Incident Waveguide

[0078] 204j input coupler

[0079] 204k array waveguide

[0080] 204L Output Coupler

[0081] 204m outgoing waveguide

[0082] 204n microlens array

[0083] 205 Micro-ring Resonator Structure

[0084] 205a Ring Waveguide

[0085] 205b strip waveguide

[0086] 205c metal block

[0087] 206 First Lens

[0088] 207 Second Lens

[0089] 3 Image sensor chip

[0090] 4. Laser

[0091] 5 optical fibers

[0092] 501 single-mode fiber

[0093] 6. Chip-based spectrometer

[0094] 7 molecules

[0095] 8. Data processing equipment

[0096] M surface plasmons Detailed Implementation

[0097] The following specific examples illustrate the implementation of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and various details in this specification can also be modified or changed based on different viewpoints and applications without departing from the spirit of the present invention.

[0098] Please see Figures 1a to 20 It should be noted that the illustrations provided in this embodiment are only schematic representations of the basic concept of the present invention. Therefore, the drawings only show the components related to the present invention and are not drawn according to the actual number, shape and size of the components in the actual implementation. In the actual implementation, the form, quantity and proportion of each component can be arbitrarily changed, and the layout of the components may also be more complex.

[0099] This invention provides a plasmonic optical enhancement chip system; please refer to [link / reference]. Figure 1a The diagram shows an architecture and schematic of a plasmonic optical enhancement chip system, including a nanopore chip 1, an optical chipset, and an image sensor chip 3. The nanopore chip 1 includes a substrate layer (not shown in Figure 1), an excitation light guiding layer 106, a microcavity layer 101, and a metal film 102. The excitation light guiding layer 106 is located between the substrate layer and the microcavity layer 101. At least one reaction unit is provided in the microcavity layer 101, including a Bragg mirror 103 and a microcavity 104. The microcavity 104 opens from the top surface of the microcavity layer 101 and extends to the bottom surface of the microcavity layer 101 to form a nano-opening 105. The Bragg mirror 103 is distributed on both sides of the microcavity 104 and spaced at a predetermined distance from the microcavity 104. The excitation light... The inlet layer 106 has a through-hole 107 communicating with the microcavity 104 via the nano-aperture 105. The metal film 102 is located on the upper surface of the microcavity layer 101 and covers the surface of the Bragg reflector 103 and the surface of the microcavity 104. The optical chip group is located above the nano-aperture chip 1 and includes relay optical chips 2a and integrated optical chips 2b stacked from bottom to top to form at least one optical unit, which is used to receive the optical signal excited at the nano-aperture 105 and collimate and converge it in sequence, collect the converged optical signal, process it and output it. The image sensor chip 3 is located above the optical chip group. The image sensor chip 3 includes at least one photoelectric conversion unit, which is used to receive the optical signal output by the optical chip group and convert it into an electrical signal.

[0100] As an example, the image sensor chip 3 is connected to the data processing device 8.

[0101] As an example, the substrate layer is made of silicon dioxide, the excitation light guiding layer 106 is made of silicon nitride, the microcavity layer 101 is made of silicon, and the metal film 102 includes at least one of gold, silver, copper and platinum films.

[0102] As an example, the opening area of ​​the microcavity 104 gradually decreases from top to bottom, and the nano-opening 105 at the bottom of the microcavity 104 has a size at least in one dimension that is at the nanometer level (e.g., 0.1-1000 nm).

[0103] As an example, the Bragg reflector 103 includes a plurality of grating grooves formed in the microcavity layer 101. The grating grooves open from the top surface of the microcavity layer 101 and extend toward the bottom surface of the microcavity layer 101, but do not penetrate the bottom surface of the microcavity layer 101.

[0104] For example, please refer to Figure 2 The image shows a partial top view of the nanoporous chip 1, wherein the nano-openings 105 are in the form of nano-slits. Please refer to... Figure 3 The image shows another partial top view of the nanopore chip 1, wherein the nano-apertures 105 are in the form of nanopores. It should be noted that the shape of the nano-apertures 105 can be adjusted as needed, including but not limited to rectangles, squares, and circles. The arrangement of the multiple grating grooves of the Bragg reflector 103 can also be adjusted as needed, without being limited to... Figure 2 and Figure 3 The above is the limit.

[0105] Please see Figure 4 The diagram illustrates the working principle of the nanoporous chip 1. Excitation light (indicated by the horizontal arrow) enters the nanoporous chip and is confined within the excitation light guiding layer 106 for transmission. The excitation light guiding layer 106 may include a single-mode waveguide. Evanescent waves from the surface of the excitation light guiding layer 106 couple into the nano-aperture 105, generating a highly localized enhanced electric field of plasmon resonance at the nano-aperture 105. This field excites the optical signals of the molecules 7 within the nano-aperture 105, such as fluorescence / Raman / vibrational / rotational / absorption / reflection spectra, exhibiting a very high enhancement efficiency and enabling single-molecule detection sensitivity (e.g., it can enhance Raman scattering effects by 10). 5 -10 20 (This provides a multiple enhancement effect). The enhanced electric field generated at the nano-aperture 105, due to plasmon resonance, can propagate along the surface of the metal film 102 (surface plasmons M are shown in the figure). The Bragg mirrors 103 on both sides of the microcavity 104 on the surface of the nanopore chip 1 act as reflectors, partially reflecting the optical signal generated within the nano-aperture 105 back, thereby reducing the propagation loss of signal photons on the surface and enhancing the intensity of the optical signal. The detected molecule 7 can be transported to the nano-aperture 105 from above or below the nanopore chip 1.

[0106] For example, please refer back to [link / reference]. Figure 1a The plasmonic optical enhancement chip system also includes a laser 4 and an optical fiber 5. The nanopore chip 1 is connected to the laser 4 via the optical fiber 5. The laser 4 and optical fiber 5 are essential optical components outside the chip architecture, providing the optical excitation function in the chip. The laser 4 outputs an excitation light source through the optical fiber 5, and the excitation light is coupled into the nanopore chip 1 through grating coupling or end-face coupling.

[0107] As an example, the optical fiber 5 can be a single-mode optical fiber or a single-mode optical fiber lens.

[0108] For example, please refer to Figure 5 The diagram shows a schematic of an end-face coupling method, in which the excitation light is directly and closely aligned with the end face of the optical waveguide 110 on the substrate layer 109 of the nanopore chip 1 through a single-mode optical fiber 501. The light emitted from the single-mode optical fiber 501 can be coupled into the optical waveguide 110 for further transmission.

[0109] For example, please refer to Figure 6 The diagram illustrates a principle of grating coupling, in which excitation light is emitted through a single-mode fiber 501 to a grating structure 111 on the substrate 109 of the nanopore chip 1, and coupled into a waveguide 112 by the grating structure 111 for further propagation. The central axis of the single-mode fiber 501 is offset from the normal by a preset angle θ.

[0110] For example, please refer to Figures 7 to 9 The diagram shows top views of several common coupling gratings, among which... Figure 7 The diagram shows a rectangular grating used in the coupling grating structure 111. Figure 8 The diagram shows a sector grating used in the coupling grating structure 111. Figure 9 The diagram shows a subwavelength grating as the grating structure 111 in the coupling grating. In this embodiment, the overall structure of the coupling grating includes the periodic grating structure 111 and a planar waveguide 112a and a single-mode waveguide 112b connected to the output end of the grating structure 111. After the excitation light outside the nanopore chip 1 is coupled into the grating, it continues to be transmitted through the single-mode waveguide 112b.

[0111] Please refer back to this. Figure 1a In the optical chipset, the optical unit includes a lens group located in the relay optical chip 2a. As part of the optical unit, the lens group helps to reduce the size of the collection coupling grating in the optical integrated chip 2b, reduce chip manufacturing costs, and the lens group has higher collection efficiency, which can improve the collection efficiency of the entire chip structure for optical signals.

[0112] As an example, the lens group includes a first lens 206 and a second lens 207 spaced apart in the vertical direction. The first lens 206 is used to collimate the optical signal excited at the nano-aperture 105, and the second lens 207 is used to converge the optical signal collimated by the first lens 206 to the integrated optical chip 2b.

[0113] As an example, the first lens 206 includes a microlens or a Fresnel lens, and the second lens 207 includes a microlens or a Fresnel lens. Figure 1a The image shows a case where both the first lens 206 and the second lens 207 are microlenses. The diameter of the microlens can be in the range of 50-5000μm, preferably 200μm, and the focal length can be in the range of 0.1-500μm, preferably 10μm.

[0114] For example, please refer to Figure 1b The diagram shows another architecture and schematic of the plasmonic optical enhancement chip system, in which the first lens 206 and the second lens 207 are both Fresnel lenses. The diameter of the Fresnel lens can be 50-5000μm, preferably 200μm, and the focal length can be 0.1-500μm, preferably 10μm.

[0115] As an example, in the optical chipset, the optical unit further includes a collection grating coupler 201, a planar waveguide 202, a multimode waveguide 203, and a static interferometer 204 located in the integrated optical chip 2b. The collection grating coupler 201 is used to collect the optical signal converged by the relay optical chip 2a and transmit it sequentially through the planar waveguide 202 and the multimode waveguide 203 to the static interferometer 204. The static interferometer 204 is used to generate an interference signal and project it into the image sensor chip 3.

[0116] Specifically, the collecting grating coupler 201 utilizes the principle of a diffraction grating to control the direction of beam propagation, achieving an optical collecting effect. To increase the collecting efficiency, the overall size of the collecting grating coupler 201 can be made relatively large, with a size range of 50-5000 μm.

[0117] For example, please refer to Figure 10 and Figure 11 The diagram shows a sequential connection of the collecting grating coupler 201, the planar waveguide 202, and the multimode waveguide 203. The collecting grating coupler 201 can be as follows: Figure 10 The semi-ellipse shown can also be as follows: Figure 11 The semicircle shown.

[0118] As an example, the optical unit also includes a microring resonator structure 205 located in the integrated optical chip 2b, the microring resonator structure 205 being disposed next to the multimode waveguide 203 to filter out excitation light.

[0119] For example, please refer to Figure 12The diagram shows the schematic of the micro-ring resonator structure 205, which includes a ring waveguide 205a, a strip waveguide 205b, and a metal block 205c. The ring waveguide 205a is located between the multimode waveguide 203 and the strip waveguide 205b, and the metal block 205c is connected to the output end of the strip waveguide 205b. By designing the dimensions of the ring waveguide 205a, a specific wavelength can be selected. The selected wavelength photon is coupled into the ring waveguide 205a via an evanescent wave. When the optical path length of the photon in the ring waveguide 205a is equal to an integer multiple of the wavelength, interference enhancement occurs, forming a whispering gallery mode. The photon then remains within the ring waveguide 205a and propagates. The photon is then coupled out of the ring waveguide 205a through another shorter strip waveguide 205b. The photon is absorbed by the metal block 205c, thereby eliminating the photon of that wavelength from the original input photon and enabling filtering of the excitation light of the spectral signal.

[0120] For example, please refer to Figure 13 The diagram shows a schematic of a chip-type spectrometer 6 formed by packaging the static interferometer 204 and the image sensor chip 3. The static interferometer 204 has a multimode interference coupler structure 204a at its coupling end. The spectral signal propagates through the multimode waveguide 203 and couples into the multimode interference coupler structure 204a. The signal is then split in two by the multimode interference coupler structure 204a and propagates forward through two parallel optical waveguides (which may be made of silicon nitride). The two optical waveguides are designed with different widths, resulting in a phase difference between the photons propagating in the two waveguides. Furthermore, when the two optical signals propagate within the waveguides, the evanescent fields generated by total internal reflection overlap between the two parallel waveguides, producing an interference signal. A periodic grating structure 204b is fabricated in the region between the two waveguides to diffract the interference signal upwards into the image sensor chip 3. The image sensor chip 3 can be a linear or rectangular CCD array to receive the interference signal and obtain the interference pattern. The interference pattern can be processed by Fourier transform to obtain spectral information.

[0121] For example, please refer to Figure 14The diagram shows a multi-array configuration of the plasmonic optical enhancement chip system, comprising multiple reaction units, multiple optical units, and multiple photoelectric conversion units to form multiple detection units. Each detection unit includes one reaction unit, one optical unit, and one photoelectric conversion unit. The nanopore chip 1 also includes a multi-stage multimode interference coupler 108, which splits the excitation light input from the excitation source into the nanopore chip 1 into multiple beams for input to different reaction units. The image sensor chip 3 is connected to a data processing device 8.

[0122] For example, please refer to Figure 15 The diagram shows a schematic of a multimode interference coupler structure. Multimode interference couplers are commonly used micro / nano optical devices in integrated optics, allowing light waves to propagate and be controlled to split into two beams. An ideal 1×2 multimode interference coupler structure is a 50 / 50 beam splitter, separating the incoming light waves into two beams with a 50 / 50 ratio. (See also...) Figure 16 The diagram shows a multi-stage multimode interference coupler structure. According to the principle of splitting light into two, the multi-stage MMI structure can split the light wave into many beams of equal intensity, and then the light wave continues to propagate in the waveguide.

[0123] The working principle of the plasmonic optical enhancement chip system of the present invention is as follows: The laser 4 outputs an excitation light source through the optical fiber 5. The excitation light is coupled into the multi-level multimode interference coupler 108 in the nanopore chip 1 through grating coupling or end-face coupling. The multi-level multimode interference coupler 108 divides the excitation light into multiple beams of equal power, which are then transmitted into the excitation light guide layer 106 (the output structure of the multi-level multimode interference coupler 212 is connected to the excitation light guide layer 106), exciting the optical signal of the molecule 7 at the nano-opening 105 at the bottom of the microcavity 104. The excited optical signal is scattered upwards, collected and collimated by the first lens 206, and then collected and converged by the second lens 207 to the collecting grating coupler 201. It is then converged into the multimode waveguide 203 through the planar waveguide 202 and transmitted into the static interferometer 204. The micro-ring resonator structure 205 next to the multimode waveguide 203 can filter out the excitation light. The optical signal after the excitation light is filtered out enters the static interferometer 204. Photons of different wavelengths interfere in the static interferometer 204 and are projected upward into the image sensor chip 3 by the scattering grating in the static interferometer 204 to form an interference pattern. The spectral information of the optical signal can be obtained by performing a Fourier transform on the interference pattern.

[0124] It should be noted that the static interferometer 204 is not limited to that shown in Figure 1. Figure 13 , Figure 14 The types shown, for example, can also be adopted as... Figures 17 to 20 The type presented in any given image.

[0125] Specifically, Figure 17 The presented static interferometer includes a multi-stage multimode interference coupler structure 204c and multiple interferometer unit structures 204d. Each interferometer unit structure 204d includes a Fabry-Perot interferometer cavity, and the cavity lengths of the Fabry-Perot interferometer cavities in each interferometer unit structure 204d are different. The length differences are designed using a gradient, which can ultimately acquire multiple sets of interference patterns with different fringe spacings and peak intensities, resolving precise spectra. In the chip structure, the more interferometer unit structures there are, the wider the spectral range that can be resolved.

[0126] Specifically, Figure 18 The presented static interferometer includes a multimode waveguide 204e and a reflector 204f placed at the end of the multimode waveguide 204e. The spectral signal propagates forward in the multimode waveguide 204e to the reflector 204f and is reflected back. The incident signal photon and the reflected signal photon undergo standing wave interference at the center of the multimode waveguide 204e (multiple elongated ellipses are used to illustrate this in the figure). The interference pattern can be captured using a linear image sensor chip, and the spectral information is obtained after Fourier transform.

[0127] Specifically, Figure 19 The presented static interferometer includes a multimode interference coupler 204g and a loop waveguide 204h. The spectral signal propagates in the multimode waveguide to the multimode interference coupler 204g, which splits the incident signal photons into two beams that enter the loop waveguide 204h. The two beams of signal photons eventually meet at the center of the loop waveguide 204h, resulting in standing wave interference (shown as multiple elongated ellipses in the figure). The interference pattern can be captured using a linear image sensor chip, and the spectral information is obtained after Fourier transform.

[0128] Specifically, Figure 20The presented static interferometer employs an arrayed waveguide grating (AWG). Signal photons enter the input coupler 204j from the incident waveguide 204i. The input coupler 204j is a planar waveguide. Signal photons are diffracted at the interface between the input coupler 204j and the incident waveguide 204i, and their intensity in the direction perpendicular to the propagation follows a Gaussian distribution before entering the array waveguide 204k. The interface between the array waveguide 204k and the input coupler 204j is curved, ensuring that diffracted light at all positions arrives at the end face of the array waveguide 204k with the same phase. The array waveguide 204k consists of a series of similarly shaped strip waveguides with adjacent waveguides having the same length difference. Throughout the array, the total length of each waveguide increases / decreases gradually. Due to the length difference, light of different wavelengths propagates in the array waveguide 204k and possesses the same phase difference. Signal photons enter the output coupler 204l from the arrayed waveguide 204k. The output coupler 204l is also a planar waveguide structure with curved surfaces at both ends, and the two curved surfaces lie on the same circumference. The other end of the output coupler 204l is connected to the outgoing waveguide 204m. Due to the phase difference, signal photons of different wavelengths are diffracted in the planar waveguide of the output coupler 204l and focused into different outgoing waveguides 204m, achieving wavelength separation (the figure illustrates n wavelengths: λ1~λ2). n The outgoing waveguide 204m focuses the wavelength-separated signal photons onto the linear image sensor chip 3 through the microlens array 204n, obtaining an interference pattern, which is then transformed by inverse Fourier transform to obtain spectral information.

[0129] Of course, in other embodiments, the static interferometer 204 may also be of other suitable types, and the scope of protection of the present invention should not be overly limited here.

[0130] The plasmonic optical enhancement chip system of the present invention can be applied to detect the optical signals of molecules, achieving ultra-high sensitivity optical detection down to the lowest possible single molecule. The optical signals include at least one of spectral signals and fluorescence signals. Furthermore, the plasmonic optical enhancement chip system can be used for DNA sequencing or RNA sequencing.

[0131] It should be noted that the image sensor 3 may include arrayed or linear optical multiplier tubes (PMTs), single-photon avalanche diodes (SPADs), charge-coupled devices (CCDs), silicon photomultiplier tubes (SiPMs), or individual PMTs, SPADs, CCDs, SiPMs, or photodiodes. If it is a single PMT, SPAD, CCD, SiPM, or photodiode, the plasmonic optical enhancement chip system of the present invention can be used to detect the fluorescence signal intensity of a single molecule.

[0132] In summary, the plasmonic optical enhancement chip system of this invention possesses ultra-high sensitivity detection capability, enabling ultra-high sensitivity optical detection down to the lowest single molecule level. The principle is based on the amplification effect of the plasmonic enhanced electric field to efficiently excite molecules within the optical enhancement antenna structure, thereby obtaining a single-molecule sensitive optical signal, which includes spectral signals and / or fluorescence. The plasmonic optical enhancement chip system of this invention can be applied to single-molecule detection and DNA / RNA sequencing. Therefore, this invention effectively overcomes the various shortcomings of existing technologies and has high industrial applicability.

[0133] The above embodiments are merely illustrative of the principles and effects of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or alter the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or alterations made by those skilled in the art without departing from the spirit and technical concept disclosed in the present invention should still be covered by the claims of the present invention.

Claims

1. A plasmonic optical enhancement chip system, characterized in that, include: A nanoporous chip includes a substrate, an excitation light guiding layer, a microcavity layer, and a metal film. The excitation light guiding layer is located between the substrate and the microcavity layer. The microcavity layer has at least one reaction unit, which includes a Bragg mirror and a microcavity. The microcavity opens from the top surface of the microcavity layer and extends to the bottom surface of the microcavity layer to form a nano-opening. The Bragg mirror is distributed on both sides of the microcavity and is spaced at a predetermined distance from the microcavity. The excitation light guiding layer has a through-hole communicating with the microcavity through the nano-opening. The metal film is located on the upper surface of the microcavity layer and covers the surface of the Bragg mirror and the surface of the microcavity. The metal film includes at least one of gold, silver, copper, and platinum films. An optical chip assembly is located above the nanopore chip. The optical chip assembly includes relay optical chips and integrated optical chips stacked sequentially from bottom to top to form at least one optical unit, which is used to receive the optical signals excited at the nanopore opening and collimate and converge them sequentially, collect the converged optical signals, process them and output them. An image sensor chip is located above the optical chip group. The image sensor chip includes at least one photoelectric conversion unit for receiving optical signals output by the optical chip group and converting them into electrical signals. The optical unit includes a collection grating coupler, a planar waveguide, a multimode waveguide, and a static interferometer located in the integrated optical chip; The static interferometer and the image sensor chip are packaged together to form a chip-type spectrometer; The collecting grating coupler is used to collect the optical signals converged by the relay optical chip and transmit them sequentially through the planar waveguide and the multimode waveguide to the static interferometer. The static interferometer is used to generate interference signals and project them into the image sensor chip. The image sensor chip is used to receive interference signals and obtain interference patterns. The interference patterns can be processed by Fourier transform to obtain spectral information.

2. The plasmonic optical enhancement chip system according to claim 1, characterized in that: The optical unit includes a lens group located in the relay optical chip. The lens group includes a first lens and a second lens spaced apart in the vertical direction. The first lens is used to collimate the optical signal excited at the nano-aperture, and the second lens is used to converge the optical signal collimated by the first lens to the integrated optical chip.

3. The plasmonic optical enhancement chip system according to claim 2, characterized in that: The first lens includes a microlens or a Fresnel lens, and the second lens includes a microlens or a Fresnel lens.

4. The plasmonic optical enhancement chip system according to claim 1, characterized in that: The excitation light guiding layer includes a single-mode waveguide.

5. The plasmonic optical enhancement chip system according to claim 1, characterized in that: The substrate layer is made of silicon dioxide; the excitation light guiding layer is made of silicon, and the microcavity layer is made of silicon nitride; or the excitation light guiding layer is made of silicon nitride, and the microcavity layer is made of silicon.

6. The plasmonic optical enhancement chip system according to claim 1, characterized in that: The opening area of ​​the microcavity gradually decreases from top to bottom.

7. The plasmonic optical enhancement chip system according to claim 1, characterized in that: The shape of the nano-aperture includes one of rectangle, square and circle.

8. The plasmonic optical enhancement chip system according to claim 1, characterized in that: The optical unit also includes a microring resonator structure located in the integrated optical chip, the microring resonator structure being disposed next to the multimode waveguide to filter out excitation light.

9. The plasmonic optical enhancement chip system according to claim 8, characterized in that: The microring resonator structure includes a ring waveguide, a strip waveguide, and a metal block. The ring waveguide is located between the multimode waveguide and the strip waveguide, and the metal block is connected to the output end of the strip waveguide.

10. The plasmonic optical enhancement chip system according to claim 1, characterized in that: The plasmonic optical enhancement chip system also includes a laser and an optical fiber, and the nanopore chip is connected to the laser via the optical fiber.

11. The plasmonic optical enhancement chip system according to claim 10, characterized in that: The excitation light generated by the laser enters the nanopore chip through the optical fiber in either end-face coupling or grating coupling.

12. The plasmonic optical enhancement chip system according to claim 1, characterized in that: The plasmonic optical enhancement chip system includes multiple reaction units, multiple optical units, and multiple photoelectric conversion units to form multiple detection units. Each detection unit includes a reaction unit, an optical unit, and a photoelectric conversion unit.

13. The plasmonic optical enhancement chip system according to claim 12, characterized in that: The nanopore chip also includes a multi-level multimode interference coupler connected to the excitation light guiding layer. The multi-level multimode interference coupler is used to split the excitation light in the nanopore chip into multiple beams to input different reaction units.

14. An application of a plasmonic optical enhancement chip system, characterized in that: The optical signal of a molecule is detected using the plasmonic optical enhancement chip system as described in any one of claims 1-13.

15. The application of the plasmonic optical enhancement chip system according to claim 14, characterized in that: Obtain optical signals with single-molecule sensitivity.

16. The application of the plasmonic optical enhancement chip system according to claim 14, characterized in that: The optical signal includes at least one of fluorescence spectral signal, Raman spectral signal, vibrational spectral signal, rotational spectral signal, absorption spectral signal, and reflection spectral signal.

17. The application of the plasmonic optical enhancement chip system according to claim 14, characterized in that: DNA sequencing or RNA sequencing is performed using the aforementioned plasmonic optical enhancement chip system.

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