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CN111208069A - Grating waveguide multi-microchannel detection system - Google Patents

Grating waveguide multi-microchannel detection system Download PDF

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CN111208069A
CN111208069A CN202010053889.5A CN202010053889A CN111208069A CN 111208069 A CN111208069 A CN 111208069A CN 202010053889 A CN202010053889 A CN 202010053889A CN 111208069 A CN111208069 A CN 111208069A
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grating
micro
waveguide
light
grating waveguide
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陈昌
刘博�
王靖
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Shanghai Jinguan Technology Co ltd
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Shanghai Industrial Utechnology Research Institute
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/255Details, e.g. use of specially adapted sources, lighting or optical systems
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
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    • G01N21/6428Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64Fluorescence; Phosphorescence
    • G01N21/6486Measuring fluorescence of biological material, e.g. DNA, RNA, cells
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/10Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept

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Abstract

The invention provides a grating waveguide multi-micro-channel detection system, which comprises a micro-fluid chip, a microscope, a measuring device and an analysis device, wherein the micro-fluid chip is arranged on the micro-fluid chip; the microfluidic chip comprises a microfluidic set comprising a first quantity of microfluidics; the microfluid comprises a grating waveguide group and a microchannel, wherein the grating waveguide group comprises a second number of grating waveguides, and each grating waveguide comprises an emergent grating which is positioned below the microchannel and used for guiding light into the microchannel upwards along the vertical direction. Has the advantages that: the structure of an integrated matrix of the optical waveguide and the multiple micro-channels is formed, the analysis performance higher than that of a traditional optical system is realized through the multiple micro-fluid channels and the large-scale matrixing optical waveguide, the chip-level on-chip optical detection and analysis system of the high-flux biological sample is quickly constructed, and the high-flux chip of biological detection under the micro-nano scale is realized.

Description

Grating waveguide multi-micro-channel detection system
Technical Field
The invention relates to a grating waveguide multi-micro-channel detection system, in particular to a grating waveguide multi-micro-channel biological detection system.
Background
In modern biochemical analysis procedures, high-throughput detection devices have been widely used. Most of these devices use biochips based on microfluidic technology or microwell arrays, loaded in high performance optical systems, to perform analysis of biological samples of different sizes, such as nucleic acids, proteins, viruses, bacteria, cells, etc. The design of these optical systems is usually based on complex geometric optics, which is bulky, costly, requires optical alignment, and is costly to maintain.
In the precise medical age, miniaturized, high-performance, low-cost and mobile integrated analysis systems are of great concern. In particular, the lab on chip concept has advanced a lot of progress in manipulating a biological sample based on a microfluidic technology after decades of development, but a real lab on chip system still lacks an integrated system for chip-level on-chip optical detection and analysis of a high-throughput biological sample on a micro-nano scale.
Meanwhile, materials such as optical silicon nitride films and the like are deposited on the high polymer film, the integrated optical device taking SiN as the waveguide is separated from the silicon or glass substrate, and the polymer has certain ductility, so that the application range of the integrated optical device taking SiN and the like as the waveguide is greatly enlarged.
The lower the deposition temperature is, the better the deposition temperature is, in order to not destroy the molecular structure of the polymer, when the film is deposited on the high molecular polymer, the growth temperature of the SiN film which is the mainstream at present is about 400 ℃, and is still too high.
Disclosure of Invention
The device aims to solve a series of new requirements of miniaturization, mobility, integration and the like of the modern biochemical analysis instrument which is large in size and high in cost and meets the requirements of the precise medical era. The chip-level optical detection and analysis system is produced by an integrated circuit mass production process, the function of the traditional optical system is realized by integrating an optical device or an on-chip optical device, the traditional desktop or even large-scale optical system can be reduced to the chip size, the equal or even more excellent analysis performance is ensured, the high-flux chip-level optical detection and analysis integrated system of the biological sample under the micro-nano scale is realized, and the system cost is greatly reduced.
The invention provides a grating waveguide multi-micro-channel detection system, which comprises: microfluidic chips, microscopes, measurement devices and analysis devices; it is characterized in that the preparation method is characterized in that,
the microfluidic chip comprises a microfluidic set comprising a first quantity of microfluidics;
the micro fluid comprises a grating waveguide group and a micro channel, the grating waveguide group comprises a second number of grating waveguides, each grating waveguide comprises an emergent grating, each emergent grating is positioned below the micro channel and used for guiding light into the micro channel upwards along the vertical direction, the microscope is used for collecting optical signals in the micro channel and transmitting the optical signals to the measuring device, the measuring device is used for processing the optical signals, generating signals to be analyzed and transmitting the signals to be analyzed to the analyzing device, and the analyzing device analyzes the signals to be analyzed to form a spectrum;
the microfluidic chip further comprises: the grating waveguide group is formed by sequentially arranging a lower cladding, a waveguide layer, a protective layer, an upper cladding and a flow channel cover plate from bottom to top, wherein the waveguide layer is made of silicon nitride materials and is used for forming the grating waveguide group; the protective layer is made of silicon dioxide materials and is used for covering the grating waveguide group and protecting the emergent grating;
the micro-channel penetrates through the upper cladding to expose the protective layer;
the flow channel cover plate covers the upper opening of the micro flow channel, and the micro flow channel cover plate comprises a liquid injection port for injecting a solution containing the biomolecules to be detected into the micro flow channel;
the lower cladding is made of a high polymer material with the thickness of 15-30 mu m, the upper cladding is made of a high polymer material with the thickness of 15-30 mu m, and the width of the micro-channel is 10-100 mu m.
Preferably, the grating waveguide group comprises a second number of mutually parallel grating waveguides for guiding light into the micro channel, and the width of the grating waveguides is 300-600 nm.
Preferably, the refractive index of the waveguide layer is 1.75-2.2.
Preferably, the waveguide layer has a thickness of 150nm to 1000 nm.
Preferably, the optical waveguide further comprises a light guide structure, and the light guide structure is optically connected with the grating waveguide group.
Preferably, the light guiding structure comprises a light splitting structure.
Preferably, the light splitting structure is configured to extract a second number of second light guides upward from a second number of first light guides.
Preferably, the grating waveguide is a coupled grating waveguide;
the coupling grating waveguide also comprises an incident grating, and the light above the upper cladding is guided into the coupling grating waveguide until the light is guided into the micro-channel upwards along the vertical direction; the protective layer covers and protects the incident grating, the thickness of the waveguide layer is 150nm-1000nm, and the width of the coupling grating waveguide is 300-600 nm.
Preferably, the refractive index of the waveguide layer is 1.75-2.2. .
The invention provides a grating waveguide multi-micro-channel detection system, which has the following beneficial effects: the structure of an integrated matrix of the optical waveguide and the multiple micro-channels is formed, the analysis performance higher than that of a traditional optical system is realized through the multiple micro-fluid channels and the large-scale matrixing optical waveguide, the chip-level on-chip optical detection and analysis system of the high-flux biological sample is quickly constructed, and the high-flux chip of biological detection under the micro-nano scale is realized.
Drawings
FIG. 1 is a side view of a grating waveguide multi-microchannel detection system according to the present invention;
FIG. 2 is a side view of one of the microfluids in the chip of FIG. 1;
FIG. 3 is a top view of FIG. 2;
FIG. 4 is a schematic view of a light directing structure;
FIG. 5 is a schematic view of the structure of FIG. 4;
FIG. 6 is an enlarged view of A of FIG. 4 or 5;
FIG. 7 is an enlarged view of B of FIG. 4 or 5;
FIG. 8 is a cross-sectional view of FIG. 7;
FIG. 9 is a schematic diagram of a coupled grating waveguide multi-microchannel detection system.
Detailed Description
The following detailed description of embodiments of the invention refers to the accompanying drawings.
In the drawings, the dimensional ratios of layers and regions are not actual ratios for the convenience of description. When a layer (or film) is referred to as being "on" another layer or substrate, it can be directly on the other layer or substrate, or intervening layers may also be present. In addition, when a layer is referred to as being "under" another layer, it can be directly under, and one or more intervening layers may also be present. In addition, when a layer is referred to as being between two layers, it can be the only layer between the two layers, or one or more intervening layers may also be present. Like reference numerals refer to like elements throughout. In addition, when two components are referred to as being "connected," they include physical connections, including, but not limited to, electrical connections, contact connections, and wireless signal connections, unless the specification expressly dictates otherwise.
The invention provides a vertical grating waveguide and microfluidic channel integrated module scheme, and simultaneously provides a multi-microfluidic channel system matrixing scheme, and a chip-level on-chip optical detection and analysis integrated system of a high-flux biological sample under a micro-nano scale is quickly constructed. Wherein, the vertical grating waveguide refers to a grating waveguide for guiding light into the micro-channel upwards along the vertical direction
A grating waveguide multi-micro-channel detection system, as shown in FIGS. 1 to 4, includes: a microfluidic chip 1, a microscope 3, a measuring device 4 and an analyzing device 5;
the microfluidic chip 1 comprises a first number of microfluids (not shown), as shown in fig. 1, the first number being m;
the microfluid comprises a grating waveguide set and a micro channel, and one microfluid shown in FIG. 2 comprises a grating waveguide set 131 and a micro channel 201; the grating waveguide sets 131, 132 … m each comprise a second number n of grating waveguides, as shown in fig. 2 and 3, and the grating waveguide set 131 comprises n grating waveguides 1311, 1312 … n, to form an n × m matrixed detection system.
The grating waveguide 1311, 1312 … 131n includes an exit grating 1310, the exit grating 1310 is located below the micro channel 201 to guide light into the micro channel 201 upward in the vertical direction, a new design scheme and idea are provided for different complex integrated structures, exit gratings with different exit directions can be designed, flexibility of detection means is increased, the microscope 3 is used for collecting optical signals in the micro channel 201, 202 … 20m and transmitting the optical signals to the measuring device 4, the measuring device 4 is used for processing the optical signals and generating signals to be analyzed and transmitting the signals to be analyzed to the analyzing device 5, and the analyzing device 5 analyzes the signals to be analyzed to form a spectrum; it should be noted that the above "directing light upward along the vertical direction" may be strictly vertically upward, or may be obliquely upward, and the present invention is not limited thereto.
The microfluidic chip 1 further comprises: the waveguide layer 13 is made of silicon nitride material, and the waveguide layer 13 is used for forming the grating waveguide groups 131 and 132 … 13 m; the protective layer is made of silicon dioxide material, has light transmittance, and is used for covering the grating waveguide sets 131 and 132 … 13m and protecting the exit grating 1310;
the micro flow channels 201, 202 … 20m penetrate through the upper cladding 142 to expose the protective layer 12;
the flow channel cover plate 15 covers the upper openings of the micro flow channels 201 and 202 … 20m, and the micro flow channel cover plate 15 comprises liquid injection ports 151 and 152 … 15m for injecting a solution containing biomolecules to be detected into the micro flow channels 201 and 202 … 20 m; it should be noted that, a liquid outlet (not shown) is further included to form a circulation system corresponding to the liquid injection port 151 one by one, and the liquid outlet may be an opening on the flow passage cover plate 15; the liquid outlet may also be an opening at both ends of the micro flow channel 2, and the invention is not limited herein.
The lower cladding is a polymer material with a thickness of 15-30 μm, the upper cladding 142 is a polymer material with a thickness of 15-30 μm, and the width of the micro flow channels 201, 202 … 20 is 10-100 μm; and forming a structure of a grating waveguide and multi-micro-channel integrated matrix, and quickly constructing a chip-level on-chip optical detection and analysis integrated system of the high-flux biological sample under the micro-nano scale.
It should be noted that the first number m of microfluids may form one microfluid group, and a microfluid matrix formed by a third number of microfluid groups may also be constructed, where the third number is k, and then a detection system with a total number of grating waveguides forming n × m × k matrixing may be formed; and forming a structure of a grating waveguide and multi-micro-channel integrated matrix, and quickly constructing a chip-level on-chip optical detection and analysis integrated system of the high-flux biological sample under the micro-nano scale.
It should be noted that the grating waveguide group includes a second number n of mutually parallel grating waveguides, as shown in fig. 1, the grating waveguide group 131 includes a second number n of mutually parallel grating waveguides 1311, 1312 … 131n to guide light into the micro channel 201 upward along the vertical direction, and the width of the grating waveguides 1311, 1312 … 131n is 300-600 nm.
Wherein the directions of the introduced light sources are different according to the grating waveguide group 131, such as: fig. 1 to 2 show that the grating waveguide set 131 introduces the light source from the left end, and fig. 9 shows that the light source introduces the light source from the upper cladding 142, in the multi-micro-channel, especially matrixed, detection system, the former needs to add the light guide structure 6 shown in fig. 4 to 5 from the structure when manufacturing the matrixed chip, and the latter does not need to add the light guide structure, and the light guide structure 6 is described below with reference to fig. 1 to 8:
as shown in fig. 1 and 3, the grating waveguide set 131 includes a second number, e.g., n, of grating waveguides 1311, 1312 … 131n parallel to each other, and then the light guide structure 6 includes a second number, n, of first light guides 61 for one-to-one optical connection with the second number, n, of grating waveguides 1311, 1312 … 131n in the grating waveguide set 131, that is, the light guide structure 6 optically connected with it needs n corresponding first light guides 61 to guide light into the grating waveguides in the horizontal direction and finally upwards into the microchannel 201 in the vertical direction; in actual detection, for biomolecules with different labels in the micro-channel 201, the grating waveguides 1311, 1312 … 131n connected with n light guide lines one by one can respectively guide light with different wavelengths λ 1, λ 2 … λ n vertically upwards into the micro-channel 201, the labeled biomolecules 21 with different labels excited by the light with different wavelengths can be simultaneously identified, while the non-excited biomolecules 20 in the excited light field guided by the grating waveguides 1311, 1312 … 131n will not be identified, the non-excited biomolecules 20 are normal biomolecules without labels or biomolecules which are labeled but located outside the light field and are not excited; wherein, as shown in FIG. 3, the width of the grating waveguides 1311, 1312 … 131n is 300-600 nm.
As shown in fig. 1-2, the waveguide layer 13 has a thickness of 150nm-1000nm, i.e., the horizontal portions of the grating waveguides 1311, 1312 … 131n in fig. 1-2 have a thickness of 150nm-1000 nm.
As shown in fig. 1 and 4, the light guide structure 6 includes a trunk light guide 60, and a k-th light guide group of a first light guide group 601 and a second light guide group 602 … led out from the trunk light guide 60, so as to respectively guide light sources to k microfluidic groups. The light guide structure 6 is optically connected to the grating waveguide group 131 through the first light guide group 601, and further optically connected to all the grating waveguide groups 132..13m in the same microfluidic group along the waveguide layer 13, so that it is not necessary to match a separate light guide group for each grating waveguide group, thereby saving the process and reducing the complexity of the structure.
Aiming at the n × m matrixing detection system of the grating waveguide, the method comprises the following steps: the light guide structure 6 includes a grating waveguide 1311, 1312 … 131n in the grating waveguide group 131, and all the grating waveguide groups 132..13m in the same microfluidic group, which are respectively transmitted to the light with the wavelengths of λ 1, λ 2, λ 3 … λ n directly through the n first light guides 61 in the trunk light guide 60, in which case the n first light guides 61 in the trunk light guide 60 constitute the first light guide group 601.
For the above described grating waveguide n × m × k matrixed detection system: a first light guide group 601 and a second light guide group 602 …, which are led out from the trunk light guide 60, for respectively leading light sources to k microfluidic groups; the first light guide 61 in the trunk light guide 60 and the second light guide 62 led out to each light guide group have light splitting and crossing conditions, so that for the integrated grating waveguide multi-micro-channel chip in the matrix of the multi-channel monitoring system shown in fig. 1, a specific light guide structure 6 needs to be designed, and the light guide structures 6 shown in fig. 4 to 5 are provided and comprise the trunk light guide 60 and the light guide groups 601 and 602 … 60k led out from the trunk light guide 60; the trunk light guide 60 includes n first light guides 61, and the optical wavelengths transmitted by the first light guides are λ 1, λ 2, and λ 3 … λ n, respectively, so as to be transmitted to the grating waveguides 1311 and 1312 … 131n in the grating waveguide group 131, respectively. The leading-out nodes of the light guide groups 601 and 602 … 60k leading out from the trunk light guide 60 and the intersection nodes of the second light guide 62 and the first light guide 61 in the trunk light guide 60 (and the first light guide 61 in the same light guide group) need to be specially designed; as shown in fig. 5 to 8, the light guide groups 601 and 602 … 60k are led out from the trunk light guide 60 by using a light splitting structure a, and as shown in fig. 6, the light splitting structure a is led out from the first light guide 61 in the trunk light guide 60 and led to the second light guide 62 in the light guide groups 601 and 602 … 60 k; as shown in fig. 7 to 8, the first light guide 61 (the first light guide 61 in the trunk light guide 60 or the first light guide 61 in the same light guide group) and the second light guide 62 are crossed by the cross layer structure B; the crossed cross-layer structure B comprises a first light guide overlapping region 610 and a second light guide overlapping region 620; the first light guide 61 is broken at the intersection, and two acute angle light guide end faces are formed at two opposite ends which are broken; the second light guide 62 forms an acute angle light guide surface matched with the acute angle light guide end surface at the intersection; the first light guide overlapping region 610 includes the acute angle light guide end face and an acute angle light guide face matched with the acute angle light guide end face, and the distance between the acute angle light guide end face and the acute angle light guide face is less than 1 μm; the second light guide overlapping region 620 includes the acute angle light guide end face and an acute angle light guide face matched with the acute angle light guide end face, and the distance between the acute angle light guide end face and the acute angle light guide face is less than 1 μm; that is, the first light guide 61 is broken at the intersection, two acute angle light guide end faces are respectively formed at two opposite ends of the broken first light guide 61, two acute angle light guide faces which are matched with the two acute angle light guide end faces and have a distance less than 1 μm are formed at the intersection of the second light guide 62 led out from the trunk light guide 60, so that a first light guide overlapping area 610 and a second light guide overlapping area 620 are formed, and light transmitted from one end of the broken first light guide 61 enters the second light guide 62 through the first light guide overlapping area 610 and then enters the other end of the broken first light guide 61 through the second light guide overlapping area 620.
It should be noted that, for the detection system in which the total number of grating waveguides is n × m × k matrixing, the light source can be continuously transmitted to the next microfluidic group to the kth microfluidic group by using the light splitting structure a at the leftmost side of the first light guide 61. As shown in fig. 4, a light splitting structure a is adopted to lead out a second number of second guide lights 62 from a second number n of first guide lights 61 upwards, specifically, a second number n of second guide lights 62 are sequentially led out from a second number n of first guide lights 61 vertically upwards and folded in a direction horizontal to the first guide lights 61 in the trunk guide light 60 at a position corresponding to a next micro-fluid group 1 'to form a second number n of first guide lights 61 in a second guide light group 602, so as to transmit light sources to a next micro-fluid group 1', and so on until a kth micro-fluid group transmits light sources.
The grating waveguide multi-micro-channel detection system with the light source introduced from the upper part of the upper cladding 142 does not need to be designed with a special light guide structure: as shown in fig. 9, an input grating 1310 ' including a second number n of silicon nitride materials at one end (left end as shown) of the waveguide layer 13 and a second number n of grating waveguides 1311, 1312 … 131n included in the nearest grating waveguide set 131 in the microfluid respectively form a coupling grating waveguide, light above the cover plate 15 is guided into the waveguide layer 13 and transmitted to all microfluids (right side) in the same microfluid set along the waveguide layer 13, light is guided into the microchannels 201, 202 … 20m in a vertical direction, the upper cladding layer 142 above the input grating 1310 ', the cover plate 15 is a light-transmissive layer and the protective layer 12 are both light-transmissive, and the protective layer 12 is a silicon dioxide material to cover the grating waveguide sets 131, 132 … 13n and protect the output grating 1310 and the input grating 1310 '.
As shown in fig. 3, a micro-fluid includes a grating waveguide set 131 including a plurality of coupling grating waveguides, such as n, parallel to each other, to guide light vertically upwards into the micro-channel 201, in an actual detection, for different labeled biomolecules contained in the micro-channel 201, the coupling grating waveguides can guide light with wavelengths λ 1 and λ 2 … λ n vertically upwards into the micro-channel 201, respectively, and the labeled biomolecules 21 with different labels excited by the light with different wavelengths can simultaneously identify these biomolecules, while the non-excited biomolecules 20 in the excited light field guided by the coupling grating waveguides will not be identified, and the non-excited biomolecules 20 are normal biomolecules without labeling or biomolecules labeled but located outside the light field and not excited; as shown in fig. 4, the width of the coupling grating waveguide is 300-600nm, wherein as shown in fig. 9, the thickness of the waveguide layer 13 is 150nm-1000nm, i.e. the thickness of the horizontal portion of the grating waveguide group is 150nm-1000 nm.
In the invention, the high polymer material is SU-8 resin, polyimide, polydimethylsilane, polyethylene or benzocyclobutene.
In the present invention, the flow path cover 15 is made of PDMS or quartz, and may be made of the above-mentioned polymer material.
In the present invention, the silicon nitride waveguide layer 13 is a silicon nitride thin film layer having a thickness of 150nm to 1000nm formed at a low deposition temperature of 25 to 150 ℃; the refractive index of the silicon nitride film is 1.75-2.2. The silicon nitride film may be a film having a uniform refractive index, or may be a film having a non-uniform refractive index, such as a silicon nitride film having a layered refractive index structure.
Circulating tumor cells are a general term for various tumor cells that leave the tumor tissue and enter the blood circulation system of the human body. By detecting trace circulating tumor cells in peripheral blood and monitoring the trend of the change of the types and the quantity of the circulating tumor cells, the tumor dynamics can be monitored in real time, the treatment effect can be evaluated, and the real-time individual treatment can be realized. Referring to fig. 1, an embodiment of detecting circulating tumor cells by using the above detection system with total grating waveguides forming n × m × k matrix in the multi-microfluidic detection system with grating waveguides is described as follows:
the first step is as follows: sorting and enriching various tumor cells possibly existing in the collected m x k patient blood samples by adopting an immunomagnetic bead technology (such as immunomagnetic bead positive sorting) or a microfluidic technology to obtain a solution containing circulating tumor cells, or directly adopting the patient blood samples;
the second step is that: adding an antibody group which can be specifically combined with surface antigens of various tumor cells or an aptamer group which can be combined with the surfaces of various tumor cells into the solution or the blood sample containing the circulating tumor cells, wherein the antibody group and the aptamer group modify marks, and the antibody combined with specific tumor cells or the modified marks on the aptamer have uniqueness, so as to obtain the solution or the blood sample containing the marked circulating tumor cells; the labels are n, and can be target probes of fluorescent molecules;
the third step: as shown in fig. 1, the m × k solutions or blood samples obtained in the second step are respectively added to the micro flow channels 201 and 202 … 20m (not fully illustrated, total number of injection ports is m × k) from the injection ports 151 and 152 … 15m (not fully illustrated, total number of micro flow channels is m × k), and the light guide sets 601 and 602 … 60k (not fully illustrated, total number of light guide sets is k) introduce light of n different wavelengths, which corresponds to the n kinds of marks, into a first number m (all) of grating waveguide sets (e.g., grating waveguide sets 131 and 132 … 13m in the micro flow set, not fully illustrated, total number of grating waveguide sets is m × k) in the corresponding micro flow set along the waveguide layer 13 (e.g., grating waveguide sets 131 and 132 … m in the micro flow set, not fully illustrated, total number m × k) of grating waveguide sets n (all) of grating waveguides (e.g., as shown in fig. 1 and 4), and the n grating waveguides 1 and 1312, 1312 … 131n, and incompletely illustrated, and the total number of grating waveguides m of the micro flow channels are further introduced into the vertical direction of the micro flow channels 131k) of the micro, 202 … 20m, the labeled biomolecule 21 containing different fluorescent molecular markers is a circulating tumor cell excited by light of different wavelengths to emit fluorescence of specific wavelengths, the microscope 3 is used for collecting the fluorescence (optical signal) of specific wavelengths and transmitting the fluorescence to the measuring device 4, the measuring device 4 processes the fluorescence (light signal) collected at a specific wavelength and generates a signal to be analyzed and transmits the signal to be analyzed to the analyzing device 5, the analysis device 5 analyzes the signal to be analyzed to form a spectrum of fluorescence with a specific wavelength, and can judge the type of circulating tumor cells in the solution or blood sample by reading the spectrum, the high-throughput chip can be used for respectively detecting various tumor circulating cells of different patients at one time and realizing the detection of various tumor cells under the micro-nano scale, thereby monitoring the tumor dynamics in real time, evaluating the treatment effect and realizing the real-time individual treatment.
The invention provides a grating waveguide multi-micro-channel detection system, which has the following beneficial effects: the structure of an integrated matrix of the optical waveguide and the multiple micro-channels is formed, the analysis performance higher than that of a traditional optical system is realized through the multiple micro-fluid channels and the large-scale matrixing optical waveguide, the chip-level on-chip optical detection and analysis system of the high-flux biological sample is quickly constructed, and the high-flux chip of biological detection under the micro-nano scale is realized.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.

Claims (9)

1. A grating waveguide multi-microchannel detection system, comprising: microfluidic chips, microscopes, measurement devices and analysis devices; it is characterized in that the preparation method is characterized in that,
the microfluidic chip comprises a microfluidic set comprising a first quantity of microfluidics;
the micro fluid comprises a grating waveguide group and a micro channel, the grating waveguide group comprises a second number of grating waveguides, each grating waveguide comprises an emergent grating, each emergent grating is positioned below the micro channel and used for guiding light into the micro channel upwards along the vertical direction, the microscope is used for collecting optical signals in the micro channel and transmitting the optical signals to the measuring device, the measuring device is used for processing the optical signals, generating signals to be analyzed and transmitting the signals to be analyzed to the analyzing device, and the analyzing device analyzes the signals to be analyzed to form a spectrum;
the microfluidic chip further comprises: the grating waveguide group is formed by sequentially arranging a lower cladding, a waveguide layer, a protective layer, an upper cladding and a flow channel cover plate from bottom to top, wherein the waveguide layer is made of silicon nitride materials and is used for forming the grating waveguide group; the protective layer is made of silicon dioxide materials and is used for covering the grating waveguide group and protecting the emergent grating;
the micro-channel penetrates through the upper cladding to expose the protective layer;
the flow channel cover plate covers the upper opening of the micro flow channel, and the micro flow channel cover plate comprises a liquid injection port for injecting a solution containing the biomolecules to be detected into the micro flow channel;
the lower cladding is made of a high polymer material with the thickness of 15-30 mu m, the upper cladding is made of a high polymer material with the thickness of 15-30 mu m, and the width of the micro-channel is 10-100 mu m.
2. The system as claimed in claim 1, wherein the grating waveguide set comprises a second number of mutually parallel grating waveguides for guiding light into the microchannel, the width of the grating waveguides being 300-600 nm.
3. The system of claim 1, wherein the index of refraction of the waveguide layer is 1.75-2.2.
4. The system of claims 2-4, wherein the waveguide layer has a thickness of 150nm to 1000 nm.
5. The system of claim 1, further comprising a light guide structure optically coupled to the set of grating waveguides.
6. The system of claim 5, wherein the light directing structure comprises a light splitting structure.
7. The system of claim 6, wherein the light splitting structure is configured to extract a second quantity of the second guided light upwardly from a second quantity of the first guided light.
8. The system of claim 1, wherein the grating waveguide is a coupled grating waveguide;
the coupling grating waveguide also comprises an incident grating, and the light above the upper cladding is guided into the coupling grating waveguide until the light is guided into the micro-channel upwards along the vertical direction; the protective layer covers and protects the incident grating, the thickness of the waveguide layer is 150nm-1000nm, and the width of the coupling grating waveguide is 300-600 nm.
9. The system of claim 1, wherein the index of refraction of the waveguide layer is 1.75-2.2.
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