CN111229338B

CN111229338B - Manufacturing method of optical waveguide microfluid chip based on CMOS image sensing

Info

Publication number: CN111229338B
Application number: CN202010053316.2A
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: 2021-11-30
Anticipated expiration: 2040-01-17
Also published as: CN111229338A

Abstract

The invention provides a method for manufacturing an optical waveguide microfluidic chip based on CMOS image sensing, which comprises the following steps. Has the advantages that: the silicon nitride optical waveguide with adjustable optical performance is deposited on the CMOS image sensing layer and the high polymer material at low temperature, 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.

Description

Manufacturing method of optical waveguide microfluid chip based on CMOS image sensing

Technical Field

The invention relates to a method for manufacturing an optical waveguide microfluid chip based on CMOS image sensing, in particular to a method for manufacturing an optical waveguide microfluid biological detection chip 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 a manufacturing method of an optical waveguide microfluidic chip based on CMOS image sensing, which comprises the following steps:

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

step 2000: depositing a waveguide layer forming a silicon nitride material on the lower cladding layer at a deposition temperature of 25-150 ℃;

step 3000: forming an optical waveguide with the waveguide layer;

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 micro-channel, wherein the optical waveguide is used for guiding light into the micro-channel along the horizontal direction, and the micro-channel penetrates through the upper cladding, the waveguide layer and the lower cladding from top to bottom to expose the CMOS image sensing layer;

the width of the micro flow channel is 10-100 μm.

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

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

Preferably, in step 3000, the thickness of the waveguide layer is 150-1000nm, a photoresist is spin-coated on the waveguide layer to form a micro channel mask, the waveguide layer is etched to form a preliminary channel, and the width of the preliminary channel is 10-100 μm.

Preferably, in step 2000, said waveguide layer is formed on said lower cladding layer to a thickness of 150nm to 1000 nm;

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

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, in step 1000, the polymeric material is spin-coated on the CMOS image sensing layer, and is pre-baked at 50-120 ℃ for 1-30 minutes to form a lower cladding layer of the flexible film substrate.

Preferably, in step 4000, the polymer material is spin-coated on the waveguide layer, and pre-baked at 50-120 ℃ for 1-30 minutes to form an upper cladding layer of the flexible film substrate.

Preferably, in step 5000, the upper cladding layer is soft-baked, the position of the prepared channel on the upper cladding layer is exposed by local exposure or direct electron beam writing, and the micro channel is formed after hard baking and development.

Preferably, the high molecular polymer material is SU-8 resin, polyimide, polydimethylsilane, polyethylene or benzocyclobutene.

The invention provides a manufacturing method of an optical waveguide microfluid chip based on CMOS image sensing, which has the following beneficial effects: the silicon nitride optical waveguide with adjustable optical performance is deposited on the CMOS image sensing layer and the high polymer material at low temperature, 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.

Drawings

FIGS. 1 a-d show the manufacturing process of the optical waveguide micro-fluid chip based on CMOS image sensing according to the present invention;

FIGS. 2 a-e are the manufacturing process of the coupled optical waveguide microfluidic chip based on CMOS image sensing according to the present invention;

FIG. 3 is a top view of FIG. 1;

FIG. 4 is a top view of the sheet optical waveguide of FIG. 1;

FIG. 5 is a flow chart of the method for manufacturing the optical waveguide microfluidic chip based on CMOS image sensing according to the present invention.

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 method for manufacturing a horizontal optical waveguide and microfluidic channel integrated chip, which is used for quickly constructing a chip-level on-chip optical detection chip of a high-flux biological sample under a micro-nano scale. Here, the horizontal optical waveguide means an optical waveguide for guiding light into a microchannel in a horizontal direction.

As shown in fig. 1 to 5, a method for manufacturing an optical waveguide microfluidic chip based on CMOS image sensing includes:

step 1000: providing a CMOS image sensing layer 18, and forming a lower cladding 141 made of a high polymer material with the thickness of 15-30 mu m on the CMOS image sensing layer 18;

step 2000: depositing a waveguide layer 13 forming a silicon nitride material on the lower cladding layer 141 at a deposition temperature of 25-150 ℃;

step 3000: forming

optical waveguides

1311, 1312 … 131n with the waveguide layer 13;

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

step 5000: forming a micro channel 2, the

optical waveguides

1311, 1312 … 131n being used to introduce light into the micro channel 2 in a horizontal direction, the micro channel 2 penetrating the upper cladding 142, the waveguide layer 13 and the lower cladding 141 from top to bottom to expose the CMOS image sensing layer 18; the width of the micro flow channel 2 is 10-100 μm; the silicon nitride optical waveguide is formed on the CMOS image sensing layer 18 and the lower cladding 141 made of the high polymer material by a low-temperature growth process, so that the CMOS image sensing layer 18 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, the application scenes of the system are greatly increased, the secondary chip-level optical detection chip is produced by an integrated circuit process, the functions of the traditional optical system are realized by integrated optics 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-throughput 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.

In all embodiments, in step 2000, said waveguide layer 13 of silicon nitride material is formed by inductively coupled plasma chemical vapor deposition at a deposition temperature of 25-150 ℃ with the introduction of a reactive carrier gas comprising a silicon gas source and a nitrogen gas source.

The following describes the process for forming the silicon nitride waveguide layer 13, especially for depositing the silicon nitride waveguide layer 13 with adjustable optical properties at low temperature, to avoid softening, hardening or melting the lower cladding 141 of the polymer material and damaging the CMOS image sensing layer 18, thereby reducing the preparation work for adjusting the collection light path in the experiment and improving the experiment efficiency; the portability of the detection system is improved, the application scenes of the system are greatly increased, and the method comprises the following steps:

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 ℃, softening, hardening or melting of the lower cladding 141 of the high polymer material and damage of the CMOS image sensing layer 18 are avoided, and reaction carrier gas is introduced, 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-1000nm, so that the silicon nitride optical waveguide is integrated on a flexible substrate such as a high polymer material and the like, can be used for being attached to other detection devices or materials, and the application range is greatly increased; 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.

Wherein the light source direction is different according to the introduction of the optical waveguide assembly 131, such as: fig. 1d illustrates the introduction of a light source from an optical fiber (not shown) at the left end of the optical waveguide group 131, and fig. 2e illustrates the introduction of a light source from above the optical waveguide group 131, respectively describing the manufacturing methods thereof.

Fig. 1d, the present optical waveguide microfluidic chip with light source introduced from the optical fiber (not shown) at the left end of the optical waveguide set 131, is described as follows:

to form the mutually parallel

optical waveguides

1311, 1312 … 131n in the optical waveguide group 131 shown in fig. 3. As shown in fig. 1a, in step 3000, the thickness of the waveguide layer 13 is 150-1000nm, photoresist 16 is coated on the waveguide layer 13 to form a plurality of mutually parallel optical waveguide masks (not shown) and micro-channel masks (not shown), the waveguide layer 13 is etched to form an optical waveguide set 131 and a preliminary channel (not shown) on one micro-fluid shown in fig. 3 and 1b, the width of the preliminary channel is 10-100 μm, the optical waveguide set 131 includes a plurality of, e.g., n, mutually parallel optical waveguides 1311, 1312 … 131n to introduce light into the micro-channel 2 along the horizontal direction, in the actual detection, for different labeled biomolecules in the micro-channel 2, the optical waveguides 1311, 1312 … 131n can introduce light with wavelengths λ 1, λ 2 … λ n into the micro-channel 2 along the horizontal direction, and the differently labeled biomolecules 21 can be simultaneously identified by exciting the differently labeled biomolecules with the light with different wavelengths, while the non-excisional biomolecules 20 which are not in the excited light field introduced by the light guides 1311, 1312 … 131n will not be recognized, the non-excisional biomolecules 20 being unlabeled normal biomolecules or biomolecules which are labeled but which are 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. 1c, a layer of 15-30 μm polymer material is spin-coated on the surface of the waveguide layer 13, and then the upper cladding layer 142 of the flexible film substrate is formed by pre-baking at 50-120 ℃ for 1-30 minutes. As shown in fig. 1c, in step 5000, the upper cladding layer 142 is soft-baked, the position of the prepared channel is exposed by local exposure and direct electron beam writing, and then the prepared channel is hard-baked and developed to form a micro channel 2 with a width of 10-100um penetrating through the upper cladding layer 142, the waveguide layer 13 and the lower cladding layer 141 so as to expose the CMOS image sensing layer 18. To form an optical waveguide microfluidic chip as shown in fig. 1d and 3.

As shown in fig. 4, the whole or most of the waveguide layer 13 forms a sheet-shaped optical waveguide 1311, and the excitation light field introduced by the sheet-shaped optical waveguide 1311 can reduce the background light signal in the detection-labeled biomolecule, thereby greatly improving the detection rate of the small biomolecule. To form the slab optical waveguide 1311: as shown in fig. 1a, in step 3000, after forming the waveguide layer 13 with a thickness of 150-1000nm, spin-coating photoresist on the waveguide layer 13 to form a micro-channel mask (not shown), etching the waveguide layer 13 to form the sheet-shaped optical waveguide 1311 shown in fig. 4 and a preliminary channel (not shown) shown in fig. 1b, where the width of the preliminary channel is 10-100 μm as shown in fig. 1c, then spin-coating a layer of 15-30 μm high-molecular polymer material on the surface of the waveguide layer 13, and forming the upper cladding 142 of the flexible film substrate by pre-baking at 50-120 ℃. As shown in fig. 1c, in step 5000, the upper cladding layer 142 is soft baked, the position of the preparation flow channel is locally exposed by using local exposure, and then the preparation flow channel is hard baked and developed to form a micro flow channel 2 which penetrates through the upper cladding layer 142, the waveguide layer 13 and the lower cladding layer 141 to expose the CMOS image sensing layer 18 and has a width of 10-100um, so as to form an optical waveguide microfluidic chip including the sheet optical waveguide 1311 shown in fig. 1d and fig. 4.

The following describes a method of manufacturing an optical waveguide microfluidic chip comprising coupled optical waveguides, as shown in fig. 2e, which introduces a light source from above the optical waveguide assembly 131, as shown in fig. 2 e:

as shown in fig. 2a, in step 2000, the waveguide layer 13 with a thickness of 150nm-1000nm is formed on the lower cladding layer 141, in step 3000, photoresist (not shown) is spun on the waveguide layer 13 to form a plurality of mutually parallel optical waveguide masks, the waveguide layer 13 is etched to form a plurality of mutually parallel optical waveguides, and in this step, optical waveguides (horizontal portions) in the coupled optical waveguides shown in fig. 3 can be formed; as shown in fig. 2b and fig. 3, in step 3000, photoresist 16 is again coated to form an incident grating mask, and a plurality of incident gratings (not shown) are deposited to form a plurality of coupling optical waveguides parallel to each other with the optical waveguide, where the width of the coupling optical waveguide is 300-600 nm. Forming a micro flow channel mask on the waveguide layer 13 on which the coupling optical waveguide has been formed, using a photoresist 16, as shown in fig. 2c, and etching the waveguide layer 13 using a reactive ion etching method to form a preliminary flow channel (not shown) as shown in fig. 2 c; as shown in fig. 2d, in step 3000, a layer of 15-30 μm polymer material is spin-coated on the surface of the waveguide layer 13, and the upper cladding layer 142 of the flexible film substrate is formed by pre-baking at 50-120 ℃ for 1-30 minutes, where the upper cladding layer 142 is a light-transmissive layer. As shown in fig. 2d, in step 5000, soft-baking the upper cladding 142, exposing the positions of the prepared channels on the upper cladding 142 by using local exposure or direct electron beam writing, and then hard-baking and developing to remove all the upper cladding 142 and the lower cladding 141 corresponding to the prepared channels to expose the CMOS image sensing layer 18, as shown in fig. 2e, so as to form the micro channels 2, thereby completing the manufacturing of the optical waveguide microfluidic chip of the coupling optical waveguide group 131 as shown in fig. 2e and fig. 3.

It should be noted that, the coupling optical waveguide or the incident grating may be formed by: forming a waveguide layer 13 of silicon nitride with a thickness greater than 600nm, forming mutually parallel optical waveguide masks on the waveguide layer 13 by using photoresist, etching the waveguide layer 13 to obtain mutually parallel optical waveguides (integral parts) with a width of 300-600nm, and spin-coating photoresist to expose to form an incident grating (not shown) to form a coupled optical waveguide, i.e. a coupled optical waveguide group 131.

As shown in fig. 1d and 2e, the polymer material of the upper cladding layer 142 and the lower cladding layer 141 is SU-8 resin, polyimide, polydimethylsilane, polyethylene or benzocyclobutene.

As shown in fig. 1a to 2e, a substrate 11 is arranged below the CMOS image sensing layer 18, and the substrate 11 is a silicon substrate. The CMOS image sensing layer 18 has a filter layer (not shown) on its surface.

The manufacturing method of the optical waveguide microfluid provided by the invention produces the secondary chip-level optical detection chip by an integrated circuit process, realizes the function of the traditional optical system by integrated optics or an on-chip optical device, not only can reduce the size of the traditional desktop or even large-scale optical system to the chip size, but also ensures the equal or even more excellent analysis performance, realizes the high-flux chip-level optical detection and analysis integrated system of biological samples under the micro-nano scale, and greatly reduces the system cost.

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.

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.

Claims

1. A manufacturing method of an optical waveguide microfluidic chip based on CMOS image sensing comprises the following steps:

step 2000: depositing a waveguide layer of a silicon nitride material on the lower cladding layer at the deposition temperature of 25-150 ℃, wherein the deposition temperature is 25-150 ℃ by an inductively coupled plasma chemical vapor deposition method, and introducing reaction carrier gas comprising a silicon gas source and a nitrogen gas source to form the waveguide layer of the silicon nitride material;

step 3000: forming an optical waveguide with the waveguide layer;

the width of the micro flow channel is 10-100 μm.

2. The method as claimed in claim 1, wherein in step 3000, the thickness of the waveguide layer is 150-1000nm, a photoresist is spin-coated on the waveguide layer to form a plurality of mutually parallel optical waveguide masks, the waveguide layer is etched to form a plurality of mutually parallel optical waveguides, and the width of the optical waveguides is 300-600 nm.

3. The method as claimed in claim 1, wherein in step 3000, the thickness of the waveguide layer is 150-1000nm, a photoresist is spin-coated on the waveguide layer to form a micro flow channel mask, the waveguide layer is etched to form a preliminary flow channel, and the width of the preliminary flow channel is 10-100 μm.

4. The method of claim 1, wherein in step 2000, said waveguide layer is formed to a thickness of 150nm to 1000nm on said lower cladding layer;

5. The method of claim 1, wherein in step 2000, said waveguide layer is formed to a thickness of 150nm to 1000nm on said lower cladding layer;

6. The method of claim 1, wherein in step 1000, the polymeric material is spin coated on the CMOS image sensing layer and pre-baked at 50-120 ℃ for 1-30 minutes to form a lower cladding layer of a flexible film substrate.

7. The method of claim 1, wherein in step 4000, the polymeric material is spin coated onto the waveguide layer and pre-baked at 50-120 ℃ for 1-30 minutes to form an upper cladding layer of the flexible film substrate.

8. The method of claim 3, wherein in step 5000, the upper cladding layer is soft baked, and the positions of the prepared flow channels on the upper cladding layer are exposed by local exposure or electron beam direct writing, and then subjected to hard baking and development to form the micro flow channels.

9. The method of claim 1, wherein the polymeric material is SU-8 resin, polyimide, polydimethylsilane, polyethylene, or benzocyclobutene.