Integrated platform for exciting molecular fluorescence signal, detection chip, and optical packaging structure

Abstract

The present invention provides an integrated platform for exciting a molecular fluorescence signal, a detection chip, and an optical packaging structure. The integrated platform for exciting the molecular fluorescence signal comprises, arranged in sequence: an input optical coupling structure (1), a first filtering structure (2), an optical beam-splitter tree structure (3), a filtering structure array (4), a fluorescence excitation structure array (5), and an optical coupling-out structure array (6). The detection chip is used for detecting molecular fluorescence and comprises, arranged from bottom to top in sequence: a fluorescence detection layer (103'), a fluorescence collection layer (102'), and a fluorescence excitation layer (101'). The fluorescence excitation layer (101') comprises, arranged in sequence: an input optical coupling structure (1011'), an optical beam-splitter tree structure (1013'), a fluorescence excitation structure array (1014'), and an optical coupling-out structure array (1015'). The fluorescence excitation layer is further provided with an optical feedback structure (1012'), wherein an input end of the optical feedback structure (1012') is connected to a first output end of one branch of the optical beam-splitter tree structure (1013'). The optical packaging structure comprises an optical fiber module (2') and the detection chip (1'). The integrated platform in the present invention incorporates on-chip filters, providing an integrated fluorescence excitation solution capable of suppressing broadband background light arising from spontaneous fluorescence of lasers or waveguides, thereby improving a signal-to-noise ratio. The detection chip and the optical fiber module in the optical packaging structure in the present invention employ a passive optical coupling scheme, thereby facilitating stability of fluorescence signals and reducing complexity of external device optical paths.

Description

Integrated platform, detection chip and optical packaging structure for exciting molecular fluorescence signals Technical Field

[0001] This invention belongs to the field of biochip technology and relates to an integrated platform for exciting molecular fluorescence signals, a detection chip, and an optical packaging structure. Background Technology

[0002] Biochip technology is a comprehensive high-tech field involving biology, chemistry, medicine, precision manufacturing, optics, microelectronics, and informatics. It is a highly interdisciplinary and popular research topic. In recent years, the excitation and collection of biofluorescence signals through optically integrated chips has gradually demonstrated significant value and potential in the field of fluorescence molecule detection, especially in the field of single-molecule fluorescence detection.

[0003] This technology utilizes semiconductor manufacturing processes to achieve a monolithic integrated solution encompassing fluorescence signal excitation, collection, and detection. By massively generating nanoscale sample confinement sites on the chip surface and combining this with biochemical modification methods, spatial confinement at the single-molecule scale is achieved. Furthermore, compared to traditional optical systems for exciting and collecting fluorescence signals, this technology uses an optical waveguide to form an evanescent field for fluorescence excitation, enabling simultaneous excitation of a large number of sites. The on-chip collection structure then establishes a correspondence between the sample confinement sites and the detection pixels, achieving simultaneous collection of fluorescence signals from a large number of sites, ultimately enabling fluorescence detection of a large number of sites.

[0004] However, the effectiveness of this technology is highly dependent on its detection performance for specific fluorescence signals. The signal-to-noise ratio (SNR) and signal-to-background ratio (SPR) are used to evaluate fluorescence detection performance. Improving both SNR and SPR is crucial for enhancing fluorescence signal detection performance. Noise includes not only photodetector-related noise but also shot noise, which is often greater than photodetector noise. Improving fluorescence or suppressing background light can improve both SNR and SPR. Background light contains not only scattered excitation light but also other light with a broad spectrum. This broad-spectrum background light mainly originates from the spontaneous emission of the laser and the spontaneous emission of the optical waveguide material. Since the fluorescence signal of molecules, especially single-molecule fluorescence signals, is very weak, suppressing background light is particularly important. Although excitation light can be filtered out, how to suppress broad-spectrum background light remains a challenge.

[0005] Furthermore, the on-chip excitation power needs to remain stable to a certain extent, which largely depends on the connection stability and vibration resistance of the optical system. Current solutions that use optical feedback systems to monitor and adjust the coupling between the external light source and the chip in real time can stabilize the on-chip optical power, but they require complex, high-precision opto-electromechanical systems with high response frequencies, which significantly increases the cost of sequencing instruments.

[0006] Therefore, how to provide an integrated platform, molecular fluorescence detection chip and its optical packaging structure for exciting molecular fluorescence signals to improve the signal-to-noise ratio and signal-to-background ratio of biochips, while achieving stable on-chip optical power and reducing the cost of sequencers, has become an important technical problem that needs to be solved by those skilled in the art.

[0007] It should be noted that the above introduction to the technical background is only for the purpose of providing a clear and complete explanation of the technical solutions of this application and facilitating understanding by those skilled in the art. It should not be assumed that these technical solutions are known to those skilled in the art simply because they have been described in the background section of this application. Summary of the Invention

[0008] In view of the shortcomings of the prior art described above, the purpose of this invention is to provide an integrated platform, detection chip and optical packaging structure for exciting molecular fluorescence signals, in order to solve the problems of low signal-to-noise ratio and low signal-to-background ratio of existing biochips, as well as the difficulty in achieving stable on-chip optical power at a low cost.

[0009] To achieve the above and other related objectives, the present invention provides an integrated platform for exciting molecular fluorescence signals, comprising:

[0010] An input optical coupling structure is used to couple laser light emitted from an external laser into the chip.

[0011] A first filtering structure, wherein the input end of the first filtering structure is connected to the output end of the input optical coupling structure, is used to allow a certain wavelength of incident laser to pass through and block the spontaneous emission background fluorescence of the laser.

[0012] A light beam splitting tree structure, wherein the input end of the light beam splitting tree structure is connected to the output end of the first filter structure, is used to split one input light into multiple output lights and form multiple output ends;

[0013] The filter structure array includes multiple second filter structures, the input ends of which are connected one-to-one with the multiple output ends of the optical beam splitting tree structure, for allowing incident laser of a certain wavelength to pass through and blocking the spontaneous emission background fluorescence of the waveguide material.

[0014] A fluorescence excitation structure array includes multiple fluorescence excitation structures, with the input ends of the multiple fluorescence excitation structures connected one-to-one with the output ends of the multiple second filter structures, for confining the physical space of fluorescent molecules and exciting fluorescent molecules to generate fluorescence radiation;

[0015] An optical coupling structure array includes multiple optical coupling structures, with the input ends of the multiple optical coupling structures connected one-to-one with the output ends of the multiple fluorescent excitation structures, for coupling out the remaining excitation light after passing through the fluorescent excitation structure array.

[0016] Optionally, the input optical coupling structure includes a waveguide grating coupler or an edge coupler, and the 3dB linewidth of the input optical coupling structure is greater than 10nm.

[0017] Optionally, the first filtering structure includes one of a micro-ring filter, a waveguide grating filter, and a cascaded directional coupler structure filter, and the second filtering structure includes a waveguide grating filter or a cascaded directional coupler structure.

[0018] Optionally, the waveguide grating filter employs a waveguide distributed Bragg reflector, which includes a straight waveguide and a trench array. The trench array includes multiple rectangular trenches arranged sequentially and at equal intervals along the length direction of the straight waveguide. The length direction of the rectangular trenches is perpendicular to the length direction of the straight waveguide, and the length of the rectangular trenches is equal to the width of the straight waveguide. The rectangular trenches open from the upper surface of the straight waveguide, and the depth of the rectangular trenches is less than the thickness of the straight waveguide. The rectangular trenches are filled with a dielectric material, and the refractive index of the dielectric material is different from that of the straight waveguide.

[0019] Optionally, the waveguide grating filter employs a waveguide distributed Bragg reflector. The waveguide distributed Bragg reflector includes a straight waveguide and a trench array. The trench array includes multiple trench groups arranged sequentially and at equal intervals along the length direction of the straight waveguide. Each trench group includes a first trench and a second trench spaced apart along the width direction of the straight waveguide. Both the first trench and the second trench open from the upper surface of the straight waveguide, and the depth of both the first trench and the second trench is less than the thickness of the straight waveguide. The opposite ends of the first trench and the second trench penetrate the side surface of the straight waveguide. Both the first trench and the second trench are filled with a dielectric material, and the refractive index of the dielectric material is different from that of the straight waveguide.

[0020] Optionally, the waveguide grating filter employs a waveguide distributed Bragg reflector, which includes a straight waveguide and an array of island structures. The array of island structures includes multiple island structure groups arranged sequentially and at equal intervals along the length direction of the straight waveguide. Each island structure group includes a first island structure and a second island structure spaced apart along the width direction of the straight waveguide. The first island structure and the second island structure are distributed on opposite sides of the straight waveguide and are symmetrical about the straight waveguide axis. The thickness of both the first island structure and the second island structure is equal to the thickness of the straight waveguide.

[0021] Optionally, the waveguide grating filter employs a waveguide distributed Bragg reflector. The waveguide distributed Bragg reflector includes a waveguide body and a side wing array. The waveguide body includes a first straight waveguide, a second straight waveguide, and a third straight waveguide connected sequentially along a specified direction. The widths of the first and third straight waveguides are the same and greater than the width of the second straight waveguide. The side wing array includes a first side wing and a second side wing arranged along the width direction of the second straight waveguide. The first and second side wings are connected to opposite sides of the second straight waveguide and are symmetrically arranged about the axis of the second straight waveguide. The thicknesses of the first and second side wings are both equal to the thickness of the second straight waveguide.

[0022] Optionally, the operating light source wavelength range of the first filter structure is 400nm to 800nm, and the operating light source wavelength range of the second filter structure is 400nm to 800nm.

[0023] Optionally, the optical beam splitting tree structure splits one input light into multiple output lights according to the same splitting ratio.

[0024] Optionally, the optical beam splitting tree structure includes one or more optical beam splitter units, wherein the optical beam splitter unit includes one or more of the following: a Y-branch structure, a 2×2 directional coupler, a 1×2 multimode interference coupler, a 2×2 multimode interference coupler, a 1×3 multimode interference coupler, and a 1×5 multimode interference coupler.

[0025] Optionally, the fluorescence excitation structure includes a cladding and a waveguide structure encased in the cladding. The surface of the cladding above the waveguide structure is provided with sample wells arranged at a certain period along the waveguide propagation direction. The sample wells are used to load molecular substances that can excite fluorescence. The distance between the bottom surface of the sample well and the top surface of the waveguide structure is less than the evanescent wave penetration distance of the waveguide structure.

[0026] Optionally, the waveguide structure is a straight waveguide, and the sample well is located directly above the straight waveguide; or the waveguide structure includes a straight waveguide and a plurality of grating structures located on one side of the straight waveguide and connected to the straight waveguide, and the sample well is located directly above the grating structures; or the waveguide structure includes a straight waveguide and a V-shaped metal grating structure located on the straight waveguide, and the sample well is located directly above the V-shaped metal grating structure.

[0027] Optionally, the optical output structure employs a grating coupler, and the 3dB linewidth of the optical output structure is greater than 10nm.

[0028] The present invention also provides a molecular fluorescence detection chip, comprising, from bottom to top, a fluorescence detection layer, a fluorescence collection layer, and a fluorescence excitation layer, wherein the fluorescence excitation layer comprises:

[0029] An input optical coupling module, wherein the input optical coupling module includes one or more input optical coupling units;

[0030] An optical beam splitter tree structure, wherein the input end of the optical beam splitter tree structure is connected to the output end of the input optical coupling module, and the optical beam splitter tree structure includes one first output end and multiple second output ends;

[0031] A fluorescent excitation structure array, wherein the input end of the fluorescent excitation structure array is connected to the second output end of the optical beam splitter tree structure;

[0032] An optically coupled structure array, wherein the input end of the optically coupled structure array is connected to the output end of the fluorescent excitation structure array;

[0033] An optical feedback structure, wherein the input end of the optical feedback structure is connected to the first output end of the optical beam splitter tree structure.

[0034] Optionally, the input optical coupling module includes a plurality of input optical coupling units, and the fluorescence excitation layer further includes an optical power equalization module, which is connected between the input optical coupling module and the optical beam splitter tree structure.

[0035] Optionally, the optical power equalization module includes an N×N optical beam combining structure, wherein N is the same as the number of input optical coupling units. The N×N optical beam combining structure includes a 2×2 optical coupler, or includes multiple cascaded 2×2 optical couplers. The 2×2 optical coupler is a directional coupler or a multimode interference coupler.

[0036] Optionally, the optical feedback structure includes a 1×2 optical beamsplitter, a first feedback optical coupling unit, and a second feedback optical coupling unit. The input optical coupling module is located between the first feedback optical coupling unit and the second feedback optical coupling unit. The first feedback optical coupling unit, the input optical coupling unit, and the second feedback optical coupling unit are arranged in a straight line at equal intervals perpendicular to the light propagation direction. The input end of the 1×2 optical beamsplitter is connected to the first output end of the beamsplitter tree structure. The input end of the first feedback optical coupling unit is connected to the first output end of the 1×2 optical beamsplitter. The input end of the second feedback optical coupling unit is connected to the second output end of the 1×2 optical beamsplitter. The output ends of the first feedback optical coupling unit, the input end of the input optical coupling unit, and the output end of the second feedback optical coupling unit are all used to connect to an optical fiber module. The optical fiber module includes a first optical feedback channel, an optical input channel, and a second optical feedback channel arranged side by side. The output end of the first feedback optical coupling unit is connected to the first optical feedback channel. The input end of the input optical coupling unit is connected to the optical input channel. The output end of the second feedback optical coupling unit is connected to the second optical feedback channel.

[0037] Optionally, the emission angle range of the first feedback optical coupling unit and the second feedback optical coupling unit is 8 to 10 degrees, and the near-field spot diameter range is 3 to 5 micrometers.

[0038] Optionally, the optical feedback structure includes a feedback optical coupling unit, the input end of which is connected to the first output end of the optical beam splitter tree structure, and the output end of which is used to connect to an off-chip optical system.

[0039] Optionally, the emission angle of the feedback optical coupling unit is in the range of 30 to 60 degrees, the near-field spot diameter is in the range of 30 to 60 micrometers, and the emitted spot is collected in free space by the off-chip optical system.

[0040] Optionally, the optical feedback structure includes a first 1×2 optical beamsplitter, a second 1×2 optical beamsplitter, a first feedback optical coupling unit, a second feedback optical coupling unit, and a third feedback optical coupler. The input optical coupling module is located between the first feedback optical coupling unit and the second feedback optical coupling unit. The first feedback optical coupling unit, the input optical coupling unit, and the second feedback optical coupling unit are arranged in a straight line at equal intervals perpendicular to the light propagation direction. The input end of the first 1×2 optical beamsplitter is connected to the first output end of the optical beamsplitter tree structure. The input end of the second 1×2 optical beamsplitter is connected to the first output end of the first 1×2 optical beamsplitter. The input end of the first feedback optical coupling unit is connected to the first output end of the second 1×2 optical beamsplitter. The input terminal of the second feedback optical coupling unit is connected to the second output terminal of the second 1×2 optical beam splitter, and the input terminal of the third feedback optical coupling unit is connected to the second output terminal of the first 1×2 optical beam splitter. The output terminals of the first feedback optical coupling unit, the input terminal of the input optical coupling unit, and the output terminal of the second feedback optical coupling unit are all used to connect to an optical fiber module. The optical fiber module includes a first optical feedback channel, an optical input channel, and a second optical feedback channel arranged side by side. The output terminal of the first feedback optical coupling unit is connected to the first optical feedback channel, the input terminal of the input optical coupling unit is connected to the optical input channel, and the output terminal of the second feedback optical coupling unit is connected to the second optical feedback channel. The output terminal of the third feedback optical coupling unit is used to connect to an off-chip optical system.

[0041] Optionally, the emission angle range of the first feedback optical coupling unit and the second feedback optical coupling unit is 8 to 10 degrees, and the near-field spot diameter range is 3 to 5 micrometers; the emission angle range of the third feedback optical coupling unit is 30 to 60 degrees, and the near-field spot diameter range is 30 to 60 micrometers, and the emitted spot is collected by the off-chip optical system in free space.

[0042] Optionally, the optical beam splitter tree structure includes one or more optical beam splitter units, and the optical beam splitter unit includes one or more of the following: a Y-branch structure, a 2×2 directional coupler, a 1×2 multimode interference coupler, a 2×2 multimode interference coupler, a 1×3 multimode interference coupler, and a 1×5 multimode interference coupler.

[0043] Optionally, the fluorescence excitation structure array includes a cladding and one or more waveguide structures cladding the cladding. The cladding surface above the waveguide structure is provided with sample wells arranged at a certain period along the waveguide propagation direction. The sample wells are used to load molecular substances that can excite fluorescence. The distance between the bottom surface of the sample well and the top surface of the waveguide structure is less than the evanescent wave penetration distance of the waveguide structure.

[0044] Optionally, the waveguide structure is a straight waveguide, and the sample well is located directly above the straight waveguide; or the waveguide structure includes a straight waveguide and a plurality of grating structures located on one side of the straight waveguide and connected to the straight waveguide, and the sample well is located directly above the grating structures; or the waveguide structure includes a straight waveguide and a V-shaped metal grating structure located on the straight waveguide, and the sample well is located directly above the V-shaped metal grating structure.

[0045] Optionally, the optical output structure array includes multiple optical output units, and the optical output units employ grating couplers.

[0046] Optionally, the fluorescence collection layer includes a fluorescence filter layer, an aperture layer, and a microlens array layer.

[0047] Optionally, the fluorescence detection layer includes one or more of the following: a CCD chip, a CMOS image sensor chip, a PD array, a SPAD array, a PMT array, and a SiPM array.

[0048] The present invention also provides an optical packaging structure, including an optical fiber module and a molecular fluorescence detection chip as described in any of the above claims. The optical fiber module is fixed at a preset position of the molecular fluorescence detection chip. The optical fiber module includes one or more optical input channels, and the optical input channels are aligned with the input optical coupling unit.

[0049] Optionally, the fiber module is fixed to a preset position of the molecular fluorescence detection chip by optical coupling adhesive, or the fiber module is fixed to a preset position of the molecular fluorescence detection chip by bonding.

[0050] Optionally, the optical fiber module includes a substrate, a cover plate, and one or more optical fibers. One side of the substrate is provided with a single V-groove or multiple V-grooves arranged side by side and spaced apart. The optical fiber is located in the V-groove. The cover plate is arranged opposite to the substrate to cover the V-groove.

[0051] Optionally, the input optical coupling unit adopts an edge coupler, the initial direction of the pigtail of the optical fiber module is parallel to the plane where the molecular fluorescence detection chip is located, the optical fiber module is fixed to the side of the molecular fluorescence detection chip, and the optical input channel of the optical fiber module is aligned with the waveguide core of the edge coupler.

[0052] Optionally, the input optical coupling unit includes a grating coupler, and the optical fiber module further includes a glass waveguide device. The first end face of the glass waveguide device is fixedly connected to the side of the substrate and the cover plate, and the waveguide core of the glass waveguide device is aligned with the optical fiber in the V-groove. The initial direction of the pigtail of the optical fiber module and the extension direction of the waveguide core of the glass waveguide device are parallel to the plane where the molecular fluorescence detection chip is located. The glass waveguide device is fixed above the grating coupler, and the second end face of the glass waveguide device is inclined to serve as a reflective surface to reflect the light entering the glass waveguide device to the grating coupler.

[0053] Optionally, the second end face of the glass waveguide device is provided with a reflective film.

[0054] Optionally, the input optical coupling unit adopts a grating coupler, the initial direction of the pigtail of the optical fiber module is not parallel to the plane where the molecular fluorescence detection chip is located, the optical fiber module is fixed to the upper surface of the molecular fluorescence detection chip and the optical input channel of the optical fiber module is aligned with the grating coupler, and the end face polishing angle of the optical fiber module is consistent with the emission angle of the grating coupler.

[0055] As described above, the integrated platform for exciting molecular fluorescence signals of the present invention includes, in sequence, an input optical coupling structure, a first filter structure, an optical beam splitter tree structure, a filter structure array, a fluorescence excitation structure array, and an optical coupling output structure array, providing an integrated fluorescence excitation scheme for the detection of fluorescence signals in biological samples. Compared with traditional excitation schemes, the present invention introduces an on-chip filter, which can reduce the broadband background light composed of spontaneous emission fluorescence from lasers or waveguides, thereby reducing shot noise and improving the signal-to-noise ratio and signal-to-background ratio. The molecular fluorescence detection chip of the present invention includes, from bottom to top, a fluorescence detection layer, a fluorescence collection layer, and a fluorescence excitation layer. The fluorescence excitation layer includes an input optical coupling module, an optical beam splitter tree structure, a fluorescence excitation structure array, an optical coupling output structure array, and an optical feedback structure. The input optical coupling module includes one or more input optical coupling units, and the input end of the optical feedback structure is connected to one output end of the optical beam splitter tree structure. The optical packaging structure of this invention includes an optical fiber module and the aforementioned molecular fluorescence detection chip. The optical fiber module is fixed at a preset position on the molecular fluorescence detection chip and includes one or more optical input channels. These optical input channels are aligned with the input optical coupling unit. This passive optical coupling scheme ensures that the optical coupling efficiency remains unchanged regardless of environmental mechanical vibrations, thereby improving the stability of the on-chip excitation light and thus contributing to the stability of the fluorescence signal. It also reduces the complexity of the optical path of external devices, saving equipment costs. Furthermore, this invention can employ a multi-channel coupling method to increase the number of lasers, thereby increasing the on-chip excitation light power and improving the signal-to-noise ratio. Attached Figure Description

[0056] Figure 1 shows a schematic diagram of the integrated platform for exciting molecular fluorescence signals according to the present invention.

[0057] Figure 2 shows a schematic diagram of an edge coupler used in one embodiment of the input optical coupling structure.

[0058] Figure 3 shows a schematic diagram of the grating coupler used in the input optical coupling structure in another embodiment.

[0059] Figure 4 shows a schematic diagram of the micro-ring filter used in the first filtering structure in one embodiment.

[0060] Figure 5 shows a top view of a waveguide distributed Bragg reflector used in the first filtering structure in one embodiment.

[0061] Figure 6 shows a side view of the structure shown in Figure 5.

[0062] Figure 7 shows a top view of another waveguide distributed Bragg reflector used in the first filtering structure in one embodiment.

[0063] Figure 8 shows a side view of the structure shown in Figure 7.

[0064] Figure 9 shows a top view of another waveguide distributed Bragg reflector used in the first filtering structure in one embodiment.

[0065] Figure 10 shows a side view of the structure shown in Figure 9.

[0066] Figure 11 shows a top view of another waveguide distributed Bragg reflector used in the first filtering structure in one embodiment.

[0067] Figure 12 shows a side view of the structure shown in Figure 11.

[0068] Figure 13 shows a schematic diagram of a cascaded directional coupler structure filter used in the first filtering structure in one embodiment.

[0069] Figure 14 shows a schematic diagram of the Y-branch structure.

[0070] Figure 15 shows a schematic diagram of a 1×2 multimode interference coupler.

[0071] Figure 16 shows a schematic diagram of a 2×2 multimode interference coupler.

[0072] Figure 17 shows a schematic diagram of a 2×2 directional coupler.

[0073] Figure 18 shows a schematic diagram of a 1×5 multimode interference coupler.

[0074] Figure 19 shows a schematic diagram of a 1×3 multimode interference coupler.

[0075] Figure 20 shows a schematic diagram of a 1×N optical beam splitter unit.

[0076] Figure 21 shows a side view of a fluorescent excitation structure array in one embodiment.

[0077] Figure 22 shows a top view of the structure shown in Figure 21.

[0078] Figure 23 shows another side view of the structure shown in Figure 21.

[0079] Figure 24 shows a side view of a fluorescent excitation structure array in another embodiment.

[0080] Figure 25 shows a top view of the structure shown in Figure 24.

[0081] Figure 26 shows a side view of the fluorescent excitation structure array in another embodiment.

[0082] Figure 27 shows a top view of the structure shown in Figure 26.

[0083] Figure 28 shows a structural block diagram of the molecular fluorescence detection chip of the present invention.

[0084] Figure 29 shows a planar layout of the fluorescence excitation layer of the molecular fluorescence detection chip of the present invention in one embodiment.

[0085] Figure 30 shows a side view of the optical encapsulation structure of the present invention in one embodiment.

[0086] Figure 31 shows a partial cross-sectional view of the optical fiber module in one embodiment of the optical encapsulation structure of the present invention.

[0087] Figure 32 shows a top view of an embodiment where the input optical coupling unit uses an edge coupler and is fixedly connected to the optical fiber module by optical coupling adhesive.

[0088] Figure 33 shows a side view of an embodiment where the input optical coupling unit uses an edge coupler and is fixedly connected to the optical fiber module by optical coupling adhesive.

[0089] Figure 34 shows a schematic diagram of an input optical coupling unit employing a grating coupler and an optical fiber module including a glass waveguide device in another embodiment.

[0090] Figure 35 shows a schematic diagram of an input optical coupling unit using a grating coupler and fixedly connected to the optical fiber module by optical coupling adhesive in another embodiment.

[0091] Figure 36 shows a cross-sectional view of the optical fiber module in one embodiment.

[0092] Figure Label Explanation 1 Input Optical Coupling Structure 101 Edge Coupler 102 Grating Coupler 2 First Filter Structure 201 Waveguide 202 First Micro-ring 203 Second Micro-ring 211, 221, 231 Straight Waveguide 212, 222 Trench Array 213 Rectangular Trench 232 Island Structure Array 241 Waveguide Body 2411 First Straight Waveguide 2412 Second Straight Waveguide 2413 Third Straight Waveguide 242 Side Wing Array 251 First Directional Coupler 252 Second Directional Coupler 3 Optical Beam Splitting Tree Structure 301 Optical Beam Splitter Unit 4 Filter Structure Array 401 Second Filter Structure 5 Fluorescence Excitation Structure Array 501 Fluorescence Excitation Structure 502 Cladding 503 Waveguide Structure 5031, 5033 Straight Waveguide 5032 Grating Structure 5034 V-shaped Metal Grating Structure 504 Sample Well 6 Optical Output Structure Array 601 Optical coupling structure 7, 9; external optical fiber 8, 10Straight waveguide 1' Molecular fluorescence detection chip 101' Fluorescence excitation layer 1011' Input optical coupling module 1011a' Edge coupler 1011b' Grating coupler 1012' Optical feedback structure 1012a' First 1×2 optical beamsplitter 1012b' Second 1×2 optical beamsplitter 1012c' First feedback optical coupling unit 1012d' Second feedback optical coupling unit 1012e' Third feedback optical coupler 1013' Optical beamsplitter tree structure 1014' Fluorescence excitation structure array 1015' Optical output structure array 1016' Optical power equalization module 102' Fluorescence collection layer 103' Fluorescence detection layer 104' Substrate 2' Fiber optic module 201' Substrate 2011' V-groove 202' Cover plate 203' Fiber optic cable 204' Input channel group 205' First optical feedback channel 206' Second optical feedback channel 207' Glass waveguide device 208', reflective film 3', optical coupling adhesive Detailed Implementation

[0093] 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.

[0094] It should be emphasized that the term "including / comprises" as used herein refers to the presence of a feature, whole, step, or component, but does not exclude the presence or addition of one or more other features, wholes, steps, or components.

[0095] Features described and / or illustrated for one embodiment may be used in the same or similar manner in one or more other embodiments, combined with features in other embodiments, or substituted for features in other embodiments.

[0096] In the detailed description of embodiments of the present invention, for ease of explanation, the schematic diagrams illustrating the device structure may be partially enlarged without adhering to the general scale, and the schematic diagrams are merely examples and should not limit the scope of protection of the present invention. Furthermore, in actual manufacturing, the three-dimensional spatial dimensions of length, width, and depth should be included.

[0097] For ease of description, spatial relation terms such as “below,” “under,” “lower than,” “below,” “above,” and “upper” may be used herein to describe the relationship between one element or feature shown in the accompanying drawings and other elements or features. It will be understood that these spatial relation terms are intended to include directions other than those depicted in the drawings for devices in use or operation. Furthermore, when a layer is referred to as being “between” two layers, it may be the only layer between the two layers, or there may be one or more layers in between.

[0098] In the context of this application, the structure described above the first feature may include embodiments in which the first and second features are in direct contact, or embodiments in which additional features are formed between the first and second features, such that the first and second features may not be in direct contact.

[0099] 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 illustrations 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.

[0100] Example 1

[0101] Please refer to Figure 1, which shows a schematic diagram of the integrated platform for exciting molecular fluorescence signals according to the present invention, including an input light coupling structure 1, a first filter structure 2, a light beam splitting tree structure 3, a filter structure array 4, a fluorescence excitation structure array 5, and a light coupling output structure array 6 arranged sequentially.

[0102] Specifically, the integrated platform for exciting molecular fluorescence signals of the present invention exists in the form of a chip, and the input optical coupling structure 1 is used to couple the laser emitted by the external laser into the chip.

[0103] As an example, the input optical coupling structure 1 adopts a waveguide grating coupler or an edge coupler, and the 3dB linewidth of the input optical coupling structure is greater than 10nm.

[0104] As an example, please refer to Figure 2, which shows a schematic diagram of the edge coupler 101 used in the input optical coupling structure 1 in one embodiment. The edge coupler 101 adopts an inverted conical waveguide structure, the tip of which is located at the edge of the chip, the off-chip optical fiber 7 is aligned with the tip of the inverted conical waveguide structure, and the extended end of the inverted conical waveguide structure is connected to a straight waveguide 8.

[0105] As an example, please refer to Figure 3, which shows a schematic diagram of the grating coupler 102 used in the input optical coupling structure 1 in another embodiment, wherein an off-chip optical fiber 9 is aligned with the grating coupler 102 approximately perpendicular to the chip surface, and the tail end of the grating coupler 102 is connected to a straight waveguide 10.

[0106] Specifically, the input end of the first filter structure 2 is connected to the output end of the input optical coupling structure 1, which is used to allow incident laser of a certain wavelength to pass through and block the spontaneous emission background fluorescence of the laser. In other words, the first filter structure 2 can filter out the component of the laser in the fluorescence band.

[0107] As an example, the operating light source wavelength range of the first filter structure 2 is 400nm to 800nm.

[0108] As an example, the first filtering structure 2 can be one of a micro-ring filter, a waveguide grating filter, and a cascaded directional coupler structure filter. The micro-ring filter can be implemented as a single micro-ring structure or a multi-micro-ring cascade method, and the waveguide grating filter can be a waveguide distributed Bragg mirror.

[0109] As an example, please refer to Figure 4, which shows a schematic diagram of the micro-ring filter used in the first filtering structure 2 in one embodiment. It includes a waveguide 201 and a first micro-ring 202 and a second micro-ring 203 coupled to the waveguide 201. The desired filtering effect can be achieved by optimizing parameters such as the micro-ring radius, waveguide width, and spacing between the waveguide and the micro-ring.

[0110] As an example, please refer to Figures 5 and 6. Figure 5 shows a top view of a waveguide distributed Bragg reflector used in the first filter structure 2 in one embodiment, and Figure 6 shows a side view of the structure shown in Figure 5. The waveguide distributed Bragg reflector includes a straight waveguide 211 and a trench array 212. The trench array 212 includes multiple rectangular trenches 213 arranged sequentially and at equal intervals along the length direction of the straight waveguide 211. The length direction of the rectangular trenches 213 is perpendicular to the length direction of the straight waveguide 211, and the length of the rectangular trenches 213 is equal to the width of the straight waveguide 211. The rectangular trenches 213 open from the upper surface of the straight waveguide 211, and the depth of the rectangular trenches is less than the thickness of the straight waveguide 211. The rectangular trenches may be selectively filled with a dielectric material, and the refractive index of the dielectric material is different from that of the straight waveguide 211.

[0111] As an example, the trench array 212 can be formed on the surface of the straight waveguide 211 by a shallow etching process, and the morphology after etching is an alternating rectangle, thereby achieving a periodic change in refractive index difference.

[0112] As an example, please refer to Figures 7 and 8. Figure 7 shows a top view of another waveguide distributed Bragg reflector used in the first filter structure 2 in one embodiment, and Figure 8 shows a side view of the structure shown in Figure 7. The waveguide distributed Bragg reflector includes a straight waveguide 221 and a trench array 222. The trench array 222 includes a plurality of trench groups arranged sequentially and at equal intervals along the length direction of the straight waveguide 221. The trench group includes a first trench and a second trench spaced apart in the width direction of the straight waveguide 221. The first trench and the second trench both open from the upper surface of the straight waveguide 221, and the depth of the first trench and the second trench is less than the thickness of the straight waveguide. The opposite ends of the first trench and the second trench respectively penetrate the side surface of the straight waveguide 221. The first trench and the second trench can be selectively filled with a dielectric material 3, and the refractive index of the dielectric material 3 is different from the refractive index of the straight waveguide 221.

[0113] As an example, the trench array 222 can be formed on the surface of the straight waveguide by a shallow etching process, and the morphology after etching is fishbone-shaped, which can also achieve periodic changes in refractive index difference.

[0114] As an example, please refer to Figures 9 and 10. Figure 9 shows a top view of another waveguide distributed Bragg reflector used in the first filter structure 2 in one embodiment, and Figure 10 shows a side view of the structure shown in Figure 9. The waveguide distributed Bragg reflector includes a straight waveguide 231 and an island structure array 232. The island structure array 232 includes a plurality of island structure groups arranged sequentially and at equal intervals along the length direction of the straight waveguide 231. The island structure group includes a first island structure and a second island structure spaced apart in the width direction of the straight waveguide 231. The first island structure and the second island structure are distributed on opposite sides of the straight waveguide 231 and are symmetrical about the straight waveguide 231. The thickness of the first island structure and the second island structure is equal to the thickness of the straight waveguide 231.

[0115] As an example, the island-shaped structure array 232 can be formed on both sides of the straight waveguide 231 by a full etching process to achieve periodic changes in refractive index difference.

[0116] As an example, please refer to Figures 11 and 12. Figure 11 shows a top view of another waveguide distributed Bragg reflector used in the first filter structure 2 in one embodiment, and Figure 12 shows a side view of the structure shown in Figure 11. The waveguide distributed Bragg reflector includes a waveguide body 241 and a side wing array 242. The waveguide body 241 includes a first straight waveguide 2411, a second straight waveguide 2412, and a third straight waveguide 2413 connected sequentially along a specified direction. The widths of the first straight waveguide 2411 and the third straight waveguide 2413 are the same and greater than the width of the second straight waveguide 2412. The side wing array 242 includes a first side wing and a second side wing arranged along the width direction of the second straight waveguide 2411. The first side wing and the second side wing are connected to opposite sides of the second straight waveguide 2412 and are symmetrically arranged about the axis 2412 of the second straight waveguide. The thicknesses of the first side wing and the second side wing are both equal to the thickness of the second straight waveguide 2412.

[0117] As an example, the side wing array 242 can be formed on both sides of the second straight waveguide 2412 by a full etching process. After etching, the morphology is fishbone-shaped, realizing the periodic change of refractive index difference. The ends of the first side wing and the second side wing can protrude relatively from the sides of the first straight waveguide 2411 and the third straight waveguide 2413.

[0118] As an example, please refer to Figure 13, which shows a schematic diagram of a cascaded directional coupler structure filter used in the first filter structure 2 in one embodiment. It includes a cascaded first directional coupler 251 and a second directional coupler 252. The desired filtering effect can be achieved by designing the coupling length, coupling spacing and other parameters of the first directional coupler 251 and the second directional coupler 252.

[0119] Specifically, the input end of the optical beam splitting tree structure 3 is connected to the output end of the first filter structure 2, which is used to split one input light into multiple output lights and form multiple output ends, so that the input light is split into more branches, so as to expand the fluorescence excitation sites in the future.

[0120] As an example, the optical beam splitting tree structure 3 splits one input light into multiple output lights according to the same splitting ratio.

[0121] As an example, the optical beam splitting tree structure 3 includes one or more optical beam splitter units 301, which include one or more of the following: Y-branch structure, 2×2 directional coupler, 1×2 multimode interference coupler, 2×2 multimode interference coupler, 1×3 multimode interference coupler, and 1×5 multimode interference coupler.

[0122] As examples, please refer to Figures 14 to 20, which show various example structures of the optical beam splitter unit. Figure 14 shows a schematic diagram of a Y-branch structure, Figure 15 shows a schematic diagram of a 1×2 multimode interference coupler, Figure 16 shows a schematic diagram of a 2×2 multimode interference coupler, Figure 17 shows a schematic diagram of a 2×2 directional coupler, Figure 18 shows a schematic diagram of a 1×5 multimode interference coupler, Figure 19 shows a schematic diagram of a 1×3 multimode interference coupler, and Figure 20 shows a schematic diagram of a 1×N optical beam splitter unit.

[0123] Specifically, the filter structure array 4 includes multiple second filter structures 401, and the input ends of the multiple second filter structures 401 are connected one-to-one with the multiple output ends of the optical beam splitting tree structure 3, so as to allow incident laser of a certain wavelength to pass through and block the spontaneous emission background fluorescence of the waveguide material.

[0124] As an example, the operating light source wavelength range of the second filter structure 401 is 400nm to 800nm.

[0125] As an example, the second filtering structure 401 can be a waveguide grating filter or a cascaded directional coupler structure. The waveguide grating filter can be a waveguide distributed Bragg mirror, such as the waveguide distributed Bragg mirror structure shown in Figures 5 and 6, 7 and 8, 9 and 10, or Figures 11 and 12, or other suitable structures. The cascaded directional coupler structure can be the structure shown in Figure 13 or other suitable structures.

[0126] Specifically, the fluorescence excitation structure array 5 includes multiple fluorescence excitation structures 501, and the input ends of the multiple fluorescence excitation structures 501 are connected one-to-one with the output ends of the multiple second filter structures 401, which are used to confine the physical space of fluorescent molecules and excite fluorescent molecules to generate fluorescence radiation.

[0127] Specifically, the fluorescence excitation structure 501 excites fluorescence through a waveguide evanescent wave field.

[0128] As an example, please refer to Figures 21, 22, and 23, which show schematic diagrams of the fluorescence excitation structure array 5 in one embodiment. Figure 21 is a side view, Figure 22 is a top view (cladding omitted), and Figure 23 is another side view. The fluorescence excitation structure array 5 includes a cladding 502 and a waveguide structure 503 encased in the cladding 502. Sample wells 504 are arranged periodically along the waveguide propagation direction on the surface of the cladding 502 above the waveguide structure 503. The sample wells 504 are used to load molecules that can excite fluorescence. The distance between the bottom surface of the sample well 504 and the top surface of the waveguide structure 503 is less than the waveguide evanescent wave penetration distance.

[0129] As an example, the waveguide structure 503 is a straight waveguide, and the sample well 504 is located directly above the straight waveguide.

[0130] As an example, the sample well 504 can be in the form of a cylinder, a frustum, a cuboid, or other suitable shape, and the size of the sample well 504 (e.g., diameter, side length, etc.) can be on the order of tens to hundreds of nanometers.

[0131] As an example, fluorescent molecules are fixed to the bottom of the sample well 504 by a chemical surface modification method, thereby being excited by the waveguide evanescent wave light field and generating a fluorescent signal.

[0132] As an example, please refer to Figures 24 and 25, which show a schematic diagram of the structure of the fluorescence excitation structure array 5 in another embodiment. Figure 24 is a side view and Figure 25 is a top view (cladding omitted). The waveguide structure 503 includes a straight waveguide 5031 and a plurality of grating structures 5032 located on one side of the straight waveguide 5031 and connected to the straight waveguide 5031. The sample well 504 is located directly above the grating structures 5032.

[0133] As an example, please refer to Figures 26 and 27, which show a schematic diagram of the structure of the fluorescence excitation structure array 5 in another embodiment, wherein Figure 26 is a side view and Figure 27 is a top view (cladding omitted). The waveguide structure 503 includes a straight waveguide 5033 and a V-shaped metal grating structure 5034 located on the straight waveguide 5033, and the sample well 504 is located directly above the V-shaped metal grating structure 5034.

[0134] Specifically, the optical coupling structure array 6 includes multiple optical coupling structures 601, with the input ends of the multiple optical coupling structures 601 connected one-to-one with the output ends of the multiple fluorescent excitation structures 501, for coupling out the remaining excitation light after passing through the fluorescent excitation structure array 5, and preventing echo reflection.

[0135] As an example, the optical output structure 601 employs a grating coupler, and the 3dB linewidth of the optical output structure 601 is greater than 10nm.

[0136] As shown above, the integrated platform for exciting molecular fluorescence signals of the present invention includes an input optical coupling structure, a first filtering structure, an optical beam splitting tree structure, a filtering structure array, a fluorescence excitation structure array, and an optical coupling structure array arranged sequentially, providing an integrated fluorescence excitation scheme for the detection of fluorescence signals in biological samples. Compared with traditional excitation schemes, the present invention introduces an on-chip filter, which can reduce the broadband background light composed of spontaneous emission fluorescence from lasers or waveguides, thereby reducing shot noise and improving the signal-to-noise ratio and signal-to-background ratio.

[0137] Example 2

[0138] Please refer to Figure 28, which shows a structural block diagram of the molecular fluorescence detection chip 1' of the present invention, including a fluorescence detection layer 103', a fluorescence collection layer 102' and a fluorescence excitation layer 101' arranged sequentially from bottom to top, wherein the fluorescence detection layer 103' can be grown on a substrate 104'.

[0139] Specifically, the fluorescence excitation layer 101' is used to excite fluorescence signals, the fluorescence collection layer 102' is used to collect fluorescence signals, and the fluorescence detection layer 103' is used to detect fluorescence signals. The fluorescence collection layer 102' may include a fluorescence filter layer, an aperture layer, and a microlens array layer (the specific layout of each component can be set according to actual needs, and no specific limitation is made in this invention). The fluorescence detection layer 103' may be one or more of the following: a CCD chip, a CMOS image sensor chip, a PD array, a SPAD array, a PMT array, and a SiPM array.

[0140] Specifically, please refer to Figure 29, which shows a planar layout of the fluorescence excitation layer 101', including an input optical coupling module 1011', an optical beam splitter tree structure 1013', a fluorescence excitation structure array 1014', an optical output structure array 1015', and an optical feedback structure 1012'.

[0141] Specifically, the input end of the optical beam splitter tree structure 1013' is connected to the output end of the input optical coupling module 1011'. It should be noted that the input optical coupling module 1011' may include one or more input optical coupling units, meaning the molecular fluorescence detection chip 1' can be a single-channel chip or a multi-channel chip. In the embodiment shown in Figure 29, the number of input optical coupling units in the input optical coupling module 1011' is taken as multiple (e.g., four). To achieve multi-channel power equalization, an optical power equalization module 1016' can be optionally provided in the fluorescence excitation layer 101', and the optical power equalization module 1016' is connected between the input optical coupling module 1011' and the optical beam splitter tree structure 1013'.

[0142] As an example, the optical power equalization module 1016' includes an N×N optical beam combining structure, which is used to combine the power of multiple input beams and then split them, thereby achieving N-channel power equalization. Here, N is the same as the number of input optical coupling units of the input optical coupling module 1011'. The N×N optical beam combining structure includes a 2×2 optical coupler, or includes multiple cascaded 2×2 optical couplers. The 2×2 optical coupler can be a directional coupler (DC) or a multimode interferometer coupler (MMI).

[0143] Specifically, the optical beam splitter tree structure 1013' includes multiple output terminals, one of which serves as the first output terminal and the other multiple output terminals serve as the second output terminals. The input terminal of the fluorescence excitation structure array 1014' is connected to the second output terminal of the optical beam splitter tree structure 1013', the input terminal of the optical coupling structure array 1015' is connected to the output terminal of the fluorescence excitation structure array 1014', and the input terminal of the optical feedback structure 1012' is connected to the first output terminal of the optical beam splitter tree structure 1013'.

[0144] The following details the function and structure of each module in the fluorescence excitation layer 101', in conjunction with the optical packaging structure of the molecular fluorescence detection chip 1'.

[0145] As an example, please refer to Figure 30, which shows a side view of the optical packaging structure in one embodiment, including the molecular fluorescence detection chip 1' and the optical fiber module 2'. The optical fiber module 2' is fixed at a preset position of the molecular fluorescence detection chip 1' and includes one or more optical input channels. The optical input channels are aligned with the input optical coupling unit. The main function of the optical feedback structure 1012' in the molecular fluorescence detection chip 1' is to provide feedback light when the molecular fluorescence detection chip 1' and the optical fiber module 2' are coupled, so as to optimize alignment. In addition, the optical feedback structure 1012' can also be used for chip insertion loss calibration.

[0146] In some embodiments, such as as shown in FIG30, the optical fiber module 2' is bonded and fixed to the preset position of the molecular fluorescence detection chip 1' by optical coupling adhesive 3'. In other embodiments, the optical fiber module 2' can also be fixed to the preset position of the molecular fluorescence detection chip 1 by bonding.

[0147] Specifically, the passive optical coupling scheme adopted by the optical packaging structure enables the optical coupling efficiency to remain unchanged by environmental mechanical vibration, which is beneficial to improving the stability of on-chip excitation light and thus to stabilizing the fluorescence signal. It also reduces the complexity of the optical path of external devices, which helps to save equipment costs.

[0148] Specifically, when there is one input optical coupling unit, the optical fiber module 2' includes one optical input channel. When there are multiple input optical coupling units, the optical fiber module 2' also includes multiple optical input channels. In this case, the multiple input optical coupling units form an array with a fixed spacing perpendicular to the light propagation direction. The spacing between the input channels of the optical fiber module 2' is the same as the spacing between the input optical coupling unit array.

[0149] In some embodiments, the fiber optic module 2' preferably employs multiple optical input channels to increase the number of lasers by coupling multiple channels, thereby increasing the on-chip excitation power and thus improving the signal-to-noise ratio.

[0150] Specifically, when the optical feedback structure 1012' adopts an optical fiber module feedback scheme (which will be described in detail in subsequent sections), the optical fiber module 2' further includes a first optical feedback channel and a second optical feedback channel.

[0151] Specifically, each optical input channel is aligned with a corresponding input optical coupling unit, and each optical feedback channel is aligned with a corresponding feedback optical coupling unit.

[0152] Specifically, the function of the optical fiber module 2' is to fix the bare optical fiber so that it can be connected to the chip, thereby coupling the input light into the chip or receiving the feedback light from the chip. Please refer to Figure 31, which shows a partial cross-sectional structural diagram of the optical fiber module 2' in one embodiment, including a substrate 201', a cover plate 202' and one or more optical fibers 203'. One side of the substrate 201' is provided with a single V-groove 2011' or multiple V-groos 2011' arranged side by side and spaced apart. The optical fiber 203' is located in the V-groove 2011'. The cover plate 202' is arranged opposite to the substrate 201' to cover the V-groove 2011'.

[0153] Specifically, the optical fiber module 2' includes one or more input optical fibers (corresponding to one or more optical input channels), and optionally includes two feedback optical fibers (corresponding to the first optical feedback channel and the second optical feedback channel, respectively), wherein the input optical fiber and the feedback optical fiber are respectively housed in the corresponding V-groove 2011'.

[0154] Specifically, in the input optical coupling module 1011', the input optical coupling unit can take various forms. As an example, please refer to Figures 32 and 33, which show a schematic diagram in one embodiment where the input optical coupling unit adopts an edge coupler 1011a' and is fixedly connected to the optical fiber module 2' by optical coupling adhesive 3'. Figure 32 is a top view and Figure 33 is a side view. The initial direction of the pigtail of the optical fiber module 2' is parallel to the plane where the molecular fluorescence detection chip 1' is located. The optical fiber module 2' is fixed to the side of the molecular fluorescence detection chip 1' and the optical input channel of the optical fiber module 2' is aligned with the waveguide core of the edge coupler 1011a'.

[0155] As an example, please refer to Figure 34, which shows a schematic diagram of an input optical coupling unit using a grating coupler 1011b' in another embodiment, and the optical fiber module 2' further including a glass waveguide device 207'. In this embodiment, the first end face of the glass waveguide device 207' is fixedly connected to the side of the substrate and the cover plate, and the waveguide core of the glass waveguide device 207' is aligned with the optical fiber in the V-groove. The initial direction of the pigtail of the optical fiber module 2' and the extension direction of the waveguide core of the glass waveguide device 207' are parallel to the plane where the molecular fluorescence detection chip 1' is located. The glass waveguide device 207' is fixed above the grating coupler 1011b', and the second end face of the glass waveguide device 207' is inclined to serve as a reflective surface to reflect the light entering the glass waveguide device 207' back to the grating coupler 1011b'.

[0156] Specifically, the glass waveguide device 207' is a type of planar optical waveguide device (PLC device). In this embodiment, the first end face of the glass waveguide device 207' is fixedly connected to the side of the substrate and the cover plate by optical coupling adhesive 3', and the bottom face of the glass waveguide device 207' is fixed above the grating coupler 1011b' by optical coupling adhesive 3'.

[0157] As an example, the angle between the second end face of the glass waveguide device 207' and the bottom face of the glass waveguide device 207' is in the range of 35° to 50°.

[0158] In some embodiments, the second end face of the glass waveguide device 207' may be provided with a reflective film 208', such as a metal coating, to increase reflectivity.

[0159] As an example, please refer to Figure 35, which shows a schematic diagram of an input optical coupling unit in another embodiment using a grating coupler 1011b' and fixedly connected to the optical fiber module 2' by optical coupling adhesive 3'. In this case, the initial direction of the pigtail of the optical fiber module 2' is not parallel to (for example, nearly perpendicular to) the plane where the molecular fluorescence detection chip is located. The optical fiber module 2' is fixed to the upper surface of the molecular fluorescence detection chip 1' and the optical input channel of the optical fiber module 2' is aligned with the grating coupler 1011b'. The end face polishing angle of the optical fiber module 2' is consistent with the emission angle of the grating coupler 1011b'.

[0160] Specifically, the function of the optical beam splitter tree structure 1013' is to split a single beam into multiple branches to facilitate the subsequent expansion of fluorescence excitation sites.

[0161] As an example, the optical beam splitter tree structure 1013' includes one or more optical beam splitter units, such as the four 1×N optical beam splitter units shown in Figure 29. The beam splitting characteristic of the 1×N optical beam splitter unit is that it splits one input light into N output beams, each beam having the same splitting ratio.

[0162] As an example, the optical beam splitter unit may be selected from one of the following: a Y-branch structure (refer to Figure 14 above), a 2×2 directional coupler (refer to Figure 17 above), a 1×2 multimode interference coupler (refer to Figure 15 above), a 2×2 multimode interference coupler (refer to Figure 16 above), a 1×3 multimode interference coupler (refer to Figure 19 above), and a 1×5 multimode interference coupler (refer to Figure 18 above), or a combination of several of these (1×N optical beam splitter unit, refer to Figure 20 above).

[0163] Specifically, the function of the fluorescence excitation structure array 1014' is to excite the fluorescent molecules by physically confining them and designing the evanescent wave mode field, thereby generating fluorescence radiation.

[0164] As an example, referring to Figures 21, 22 and 23 above, similar to the fluorescence excitation structure array 5 in one embodiment, the fluorescence excitation structure array 1014' includes a cladding and one or more waveguide structures cladding the cladding. The cladding surface above the waveguide structure is provided with sample wells arranged at a certain period along the waveguide propagation direction. The sample wells are used to load molecular substances that can excite fluorescence. The distance between the bottom surface of the sample well and the top surface of the waveguide structure is less than the waveguide evanescent wave penetration distance.

[0165] As an example, the waveguide structure is a straight waveguide, and the sample well is located directly above the straight waveguide.

[0166] As an example, the sample well can be in the form of a cylinder, frustum, cuboid or other suitable shape, and the size of the sample well (e.g., diameter, side length, etc.) can be on the order of tens to hundreds of nanometers.

[0167] As an example, fluorescent molecules are fixed to the bottom of the sample well by a chemical surface modification method, thereby being excited by the waveguide evanescent wave light field and generating a fluorescent signal.

[0168] As an example, referring to Figures 24 and 25 above, similar to the fluorescence excitation structure array 5 in another embodiment, the waveguide structure of the fluorescence excitation structure array 1014' includes a straight waveguide and a plurality of grating structures located on one side of the straight waveguide and connected to the straight waveguide, and the sample well is located directly above the grating structures.

[0169] As an example, referring to Figures 26 and 27 above, similar to the fluorescence excitation structure array 5 in another embodiment, the waveguide structure of the fluorescence excitation structure array 1014' includes a straight waveguide and a V-shaped metal grating structure located on the straight waveguide, and the sample well is located directly above the V-shaped metal grating structure.

[0170] Specifically, the function of the optical coupling structure array 1015' is to couple out the remaining excitation light after it has passed through the fluorescent excitation structure array 1014' from inside the chip. This prevents the light from being reflected inside the chip, thereby forming a standing wave distribution in the fluorescent excitation structure array 1014' and causing uneven distribution of the excitation light field.

[0171] As an example, the optical output structure array 1015' includes a plurality of optical output units, each of which is connected to one output terminal of the fluorescence excitation structure array 1014'.

[0172] As an example, the optical output unit uses a grating coupler with a 3dB linewidth greater than 10nm.

[0173] Specifically, as mentioned above, a key function of the optical feedback structure 1012' is to provide feedback light when the molecular fluorescence detection chip 1' is coupled to the optical fiber module 2', in order to optimize alignment.

[0174] In some embodiments, the optical feedback structure 1012' adopts an optical fiber module optical feedback scheme, including a 1×2 optical beamsplitter, a first feedback optical coupling unit, and a second feedback optical coupling unit. The first and second feedback optical coupling units achieve optical feedback by coupling feedback light into the optical feedback channel of the optical fiber module 2'. The input optical coupling module 1011' is located between the first and second feedback optical coupling units. The first, input, and second feedback optical coupling units are arranged in a straight line at equal intervals perpendicular to the light propagation direction. The input end of the 1×2 optical beamsplitter is connected to one output of the beamsplitter's tree-like structure. The first feedback optical coupling unit has its input terminal connected to the first output terminal of the 1×2 optical beam splitter, and its input terminal is connected to the second output terminal of the 1×2 optical beam splitter. The output terminals of the first feedback optical coupling unit, the input terminal of the input optical coupling unit, and the output terminal of the second feedback optical coupling unit are all used to connect to the optical fiber module. The optical fiber module includes a first optical feedback channel, an optical input channel, and a second optical feedback channel arranged side-by-side. The output terminal of the first feedback optical coupling unit is connected to the first optical feedback channel, the input terminal of the input optical coupling unit is connected to the optical input channel, and the output terminal of the second feedback optical coupling unit is connected to the second optical feedback channel.

[0175] As an example, the emission angle range of the first feedback optical coupling unit and the second feedback optical coupling unit is 8 to 10 degrees, and the near-field spot diameter range is 3 to 5 micrometers.

[0176] In other embodiments, the optical feedback structure 1012' adopts a spatial optical feedback scheme, including a feedback optical coupling unit. The input end of the feedback optical coupling unit is connected to one output end of the optical beam splitter tree structure, and the output end of the feedback optical coupling unit is connected to an off-chip optical system. The emitted light spot is collected by the off-chip optical system in free space.

[0177] As an example, the emission angle of the feedback optical coupling unit is in the range of 30 to 60 degrees, the near-field spot diameter is in the range of 30 to 60 micrometers, and the emitted spot is collected in free space by the off-chip optical system.

[0178] In some other embodiments, the optical feedback structure 1012' can reuse the two optical feedback schemes described above. During use, one or both can be selected as needed. For example, when the molecular fluorescence detection chip 1' has a large number of channels, an optical fiber module optical feedback scheme is preferred, and a spatial optical feedback scheme can be used as an auxiliary. Conversely, when the molecular fluorescence detection chip 1' has a small number of channels, such as when the molecular fluorescence detection chip 1' uses a single or dual channel, only the spatial optical feedback scheme can be used.

[0179] As an example, in the embodiment shown in Figure 30, the optical feedback structure 1012' includes both of the above-mentioned optical feedback schemes, including a first 1×2 optical beamsplitter 1012a', a second 1×2 optical beamsplitter 1012b', a first feedback optical coupling unit 1012c', a second feedback optical coupling unit 1012d', and a third feedback optical coupler 1012e'. The input optical coupling module 1011' is located between the first feedback optical coupling unit 1012c' and the second feedback optical coupling unit 1012d'. Between the first feedback optical coupling unit 1012c', the input optical coupling unit, and the second feedback optical coupling unit 1012d', the first feedback optical coupling unit 1012c', the input optical coupling unit, and the second feedback optical coupling unit 1012d' are arranged in a straight line at equal intervals perpendicular to the light propagation direction. The input end of the first 1×2 optical beamsplitter 1012a' is connected to the first output end of the optical beamsplitter tree structure 1013', and the input end of the second 1×2 optical beamsplitter 1012b' is connected to the first output end of the first 1×2 optical beamsplitter 1012a'. The first feedback optical coupling unit 1012c', the first feedback optical coupling unit 1012d', and the second feedback optical coupling unit 1012d' are arranged in a straight line at equal intervals perpendicular to the light propagation direction. The input terminal of 12c' is connected to the first output terminal of the second 1×2 optical beam splitter 1012b', the input terminal of the second feedback optical coupling unit 1012d' is connected to the second output terminal of the second 1×2 optical beam splitter 1012d', and the input terminal of the third feedback optical coupling unit 1012e' is connected to the second output terminal of the first 1×2 optical beam splitter 1012a'. The output terminals of the first feedback optical coupling unit 1012c', the input terminal of the input optical coupling unit, and the output terminal of the second feedback optical coupling unit 1012d' are all used to connect to an optical fiber module. The optical fiber module includes a first optical feedback channel, an optical input channel, and a second optical feedback channel arranged side by side. The output terminal of the first feedback optical coupling unit 1012c' is connected to the first optical feedback channel, the input terminal of the input optical coupling unit is connected to the optical input channel, the output terminal of the second feedback optical coupling unit 1012d' is connected to the second optical feedback channel, and the output terminal of the third feedback optical coupling unit 1012e' is connected to an off-chip optical system.

[0180] As an example, please refer to Figure 36, which shows a cross-sectional structural diagram of the optical fiber module 2' in one embodiment, including an input channel group 204' (taking four input channels as an example) and a first optical feedback channel 205' and a second optical feedback channel 206' distributed on both sides of the input channel group 204'.

[0181] As an example, during the packaging process, the optical fiber module 2' is clamped and fixed on the displacement stage (e.g., a 6-axis displacement stage) by a fixture, and the molecular fluorescence detection chip 1' is fixed on the platform. With the assistance of a camera, the alignment position is initially determined. After the light feedback structure 1012' emits light, the optical fiber module 2' is aligned with the molecular fluorescence detection chip 1' by adjusting the displacement stage, and then coupled using UV glue or bonding after alignment.

[0182] Specifically, for the optical feedback scheme of the optical fiber module, the optical feedback channel of the optical fiber module 2' is connected to the photodiode (PD). By adjusting the displacement stage, the optical fiber module 2' is displaced so that the readings of the photodiodes on both sides reach the optimal at the same time. At this time, it is indicated that the optical fiber module 2' has reached the optimal position and is aligned with the molecular fluorescence detection chip 1'.

[0183] Specifically, for the spatial light feedback scheme, the displacement stage is adjusted to make the fiber optic module 2' move, so that the reading of the photodiode of the off-chip optical system is maximized. At this time, it means that the fiber optic module 2' has reached the optimal position and is aligned with the molecular fluorescence detection chip 1'.

[0184] As an example, the emission angle range of the first feedback optical coupling unit 1012c' and the second feedback optical coupling unit 1012d' is 8 to 10 degrees, and the near-field spot diameter range is 3 to 5 micrometers. The smaller emission angle facilitates coupling with the optical fiber module 2'.

[0185] As an example, the emission angle of the third feedback optical coupling unit is in the range of 30 to 60 degrees, and the near-field spot diameter is in the range of 30 to 60 micrometers. A larger emission angle facilitates spatial optical feedback, and oblique emission helps to avoid obstacles.

[0186] Specifically, in addition to assisting alignment during optical encapsulation, the optical feedback structure 1012' can also provide the following functions during the usage phase:

[0187] (1) Chip polarization state calibration;

[0188] (2) Monitor the on-chip optical power and check whether the initial optical power is abnormal. For example, check whether the chip is damaged during storage and transportation (which is often not easily detected by the naked eye), resulting in a decrease in on-chip optical intensity, or whether an accident occurs during use, resulting in a decrease in on-chip optical intensity.

[0189] As described above, the molecular fluorescence detection chip of the present invention includes a fluorescence detection layer, a fluorescence collection layer, and a fluorescence excitation layer arranged sequentially from bottom to top. The fluorescence excitation layer includes an input optical coupling module, a beam splitter tree structure, a fluorescence excitation structure array, an optical output structure array, and an optical feedback structure. The input optical coupling module includes one or more input optical coupling units, and the input end of the optical feedback structure is connected to one output end of the beam splitter tree structure. The optical packaging structure of the present invention includes an optical fiber module and the aforementioned molecular fluorescence detection chip. The optical fiber module is fixed at a preset position on the molecular fluorescence detection chip and includes one or more optical input channels. The optical input channels are aligned with the input optical coupling units. This passive optical coupling scheme ensures that the optical coupling efficiency does not change with environmental mechanical vibration, thereby improving the stability of the on-chip excitation light and thus being more conducive to the stability of the fluorescence signal. It also reduces the complexity of the optical path of external devices and saves equipment costs. In addition, the present invention can use a multi-channel coupling method to increase the number of lasers, thereby increasing the on-chip excitation light power and improving the signal-to-noise ratio.

[0190] In summary, the integrated platform for exciting molecular fluorescence signals of the present invention comprises, in sequence, an input optical coupling structure, a first filtering structure, an optical beam splitter tree structure, a filtering structure array, a fluorescence excitation structure array, and an optical coupling output structure array, providing an integrated fluorescence excitation scheme for the detection of fluorescence signals in biological samples. Compared with traditional excitation schemes, the present invention introduces an on-chip filter, which can reduce the broadband background light composed of spontaneous emission fluorescence from lasers or waveguides, thereby reducing shot noise and improving the signal-to-noise ratio and signal-to-background ratio. The molecular fluorescence detection chip of the present invention comprises, from bottom to top, a fluorescence detection layer, a fluorescence collection layer, and a fluorescence excitation layer. The fluorescence excitation layer includes an input optical coupling module, an optical beam splitter tree structure, a fluorescence excitation structure array, an optical coupling output structure array, and an optical feedback structure. The input optical coupling module includes one or more input optical coupling units, and the input end of the optical feedback structure is connected to one output end of the optical beam splitter tree structure. The optical packaging structure of this invention includes an optical fiber module and the aforementioned molecular fluorescence detection chip. The optical fiber module is fixed at a preset position on the molecular fluorescence detection chip and includes one or more optical input channels. These optical input channels are aligned with the input optical coupling unit. This passive optical coupling scheme ensures that the optical coupling efficiency remains unchanged regardless of environmental mechanical vibrations, thereby improving the stability of the on-chip excitation light and thus contributing to the stability of the fluorescence signal. It also reduces the complexity of the optical path of external devices, saving equipment costs. Furthermore, this invention can employ a multi-channel coupling method to increase the number of lasers, thereby increasing the on-chip excitation light power and improving the signal-to-noise ratio. Therefore, this invention effectively overcomes the various shortcomings of the prior art and has high industrial applicability.

[0191] 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. An integrated platform for exciting molecular fluorescence signals, characterized in that, include: An input optical coupling structure is used to couple laser light emitted from an external laser into the chip. A first filtering structure, wherein the input end of the first filtering structure is connected to the output end of the input optical coupling structure, is used to allow a certain wavelength of incident laser to pass through and block the spontaneous emission background fluorescence of the laser. A light beam splitting tree structure, wherein the input end of the light beam splitting tree structure is connected to the output end of the first filter structure, is used to split one input light into multiple output lights and form multiple output ends; The filter structure array includes multiple second filter structures, the input ends of which are connected one-to-one with the multiple output ends of the optical beam splitting tree structure, for allowing incident laser of a certain wavelength to pass through and blocking the spontaneous emission background fluorescence of the waveguide material. A fluorescence excitation structure array includes multiple fluorescence excitation structures, with the input ends of the multiple fluorescence excitation structures connected one-to-one with the output ends of the multiple second filter structures, for confining the physical space of fluorescent molecules and exciting fluorescent molecules to generate fluorescence radiation; An optical coupling structure array includes multiple optical coupling structures, with the input ends of the multiple optical coupling structures connected one-to-one with the output ends of the multiple fluorescent excitation structures, for coupling out the remaining excitation light after passing through the fluorescent excitation structure array.

2. The integrated platform for exciting molecular fluorescence signals according to claim 1, characterized in that: The input optical coupling structure includes a waveguide grating coupler or an edge coupler, and the 3dB linewidth of the input optical coupling structure is greater than 10nm.

3. The integrated platform for exciting molecular fluorescence signals according to claim 1, characterized in that: The first filtering structure includes one of a micro-ring filter, a waveguide grating filter, and a cascaded directional coupler structure filter, and the second filtering structure includes a waveguide grating filter or a cascaded directional coupler structure.

4. The integrated platform for exciting molecular fluorescence signals according to claim 3, characterized in that: The waveguide grating filter employs a waveguide distributed Bragg reflector, which includes a straight waveguide and a trench array. The trench array includes multiple rectangular trenches arranged sequentially and at equal intervals along the length direction of the straight waveguide. The length direction of each rectangular trench is perpendicular to the length direction of the straight waveguide, and the length of the rectangular trench is equal to the width of the straight waveguide. The rectangular trenches open from the upper surface of the straight waveguide, and the depth of the rectangular trenches is less than the thickness of the straight waveguide. The rectangular trenches are filled with a dielectric material, and the refractive index of the dielectric material is different from that of the straight waveguide.

5. The integrated platform for exciting molecular fluorescence signals according to claim 3, characterized in that: The waveguide grating filter employs a waveguide distributed Bragg reflector, which includes a straight waveguide and a trench array. The trench array includes multiple trench groups arranged sequentially and at equal intervals along the length of the straight waveguide. Each trench group includes a first trench and a second trench spaced apart along the width of the straight waveguide. Both the first trench and the second trench open from the upper surface of the straight waveguide, and the depth of both the first trench and the second trench is less than the thickness of the straight waveguide. The opposite ends of the first trench and the second trench penetrate the sidewall of the straight waveguide. Both the first trench and the second trench are filled with a dielectric material, and the refractive index of the dielectric material is different from that of the straight waveguide.

6. The integrated platform for exciting molecular fluorescence signals according to claim 3, characterized in that: The waveguide grating filter employs a waveguide distributed Bragg reflector, which includes a straight waveguide and an array of island structures. The array of island structures includes multiple island structure groups arranged sequentially and at equal intervals along the length of the straight waveguide. Each island structure group includes a first island structure and a second island structure spaced apart along the width of the straight waveguide. The first island structure and the second island structure are distributed on opposite sides of the straight waveguide and are symmetrical about the straight waveguide axis. The thickness of both the first island structure and the second island structure is equal to the thickness of the straight waveguide.

7. The integrated platform for exciting molecular fluorescence signals according to claim 3, characterized in that: The waveguide grating filter employs a waveguide distributed Bragg reflector, which includes a waveguide body and a side wing array. The waveguide body includes a first straight waveguide, a second straight waveguide, and a third straight waveguide connected sequentially along a specified direction. The widths of the first and third straight waveguides are the same and greater than the width of the second straight waveguide. The side wing array includes a first side wing and a second side wing arranged along the width direction of the second straight waveguide. The first and second side wings are connected to opposite sides of the second straight waveguide and are symmetrically arranged about the axis of the second straight waveguide. The thicknesses of the first and second side wings are both equal to the thickness of the second straight waveguide.

8. The integrated platform for exciting molecular fluorescence signals according to claim 1, characterized in that: The operating light source wavelength range of the first filter structure is 400nm to 800nm, and the operating light source wavelength range of the second filter structure is 400nm to 800nm.

9. The integrated platform for exciting molecular fluorescence signals according to claim 1, characterized in that: The optical beam splitting tree structure splits one input beam into multiple output beams with the same splitting ratio.

10. The integrated platform for exciting molecular fluorescence signals according to claim 1, characterized in that: The optical beam splitting tree structure includes one or more optical beam splitter units, which include one or more of the following: a Y-branch structure, a 2×2 directional coupler, a 1×2 multimode interference coupler, a 2×2 multimode interference coupler, a 1×3 multimode interference coupler, and a 1×5 multimode interference coupler.

11. The integrated platform for exciting molecular fluorescence signals according to claim 1, characterized in that: The fluorescence excitation structure includes a cladding and a waveguide structure encased in the cladding. The surface of the cladding above the waveguide structure is provided with sample wells arranged at a certain period along the waveguide propagation direction. The sample wells are used to load molecular substances that can excite fluorescence. The distance between the bottom surface of the sample well and the top surface of the waveguide structure is less than the evanescent wave penetration distance of the waveguide structure.

12. The integrated platform for exciting molecular fluorescence signals according to claim 11, characterized in that: The waveguide structure is a straight waveguide, and the sample well is located directly above the straight waveguide; or the waveguide structure includes a straight waveguide and a plurality of grating structures located on one side of the straight waveguide and connected to the straight waveguide, and the sample well is located directly above the grating structures; or the waveguide structure includes a straight waveguide and a V-shaped metal grating structure located on the straight waveguide, and the sample well is located directly above the V-shaped metal grating structure.

13. The integrated platform for exciting molecular fluorescence signals according to claim 1, characterized in that: The optical output structure employs a grating coupler, and the 3dB linewidth of the optical output structure is greater than 10nm.

14. A molecular fluorescence detection chip, characterized in that, It includes, from bottom to top, a fluorescence detection layer, a fluorescence collection layer, and a fluorescence excitation layer, wherein the fluorescence excitation layer includes: An input optical coupling module, wherein the input optical coupling module includes one or more input optical coupling units; An optical beam splitter tree structure, wherein the input end of the optical beam splitter tree structure is connected to the output end of the input optical coupling module, and the optical beam splitter tree structure includes one first output end and multiple second output ends; A fluorescent excitation structure array, wherein the input end of the fluorescent excitation structure array is connected to the second output end of the optical beam splitter tree structure; An optically coupled structure array, wherein the input end of the optically coupled structure array is connected to the output end of the fluorescent excitation structure array; An optical feedback structure, wherein the input end of the optical feedback structure is connected to the first output end of the optical beam splitter tree structure.

15. The molecular fluorescence detection chip according to claim 14, characterized in that: The input optical coupling module includes multiple input optical coupling units, and the fluorescence excitation layer further includes an optical power equalization module, which is connected between the input optical coupling module and the optical beam splitter tree structure.

16. The molecular fluorescence detection chip according to claim 15, characterized in that: The optical power equalization module includes an N×N optical beam combining structure, wherein N is the same as the number of input optical coupling units. The N×N optical beam combining structure includes a 2×2 optical coupler, or includes multiple cascaded 2×2 optical couplers. The 2×2 optical coupler is a directional coupler or a multimode interference coupler.

17. The molecular fluorescence detection chip according to claim 14, characterized in that: The optical feedback structure includes a 1×2 optical beamsplitter, a first feedback optical coupling unit, and a second feedback optical coupling unit. The input optical coupling module is located between the first feedback optical coupling unit and the second feedback optical coupling unit. The first feedback optical coupling unit, the input optical coupling unit, and the second feedback optical coupling unit are arranged in a straight line at equal intervals perpendicular to the light propagation direction. The input end of the 1×2 optical beamsplitter is connected to the first output end of the optical beamsplitter tree structure. The input end of the first feedback optical coupling unit is connected to the first output end of the 1×2 optical beamsplitter. The input end of the second feedback optical coupling unit is connected to the second output end of the 1×2 optical beamsplitter. The output end of the first feedback optical coupling unit, the input end of the input optical coupling unit, and the output end of the second feedback optical coupling unit are all used to connect to the optical fiber module. The optical fiber module includes a first optical feedback channel, an optical input channel, and a second optical feedback channel arranged side by side. The output end of the first feedback optical coupling unit is connected to the first optical feedback channel, the input end of the input optical coupling unit is connected to the optical input channel, and the output end of the second feedback optical coupling unit is connected to the second optical feedback channel.

18. The molecular fluorescence detection chip according to claim 17, characterized in that: The emission angle range of the first feedback optical coupling unit and the second feedback optical coupling unit is 8 to 10 degrees, and the near-field spot diameter range is 3 to 5 micrometers.

19. The molecular fluorescence detection chip according to claim 14, characterized in that: The optical feedback structure includes a feedback optical coupling unit. The input end of the feedback optical coupling unit is connected to the first output end of the optical beam splitter tree structure, and the output end of the feedback optical coupling unit is used to connect to an off-chip optical system.

20. The molecular fluorescence detection chip according to claim 19, characterized in that: The emission angle of the feedback optical coupling unit is in the range of 30 to 60 degrees, and the near-field spot diameter is in the range of 30 to 60 micrometers. The emitted spot is collected in free space by the off-chip optical system.

21. The molecular fluorescence detection chip according to claim 14, characterized in that: The optical feedback structure includes a first 1×2 optical beamsplitter, a second 1×2 optical beamsplitter, a first feedback optical coupling unit, a second feedback optical coupling unit, and a third feedback optical coupler. The input optical coupling module is located between the first feedback optical coupling unit and the second feedback optical coupling unit. The first feedback optical coupling unit, the input optical coupling unit, and the second feedback optical coupling unit are arranged in a straight line at equal intervals perpendicular to the light propagation direction. The input end of the first 1×2 optical beamsplitter is connected to the first output end of the optical beamsplitter tree structure. The input end of the second 1×2 optical beamsplitter is connected to the first output end of the first 1×2 optical beamsplitter. The input end of the first feedback optical coupling unit is connected to the first output end of the second 1×2 optical beamsplitter. The input end of the second feedback optical coupling unit is connected to the second output end of the second 1×2 optical beamsplitter. The input end of the third feedback optical coupling unit is connected to the second output end of the first 1×2 optical beamsplitter. The output end of the first feedback optical coupling unit, the input end of the input optical coupling unit, and the output end of the second feedback optical coupling unit are all used to connect to the optical fiber module. The optical fiber module includes a first optical feedback channel, an optical input channel, and a second optical feedback channel arranged side by side. The output end of the first feedback optical coupling unit is connected to the first optical feedback channel, the input end of the input optical coupling unit is connected to the optical input channel, and the output end of the second feedback optical coupling unit is connected to the second optical feedback channel. The output of the third feedback optical coupling unit is used to connect to an off-chip optical system.

22. The molecular fluorescence detection chip according to claim 21, characterized in that: The first feedback optical coupling unit and the second feedback optical coupling unit have an emission angle range of 8 to 10 degrees and a near-field spot diameter range of 3 to 5 micrometers; the third feedback optical coupling unit has an emission angle range of 30 to 60 degrees and a near-field spot diameter range of 30 to 60 micrometers, and the emitted spot is collected in free space by the off-chip optical system.

23. The molecular fluorescence detection chip according to claim 14, characterized in that: The optical beam splitter tree structure includes one or more optical beam splitter units, and the optical beam splitter unit includes one or more of the following: Y-branch structure, 2×2 directional coupler, 1×2 multimode interference coupler, 2×2 multimode interference coupler, 1×3 multimode interference coupler, and 1×5 multimode interference coupler.

24. The molecular fluorescence detection chip according to claim 14, characterized in that: The fluorescence excitation structure array includes a cladding and one or more waveguide structures cladding the cladding. The cladding surface above the waveguide structure is provided with sample wells arranged at a certain period along the waveguide propagation direction. The sample wells are used to load molecular substances that can excite fluorescence. The distance between the bottom surface of the sample well and the top surface of the waveguide structure is less than the evanescent wave penetration distance of the waveguide structure.

25. The molecular fluorescence detection chip according to claim 24, characterized in that: The waveguide structure is a straight waveguide, and the sample well is located directly above the straight waveguide; or the waveguide structure includes a straight waveguide and a plurality of grating structures located on one side of the straight waveguide and connected to the straight waveguide, and the sample well is located directly above the grating structures; or the waveguide structure includes a straight waveguide and a V-shaped metal grating structure located on the straight waveguide, and the sample well is located directly above the V-shaped metal grating structure.

26. The molecular fluorescence detection chip according to claim 14, characterized in that: The optical output structure array includes multiple optical output units, and each optical output unit employs a grating coupler.

27. The molecular fluorescence detection chip according to claim 14, characterized in that: The fluorescence collection layer includes a fluorescence filter layer, an aperture layer, and a microlens array layer.

28. The molecular fluorescence detection chip according to claim 14, characterized in that: The fluorescence detection layer includes one or more of the following: CCD chip, CMOS image sensor chip, PD array, SPAD array, PMT array, and SiPM array.

29. An optical encapsulation structure, characterized in that, The device includes an optical fiber module and a molecular fluorescence detection chip as described in any one of claims 14-28, wherein the optical fiber module is fixed at a preset position on the molecular fluorescence detection chip, and the optical fiber module includes one or more optical input channels, the optical input channels being aligned with the input optical coupling unit.

30. The optical packaging structure according to claim 29, characterized in that: The fiber module is fixed to a preset position on the molecular fluorescence detection chip by optical coupling adhesive, or the optical fiber module is fixed to a preset position on the molecular fluorescence detection chip by bonding.

31. The optical packaging structure according to claim 29, characterized in that: The optical fiber module includes a substrate, a cover plate, and one or more optical fibers. One side of the substrate has a single V-groove or multiple V-grooves arranged side by side and spaced apart. The optical fiber is located in the V-groove. The cover plate is arranged opposite to the substrate to cover the V-groove.

32. The optical packaging structure according to claim 29, characterized in that: The input optical coupling unit adopts an edge coupler. The initial direction of the pigtail of the optical fiber module is parallel to the plane where the molecular fluorescence detection chip is located. The optical fiber module is fixed to the side of the molecular fluorescence detection chip and the optical input channel of the optical fiber module is aligned with the waveguide core of the edge coupler.

33. The optical packaging structure according to claim 29, characterized in that: The input optical coupling unit includes a grating coupler, and the optical fiber module further includes a glass waveguide device. The first end face of the glass waveguide device is fixedly connected to the side of the substrate and the cover plate, and the waveguide core of the glass waveguide device is aligned with the optical fiber in the V-groove. The initial direction of the pigtail of the optical fiber module and the extension direction of the waveguide core of the glass waveguide device are parallel to the plane where the molecular fluorescence detection chip is located. The glass waveguide device is fixed above the grating coupler, and the second end face of the glass waveguide device is inclined to serve as a reflective surface to reflect the light entering the glass waveguide device to the grating coupler.

34. The optical packaging structure according to claim 33, characterized in that: The second end face of the glass waveguide device is provided with a reflective film.

35. The optical packaging structure according to claim 29, characterized in that: The input optical coupling unit adopts a grating coupler. The initial direction of the pigtail of the optical fiber module is not parallel to the plane where the molecular fluorescence detection chip is located. The optical fiber module is fixed to the upper surface of the molecular fluorescence detection chip and the optical input channel of the optical fiber module is aligned with the grating coupler. The end face polishing angle of the optical fiber module is consistent with the emission angle of the grating coupler.

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