A multi-channel microring sensor and its preparation and use methods

Abstract

The present invention discloses a multi-channel micro-ring sensor and its preparation and use methods, which include a sensing substrate, a waveguide micro-ring, a coated and exposed sensing area, and an optical fiber array. The waveguide micro-ring is fabricated on the sensing substrate by using a standard wafer process. The waveguide micro-ring includes an input waveguide, two output waveguides, and a micro-ring. The present invention improves the multi-parameter detection purpose that traditionally requires a microfluidic channel by using the hydrophobic effect of parylene C film in combination with a micro-spotting instrument to immobilize specific proteins on the surface of the micro-ring in one step, simplifying the chip preparation and modification processes. Moreover, in the traditional method using a microfluidic channel, the chip size cannot be too small, while the method of the present invention that does not rely on a microfluidic channel is conducive to reducing the chip size and achieving a higher integration degree. At the same time, specific antibodies are immobilized in one step by using parylene C film. After the detection is completed, parylene C can be removed, enabling the chip to be recycled and reducing the cost.

Description

Technical Field

[0001] The present invention relates to the technical fields of semiconductor devices, micro-nano processing, and biosensing technology, and particularly relates to a multi-channel micro-ring sensor and its preparation and use methods. Background Art

[0002] Biosensors are a class of devices that can detect biological signals and are widely used in biomedicine, healthcare, environmental monitoring, drug detection, national defense security, pesticide residues, etc. Among numerous sensors, optical sensors have attracted the attention of researchers due to their advantages such as label-free, high sensitivity, and high integration. Among them, micro-ring biosensors are optical sensor devices based on the optical coupling theory, and have the advantages of small size, high sensitivity, easy portability, easy integration, and compatibility with CMOS processes;

[0003] Micro-ring sensors have the advantages of high sensitivity and high integration. The micro-ring structure is fabricated by a wafer process, including electron beam lithography. Numerous micro-ring structures are integrated on a chip of several millimeters. When used for sensing and detecting multiple biomarkers in body fluids such as blood and urine, the application of micro-ring devices is limited. The reason is that the commonly used way to achieve multi-channel detection in sensors is to integrate with a microfluidic chip. The structure of the microfluidic chip is between dozens of micrometers and hundreds of micrometers, and the difference in size makes it difficult to effectively integrate the highly integrated micro-ring structure with the microfluidic chip;

[0004] The input and output of optical signals in micro-ring sensors rely on fiber optic coupling, that is, light waves are coupled from the optical fiber into the waveguide, and then coupled from the output waveguide to the output optical fiber. The coupling between the waveguide and the optical fiber is an important part of the micro-ring sensing structure. Conventional laboratory test platforms need to add a three-dimensional moving stage to continuously adjust the position of the optical fiber to accurately align the coupling grating of the optical fiber and the waveguide to achieve coupling. This alignment takes a long time. In actual sensing tests, in order to maintain the biological activity of the enzyme as much as possible, the shorter the test time for each step, the better. This requires that when designing the chip, the waveguide and the optical fiber on the chip are directly aligned and coupled, so that no further alignment is required during subsequent tests, shortening the test time and retaining the biological activity of the enzyme. However, micro-ring sensing chips processed by the above processes are often expensive. Therefore, the present invention proposes a multi-channel micro-ring sensor and its preparation and use methods to solve the problems existing in the prior art. Summary of the Invention

[0005] Aiming at the above problems, the purpose of the present invention is to propose a multi-channel micro-ring sensor and its preparation and use methods. This method combines the hydrophobic effect of parylene C film and a micro-spotting instrument to immobilize specific proteins on the surface of the micro-ring in one step, simplifies the chip preparation and modification process, reduces the chip area, improves the chip integration, and at the same time enables the chip to be recycled.

[0006] To achieve the objectives of the present invention, the present invention is implemented through the following technical solutions: A multi-channel micro-ring sensor includes a sensing substrate, waveguide micro-rings, a coated and exposed sensing area, and an optical fiber array. The waveguide micro-rings are fabricated on the sensing substrate using a standard wafer process. The waveguide micro-rings include an input waveguide, two output waveguides, and a micro-ring. The optical fiber array is embedded in quartz material. The input waveguide and output waveguides of the waveguide micro-rings are respectively aligned and connected to the input optical fiber array and output optical fiber array in the optical fiber array, and are bonded using ultraviolet curable glue to achieve coupling.

[0007] A preparation method of a multi-channel micro-ring sensor includes first preparing a micro-ring structure on a substrate, then depositing a parylene C film on the micro-ring structure, and finally covering a protective layer on the micro-ring structure and exposing the micro-ring area covered by the parylene C film.

[0008] A further improvement lies in that: the micro-ring structure is obtained by electron beam lithography (EBL) and reactive ion etching (RIE) processes on an SOI substrate.

[0009] A usage method of a multi-channel micro-ring sensor includes the following steps:

[0010] Step 1:

[0011] After the waveguide array and the optical fiber array are coupled, the original spectrum λ0 is measured. The mask plate for depositing parylene C is aligned with the micro-ring substrate, and the micro-ring holes are respectively aligned with the corresponding micro-ring areas on the substrate. The parylene C substrate is weighed and the parylene C thin film is deposited by chemical vapor deposition to obtain a parylene C film. Then, the spectrum λ1 of the micro-ring after depositing the parylene C thin film is measured.

[0012] Step 2:

[0013] The mask plate is removed, a protective layer is coated on the chip surface, photoresist is spin-coated evenly on the chip after depositing parylene C, and the chip coated with photoresist is covered with the mask plate.

[0014] Step 3

[0015] Specific antibodies are spotted on the parylene C area using a microarray spotter. Under the physical adsorption ability of the parylene C thin film, the specific antibodies are adsorbed on the micro-ring, and the antibody spectrum λ2 is measured.

[0016] Step 4

[0017] Unbound antibodies are washed away, the protein to be tested is added, and the spectrum λ3 is measured after the reaction ends. Step 5

[0018] Clean the sensing chip, and repeat steps 1 to 4 in a cycle for the next sensing test to enable the repeated use of the sensing chip.

[0019] A further improvement lies in that: in step 1, the spacing of the waveguide array is set according to the spacing of the fiber optic array and is the same as the spacing of the fiber optic array.

[0020] A further improvement lies in that: in step 2, the mask material is preferably PDMS. After depositing a parylene C thin film, its thickness is measured using AFM.

[0021] A further improvement lies in that: in step 5, the specific steps for cleaning the sensing chip are as follows: first, soak the used sensing chip in acetone to remove PMMA, and then soak it in tetrahydrofuran to remove parylene C, so that the chip returns to its original state.

[0022] The beneficial effects of the present invention are as follows: the present invention improves the multi-parameter detection purpose that traditionally requires a microfluidic channel, and uses the hydrophobic effect of the parylene C thin film in combination with a microspotter to immobilize specific proteins on the surface of the micro-ring in one step, simplifying the chip preparation and modification process. Moreover, in the traditional method using a microfluidic channel, the chip size cannot be too small, while the method of the present invention that does not rely on a microfluidic channel is conducive to reducing the chip size and achieving a higher integration level. At the same time, specific antibodies are immobilized in one step using the parylene C thin film. After the detection is completed, parylene C can be removed to enable the repeated use of the chip, reducing the cost. Description of the Drawings

[0023] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for use in the description of the embodiments or the prior art. Obviously, the following drawings are only some embodiments of the present invention. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without creative efforts.

[0024] Figure 1 It is a schematic structural diagram of the multi-channel micro-ring sensor of the present invention;

[0025] Figure 2 It is a schematic diagram of the preparation process of the multi-channel micro-ring sensor of the present invention;

[0026] Figure 3 It is a schematic diagram of the micro-ring structure in the embodiment of the present invention;

[0027] Figure 4 It is a schematic diagram of the mask structure for depositing parylene C in the embodiment of the present invention;

[0028] Figure 5It is the result graph of measuring the thickness by using AFM in the embodiment of the present invention;

[0029] Figure 6 It is the test spectrogram in the embodiment of the present invention. Specific Embodiments

[0030] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative efforts belong to the scope of protection of the present invention.

[0031] In the description of the present invention, it should be noted that the orientation or positional relationship indicated by the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc. is based on the orientation or positional relationship shown in the accompanying drawings, and is only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation of the present invention. In addition, the terms "first", "second", "third", "fourth", etc. are only used for descriptive purposes and cannot be understood as indicating or implying relative importance.

[0032] In the description of the present invention, it should be noted that unless otherwise clearly specified and limited, the terms "installation", "connection", and "connection" should be understood in a broad sense. For example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be directly connected or indirectly connected through an intermediate medium, and it can be the communication inside two elements. For those of ordinary skill in the art, the specific meanings of the above terms in the present invention can be understood according to specific situations.

[0033] See Figure 1 , this embodiment provides a multi-channel micro-ring sensor, which includes a sensing substrate 100, a waveguide micro-ring 101, a coated bare sensing area 102, and an optical fiber array 103. From top to bottom, it is composed of a silicon substrate layer, a micro-ring waveguide layer, a parylene C (polychlorinated p-xylene) thin film layer, and a protective layer. The waveguide micro-ring 101 is fabricated on the sensing substrate 100 by using a standard wafer process. The waveguide micro-ring 101 includes an input waveguide, two output waveguides, and a micro-ring. The dual waveguides are more conducive to spectral stability. The optical fiber array 103 is embedded in quartz material. The input waveguide and the output waveguide of the waveguide micro-ring 101 are respectively aligned and connected to the input optical fiber array and the output optical fiber array in the optical fiber array, and are bonded with ultraviolet curable glue to achieve coupling.

[0034] SeeFigure 2 , this embodiment also provides a preparation method of a multi-channel micro-ring sensor, which is characterized in that: first, a micro-ring structure 201 is prepared on a substrate 200, then a parylene C film 202 is evaporated on the micro-ring structure 201, and finally a protective layer 203 is covered on the micro-ring structure 201 and the parylene C film-covered micro-ring area is exposed. Taking a single micro-ring as an example, the micro-ring structure is as Figure 3 shown. This micro-ring is prepared by using the 180nm silicon photonics product line of the Institute of Microelectronics. On an SOI substrate, through electron beam lithography (EBL) and reactive ion etching (RIE) processes. This micro-ring chip is composed of an optical coupler, a micro-ring, a through-end and a download end. The radius of the micro-ring is 20μm, the gap between the micro-ring and the through-end is 250nm, the height of the ridge waveguide is 70nm, and the width is 450nm.

[0035] This embodiment also provides a usage method of the multi-channel micro-ring sensor, that is, a multi-channel detection method, including the following steps:

[0036] Step 1:

[0037] The spacing of the waveguide array is set according to the spacing of the light ray array and is the same as the spacing of the light ray array. After the waveguide array and the optical fiber array are coupled, the original spectrum λ0 is measured. The mask plate for evaporating parylene C (as Figure 4 shown) is aligned with the micro-ring substrate. The eight micro-ring holes are respectively aligned with the eight micro-ring areas on the substrate, and a parylene C thin film is evaporated. Weigh 0.05g of parylene C substrate and evaporate it by chemical vapor deposition to obtain a parylene C film with a thickness of 20nm. The mask plate material is preferably PDMS (polydimethylsiloxane) because it is soft and adheres to the substrate through van der Waals forces, and there is no trace left on the substrate after removing the PDMS. Measure the spectrum λ1 of the micro-ring after evaporating the parylene C thin film. After evaporating the parylene C thin film, use AFM to measure its thickness, which is 24.732nm, as Figure 5 shown;

[0038] Step 2:

[0039] Remove the mask plate and coat a protective layer on the chip surface. Taking the e-beam resist PMMA as an example, spin-coat the photoresist evenly on the chip after evaporating parylene C, and cover the chip coated with the photoresist with the mask plate. The pattern of the mask plate is as Figure 4 shown. The middle cavity is the exposure area. Since PMMA is a positive photoresist, the exposure area will dissolve during development, exposing the underlying parylene C thin film. The parylene C film will not be corroded by acetone, and the other areas of the chip are protected by PMMA;

[0040] Step 3

[0041] The micro-ring sensing area covered only by the parylene C film in the whole area is exposed. Specific antibodies are spotted on eight parylene C areas using a microarray spotter. Under the physical adsorption ability of the parylene C film, the specific antibodies are adsorbed on the micro-ring, and the antibody spectrum λ2 is measured.

[0042] Step Four

[0043] The unbound antibodies are washed away, and the protein to be tested is added. After the reaction ends, the spectrum λ3 is measured. Step Five

[0044] To realize the reuse of the micro-ring, the used sensing chip is first soaked in acetone to remove PMMA, and then soaked in tetrahydrofuran to remove parylene. The chip returns to its original state. Steps one to four are cycled for the next sensing test to enable the repeated use of the sensing chip.

[0045] In the embodiment, the spectra measured in the whole process are as Figure 6 shown. 1-1 represents the original spectrum λ0 of the micro-ring, 1-2 represents the spectrum λ1 after vaporizing the parylene C film, 1-3 represents the spectrum λ2 of the conjugated specific antibody, and 1-4 represents the spectrum λ3 after the specific binding of antigen and antibody.

[0046] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A multi-channel micro-ring sensor, comprising a sensing substrate (100), a waveguide micro-ring (101), a coated and exposed sensing area (102) and an optical fiber array (103), which is composed of a silicon substrate layer, a micro-ring waveguide layer, a parylene film layer and a protective layer from top to bottom, and is characterized in that: The waveguide micro-ring (101) is fabricated on the sensing substrate (100) using a standard chip fabrication process. The waveguide micro-ring (101) includes an input waveguide, two output waveguides, and a micro-ring. The fiber array (103) is embedded in quartz material. The input waveguide and output waveguides of the waveguide micro-ring (101) are respectively aligned and connected to the input fiber array and output fiber array in the fiber array, and are bonded with ultraviolet curable glue to achieve coupling.

2. A preparation method of a multi-channel micro-ring sensor, characterized in that: First, a micro-ring structure (201) is prepared on the substrate (200), then a parylene C film (202) is deposited on the micro-ring structure (201), and finally a protective layer (203) is covered on the micro-ring structure (201) and the parylene C film-covered micro-ring region is exposed. The micro-ring structure (201) is obtained by electron beam lithography (EBL) and reactive ion etching (RIE) processes on an SOI substrate (200).

3. A method for using a multi-channel micro-ring sensor, characterized in that, It includes the following steps: Step 1: After the waveguide array and the fiber array are coupled, the original spectrum λ0 is measured. The mask plate for depositing parylene C is aligned with the micro-ring substrate, and the micro-ring holes are respectively aligned with the corresponding micro-ring regions on the substrate. The parylene C substrate is weighed and the parylene C thin film is deposited by chemical vapor deposition to obtain the parylene C film. Then, the spectrum λ1 of the micro-ring after depositing the parylene C thin film is measured. Step 2: The mask plate is removed, a protective layer is coated on the chip surface, photoresist is spin-coated uniformly on the chip after depositing parylene C, and the chip coated with the photoresist is covered with the mask plate. Step 3 The specific antibody is spotted on the parylene C region using a microarray spotter. Under the physical adsorption ability of the parylene C thin film, the specific antibody is adsorbed on the micro-ring, and the antibody spectrum λ2 is measured. Step 4 The unbound antibody is washed, the protein to be detected is added, and the spectrum λ3 is measured after the reaction ends. Step 5 The sensing chip is washed, and steps 1 to 4 are repeated for the next sensing test to enable the repeated use of the sensing chip.

4. The method for using a multi-channel microring sensor according to claim 3, wherein: In step 1, the spacing of the waveguide array is set according to the spacing of the fiber array and is the same as the fiber array spacing.

5. The method for using a multi-channel micro-ring sensor according to claim 3, characterized in that: In step 2, the mask plate material is PDMS. After depositing the parylene C thin film, its thickness is measured using AFM.

6. The method for using a multi-channel microring sensor according to claim 3, characterized in that: In step 5, the specific steps for washing the sensing chip are as follows: First, the used sensing chip is soaked in acetone to remove PMMA, and then soaked in tetrahydrofuran to remove parylene C, so that the chip returns to its original state.

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