CN211785572U - Optical waveguide microfluid detection system - Google Patents
Optical waveguide microfluid detection system Download PDFInfo
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- CN211785572U CN211785572U CN202020114578.0U CN202020114578U CN211785572U CN 211785572 U CN211785572 U CN 211785572U CN 202020114578 U CN202020114578 U CN 202020114578U CN 211785572 U CN211785572 U CN 211785572U
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Abstract
The utility model provides an optical waveguide microfluid detection system, which comprises a microfluid chip, a microscope, a measuring device and an analysis device; the microfluidic chip includes: the optical waveguide is used for guiding light into the micro-channel along the horizontal direction; further comprising: the substrate, the lower cladding, the waveguide layer, the upper cladding and the flow channel cover plate are arranged from bottom to top in sequence, the waveguide layer is made of silicon nitride materials and is used for forming an optical waveguide; the micro-channel penetrates through the upper cladding, the waveguide layer and the lower cladding from top to bottom and extends into the substrate; the lower cladding layer is made of silicon dioxide with the thickness of 2-3 mu m, the upper cladding layer is made of a high polymer material with the thickness of 15-30 mu m, the micro-channel extends into the substrate by 10-15 mu m, and the width of the micro-channel is 10-100 mu m. Has the advantages that: the traditional desktop or even large-scale optical system is 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.
Description
Technical Field
The invention relates to an optical waveguide microfluid detection system, in particular to an optical waveguide microfluid biological detection system.
Background
In modern biochemical analysis procedures, high-throughput detection devices have been widely used. Most of these devices use biochips based on microfluidic technology or microwell arrays, loaded in high performance optical systems, to perform analysis of biological samples of different sizes, such as nucleic acids, proteins, viruses, bacteria, cells, etc. The design of these optical systems is usually based on complex geometric optics, which is bulky, costly, requires optical alignment, and is costly to maintain.
In the precise medical age, miniaturized, high-performance, low-cost and mobile integrated analysis systems are of great concern. In particular, the lab on chip concept has advanced a lot of progress in manipulating a biological sample based on a microfluidic technology after decades of development, but a real lab on chip system still lacks an integrated system for chip-level on-chip optical detection and analysis of a high-throughput biological sample on a micro-nano scale.
SUMMERY OF THE UTILITY MODEL
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 an optical waveguide microfluid detection system, comprising: microfluidic chips, microscopes, measurement devices and analysis devices; characterized in that the microfluidic chip comprises: the optical waveguide is used for guiding light into the micro-channel along the horizontal direction, the microscope is used for collecting optical signals in the micro-channel and transmitting the optical signals to the measuring device, the measuring device is used for processing the optical signals, generating signals to be analyzed and transmitting the signals to be analyzed to the analyzing device, and the analyzing device analyzes the signals to be analyzed to form a spectrum;
the microfluidic chip further comprises: the substrate, the lower cladding, the waveguide layer, the upper cladding and the flow channel cover plate are arranged from bottom to top in sequence, the waveguide layer is made of silicon nitride materials and is used for forming the optical waveguide;
the micro-channel penetrates through the upper cladding, the waveguide layer and the lower cladding from top to bottom and extends into the substrate;
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 silicon dioxide with the thickness of 2-3 mu m, the upper cladding is a high polymer material with the thickness of 15-30 mu m, the micro-channel extends into the substrate by 10-15 mu m, and the width of the micro-channel is 10-100 mu m.
Preferably, a plurality of the optical waveguides are parallel to each other to guide light into the micro flow channel, and the width of the optical waveguide is 300-600 nm.
Preferably, the entire or a majority of the waveguide layers form a slab of the optical waveguide.
Preferably, the waveguide layer thickness is 150-1000 nm.
Preferably, the optical waveguide further comprises an incident grating made of silicon nitride material to form a coupled optical waveguide with the optical waveguide, and the light above the upper cladding is guided into the optical waveguide until the micro channel is guided; the incident grating protrudes from the waveguide layer and extends upwards into the upper cladding layer.
Preferably, a plurality of said coupling optical waveguides are included, parallel to each other.
Preferably, the thickness of the waveguide layer is 150-1000nm, and the width of the coupling optical waveguide is 300-600 nm.
Preferably, an optical fiber is further included, the optical fiber being optically coupled with the optical waveguide.
Preferably, the substrate is a silicon substrate.
Preferably, the high molecular polymer material is SU-8 resin, polyimide, polydimethylsilane, polyethylene or benzocyclobutene.
The invention provides an optical waveguide microfluid detection system, which realizes the function of a traditional optical system through an integrated optical device or an on-chip optical device, not only can reduce the size of a chip of the traditional desktop or even large-scale optical system, but also ensures the same or even more excellent analysis performance, realizes a high-flux chip-level optical detection and analysis integrated system of a biological sample under the micro-nano scale, and greatly reduces the system cost.
Drawings
FIG. 1 is a side view of an optical waveguide microfluidic detection system according to the present invention;
FIG. 2 is a side view of a coupled optical waveguide microfluidic detection system according to the present invention;
FIG. 3 is a top view of the microfluidic chip of FIG. 2;
FIG. 4 is a top view of the microfluidic chip of FIG. 1;
FIG. 5 is the optical waveguide microfluidic chip of FIG. 1;
fig. 6 is the coupled optical waveguide microfluidic chip of fig. 2.
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 horizontal optical waveguide microfluid detection system, which brings a chip-level on-chip optical detection chip of a high-flux biological sample under a micro-nano scale into a detection and analysis system. 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 4, an optical waveguide microfluidic detection system includes: a microfluidic chip (not shown), a microscope 3, a measuring device 4 and an analyzing device 5; the microfluidic chip includes: optical waveguides 1311, 1312 … 131n and a microchannel 2, wherein the optical waveguides 1311, 1312 … 131n are used for guiding light into the microchannel 2 along a horizontal direction, the microscope 3 is used for collecting optical signals in the microchannel 2 and transmitting the optical signals to the measuring device 4, the measuring device 4 is used for processing the optical signals and generating signals to be analyzed and transmitting the signals to be analyzed to the analyzing device 5, and the analyzing device 5 analyzes the signals to be analyzed to form a spectrum; it is characterized in that the preparation method is characterized in that,
the microfluidic chip further comprises: the substrate 11, the lower cladding layer 12, the waveguide layer 13, the upper cladding layer 14 and the flow channel cover plate 15 are sequentially arranged from bottom to top, the waveguide layer 13 is made of silicon nitride material, and the waveguide layer 13 is used for forming the optical waveguides 1311, 1312 … 131 n;
the micro channel 2 extends into the substrate 11 from top to bottom through the upper cladding layer 14, the waveguide layer 13 and the lower cladding layer 12;
the flow channel cover plate 15 covers the upper opening of the micro flow channel 2, and the micro flow channel cover plate 15 comprises a liquid injection port 151 used for injecting a solution containing biomolecules to be detected into the micro flow channel 2; 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, and the invention is not limited herein.
The lower cladding 12 is made of silicon dioxide with the thickness of 2-3 mu m, the upper cladding 14 is made of a high polymer material with the thickness of 15-30 mu m, the micro-channel 2 extends into the substrate by 10-15 mu m, the width of the micro-channel 2 is 10-100 mu m, a traditional desktop or even large-scale optical system is reduced to the size of a chip, the same or even more excellent analysis performance is ensured, a high-flux chip for biological sample detection under the micro-nano scale is realized, and the system cost is greatly reduced.
Wherein the light source direction is different according to the introduction of the optical waveguide assembly 131, such as: fig. 5 illustrates the introduction of the light source from the optical fiber 130 at the left end of the optical waveguide assembly 131, and fig. 6 illustrates the introduction of the light source from above the optical waveguide assembly 131, respectively.
Fig. 5 is described below, which shows the present optical waveguide microfluidic chip with light source introduced from the optical fiber 130 at the left end of the optical waveguide group 131:
as shown in fig. 5 and 2, the optical waveguide in the optical waveguide microfluidic chip may include only one optical waveguide.
As shown in fig. 5 and 3, the optical waveguide set 131 on one microfluidic includes several, e.g. n, optical waveguides 1311, 1312 … 131n parallel to each other to guide light into the microfluidic channel 2 in the horizontal direction, in the actual detection, for biomolecules with different labels in the microfluidic channel 2, the optical waveguides 1311, 1312 … 131n can guide light with wavelengths λ 1, λ 2 … λ n into the microfluidic channel 2 in the horizontal direction, respectively, and the excitation of the labeled biomolecules 21 with different labels by the light with different wavelengths can simultaneously identify these 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 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.
As shown in FIGS. 3-4, the thickness of the waveguide layer 13 is 150-1000nm, i.e., the thickness of the optical waveguides 1311, 1312 … 131n in FIGS. 5 and 3-4 is 150-1000 nm.
The optical fiber is optically connected to the optical waveguide group 131, and further optically connected to the optical waveguides 1311, 1312 … 131n in the optical waveguide group 131.
Fig. 6 is described below, i.e., the present optical waveguide microfluidic chip with light sources introduced from above the optical waveguide group 131:
as shown in fig. 6, an incident grating (not shown) of silicon nitride material is further included to couple with the optical waveguides 1311, 1312 … 131n to form coupling optical waveguides, and light above the upper cladding 14 is guided into the optical waveguides until the micro flow channels 2 are introduced, and the upper cladding 14 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 14.
As shown in fig. 6 and 3, the optical waveguide set 131 on one microfluidic includes a plurality of, e.g., n, coupling optical waveguides 1311, 1312 … 131n parallel to each other to introduce light into the microchannel 2 in a horizontal direction, in an actual detection, for biomolecules with different labels in the microchannel 2, the coupling optical waveguides 1311, 1312 … 131n can introduce light with wavelengths λ 1, λ 2 … λ n into the microchannel 2 in the horizontal direction, and the labeled biomolecules 21 with different labels excited by the light with different wavelengths can simultaneously identify these biomolecules, while the non-excited biomolecules 20 in the excitation light field introduced by the coupling optical waveguides 1311, 1312 … 131n will not be identified, and the non-excited biomolecules 20 are normal biomolecules without labeling or biomolecules with labeling but outside the light field but without excitation; as shown in FIG. 3, the widths of the coupling optical waveguides 1311, 1312 … 131n are 300-600nm, and the thickness of the waveguide layer 13 is 300-600nm as shown in FIG. 6.
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, the silicon nitride waveguide layer 13 is a silicon nitride thin film layer having a thickness of 150nm to 500nm formed at a low deposition temperature of 25 to 150 ℃; the refractive index of the silicon nitride film is 1.75-2.2. The silicon nitride film may be a film having a uniform refractive index, or may be a film having a non-uniform refractive index, such as a silicon nitride film having a layered refractive index structure.
Circulating tumor cells are a general term for various tumor cells that leave the tumor tissue and enter the blood circulation system of the human body. By detecting trace circulating tumor cells in peripheral blood and monitoring the trend of the change of the types and the quantity of the circulating tumor cells, the tumor dynamics can be monitored in real time, the treatment effect can be evaluated, and the real-time individual treatment can be realized. The following describes an embodiment of detecting and analyzing circulating tumor cells by using the optical waveguide micro-fluidic detection system of the present invention, which mainly comprises the following steps:
the first step is as follows: the method comprises the following steps of (1) sorting and enriching various tumor cells possibly existing in collected 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 solution or blood sample obtained in the second step is added into the micro flow channel 2 from the liquid injection port 151, the optical fiber 130 guides n lights with different wavelengths corresponding to the n labels into the optical waveguides 1311, 1312 … 131n in the optical waveguide group 131 and further into the micro flow channel 2 along the horizontal direction, the labeled biomolecules 21 containing different fluorescent molecular labels are the circulating tumor cells excited by the lights with different wavelengths to emit fluorescence with specific wavelengths, the microscope 3 is used for collecting the fluorescence (optical signal) with specific wavelengths and transmitting the fluorescence to the measuring device 4, the measuring device 4 processes and collects the fluorescence (optical signal) with specific wavelengths and generates the signal to be analyzed and transmits the signal to be analyzed to the analyzing device 5, the analyzing device 5 analyzes the signal to be analyzed to form the spectrum of the fluorescence with specific wavelengths, the type of the circulating tumor cells in the solution or blood sample can be determined by reading the spectrum, the high-throughput chip can be used for respectively detecting various tumor circulating cells at one time and realizing the detection of various tumor cells under the micro-nano scale, thereby monitoring the tumor dynamics in real time, evaluating the treatment effect and realizing the real-time individual treatment.
The optical waveguide microfluid detection system provided by the invention has the beneficial effects that: the traditional desktop even large-scale optical system is reduced to the size of a chip, the same or more excellent analysis performance is ensured, the analysis performance higher than that of the traditional optical system is realized through a plurality of micro-fluid channels and a large-scale matrixing optical waveguide, and the high-flux chip for detecting the biological sample under the micro-nano scale is realized.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.
Claims (10)
1. An optical waveguide microfluidic detection system comprising: microfluidic chips, microscopes, measurement devices and analysis devices; characterized in that the microfluidic chip comprises: the optical waveguide is used for guiding light into the micro-channel along the horizontal direction, the microscope is used for collecting optical signals in the micro-channel and transmitting the optical signals to the measuring device, the measuring device is used for processing the optical signals, generating signals to be analyzed and transmitting the signals to be analyzed to the analyzing device, and the analyzing device analyzes the signals to be analyzed to form a spectrum;
the microfluidic chip further comprises: the substrate, the lower cladding, the waveguide layer, the upper cladding and the flow channel cover plate are arranged from bottom to top in sequence, the waveguide layer is made of silicon nitride materials and is used for forming the optical waveguide;
the micro-channel penetrates through the upper cladding, the waveguide layer and the lower cladding from top to bottom and extends into the substrate;
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 silicon dioxide with the thickness of 2-3 mu m, the upper cladding is a high polymer material with the thickness of 15-30 mu m, the micro-channel extends into the substrate by 10-15 mu m, and the width of the micro-channel is 10-100 mu m.
2. The system as claimed in claim 1, wherein a plurality of the optical waveguides are parallel to each other to guide light into the micro flow channel, and the width of the optical waveguides is 300-600 nm.
3. The system of claim 1, wherein the entire or a majority of the waveguide layers 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, further comprising an incident grating of silicon nitride material to form a coupled optical waveguide with the optical waveguide, guiding light above the upper cladding into the optical waveguide until the microchannel is introduced; the incident grating protrudes from the waveguide layer and extends upwards into the upper cladding layer.
6. The system of claim 5, comprising a plurality of said coupling optical waveguides parallel to each other.
7. The system as claimed in claim 5, wherein the waveguide layer has a thickness of 150-1000nm and the coupling optical waveguide has a width of 300-600 nm.
8. The system of claim 1, further comprising an optical fiber optically coupled with the optical waveguide.
9. The system of claim 1, wherein the substrate is a silicon substrate.
10. The system of claim 1, wherein the polymeric material is SU-8 resin, polyimide, polydimethylsilane, polyethylene, or benzocyclobutene.
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| CN111157728A (en) * | 2020-01-17 | 2020-05-15 | 上海新微技术研发中心有限公司 | Optical waveguide microfluid detection system |
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| CN111157728A (en) * | 2020-01-17 | 2020-05-15 | 上海新微技术研发中心有限公司 | Optical waveguide microfluid detection system |
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Effective date of registration: 20211112 Address after: 201800 J, building 1, No. 2222, Huancheng Road, Jiading District, Shanghai Patentee after: Shanghai Jinguan Technology Co.,Ltd. Address before: 201800 Building 1, No. 235, Chengbei Road, Jiading District, Shanghai Patentee before: Shanghai Industrial UTechnology Research Institute |
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