A Plasmonic Optical Enhancement Chip System and Its Applications
By designing a plasmon optical enhancement chip system, the optical signal is enhanced by using the structure of nanopore chips and integrated optical chips, the problem of low detection sensitivity of biochips is solved, and single-molecule detection and efficient detection of DNA/RNA sequencing is achieved.
Patent Information
- Application Number
- CN202110927835.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2021-08-11
- Publication Date
- 2025-08-01
- Estimated Expiration
- 2041-08-11
AI Technical Summary
Existing biochips have low detection sensitivity and are difficult to achieve efficient single-molecular detection.
A plasmon optical enhancement chip system is designed, including nanopore chips, integrated optical chips and image sensor chips, and the optical signal is amplified by using plasmon enhancement electric field, and the optical signal is enhanced through the Bragg mirror and microcavity structure in the nanopore chip, and the integrated optical chip is used for signal processing, which is finally converted into an electrical signal from the image sensor chip.
It realizes optical detection of single-molecule sensitivity, which can efficiently excite molecules inside the antenna structure and enhance optical signal intensity, and is suitable for single-molecule detection and DNA/RNA sequencing.
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Figure CN115896257B_ABST
Abstract
Description
Technical Field
[0001] The present invention belongs to the technical field of biochips, and relates to a plasmonic optical enhancement chip system and its application. Background Art
[0002] Biochips have a wide range of uses and have extensive applications in various fields such as life science research and practice, medical research and clinical, drug design, environmental protection, agriculture, and military, with broad economic, social, and scientific research prospects. How to improve the detection sensitivity of biochips has become an important technical problem that needs to be solved urgently by those skilled in the art. Summary of the Invention
[0003] In view of the above-mentioned disadvantages of the prior art, the purpose of the present invention is to provide a plasmonic optical enhancement chip system and its application, which are used to solve the problem of low detection sensitivity of biochips in the prior art.
[0004] To achieve the above purpose and other related purposes, the present invention provides a plasmonic optical enhancement chip system, including:
[0005] A nanopore chip, including a substrate layer, an excitation light introduction layer, a microcavity layer, and a metal film. The excitation light introduction layer is located between the substrate layer and the microcavity layer. At least one reaction unit is provided in the microcavity layer. The reaction unit includes a Bragg reflector 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 reflectors are distributed on both sides of the microcavity and are spaced apart from the microcavity by a preset distance. A through hole communicating with the microcavity via the nano-opening is provided in the excitation light introduction layer. The metal film is located on the upper surface of the microcavity layer and covers the surfaces of the Bragg reflector and the microcavity.
[0006] An integrated optical chip, located above the nanopore chip. The integrated optical chip includes at least one optical unit, which is used to collect the optical signals excited at the nano-opening and output the collected optical signals after processing.
[0007] An image sensor chip, located above the integrated optical chip. The image sensor chip includes at least one photoelectric conversion unit, which is used to receive the optical signals output by the integrated optical chip and convert them into electrical signals.
[0008] Optionally, the excitation light introduction layer includes a single-mode waveguide.
[0009] Optionally, the material of the substrate layer includes silicon dioxide, the material of the excitation light introduction layer includes silicon nitride, and the material of the microcavity layer includes silicon.
[0010] Optionally, the opening area of the microcavity gradually decreases from top to bottom.
[0011] Optionally, the shape of the nano-opening includes one of a rectangle, a square, and a circle.
[0012] Optionally, the optical unit includes a collection grating coupler, a planar waveguide, a multimode waveguide, and a static interferometer. The collection grating coupler is configured to collect the optical signals excited at the nano-opening and transmit them to the static interferometer through the planar waveguide and the multimode waveguide in sequence. The static interferometer is configured to generate interference signals and project them into the image sensor chip.
[0013] Optionally, the optical unit further includes a microring resonator structure, which is disposed beside the multimode waveguide to filter out the excitation light.
[0014] Optionally, 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.
[0015] Optionally, the plasmonic optical enhancement chip system further includes a laser and an optical fiber, and the nanopore chip is connected to the laser through the optical fiber.
[0016] Optionally, the excitation light generated by the laser enters the nanopore chip through the optical fiber in an end-coupling manner or a grating-coupling manner.
[0017] Optionally, the plasmonic optical enhancement chip system includes a plurality of the reaction units, a plurality of the optical units, and a plurality of the photoelectric conversion units to form a plurality of detection units. One detection unit includes one reaction unit, one optical unit, and one photoelectric conversion unit.
[0018] Optionally, the nanopore chip further includes a multi-stage multimode interference coupler connected to the excitation light introduction layer, and the multi-stage multimode interference coupler is configured to divide the excitation light in the nanopore chip into multiple beams to be input into different reaction units.
[0019] The present invention also provides an application of a plasmonic optical enhancement chip system, which uses the plasmonic optical enhancement chip system as described in any one of the above to detect the optical signals of molecules.
[0020] Optionally, optical signals with single-molecule sensitivity are obtained.
[0021] Optionally, the optical signals include at least one of a spectral signal and a fluorescence signal.
[0022] Optionally, the plasmonic optical enhancement chip system is used for DNA sequencing or RNA sequencing.
[0023] As described above, the plasmonic optical enhancement chip system of the present invention has ultra-high sensitive detection ability and can achieve ultra-high sensitive optical detection of a minimum of single molecules. The principle is to utilize the amplification effect of the plasmonic enhanced electric field to efficiently excite the molecules inside the optical enhancement antenna structure, thereby obtaining an optical signal with single molecule sensitivity, and this optical signal includes spectral signals and / or fluorescence. The plasmonic optical enhancement chip system of the present invention can be applied to the fields of single molecule detection and DNA / RNA sequencing. Description of the Drawings
[0024] Figure 1 Shows the architecture and schematic diagram of the plasmonic optical enhancement chip system of the present invention.
[0025] Figure 2 Shows a partial top view of the nanopore chip.
[0026] Figure 3 Shows another partial top view of the nanopore chip.
[0027] Figure 4 Shows the working principle diagram of the nanopore chip.
[0028] Figure 5 Shows a schematic diagram of one type of end-face coupling method.
[0029] Figure 6 Shows a schematic diagram of one type of grating coupling method.
[0030] Figure 7 Shows a schematic diagram of selecting a rectangular grating for the grating structure in the coupling grating.
[0031] Figure 8 Shows a schematic diagram of selecting a sector grating for the grating structure in the coupling grating.
[0032] Figure 9 Shows a schematic diagram of selecting a sub-wavelength grating for the grating structure in the coupling grating.
[0033] Figure 10 Shows a schematic diagram of the collection grating coupler being semi-elliptical.
[0034] Figure 11 Shows a schematic diagram of the collection grating coupler being semi-circular.
[0035] Figure 12 Shows the schematic diagram of the micro-ring resonator structure.
[0036] Figure 13Shown is a schematic diagram of the structure of a chip-based spectrometer formed by packaging a static interferometer and an image sensor chip.
[0037] Figure 14 Shown is a schematic diagram of a multi-array format of the plasmonic optical enhancement chip system.
[0038] Figure 15 Shown is a schematic diagram of a multimode interference coupler structure.
[0039] Figure 16 Shown is a schematic diagram of a multi-stage multimode interference coupler structure.
[0040] Figure 17 Shown is a schematic diagram of the structure of the second type of static interferometer.
[0041] Figure 18 Shown is a schematic diagram of the structure of the third type of static interferometer.
[0042] Figure 19 Shown is a schematic diagram of the structure of the fourth type of static interferometer.
[0043] Figure 20 Shown is a schematic diagram of the structure of the fifth type of static interferometer.
[0044] Component number description
[0045] 1 Nanopore Chip
[0046] 101 Microcavity Layer
[0047] 102 metal film
[0048] 103 Bragg reflector
[0049] 104 Microcavity
[0050] 105 nm opening
[0051] 106 excitation light introduction layer
[0052] 107 through holes
[0053] 108 Multi-stage Multimode Interference Coupler
[0054] 109 substrate layer
[0055] 110 optical waveguide
[0056] 111 grating structure
[0057] 112 waveguide
[0058] 112a Planar waveguide
[0059] 112b single-mode waveguide
[0060] 2 Integrated optical chip
[0061] 201 Collector grating coupler
[0062] 202 Planar waveguide
[0063] 203 Multimode waveguide
[0064] 204 Static interferometer
[0065] 204a Multimode interference coupler structure
[0066] 204b Grating structure
[0067] 204c Multistage multimode interference coupler structure
[0068] 204d Interferometer unit structure
[0069] 204e Multimode waveguide
[0070] 204f Mirror
[0071] 204g Multimode interference coupler
[0072] 204h Loop waveguide
[0073] 204i Incident waveguide
[0074] 204j Input coupler
[0075] 204k Array waveguide
[0076] 204l Output coupler
[0077] 204m Exit waveguide
[0078] 204n Microlens array
[0079] 205 Micro-ring resonator structure
[0080] 205a Ring waveguide
[0081] 205b Strip waveguide
[0082] 205c Metal block
[0083] 3 Image sensor chip
[0084] 4 Laser
[0085] 5 Optical fiber
[0086] 501 Single-mode optical fiber
[0087] 6 Chip-based spectrometer
[0088] 7 molecules
[0089] 8 data processing devices
[0090] M surface plasmon Detailed implementation manners
[0091] The following uses specific specific examples to illustrate the implementation manners 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 implementation manners. 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.
[0092] Please refer to Figures 1 to 20 . It should be noted that the diagrams provided in this embodiment only illustrate the basic concept of the present invention in a schematic manner. Therefore, only the components related to the present invention are shown in the diagrams, rather than being drawn according to the number, shape, and size of the components in actual implementation. The types, quantities, and proportions of the components in actual implementation can be arbitrarily changed, and the component layout type may also be more complex.
[0093] The present invention provides a plasmonic optical enhancement chip system. Please refer to Figure 1 , which shows the architecture and schematic diagram of the plasmonic optical enhancement chip system, including a nanopore chip 1, an integrated optical chip 2, and an image sensor chip 3. Among them, the nanopore chip 1 includes a substrate layer ( Figure 1 not shown in the figure), an excitation light introduction layer 106, a microcavity layer 101, and a metal film 102. The excitation light introduction 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. The reaction unit includes a Bragg reflector 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 reflectors 103 are distributed on both sides of the microcavity 104 and are spaced a preset distance from the microcavity 104. A through - hole 107 communicating with the microcavity 104 via the nano - opening 105 is provided in the excitation light introduction layer 106. The metal film 102 is located on the upper surface of the microcavity layer 101 and covers the surfaces of the Bragg reflector 103 and the microcavity 104; the integrated optical chip 2 is located above the nanopore chip 1. The integrated optical chip 2 includes at least one optical unit for collecting the optical signals excited at the nano - opening 105 and outputting the collected optical signals after processing; the image sensor chip 3 is located above the integrated optical chip 2. The image sensor chip 3 includes at least one photoelectric conversion unit for receiving the optical signals output by the integrated optical chip 2 and converting them into electrical signals.
[0094] As an example, the image sensor chip 3 is connected to the data processing device 8.
[0095] As an example, the material of the substrate layer includes silicon dioxide, the material of the excitation light guiding layer 106 includes silicon nitride, the material of the microcavity layer 101 includes silicon, and the metal film 102 includes at least one of a gold film, a silver film, a copper film, and a platinum film.
[0096] As an example, the opening area of the microcavity 104 gradually decreases from top to bottom, and the size of the nano-opening 105 at the bottom of the microcavity 104 is at the nano-scale (e.g., 0.1 - 1000 nm) in at least one dimension.
[0097] 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 towards the bottom surface of the microcavity layer 101, but do not penetrate the bottom surface of the microcavity layer 101.
[0098] As an example, please refer to Figure 2 , which shows a partial top view of the nanopore chip 1. Among them, the nano-opening 105 is in the form of a nano-slit. Please refer to Figure 3 , which shows another partial top view of the nanopore chip 1. Among them, the nano-opening 105 is in the form of a nanopore. It should be noted that the shape of the nano-opening 105 can be adjusted as needed, including but not limited to one of a rectangle, a square, and a circle. The arrangement rule of the multiple grating grooves of the Bragg reflector 103 can also be adjusted as needed, not limited to Figure 2 as shown in Figure 3 .
[0099] Please refer to Figure 4 , which shows the working principle diagram of the nanopore chip 1. Among them, the excitation light (as shown by the horizontal arrow in the figure) enters the nanopore chip and is confined to be transmitted in the excitation light guiding layer 106. Among them, the excitation light guiding layer 106 may include a single-mode waveguide. The evanescent wave on the surface of the excitation light guiding layer 106 is coupled into the nano-opening 105, generating a highly localized enhanced electric field of surface plasmon resonance at the nano-opening 105, exciting the optical signal of the molecule 7 in the nano-opening 105, such as fluorescence / Raman / vibration / rotation / absorption / reflection spectra, with a very high-efficiency enhancement effect, and can achieve single-molecule detection sensitivity (e.g., it can generate 10 5 -10 20(Enhancement effect by a factor of...). Among them, the enhanced electric field of the surface plasmon resonance generated at the nano-aperture 105 can propagate along the surface of the metal film 102 (the surface plasmon M is shown in the figure). The Bragg reflectors 103 on both sides of the microcavity 104 on the surface of the nanopore chip 1 play a role in reflection, and can partially reflect the optical signal generated in the nano-aperture 105 back, achieving the effect of reducing the propagation loss of signal photons on the surface and enhancing the optical signal intensity. Among them, the molecule 7 to be detected can be transported to the nano-aperture 105 through the upper part of the nanopore chip 1, or can be transported to the nano-aperture 105 through the lower part of the nanopore chip 1.
[0100] As an example, please refer back to Figure 1 , the surface plasmon optical enhancement chip system further includes a laser 4 and an optical fiber 5, and the nanopore chip 1 is connected to the laser 4 through the optical fiber 5. The laser 4 and the optical fiber 5, as essential optical components outside the chip architecture, provide 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 by means of grating coupling or end-face coupling.
[0101] As an example, the optical fiber 5 can be selected from a single-mode optical fiber or a single-mode optical fiber lens.
[0102] As an example, please refer to Figure 5 , which shows a schematic diagram of an end-face coupling method. Among them, 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 the single-mode optical fiber 501, and the light emitted from the single-mode optical fiber 501 can be coupled into the optical waveguide 110 for continuous transmission.
[0103] As an example, please refer to Figure 6 , which shows a schematic diagram of a grating coupling method. Among them, the excitation light is emitted from the single-mode optical fiber 501 to the grating structure 111 on the substrate layer 109 of the nanopore chip 1 and is coupled into the waveguide 112 by the grating structure 111 for continuous transmission. The central axis of the single-mode optical fiber 501 deviates from the normal direction by a preset angle θ.
[0104] As an example, please refer to Figures 7 to 9 , which shows a top view of several common coupling gratings. Among them, Figure 7 shows a schematic diagram of the grating structure 111 in the coupling grating being a rectangular grating, Figure 8 shows a schematic diagram of the grating structure 111 in the coupling grating being a sector grating, Figure 9Schematic diagram showing that the grating structure 111 in the coupling grating is a sub-wavelength grating. In this embodiment, the overall structure of the coupling grating includes the periodic grating structure 111, the planar waveguide 112a and the 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.
[0105] Please refer back to Figure 1 , in the integrated optical chip 2, the optical unit includes a collection grating coupler 201, a planar waveguide 202, a multimode waveguide 203, and a static interferometer 204. The collection grating coupler 201 is used to collect the optical signal excited at the nano-aperture 105 and transmit it to the static interferometer 204 through the planar waveguide 202 and the multimode waveguide 203 in sequence. The static interferometer 204 is used to generate an interference signal and project it into the image sensor chip 3.
[0106] Specifically, the collection grating coupler 201 uses the principle of a diffraction grating to control the propagation direction of the light beam and achieve the effect of optical collection. To increase the collection efficiency, the overall size of the collection grating coupler 201 can be made relatively large, and the size range can be controlled between 50 - 5000 μm.
[0107] As an example, please refer to Figure 10 and Figure 11 , showing a schematic diagram of the sequential connection of the collection grating coupler 201, the planar waveguide 202, and the multimode waveguide 203. Among them, the collection grating coupler 201 can be semi-elliptical as shown in Figure 10 , or semi-circular as shown in Figure 11 .
[0108] As an example, the optical unit further includes a microring resonator structure 205, and the microring resonator structure 205 is arranged beside the multimode waveguide 203 to filter out the excitation light.
[0109] As an example, please refer to Figure 12, showing the schematic diagram of the microring resonator structure 205. Among them, the microring resonator structure 205 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 size of the ring waveguide 205a, the function of selecting a specific wavelength can be achieved. The selected wavelength photons enter the ring waveguide 205a through evanescent wave coupling. When the optical path of the photons propagating in the ring waveguide 205a is equal to an integer multiple of the wavelength, interference enhancement will occur, forming a whispering gallery mode, and staying in the ring waveguide 205a to propagate. The photons in the ring waveguide 205a are coupled out through another shorter strip waveguide 205b, and the photons are absorbed by the metal block 205c, so as to achieve the function of removing the photons of this wavelength from the original input photons, and the excitation light of the spectral signal can be filtered.
[0110] As an example, please refer to Figure 1 , showing the schematic structural diagram of the chip-type spectrometer 6 formed by packaging the static interferometer 204 and the image sensor chip 3. Among them, the coupling-in end of the static interferometer 204 is a multimode interference coupler structure 204a. The spectral signal propagates through the multimode waveguide 203 and is coupled into the multimode interference coupler structure 204a. After being split into two by the multimode interference coupler structure 204a, it enters two parallel optical waveguides (the material can be silicon nitride) and continues to propagate forward. The widths of the two optical waveguides are specially designed to be different, resulting in a phase difference between the photons propagating in the two optical waveguides. When the two optical signals propagate in the waveguide, the evanescent fields generated by total internal reflection overlap between the two parallel waveguides, generating an interference signal. A periodic grating structure 204b is prepared in the region between the two waveguides to diffract the interference signal upward to the image sensor chip 3. The image sensor chip 3 can be a linear or rectangular CCD array, which is used to receive the interference signal to obtain an interference pattern. The interference pattern can obtain spectral information after Fourier transform processing.
[0111] As an example, please refer to , shown as a schematic diagram of a multi-array form of the plasmonic optical enhancement chip system, including a plurality of the reaction units, a plurality of the optical units, and a plurality of the photoelectric conversion units to form a plurality of detection units. One detection unit includes one reaction unit, one optical unit, and one photoelectric conversion unit. Among them, the nanopore chip 1 further includes a multi-stage multimode interference coupler 108, and the multi-stage multimode interference coupler 108 is used to divide the excitation light input into the nanopore chip 1 by the excitation light source into multiple beams and input them into different reaction units. The image sensor chip 3 is connected to the data processing device 8.
[0112] As an example, please refer to , shown as a schematic diagram of a multimode interference coupler structure. The multimode interference coupler structure is a common micro-nano optical device in the field of integrated optics. Light waves can propagate in it and divide the light waves into two beams and propagate out in a controllable manner. An ideal 1×2 multimode interference coupler structure is a 50 / 50 beam splitter, which divides the incoming light wave and outputs it according to the ratio of 50% and 50%. Please refer to , shown as a schematic diagram of a multi-stage multimode interference coupler structure. According to the result of one divided into two, the multi-stage MMI structure can divide the light wave into many beams of light with equal light intensity, and then the light wave continues to propagate in the waveguide.
[0113] 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-stage multimode interference coupler 108 in the nanopore chip 1 by means of grating coupling or end face coupling. The multi-stage multimode interference coupler 108 divides the excitation light into multiple beams of excitation light with the same power and enters the excitation light guiding layer 106 for transmission (the output structure of the multi-stage multimode interference coupler 108 is connected to the excitation light guiding layer 106), and excites the optical signal of the molecule 7 at the nanopore opening 105 at the bottom of the microcavity 104. The excited optical signal scatters upward and is collected by the collection grating coupler 201, and then converges through the planar waveguide 202 and enters the multimode waveguide 203, and is transmitted into the static interferometer 204. The micro-ring resonator structure 205 beside 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 with different wavelengths interfere in the static interferometer 204 and are projected upward by the scattering grating in the static interferometer 204 into the image sensor chip 3 to form an interference pattern. By performing a Fourier transform on the interference pattern, the spectral information of the optical signal can be obtained.
[0114] It should be noted that the static interferometer 204 is not limited to , , the type shown in, for example, any one of the presented types.
[0115] Specifically, the presented static interferometer includes a multi-stage multimode interference coupler structure 204c and multiple interferometer unit structures 204d. The interferometer unit structure 204d includes a Fabry-Perot interference cavity, and the cavity lengths of the Fabry-Perot interference cavities of each interferometer unit structure 204d are different. The length difference is designed with a gradient, and finally multiple interference patterns with different fringe spacings and different peak intensities can be collected, and an accurate spectrum can be resolved. In the chip structure, the more the number of interferometer unit structures, the larger the spectral range that can be resolved.
[0116] Specifically, the presented static interferometer includes a multimode waveguide 204e and a mirror 204f placed at the end of the multimode waveguide 204e. The spectral signal propagates forward in the multimode waveguide 204e to the mirror 204f and is reflected back. The incident signal photons and the reflected signal photons undergo standing-wave interference at the central position of the multimode waveguide 204e (schematically shown by multiple long ellipses in the figure). An interference pattern can be captured using a linear image sensor chip, and spectral information can be obtained after Fourier transform.
[0117] Specifically, 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. The multimode interference coupler 204g divides the incident signal photons into two beams and enters the loop waveguide 204h. The two beams of signal photons finally meet at the central position of the loop waveguide 204h and undergo standing-wave interference (schematically shown by multiple long ellipses in the figure). An interference pattern can be captured using a linear image sensor chip, and spectral information can be obtained after Fourier transform.
[0118] Specifically, The presented static interferometer uses an Arrayed Waveguide Grating (AWG). Signal photons enter the input coupler 204j from the incident waveguide 204i. The structure of the input coupler 204j is a planar waveguide. Signal photons diffract at the interface between the input coupler 204j and the incident waveguide 204i and enter the arrayed waveguide 204k with an intensity distribution in the form of a Gaussian in the direction perpendicular to the propagation direction. The interface between the arrayed waveguide 204k and the input coupler 204j is a curved surface, ensuring that diffracted light from each position arrives at the end face of the arrayed waveguide 204k with the same phase. The arrayed waveguide 204k consists of a series of bar-shaped waveguides with similar shapes, and adjacent waveguides have the same length difference. In the entire array, the total length of each waveguide increases / decreases in a gradient manner. Due to the existence of the length difference, light of different wavelengths has the same phase difference after propagating in the arrayed waveguide 204k. Signal photons enter the output coupler 204l from the arrayed waveguide 204k. The output coupler 204l is also a planar waveguide structure, and both of its end faces are curved surfaces, and the two curved surfaces are on the same circumference. The other end of the output coupler 204l is connected to the output waveguide 204m. Due to the existence of the phase difference, signal photons of different wavelengths diffract out in the planar waveguide of the output coupler 204l and are focused in different output waveguides 204m, achieving the effect of wavelength separation (n wavelengths are schematically shown in the figure: λ1~λ n ). The output waveguide 204m focuses the signal photons after wavelength separation onto the linear image sensor chip 3 through the microlens array 204n to obtain an interference pattern, and spectral information is obtained after inverse Fourier transform.
[0119] Of course, in other embodiments, the static interferometer 204 may also adopt other suitable types, and the protection scope of the present invention should not be unduly limited here.
[0120] The plasmonic optical enhancement chip system of the present invention can be applied to detect the optical signals of molecules and can achieve ultra-high sensitive optical detection of at least a single molecule. The optical signals include at least one of spectral signals and fluorescence signals. Further, DNA sequencing or RNA sequencing can be performed using the plasmonic optical enhancement chip system.
[0121] It should be noted that the image sensor 3 may include an array or linear photomultiplier tube (PMT), single photon avalanche diode (SPAD), charge coupled device (CCD), silicon photomultiplier (SiPM), or may also include a single PMT, SPAD, CCD, SiPM, or photodiode. 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.
[0122] In summary, the plasmonic optical enhancement chip system of the present invention has ultra-high sensitivity detection capabilities and can achieve ultra-high sensitivity optical detection of a minimum of single molecules. The principle is to utilize the amplification effect of the plasmon-enhanced electric field to efficiently excite the molecules inside 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 the fields of single molecule detection and DNA / RNA sequencing. Therefore, the present invention effectively overcomes various disadvantages in the prior art and has high industrial utilization value.
[0123] The above embodiments are only illustrative of the principles and effects of the present invention and are not intended to limit the present invention. Any person familiar with this technology can modify or change the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or changes made by those with ordinary knowledge in the technical field without departing from the spirit and technical ideas disclosed by 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, Comprising: A nanopore chip, including a substrate layer, an excitation light introduction layer, a microcavity layer and a metal film. The excitation light introduction layer is located between the substrate layer and the microcavity layer. At least one reaction unit is provided in the microcavity layer. The reaction unit includes a Bragg reflector 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 reflectors are distributed on both sides of the microcavity and are spaced from the microcavity by a preset distance. A through hole communicating with the microcavity via the nano-opening is provided in the excitation light introduction layer. The metal film is located on the upper surface of the microcavity layer and covers the surfaces of the Bragg reflector and the microcavity. The metal film includes at least one of a gold film, a silver film, a copper film and a platinum film; An integrated optical chip, located above the nanopore chip. The integrated optical chip includes at least one optical unit for collecting the optical signals excited at the nano-opening and outputting the collected optical signals after processing; An image sensor chip, located above the integrated optical chip. The image sensor chip includes at least one photoelectric conversion unit for receiving the optical signals output by the integrated optical chip and converting them into electrical signals.
2. The plasmonic optical enhancement chip system according to claim 1, characterized in that: The excitation light introduction layer includes a single-mode waveguide.
3. The plasmonic optical enhancement chip system according to claim 1, wherein: The material of the substrate layer includes silicon dioxide, the material of the excitation light introduction layer includes silicon nitride, and the material of the microcavity layer includes silicon.
4. 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.
5. The plasmonic optical enhancement chip system according to claim 1, wherein: The shape of the nano-opening includes one of a rectangle, a square and a circle.
6. The plasmonic optical enhancement chip system according to claim 1, wherein: The optical unit includes a collection grating coupler, a planar waveguide, a multimode waveguide and a static interferometer. The collection grating coupler is used to collect the optical signals excited at the nano-opening and transmit them to the static interferometer through the planar waveguide and the multimode waveguide in sequence. The static interferometer is used to generate interference signals and project them into the image sensor chip.
7. The plasmonic optical enhancement chip system according to claim 6, characterized in that: The optical unit further includes a microring resonator structure provided beside the multimode waveguide to filter out the excitation light.
8. The plasmonic optical enhancement chip system according to claim 7, wherein: 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.
9. The plasmonic optical enhancement chip system according to claim 1, wherein: The plasmonic optical enhancement chip system further includes a laser and an optical fiber. The nanopore chip is connected to the laser through the optical fiber.
10. The plasmonic optical enhancement chip system according to claim 9, characterized in that: The excitation light generated by the laser enters the nanopore chip through the optical fiber in an end-face coupling manner or a grating coupling manner.
11. The plasmonic optical enhancement chip system according to claim 1, wherein: The plasmonic optical enhancement chip system includes a plurality of the reaction units, a plurality of the optical units and a plurality of the photoelectric conversion units to form a plurality of detection units. One detection unit includes one reaction unit, one optical unit and one photoelectric conversion unit.
12. The plasmonic optical enhancement chip system according to claim 11, wherein: The nanopore chip further includes a multi-stage multimode interference coupler connected to the excitation light introduction layer. The multi-stage multimode interference coupler is used to divide the excitation light in the nanopore chip into multiple beams to input different reaction units.
13. Application of a plasmonic optical enhancement chip system, characterized in that: Detect the optical signal of molecules using the plasmonic optical enhancement chip system as described in any one of claims 1-12.
14. The application of the plasmonic optical enhancement chip system according to claim 13, characterized in that: Obtain an optical signal with single-molecule sensitivity.
15. The application of the plasmonic optical enhancement chip system according to claim 13, wherein: The optical signal includes at least one of a fluorescence spectrum signal, a Raman spectrum signal, a vibration spectrum signal, a rotation spectrum signal, an absorption spectrum signal, and a reflection spectrum signal.
16. The application of the plasmonic optical enhancement chip system according to claim 13, characterized in that: Use the plasmonic optical enhancement chip system for DNA sequencing or RNA sequencing.
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Patent Citations
Plasmon optical enhancement chip system
CN215668053U