CN111229337A

CN111229337A - Method for manufacturing optical waveguide multi-micro-channel chip

Info

Publication number: CN111229337A
Application number: CN202010053152.3A
Authority: CN
Inventors: 陈昌; 刘博�; 豆传国
Original assignee: Shanghai Industrial Utechnology Research Institute
Current assignee: Shanghai Industrial Utechnology Research Institute
Priority date: 2020-01-17
Filing date: 2020-01-17
Publication date: 2020-06-05
Anticipated expiration: 2040-01-17
Also published as: CN111229337B

Abstract

The invention provides a manufacturing method of an optical waveguide multi-micro-channel chip, which comprises the steps of providing a substrate, forming a sacrificial layer on the substrate, and forming a lower cladding on the sacrificial layer; forming a waveguide layer on the lower cladding layer; forming an optical waveguide with the waveguide layer; forming an upper cladding layer on the waveguide layer; forming a micro-channel; the optical waveguide is used for guiding light into the micro-channel along the horizontal direction; the micro-channel penetrates through the upper cladding and the waveguide layer from top to bottom and extends into the lower cladding; removing the sacrificial layer to strip the substrate; the width of the micro flow channel is 10-100 μm and does not penetrate through the lower cladding. 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

Method for manufacturing optical waveguide multi-micro-channel chip

Technical Field

The invention relates to a method for manufacturing an optical waveguide multi-microchannel chip, in particular to a method for manufacturing an optical waveguide multi-microchannel biological detection chip.

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 method for manufacturing an optical waveguide multi-microchannel chip, which comprises the following steps:

step 1000: providing a substrate, forming a sacrificial layer on the substrate, and forming a lower cladding layer made of a high polymer material with the thickness of 15-30 mu m on the sacrificial layer;

step 2000: forming a waveguide layer on the lower cladding layer, the waveguide layer being a silicon nitride material;

step 3000: forming a first number of optical waveguide groups with the waveguide layers, the optical waveguide groups including a second number of optical waveguides;

step 4000: forming an upper cladding layer of a high polymer material with the thickness of 15-30 mu m on the waveguide layer;

step 5000: forming a first number of micro channels, wherein the optical waveguide group and the micro channels are in one-to-one correspondence to form a first number of micro fluids to form a micro fluid group; the optical waveguide is used for guiding light into the micro-channel along the horizontal direction; the micro-channel penetrates through the upper cladding and the waveguide layer from top to bottom and extends into the lower cladding;

step 6000: removing the sacrificial layer to strip the upper cladding layer, the waveguide layer, and the lower cladding layer from the substrate; forming a flow channel cover plate on the upper cladding layer, wherein the 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 width of the micro-channel is 10-100 μm, and the micro-channel does not penetrate through the lower cladding; the corrosion selectivity of the sacrificial layer is higher than that of the upper cladding layer, the waveguide layer or the lower cladding layer, and the material of the sacrificial layer is metal, polymer or oxide.

Preferably, in step 3000, the thickness of the waveguide layer is 150-.

Preferably, in step 3000, a photoresist is spin-coated on the waveguide layer to form a mask of a light splitting structure, and the waveguide layer is etched to form a light splitting structure, where the light splitting structure is used to lead out a first number of light guide groups from the main light guide, and the light guide groups are optically connected to the light guide groups.

Preferably, in step 3000, a photoresist is spin-coated on the waveguide layer to form a first light guide mask, and the waveguide layer is etched to form a second number of first light guides, where the second number of first light guides are the trunk light guides; spin-coating an intermediate layer of polymer material on the waveguide layer, forming a second light guide groove on the intermediate layer by using electron beam direct writing, depositing a silicon nitride material in the second light guide groove and performing chemical mechanical polishing to form a first number of light guide groups of silicon nitride, wherein the light guide groups comprise a second number of second light guides, and a cross-layer structure is formed by part of the first light guides and part of the second light guides.

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.

Preferably, the second number is 1, and the whole or most of the waveguide layers corresponding to the microfluid form a sheet-like optical waveguide; the thickness of the optical waveguide is 150-1000 nm.

Preferably, in step 2000, the waveguide layer is formed by inductively coupled plasma chemical vapor deposition at a deposition temperature of 25-150 ℃ with introduction of a reaction carrier gas including a silicon gas source and a nitrogen gas source.

Preferably, in step 2000, forming the waveguide layer with a thickness of 150-1000nm on the lower cladding layer;

step 3000, spin-coating photoresist on the waveguide layer to form a plurality of parallel optical waveguide masks, and etching the waveguide layer to form a plurality of parallel optical waveguides; and spin-coating photoresist again to form an incident grating mask, depositing to form a plurality of incident gratings to form a plurality of parallel coupling optical waveguides with the optical waveguide, wherein the width of the coupling optical waveguide is 300-600 nm.

Preferably, step 5000 further includes a process of forming a mask with the upper cladding layer: soft-baking the upper cladding, carrying out local exposure on a position of the upper cladding where a micro-channel is scheduled to be formed, and forming a preparation channel which penetrates through the upper cladding and has the width of 10-100 mu m after hard baking and developing;

and etching the waveguide layer and part of the substrate below the preparation flow channel by using the upper cladding layer as a mask by using a reactive ion etching method to form the micro-flow channel.

The invention provides a manufacturing method of an optical waveguide multi-micro-channel chip, 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 schematic diagram of a light guide structure in a chip according to the present invention;

FIG. 2 is an enlarged view of A of FIG. 1;

FIG. 3 is an enlarged view of B of FIG. 1;

FIG. 4 is a cross-sectional view of FIG. 3;

FIG. 5 is a schematic view of an optical waveguide multi-microchannel chip according to the present invention;

FIG. 6 is a top view of the microfluidic device of FIG. 1;

FIG. 7 is a top view of a chip optical waveguide microfluidic;

FIG. 8 is a side view of the optical waveguide microfluidics used in FIG. 1;

fig. 9 is a side view of a coupled light waveguide microfluidic device.

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 manufacturing method of an optical waveguide multi-micro-channel chip, which forms a structure of an optical waveguide and multi-micro-channel integrated matrix and can quickly construct a chip-level on-chip optical detection and analysis integrated system of a high-flux biological sample under a micro-nano scale.

A method for manufacturing an optical waveguide multi-microchannel chip 1, as shown in fig. 5, includes:

step 1000: providing a substrate 11, forming a sacrificial layer 10 on the substrate 11, and forming a lower cladding 141 made of a high polymer material with the thickness of 15-30 μm on the sacrificial layer 10;

step 2000: forming a waveguide layer 13 on the lower cladding layer 141, the waveguide layer 13 being a silicon nitride material;

step 3000: forming a first number m of

optical waveguide groups

131, 132, 13m with said waveguide layer 13, said optical waveguide groups 131 comprising a second number n of

optical waveguides

1311, 1312 … 131n, as shown in fig. 6, to form an n x m matrixed detection system;

step 4000: forming an upper cladding 142 of a polymer material with a thickness of 15-30 μm on the waveguide layer 13;

step 5000: forming a first number m of

micro channels

201, 202 … 20m, wherein the optical waveguide group 131 and the micro channels 201 form a first number m of microfluids in a one-to-one correspondence, and the first number m of microfluids form a microfluid group; the

optical waveguides

1311, 1312 … 131n are used for guiding light into the micro channel 201 along the horizontal direction; the

micro flow channels

201, 202 … 20m extend from top to bottom through the upper cladding layer 142 and the waveguide layer 13 into the lower cladding layer 141;

step 6000: removing the sacrificial layer 10 to strip the upper cladding layer 142, the waveguide layer 13 and the lower cladding layer 141 from the substrate 11; forming a flow channel cover plate 15 on the upper cladding 142, wherein the flow channel cover plate 15 comprises

liquid injection ports

151 and 152 … 15m for injecting a solution containing a biomolecule 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 ports

151, 152 … 15m, and the liquid outlet may be an opening on the flow path cover plate 15; the liquid outlet may also be an opening at both ends of the micro flow channel, and the invention is not limited herein.

The width of the

micro channel

201, 202 … 20m is 10-100 μm, and the

micro channel

201, 202 … 20m does not penetrate the lower cladding 141; the corrosion selectivity of the sacrificial layer 10 is higher than that of the upper cladding 142, the waveguide layer 13 or the lower cladding 141, the sacrificial layer 10 is made of metal, polymer or oxide, a structure of an integrated matrix of an optical waveguide and a plurality of microchannels is formed, 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.

It should be noted that the first number m of microfluids forms a microfluid group, and a microfluid matrix formed by a third number k of microfluid groups can be constructed, and a matrixed detection system with total number n × m × k of optical waveguides can 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 optical waveguides parallel to each other, as shown in fig. 5 and 6, the optical waveguide group 131 includes a second number n of

optical waveguides

1311, 1312 … 131n parallel to each other to guide light into the micro channel 201 along the horizontal direction, and the width of the optical waveguides is 300-600 nm.

In step 3000, the thickness of the waveguide layer is 150-.

Wherein the light source directions are different according to the waveguide set 131, such as: fig. 8 shows that the light source is introduced from the left end of the optical waveguide set 131, and fig. 9 shows that the light source is introduced from above the optical waveguide set 131, in the multi-micro channel, especially the matrixing detection system, the former needs to be added with the light guide structure 6 shown in fig. 1 from the structure when the matrixing chip is manufactured, and the latter does not need to be added with the light guide structure, and the manufacturing method of the light guide structure 6 is described below with reference to the following figures:

step 3000, as shown in fig. 1-2 and fig. 6, further comprising spin-coating a photoresist (not shown) on the waveguide layer 13 to form a light splitting structure mask (not shown), etching the waveguide layer 13 to form a light splitting structure a, where the light splitting structure a is used to extract a first number m of

light guide sets

601, 602, and 60m from the trunk light guide 60, the

light guide sets

601, 602, and 60m are respectively optically connected with the

light waveguide sets

131 and 132 … 13m, and further the light guide set 601 is optically connected with the

light waveguides

1311 and 1312 … 131n in the light waveguide set 131, as shown in fig. 6, the widths of the

light waveguides

1311 and 1312 … 131n are 300-600 nm; the

light guide sets

601, 602, and 60m are led out from the trunk light guide 60 by using a light splitting structure a.

Step 3000, further comprising spin-coating a photoresist (not shown) on the waveguide layer 13 to form a first light guide mask (not shown), and etching the waveguide layer 13 to form a second number n of first light guides 61, where the second number n of the first light guides 61 is the trunk light guides 60; spin coating an intermediate layer (not shown) of polymer material on the waveguide layer 13, forming a second light guiding groove (not shown) on the intermediate layer using electron beam direct writing, depositing silicon nitride in the second light guiding groove and chemical mechanical polishing to form a first number m of second light guiding groups 62 of a second number n of silicon nitride, i.e. a total number n m of second light guiding groups 62, the second number n of second light guiding groups 62 being the light guiding group, such as 601, 602 or 60m in fig. 1; as shown in fig. 5, a cross-layer structure B is formed by a part of the first light guide 61 and a part of the second light guide 62; specifically, except for the first second light guide 62 led out from the leftmost a' region, the remaining second light guides 62 led out from the other a regions on the right intersect with the first light guide 61, that is, the light guide sets 602..60m are provided to the second micro flow channel 202 … with n light guides until the mth micro flow channel 20m along with the main light guide 60, and the second light guides 62 all intersect with the first light guide 61, so that for the integrated optical waveguide multi-micro flow channel chip 1 matrixed by the multi-flow channel monitoring system of fig. 5, a specific light guide structure 6 needs to be designed, as shown in fig. 5, for the above-mentioned detection system matrixed by n m light guides, the light guide structure 6 described in fig. 1 is provided, including the main light guide 60, and the light guide sets 601, 602 … 60m led out from the main light guide 60, so as to transmit light sources to the micro flow channels 201, 202 … 20m respectively; the trunk light guide 60 includes n first light guides 61, which transmit light with wavelengths λ 1, λ 2, λ 3 … λ n, respectively, to transmit to the optical waveguides 1311, 1312 … 131n in the optical waveguide group 131, respectively, and n optical waveguides in the other optical waveguide group. The leading-out node a of the light guide groups 601 and 602 … 60m leading out from the trunk guide light 60 and the light guide cross node B in the leading-out guide light and the trunk guide light 60 need to be specially designed; the light guide groups 601 and 602 … 60m are led out from the trunk light guide 60 by adopting a light splitting structure, as shown in fig. 2, the light splitting structure of the node a is led out, and the second light guide 62 in the light guide groups 601 and 602 … 60m is led out from the first light guide 61 in the trunk light guide 60; as shown in fig. 3 to 4, the light guide structure is a cross-layer structure of a cross node B, the trunk light guide 60 includes a first light guide 61, the light guide group 601 includes a second light guide 62, and the first light guide 61 and the second light guide 62 are crossed by the cross-layer structure; the cross-layer structure comprises a first light directing overlap region 610 and a second light directing overlap 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 acute angle light guide end surface, 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 broken end of the first light guide 61 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 through the second light guide overlapping region 620, that is, the light transmitted from the broken end of the first light guide 61 enters the first acute angle light guide surface 621 through the first acute angle light guide end surface 611, the light guide surface is consistent with the conduction direction of the light which is not reflected, and then enters the second acute angle light guide end surface 612 through, thereby completing the cross-layer conduction of light.

In the detection system in which the total number of optical waveguides is n × m × k matrix, the light source may be continuously transmitted to the next microfluidic group to the kth microfluidic group by using the light splitting structure a in sequence in each of the

light guide groups

601 and 602 … 60 m.

As shown in fig. 1 and 5, the thickness of the waveguide layer 13 finally formed after the step 3000 is 150-.

As shown in fig. 5 and 7, the optical waveguide sets 131 and 132 … 13m may include only one optical waveguide, that is, the second number n is 1, and the light guide sets 601 and 602 … 60m each include a light guide line to be optically connected to the optical waveguide sets 131 and 132 … 13m respectively; that is, the whole or most of the waveguide layer 13 corresponding to one microfluid forms a sheet waveguide 1311, the excitation optical field introduced by the sheet waveguide 1311 can reduce the background optical signal in the detection-labeled biomolecule, greatly improving the detection of small biomolecule; the thickness of the optical waveguide is 150-1000 nm.

If a multi-micro-channel chip including the coupled optical waveguide shown in fig. 9 is required to be formed, and a light guide structure is not required to be formed, in step 2000, the waveguide layer 13 with a thickness of 150-1000nm is formed on the lower cladding layer 141; in step 3000, photoresist (not shown) is coated on the waveguide layer 13 to form a plurality of mutually parallel optical waveguide masks (not shown), and the waveguide layer 13 is etched to form a second number n of mutually parallel optical waveguides 1311, 1312 … 131n, i.e. the optical waveguides (horizontal portions) in the coupled optical waveguide 131 shown in fig. 9; spin-coating photoresist (not shown) again to form an incident grating mask (not shown), depositing to form a plurality of incident gratings to form a second number n of mutually parallel coupled optical waveguides 131 with the optical waveguide, guiding the light above the upper cladding 142 into the optical waveguide until the light is guided into the microchannel 201 along the horizontal direction, wherein the upper cladding 142 and the channel cover plate 15 are light-transmissive layers; the incident grating protrudes from the waveguide layer 13 and extends upwards into the upper cladding layer 142, and the width of the coupling optical waveguide is 300-600 nm; forming a micro channel mask (not shown) on the waveguide layer 13 on which the coupling optical waveguide 131 has been formed, using a photoresist (not shown), etching the waveguide layer 13 using a reactive ion etching method, and forming a part of channels (not shown) of the micro channels 201, 202, 20m corresponding to the waveguide layer 13; an upper cladding layer 142 of 15-30 μm polymer material is spin-coated on the surface of the waveguide layer 13, and the upper cladding layer 142 is a light-transmitting layer. In step 5000, soft-baking the upper cladding 142, performing local exposure on the positions on the upper cladding 142 where the

micro channels

201, 202, 20m are to be formed, and then hard-baking and developing to remove all the upper cladding 142 and part of the lower cladding 141 corresponding to the part of the channels, so as to form the

micro channels

201, 202, 20 m. In step 6000, wet etching, dry vapor etching or reactive ion etching is used to remove the sacrificial layer 10, so as to strip the upper cladding 142, the waveguide layer 13 and the lower cladding 141 from the substrate 11, thereby completing the manufacture of the optical waveguide multi-microchannel chip containing the coupled optical waveguide group.

It should be noted that, the coupling optical waveguide or the incident grating may be formed by: in step 3000, a waveguide layer 13 of silicon nitride with a thickness greater than 600nm is formed, optical waveguide masks parallel to each other are formed on the waveguide layer 13 by using photoresist, the waveguide layer 13 is etched to obtain optical waveguides (integral parts) parallel to each other and having a width of 300 and 600nm, and the photoresist is spin-coated again to expose and form an incident grating (not shown) so as to form a coupled optical waveguide.

In the present invention, step 5000 further includes a process of forming a mask with the upper cladding layer 142: soft-baking the upper cladding 142, performing local exposure on a position of the upper cladding 142 where a micro flow channel is to be formed, and forming a preparation flow channel (not shown) penetrating the upper cladding 142 and having a width of 10-100 μm after hard-baking and developing; and etching the waveguide layer 13, the lower cladding layer 141 and a part of the substrate 11 below the preliminary flow channel by using the upper cladding layer 142 as a mask through a reactive ion etching method to form the

micro flow channels

201 and 202 … 20 m.

In the present invention, 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 present invention, in step 6000, the sacrificial layer 10 is removed using wet etching, dry vapor etching, or reactive ion etching.

In the invention, in step 2000, by an inductively coupled plasma chemical vapor deposition method, the deposition temperature is 25-150 ℃, and reaction carrier gas comprising a silicon gas source and a nitrogen gas source is introduced to form the waveguide layer 13, so as to avoid softening, hardening or melting the lower cladding 141 of the high polymer material, thereby realizing integration of the silicon nitride optical waveguide on a flexible substrate such as the high polymer material, and the like, and being capable of being attached to other detection devices or materials, and greatly increasing the application range. The following describes a process for forming a silicon nitride waveguide layer 13, particularly for depositing an optically tunable silicon nitride waveguide layer 13 at low temperatures, comprising:

depositing an optically adjustable silicon nitride film on the lower cladding 141 by an inductively coupled plasma chemical vapor deposition method, wherein the deposition temperature is 25-150 ℃, and introducing a reaction carrier gas, wherein the reaction carrier gas comprises a silicon gas source and a nitrogen gas source, the flow ratio of the nitrogen gas source to the silicon gas source is 0.5-16, and the thickness of the silicon nitride film is 150nm-1000 nm; different from the traditional generation mechanism of capacitive coupling radio frequency and other low-pressure high-density plasmas, the Inductive Coupling Plasma Chemical Vapor Deposition (ICPCVD) method applies high-frequency current on an inductive coil, and the coil excites a changing magnetic field under the drive of the radio-frequency current, and the changing magnetic field induces a cyclotron electric field. The electrons make a cyclotron motion under the acceleration of a cyclotron electric field, the reaction carrier gas molecules are collided and dissociated, a large number of active plasma groups are generated, the air flow transports the active plasma groups to the surface of the lower cladding 141 and the active plasma groups are adsorbed, and the surface of the lower cladding 141 reacts to form the silicon nitride film; the cyclotron of electrons in the inductively coupled plasma chemical vapor deposition increases the collision probability with gas molecules, and can generate higher plasma density than the traditional capacitive discharge, so that the low-temperature rapid deposition of high-quality films becomes possible; the silicon nitride film formed in the step has good compactness, small damage to the flexible substrate, good refractive index, adhesiveness, step coverage and stability, low impurity and hole content and high breakdown voltage. The temperature range of the silicon nitride film deposited in the step is 25-150 ℃, which is far lower than the PECVD deposition temperature, the silicon nitride film is deposited on the lower cladding 141 under the low-temperature process, and the refractive index of the silicon nitride film is adjusted by adjusting the reaction carrier gas, so that the optical performance of the silicon nitride film is adjustable. 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. 5 and 6, an embodiment of detecting circulating tumor cells by using a detection system comprising the optical waveguides of the optical waveguide multi-microchannel chip of the present invention, wherein the total number of the 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 and 5, 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) guide the n different wavelengths of light corresponding to the n markers one by one into the n light guides (as shown in fig. 5 and 6) 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, wherein the n light guides 1 and 1312 … 131n in the light guide set 131 are incompletely listed, total number of light guides n × k are excited by the fluorescence molecule 13121 which is excited by the light of the fluorescence molecule which emits the specific wavelength of the fluorescence molecule The non-excited biomolecule 20 is an unlabeled normal cell or a labeled tumor cell which is not excited but is located outside an optical field, the microscope (not shown) is used for collecting fluorescence (optical signal) with a specific wavelength and transmitting the fluorescence (optical signal) to the measuring device (not shown), the measuring device (not shown) is used for processing the fluorescence (optical signal) with the specific wavelength and generating a signal to be analyzed and transmitting the signal to be analyzed to the analyzing device (not shown), the analyzing device (not shown) analyzes the signal to be analyzed to form a spectrum of the fluorescence with the specific wavelength, the type of the circulating tumor cell in the solution or the blood sample can be judged by reading the spectrum, the circulating tumor cells of different patients can be detected respectively at one time, a high-flux chip for detecting the various tumor cells under the micro-nano scale is realized, thereby the tumor dynamics can be monitored in real time and the treatment effect can be evaluated, real-time individual treatment is achieved.

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

1. A method for manufacturing an optical waveguide multi-microchannel chip includes:

2. The method as claimed in claim 1, wherein in step 3000, the thickness of the waveguide layer is 150-.

3. The method of claim 2, wherein step 3000 comprises spin-coating photoresist on the waveguide layer to form a reticle, and etching the waveguide layer to form a reticle, the reticle being configured to extract a first number of light directing groups from the trunk light, the light directing groups being optically coupled to the light directing groups.

4. The method of claim 3, wherein step 3000, a first light guide mask is formed by spin coating photoresist on the waveguide layer, and the waveguide layer is etched to form a second number of first light guides, the second number of first light guides being the trunk light guides; spin-coating an intermediate layer of polymer material on the waveguide layer, forming a second light guide groove on the intermediate layer by using electron beam direct writing, depositing a silicon nitride material in the second light guide groove and performing chemical mechanical polishing to form a first number of light guide groups of silicon nitride, wherein the light guide groups comprise a second number of second light guides, and a cross-layer structure is formed by part of the first light guides and part of the second light guides.

5. The method of claim 4, 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.

6. The method 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; the thickness of the optical waveguide is 150-1000 nm.

7. The method of claim 1, wherein the waveguide layer is formed by inductively coupled plasma chemical vapor deposition at a deposition temperature of 25-150 ℃ with introduction of a reaction carrier gas comprising a silicon gas source and a nitrogen gas source in step 2000.

8. The method as claimed in claim 1, wherein the waveguide layer is formed on the lower cladding layer to a thickness of 150-1000nm in step 2000;

9. The method of claim 1, wherein step 5000 further comprises the process of forming a mask with the upper cladding layer: soft-baking the upper cladding, carrying out local exposure on a position of the upper cladding where a micro-channel is scheduled to be formed, and forming a preparation channel which penetrates through the upper cladding and has the width of 10-100 mu m after hard baking and developing;