CN211826083U - Optical waveguide multi-micro-channel detection system based on CMOS image sensing - Google Patents
Optical waveguide multi-micro-channel detection system based on CMOS image sensing Download PDFInfo
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Abstract
The utility model provides a many microchannels of optical waveguide detecting system based on CMOS image sensing, include: a microfluidic chip, a spectrum collection device and an analysis device; the micro-fluid chip comprises an optical waveguide and a micro-channel, wherein the optical waveguide is used for guiding light into the micro-channel along the horizontal direction; the spectrum collection device comprises a CMOS image sensing layer: the lower cladding, the waveguide layer, the upper cladding and the flow channel cover plate are arranged from bottom to top in sequence; the CMOS image sensing layer is positioned below the lower cladding; exposing the CMOS image sensing layer by the micro channel; the width of the micro flow channel is 10-100 μm. Has the advantages that: the structure of an optical waveguide and multi-micro-channel integrated matrix is formed, the analysis performance higher than that of a traditional optical system is realized through multi-micro-fluid channels and large-scale matrixing optical waveguides, a chip-level on-chip optical detection and analysis system of a high-flux biological sample is quickly constructed, and a high-flux chip for biological detection under micro-nano scale is realized; the preparation work such as adjustment of a collection light path in an experiment is reduced, and the portability of the detection system is improved.
Description
Technical Field
The invention relates to an optical waveguide multi-microfluid biological detection system based on CMOS image sensing, in particular to an optical waveguide multi-microfluid biological detection system based on CMOS image sensing.
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.
CMOS image sensors are active pixel sensors that utilize CMOS semiconductors, where a corresponding circuit is located near each photosensor to directly convert light energy into a voltage signal. Unlike the CCD, which is a light sensing coupling element, it does not involve signal charges. Under the same condition, the number of CMOS image sensor elements is relatively less, the power consumption is lower, the data throughput speed is higher than that of a CCD, the signal transmission distance is shorter than that of the CCD, the capacitance, the inductance and the parasitic delay are reduced, and the data output is faster by adopting an X-Y addressing mode. The data output rate of a CCD typically does not exceed 70 million pixels per second, whereas a CMOS can achieve 100 million pixels per second.
Materials such as optical silicon nitride films and the like are deposited on the high molecular polymer and the CMOS image sensor, wherein the integrated optical device taking SiN as the waveguide can be separated from a silicon or glass substrate by the flexible substrate formed by the high molecular polymer, 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 CMOS image sensor can directly form a spectrum or a graph image, can replace an optical signal collecting device and a spectrum monitoring device such as a laboratory microscope and the like, can reduce the preparation work of adjusting a collecting light path and the like in an experiment, and improves the experiment efficiency; the portability of the detection system can be improved, and the application scenes of the system are greatly increased.
The film is deposited on the high molecular polymer and the CMOS image sensor, the lower the deposition temperature is needed to be, the better the deposition temperature is, so as not to damage the molecular structure of the polymer and the CMOS image sensor, while the growth temperature of the SiN film which is mainstream at present is about 400 ℃, and is still too high, so that the high molecular polymer is easily softened and melted, and the CMOS image sensor is easily damaged.
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 functions of the traditional optical system are realized by an integrated optical or on-chip optical device, a low-temperature optical guide manufacturing process is adopted to form an optical waveguide layer on a high-molecular polymer material and a CMOS image sensing layer, softening, hardening and melting of the high-molecular polymer material and damage to a CMOS image sensor are avoided, the replacement of the CMOS is utilized, the preparation work of adjusting a collection optical path and the like in an experiment is reduced, and the experiment efficiency is improved; the portability of the detection system is improved, and the application scenes of the system are greatly increased; the conventional desktop or even large-scale optical system can be reduced to the chip size, the equivalent 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 an optical waveguide multi-micro-channel detection system based on CMOS image sensing, which comprises: a microfluidic chip, a spectrum collection device and an analysis device; 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 microfluid comprises an optical waveguide group and a microchannel, wherein the optical waveguide group comprises a second number of optical waveguides which are used for guiding light into the microchannel along the horizontal direction;
the spectrum collecting device comprises a CMOS image sensing layer, the CMOS image sensing layer is used for collecting optical signals in the micro flow channel, processing the optical signals to generate 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 or an image;
the microfluidic chip further comprises: the optical waveguide comprises a lower cladding, a waveguide layer, an upper cladding and a flow channel cover plate which are arranged from bottom to top in sequence, wherein the waveguide layer is a silicon nitride material formed at a deposition temperature of 25-150 ℃, and is used for forming the optical waveguide; the CMOS image sensing layer is positioned below the lower cladding layer;
the micro channel penetrates through the upper cladding layer, the waveguide layer and the lower cladding layer from top to bottom to expose the CMOS image sensing 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 optical waveguide group comprises a second number of optical waveguides parallel to each other to guide light into the micro flow channel, and the width of the optical waveguides is 300-600 nm.
Preferably, the second number is 1, and the whole or most of the waveguide layers corresponding to the microfluid form a sheet of the optical waveguide.
Preferably, the waveguide layer thickness is 150-1000 nm.
Preferably, the optical waveguide is a coupling optical waveguide;
the coupling optical waveguide comprises an incident grating, and light above the upper cladding is guided into the coupling optical waveguide until being guided into the micro channel; the incident grating protrudes from the waveguide layer and extends upwards into the upper cladding layer.
Preferably, the thickness of the waveguide layer is 150nm-1000nm, and the width of the coupling optical waveguide is 300-600 nm.
Preferably, the optical waveguide device further comprises a light guide structure, wherein the light guide structure comprises a trunk light guide and a light guide group, the light guide group is led out from the trunk light guide, and the light guide group is optically connected with the light guide group.
Preferably, the light guide group is led out from the trunk light guide by adopting a light splitting structure.
Preferably, the trunk light guide includes a first light guide, the light guide group includes a second light guide, and the first light guide and the second light guide are crossed by a cross-layer structure.
Preferably, the crossed cross-layer structure comprises a first light guiding overlap region and a second light guiding overlap region; the first light guide is disconnected at the intersection, and a first acute angle light guide end face and a second acute angle light guide end face are formed at two opposite disconnected ends; the second light guide forms a first acute angle light guide surface and a second acute angle light guide surface which are respectively matched with the first acute angle light guide end surface and the second acute angle light guide end surface at the intersection; the first light guide overlapping area comprises the first acute angle light guide end face and the first acute angle light guide face, and the second light guide overlapping area comprises the second acute angle light guide end face and the second acute angle light guide face.
The invention provides an optical waveguide multi-micro-channel detection system based on CMOS image sensing, which has the following beneficial effects: the structure of an optical waveguide and multi-micro-channel integrated matrix is formed, the analysis performance higher than that of a traditional optical system is realized through multi-micro-fluid channels and large-scale matrixing optical waveguides, a chip-level on-chip optical detection and analysis system of a high-flux biological sample is quickly constructed, and a high-flux chip for biological detection under micro-nano scale is realized; the preparation work such as adjustment of a collection light path in an experiment is reduced, and the portability of the detection system is improved.
Drawings
FIG. 1 is a side view of an optical waveguide multi-microchannel detection system based on CMOS image sensing according to the present invention;
FIG. 2 is a side view of a single microfluidic device of FIG. 1;
FIG. 3 is a top view of FIG. 2;
FIG. 4 is a top view of the slab optical waveguide of FIG. 2;
FIG. 5 is a schematic view of a light guide structure;
FIG. 6 is an enlarged view of A of FIG. 5;
FIG. 7 is an enlarged view of B of FIG. 5;
FIG. 8 is a cross-sectional view of FIG. 7;
figure 9 is a side view of a single coupled optical waveguide microfluid.
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 scheme of a horizontal optical waveguide and microfluidic channel integrated module, and simultaneously provides a scheme of a multi-microfluidic channel system matrixing, 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. The horizontal optical waveguide is an optical waveguide for guiding light into a microchannel in a horizontal direction
An optical waveguide multi-microchannel detection system based on CMOS image sensing, as shown in fig. 1, includes: a microfluidic chip (not shown), a spectrum collection device (not shown) and an analysis device 5;
the microfluidic chip comprises a microfluidic set (not shown) comprising a first number of microfluidics (not shown), as shown in fig. 1, the first number being m;
the microfluid comprises an optical waveguide set and a micro channel, and one microfluid shown in FIG. 2 comprises a waveguide set 131 and a micro channel 201; the optical waveguide assembly 131 comprises a second number of optical waveguides, as shown in fig. 2 and 3, the second number being n, and the optical waveguide assembly 131 comprises n optical waveguides 1311, 1312 … 131n to form an n × m matrix detection system.
As shown in fig. 3, the optical waveguides 1311, 1312 … 131n are used to guide light into the microchannel 201 in the horizontal direction;
as shown in fig. 1-2, the spectrum collecting device includes a CMOS image sensing layer 18, the CMOS image sensing layer 18 is located below the lower cladding 141, and is configured to collect optical signals of 201, 202 … 20m in the microchannel, process the optical signals to generate a signal to be analyzed, and transmit the signal to be analyzed to the analyzing device 5, and the analyzing device 5 analyzes the signal to be analyzed to form a spectrum or an image;
as shown in FIGS. 1-2, the microfluidic chip further comprises: the lower cladding layer 141, the waveguide layer 13, the upper cladding layer 142 and the flow channel cover plate 15 are sequentially arranged from bottom to top, the waveguide layer 13 is a silicon nitride material formed at a deposition temperature of 25-150 ℃, and the waveguide layer 13 is used for forming the optical waveguide group 131 and 132 … 13 m; the CMOS image sensing layer 18 is located below the lower cladding layer 141; the silicon nitride optical waveguide is formed on the CMOS image sensing layer and the high polymer material by a low-temperature growth process, so that the CMOS image sensing layer is not damaged, the preparation work of adjusting a collecting light path and the like in an experiment is reduced, and the experiment efficiency is improved; the portability of the detection system is improved, and the application scenes of the system are greatly increased;
as shown in fig. 1-2, the micro flow channels 201, 202 … 20m penetrate the upper cladding layer 142, the waveguide layer 13 and the lower cladding layer 141 from top to bottom to expose the CMOS image sensing layer 18;
as shown in fig. 1, the flow channel cover plate 15 covers the upper opening of the micro flow channel 201, 202 … 20m, and the micro flow channel cover plate 15 includes an injection port 151, 152 … 15m for injecting a solution containing a biomolecule to be detected into the micro flow channel 201, 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.
As shown in fig. 1-2, the lower cladding 141 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 micro flow channels 201, 202 … 20 have a width of 10-100 μm; and forming a structure of an integrated matrix of the optical waveguide and the multiple microchannels, 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.
The CMOS image sensing layer 18 has a filter layer (not shown) on its surface.
It should be noted that the first number m of microfluids may form one microfluid group, and a microfluid matrix of a third number of microfluid groups may be further constructed, where the third number is k, so that a detection system with a total number of optical waveguides n × m × k may be formed; and forming a structure of an integrated matrix of the optical waveguide and the multiple microchannels, 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 optical waveguide group includes a second number n of the optical waveguides parallel to each other, as shown in fig. 1 and 3, and fig. 5 and 6, the optical waveguide group 131 includes a second number n of the optical waveguides 1311, 1312 … 131n parallel to each other, so as to introduce light into the micro channel 201 along the horizontal direction, and the width of the optical waveguides is 300-600 nm.
Wherein the light source directions are different according to the waveguide set 131, such as: fig. 2 introduces the light source from the light guiding structure 6 at the left end of the optical waveguide group 131, and fig. 9 introduces the light source from above the optical waveguide group 131 without the light guiding structure.
Fig. 1 to 8 are described below, which show an optical waveguide multi-microchannel detection system with a light source introduced from the light guide structure 6 at the left end of the optical waveguide group 131:
as shown in fig. 1 and 3, the optical waveguide set 131 includes a plurality of optical waveguides 1311, 1312 … 131n, such as n, parallel to each other, to guide light into the micro flow channel 201 in a horizontal direction, in actual detection, for biomolecules with different labels in the micro flow channel 201, the optical waveguides 1311, 1312 … 131n can guide light with wavelengths λ 1, λ 2 … λ n into the micro flow channel 201 in the horizontal direction, and the labeled biomolecules 21 with different labels can be excited by the light with different wavelengths to simultaneously identify the biomolecules, while the non-excited biomolecules 20 in the excitation light field guided by the optical waveguides 1311, 1312 … 131n will not be identified, and the non-excited biomolecules 20 are normal biomolecules without labels or biomolecules that are labeled but outside the light field and are not excited; as shown in FIG. 3, the widths of the optical waveguides 1311, 1312 … 131n are 300-600 nm.
As shown in fig. 4, the entire or most of the waveguide layers 13 of a microfluidic array form a sheet-like optical waveguide 1311, i.e. the optical waveguide groups 131, 132 … 13m may comprise only one optical waveguide. The exciting light field introduced by the sheet-shaped optical waveguide 1311 can reduce background light signals in the detection-labeled biomolecules, and greatly improve the detection rate of small biomolecules.
As shown in FIGS. 1-2, the waveguide layer 13 has a thickness of 150-1000nm, i.e., the optical waveguides 1311, 1312 … 131n in FIGS. 2 and 3-4 have a thickness of 150-1000 nm.
As shown in fig. 6 to 9, for the scheme that the light guide set needs to be introduced into the light source as shown in fig. 2, the light guide structure 6 as shown in fig. 6 is provided to the detection system that the light guide n x m is matrixed, which comprises a main light guide 60 and light guide sets 601 and 602 … 60m led out from each light guide in the main light guide 60, wherein the light guide set 601 is optically connected with the light guide set 131 and further optically connected with the light guides 1311 and 1312 … 131n in the light guide set 131 to transmit the light source to the microchannels 201 and 202 … 20m respectively; 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 optical waveguides 1311, 1312 … 131n in the optical waveguide group 131, respectively. The leading-out node of the light guide group 601, 602 … 60m leading out from the trunk light guide 60 and the intersection node of the second light guide 62 leading out from the leading-out node and the first light guide 61 in the trunk light guide 60 need to be specially designed; as shown in fig. 5 to 6, the light guide groups 601 and 602 … 60m may be led out from the trunk light guide 60 by using a light splitting structure a, and the light splitting structure a may be led out from the first light guide 61 in the trunk light guide 60 to the second light guide 62 in the light guide groups 601 and 602 … 60 m; as shown in fig. 7 to 8, the intersection cross-layer structure B of the intersection node is described above, the trunk light guide 60 includes a second number n of first light guides 61, the light guide group 601 includes a second number n of second light guides 62, and the first light guides 61 and the second light guides 62 are intersected by the intersection 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 a first acute angle light guide end surface 611 and a second acute angle light guide end surface 612 are formed at two opposite ends of the broken first light guide; the second light guide 62 forms a first acute angle light guide surface 621 and a second acute angle light guide surface 622 matched with the acute angle light guide end surface at the intersection; the first light guide overlapping region 610 includes the first acute angle light guide end surface 611 and a first acute angle light guide surface 621 matched with the first acute angle light guide end surface 611, wherein a distance between surfaces of the first acute angle light guide end surface 611 and the first acute angle light guide surface 621 is less than 1 μm; the second light guiding overlapping region 620 comprises the second acute angle light guiding end surface 612 and a second acute angle light guiding surface 622 matched with the second acute angle light guiding end surface 612, wherein the distance between the opposite surfaces of the second acute angle light guiding end surface 612 and the second acute angle light guiding surface 622 is less than 1 μm; that is, the first light guide 61 is broken at the intersection, the first acute angle light guide end surface 611 and the second acute angle light guide end surface 612 are respectively formed at the two opposite ends of the broken first light guide 61, the first acute angle light guide surface 621 and the second acute angle light guide surface 622 which are matched with the first acute angle light guide end surface 611 and the second acute angle light guide end surface 612 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 as to form a first light guide overlapping region 610 and a second light guide overlapping region 620, the light transmitted from the end of the first light guide 61 which is broken enters the second light guide 62 through the first light guide overlapping region 610, and then enters the other end of the first light guide 61 which is broken through the second light guide overlapping region 620, that is, the light transmitted from the end of the first light guide 61 which is broken enters the first acute angle light guide surface 621 through the first light guide end surface 621, and then enters the second acute angle light guide end surface 612 through the second acute angle light guide surface 622, thereby completing the cross-layer conduction of light.
In the detection system in which the total number of optical waveguides is n × m × k, light can be continuously transmitted to the next and kth microchannel groups by sequentially extracting the light guide groups m k-1 times in each light guide group 601 and 602 … 60m by using the optical splitting structure a.
Fig. 9 is described below, which shows a coupled optical waveguide microfluidic chip in an optical waveguide multi-microchannel detection system with a light source introduced from above the optical waveguide group 131:
as shown in fig. 9, an incident grating (not shown) of silicon nitride material is further included to form a coupling optical waveguide with the optical waveguides 1311, 1312 … 131n, and the light above the upper cladding 142 is guided into the optical waveguide until being guided into the micro flow channel 201 in the horizontal direction, and the upper cladding 142 and the flow channel cover 15 are light-transmissive layers; the entrance grating protrudes from the waveguide layer 13 and extends up into the upper cladding layer 142.
As shown in fig. 3 and 4, the optical waveguide set 131 included in one microfluidic chip includes several, e.g., n, coupling optical waveguides parallel to each other to guide light into the microchannel 201 in a horizontal direction, in an actual detection, for biomolecules with different labels in the microchannel 201, the n coupling optical waveguides can guide light with wavelengths λ 1 and λ 2 … λ n into the microchannel 201 in the horizontal direction, and the labeled biomolecules 21 with different labels excited by light with different wavelengths can simultaneously identify the biomolecules, while the non-excited biomolecules 20 not in the excitation light field guided by the coupling optical waveguides 1311 and 1312 … 131n will not be identified, and the non-excited biomolecules 20 are normal biomolecules without labels or biomolecules that are labeled but located outside the light field and are not excited; wherein, as shown in FIG. 3, the width of the coupling optical waveguide is 300-600nm, and wherein, as shown in FIG. 9, the thickness of the waveguide layer 13 is 150-1000 nm.
In the invention, a substrate 11 is further included under the CMOS image sensing layer 18, and the substrate 11 is a silicon substrate; preferably, the substrate 11 is a 4, 8, 12 inch silicon wafer.
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 invention, the silicon nitride waveguide layer 13 is a silicon nitride film layer with the thickness of 150nm-1000nm formed at the low temperature of 25-150 ℃ of deposition temperature, so that the lower cladding 141 of a softening, hardening or melting high polymer material and the damage to the CMOS image sensing layer 18 are avoided, the preparation work of adjusting a collecting light path and the like in an experiment is reduced, and the experiment efficiency is improved; the portability of the detection system is improved, and the application scenes of the system are greatly increased; 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 optical waveguide multi-microfluidic detection system in which the total number of optical waveguides is n × m × k matrix 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 listed, total number of injection ports is m × k) from the injection ports 151 and 152 … 15m (not fully listed, total number of micro flow channels is m × k), and the light guide sets 601 and 602 … 60m (not fully listed, total number of light guide sets is m × k) introduce n light of different wavelengths corresponding to the n markers into n light guides (not fully listed, total number of light guides is m × k) in the light guide sets 131 and 132 … 13m (not fully listed, total number of light guides is m × k) and then into the micro flow channels 201 and 202 … 20m in the horizontal direction, as shown in fig. 1 and 3, n light guides 1 and 1312 … 131n in the light guide set 131 are incompletely listed, total number of light guides is n × k, and the light guides 21 are fluorescent molecular markers of the tumor cells emitting light of different wavelengths The CMOS image sensing layer 18 collects fluorescence (optical signals) with specific wavelength, processes the fluorescence (optical signals) with specific wavelength, generates signals to be analyzed, and transmits the signals to be analyzed to the analysis device 5, the analysis device 5 analyzes the signals to be analyzed to form a spectrum of the fluorescence with specific wavelength, the type of circulating tumor cells in a solution or a blood sample can be judged by reading the spectrum, various tumor circulating cells of different patients can be detected respectively at one time, and a high-throughput chip for detecting various tumor cells under the micro-nano scale is realized, so that the tumor dynamics is monitored in real time, the treatment effect is evaluated, and the real-time individual treatment is realized.
The invention provides an optical waveguide multi-micro-channel detection system based on CMOS image sensing, which has the following beneficial effects: the structure of an optical waveguide and multi-micro-channel integrated matrix is formed, the analysis performance higher than that of a traditional optical system is realized through multi-micro-fluid channels and large-scale matrixing optical waveguides, a chip-level on-chip optical detection and analysis system of a high-flux biological sample is quickly constructed, and a high-flux chip for biological detection under micro-nano scale is realized; the preparation work such as adjustment of a collection light path in an experiment is reduced, and the portability of the detection system is improved.
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 (10)
1. An optical waveguide multi-microchannel detection system based on CMOS image sensing comprises: a microfluidic chip, a spectrum collection device and an analysis device; 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 microfluid comprises an optical waveguide group and a microchannel, wherein the optical waveguide group comprises a second number of optical waveguides which are used for guiding light into the microchannel along the horizontal direction;
the spectrum collecting device comprises a CMOS image sensing layer, the CMOS image sensing layer is used for collecting optical signals in the micro flow channel, processing the optical signals to generate 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 or an image;
the microfluidic chip further comprises: the optical waveguide comprises a lower cladding, a waveguide layer, an upper cladding and a flow channel cover plate which are arranged from bottom to top in sequence, wherein the waveguide layer is a silicon nitride material formed at a deposition temperature of 25-150 ℃, and is used for forming the optical waveguide; the CMOS image sensing layer is positioned below the lower cladding layer;
the micro channel penetrates through the upper cladding layer, the waveguide layer and the lower cladding layer from top to bottom to expose the CMOS image sensing 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 optical waveguide assembly comprises a second number of optical waveguides parallel to each other for guiding light into the microchannel, the optical waveguides having a width of 300-600 nm.
3. The system of claim 1, wherein the second number is 1, and wherein the entire or a majority of the waveguide layers of the microfluidic array form a slab of the optical waveguide.
4. The system as claimed in any one of claims 2 to 3, wherein the waveguide layer has a thickness of 150 and 1000 nm.
5. The system of claim 1, wherein the optical waveguide is a coupling optical waveguide;
the coupling optical waveguide comprises an incident grating, and light above the upper cladding is guided into the coupling optical waveguide until being guided into the micro channel; the incident grating protrudes from the waveguide layer and extends upwards into the upper cladding layer.
6. The system as claimed in claim 5, wherein the waveguide layer has a thickness of 150nm-1000nm, and the coupling optical waveguide has a width of 300-600 nm.
7. The system of claim 1, further comprising a light guiding structure comprising a trunk light guide and a light guiding group, the light guiding group leading out from the trunk light guide, the light guiding group optically connected to the light guiding group.
8. The system of claim 7, wherein the light guide component is optically coupled to the trunk light guide.
9. The system of claim 7, wherein the trunk light guide comprises a first light guide, the set of light guides comprises a second light guide, and the first light guide intersects the second light guide through an intersecting cross-layer structure.
10. The system of claim 9, wherein the cross-layer structure comprises a first light directing overlap region and a second light directing overlap region; the first light guide is disconnected at the intersection, and a first acute angle light guide end face and a second acute angle light guide end face are formed at two opposite disconnected ends; the second light guide forms a first acute angle light guide surface and a second acute angle light guide surface which are respectively matched with the first acute angle light guide end surface and the second acute angle light guide end surface at the intersection; the first light guide overlapping area comprises the first acute angle light guide end face and the first acute angle light guide face, and the second light guide overlapping area comprises the second acute angle light guide end face and the second acute angle light guide face.
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