Microbubble integrated fabry-perot structure resonant cavity sensing chip and preparation method thereof

Abstract

This invention belongs to the field of optical sensing technology, specifically a microbubble-integrated Fabry-Perot resonant cavity sensor chip and its fabrication method. The optical sensor chip of this invention includes: two planar mirrors, a quartz microtube with a hollow microbubble in the middle, and two square quartz tubes; the two planar mirrors are placed parallel to each other vertically, and the two square quartz tubes are positioned on the left and right sides of the two planar mirrors to ensure that the two mirrors remain highly parallel; the hollow quartz microbubble is disposed between the two planar mirrors, and its two ends are bonded and fixed to the planar mirrors to form a microbubble-integrated Fabry-Perot resonant cavity sensor chip; the surface of the planar mirrors is coated with a metal thin film or dielectric thin film with a specific reflectivity. Based on the lens effect of microbubbles, this invention enables the sensor chip to possess the characteristics of high sensitivity, low mode volume, and high quality factor, while integrating natural microfluidic channels to achieve sensing of low-concentration chemical molecules or label-free biomolecules.

Description

Technical Field

[0001] This invention belongs to the field of optical sensor technology, specifically relating to a Fabry-Perot resonant cavity sensor chip and its fabrication method. Background Technology

[0002] Optical detection technology is commonly used for sensing physical parameters, biological or chemical samples. Sensors based on optical detection technology typically have advantages such as fast response, immunity to electromagnetic interference from the surrounding environment, and high sensitivity, and are widely used in various fields. Among them, Fabry-Perot resonators based on optical detection technology, due to their inherent high quality factor, extremely small mode volume, and strong interaction between light and matter, can achieve optical amplification of weak signals, and are therefore widely used for the detection of chemical and biological molecules.

[0003] Typically, a Fabry-Pérot resonator (FP) consists of two highly parallel mirrors. Light satisfying the resonance condition is confined within the cavity due to mirror reflection, forming a stable standing wave. The higher the reflectivity of the planar mirrors, the more times the light is reflected, resulting in stronger coherent superposition of the optical fields within the cavity, narrower optical modes output by the resonator, and higher sensing resolution. Existing Fabry-Pérot cavities can be categorized into fiber Fabry-Pérot cavities and planar mirror Fabry-Pérot cavities based on their structure. While fiber Fabry-Pérot cavities offer advantages such as ease of fabrication and integration, the low reflectivity and coupling efficiency of the fiber endfaces typically result in a lower quality factor and larger mode linewidth, limiting their ability to detect weak signals. In contrast, planar mirror Fabry-Pérot cavities achieve very high reflectivity in their mirrors, thus ensuring a higher quality factor and extremely small mode linewidth, leading to a lower detection limit.

[0004] Planar mirror Fabry-Perot cavity sensors can be categorized into active and passive cavities based on whether the analyte is fluorescently labeled. Active cavities primarily involve placing the fluorescently labeled analyte inside the cavity and converting the fluorescence signal into a laser signal through optical gain amplification, thereby improving sensing resolution. However, the detection of fluorescently labeled molecules requires specific pre-treatment or modification of the analyte, increasing the complexity and cost of detection. Fluorescently labeled molecules can also affect the activity of biomolecules. Furthermore, fluorescent molecules require specific wavelengths of pump light excitation, limiting their use to specific wavelengths and restricting practical applications. Passive cavities can effectively address these issues, but achieving high-efficiency coupling of incident light is typically difficult. Additionally, non-parallel alignment of the mirrors introduces multiple reflection losses, leading to a sharp decrease in the microcavity's quality factor. Consequently, broadened resonant modes reduce the sensor's detection limit. Due to the lack of lateral mode constraints, planar mirror Fabry-Perot cavities have large mode volumes and low optical energy densities, resulting in reduced light-matter interaction intensity.

[0005] Furthermore, traditional biomolecular detection techniques require specific modification of molecules on the surface of the resonant cavity, which increases the complexity of the sensor and introduces additional uncertainties, making it difficult to apply biomolecular detection based on optical microcavity structures in practice. Summary of the Invention

[0006] The purpose of this invention is to provide a microbubble-integrated Fabry-Perot resonant cavity sensor chip and its fabrication method that can maintain high quality factor, low mode volume, high sensitivity, and label-free sensing, while avoiding complex surface modification processes in biomolecule detection.

[0007] The microbubble-integrated Fabry-Perot resonant cavity sensing chip provided by this invention has the following structure: Figure 1 As shown, it includes: two planar mirrors, one or more quartz microtubes with a varying number of hollow microbubbles in the middle, and two square quartz tubes; wherein, the two planar mirrors are placed parallel to each other vertically, and the two square quartz tubes are of the same height and are arranged parallel to each other at the left and right edges of the two planar mirrors; the two planar mirrors are respectively bonded and fixed to the upper and lower surfaces of the two square quartz tubes, ensuring that the two mirrors remain highly parallel; the hollow quartz microbubbles of the microtubes are disposed between the two planar mirrors and in the middle of the two square quartz tubes, with their upper and lower surfaces being parallel to the two planar mirrors respectively, and the two ends of the microtubes are bonded and fixed to the planar mirrors, forming a microbubble integrated Fabry-Perot structure resonant cavity sensing chip;

[0008] The planar reflector is based on a quartz plate, and its surface is coated with a metal thin film with a specific reflectivity or multiple layers of dielectric thin films with high and low refractive indices arranged periodically.

[0009] The reflected wavelengths of the plane mirror range from near-ultraviolet to mid-infrared.

[0010] The bonding between the square quartz tube and the plane mirror, as well as the bonding between the two ends of the microtube and the plane mirror, are achieved using ultraviolet adhesive.

[0011] The microtube containing hollow quartz microbubbles can be connected to a microfluidic system at its port.

[0012] In this invention, the height of the square quartz tube does not exceed 1 mm, for example, the height is 100-1000 μm, and the height of the square quartz tube is slightly larger than the diameter of the microbubble.

[0013] In this invention, the diameter of the quartz microbubbles does not exceed 1 mm, for example, the height is 100-1000 μm; the wall thickness does not exceed 15 μm, for example, the wall thickness is 5-15 μm.

[0014] In this invention, the hollow microbubbles prepared on the quartz microtubes are elliptical in shape and number at least three, for example, three to five.

[0015] In this invention, the quartz microtube has openings at both ends, allowing it to be integrated with a microfluidic system.

[0016] In this invention, one side of the plane mirror is coated with a metal film or dielectric film with a specific reflectivity, wherein the reflectivity ranges from 80% to 100%.

[0017] In this invention, the substrate of the planar reflector is a transparent quartz sheet with a thickness of 300-500 μm.

[0018] The sensor chip described in this invention can be used for the detection of analytes such as physical parameters and chemical molecules (including gases and liquids). During specific detection, based on the characteristic of the refractive index of the analyte changing with concentration, the concentration of chemical molecules is detected in real time and rapidly using optical means, thereby achieving real-time and rapid detection of chemical solutions.

[0019] The sensor described in this invention can be used for the detection of analytes such as biomolecules. During specific detection, based on the change in refractive index caused by the specific binding of the biomolecule (specific binding of probe proteins and corresponding antibody proteins), the concentration of the biomolecule is rapidly and in real time using optical means, thereby achieving specific detection of unlabeled biomolecules.

[0020] Accordingly, the present invention also provides a method for fabricating the above-mentioned sensor chip, the specific steps of which are as follows:

[0021] (1) Select a section of quartz microtube and prepare at least three quartz microbubbles with similar diameters on it by melt blowing;

[0022] (2) Apply a layer of UV glue evenly to the lower surface of the square quartz tube and lay it horizontally on the surface of a plane mirror. Use UV glue to bond the side of the plane mirror coated with a reflective film to the square tube.

[0023] (3) Use the five-dimensional adjustment frame to adjust the microbubble to be parallel to the plane mirror and fix its two ends to the surface of the plane mirror;

[0024] (4) Apply a layer of UV glue to the upper surface of the square quartz tube and place another reflector on the upper surface of the square quartz tube, wherein the side of the reflector coated with the reflective film is bonded to the square tube.

[0025] This invention also provides a detection system based on the above-described sensor chip, see [link to relevant documentation]. Figure 3 As shown, it includes: a tunable laser (or supercontinuum light source) 5, a beam collimator 6, a beam splitter 7, a focusing objective 8, a microbubble integrated Fabry-Perot resonant cavity sensing chip 9, a focusing objective 10, a focusing objective or lens 11, and a photodetector (or spectrometer) 12 connected in sequence, forming a sensing optical path; it also includes a focusing objective or lens 13 and a CCD imaging device 14 connected in sequence to the beam splitter 7, forming an imaging optical path; wherein:

[0026] A tunable laser (or supercontinuum light source) 5 is used to emit detection laser light; the output laser light of the laser light is transmitted to a beam collimator 6 by a single-mode fiber; the beam collimator is used to collimate the diverging laser light output from the fiber into parallel light; a beam splitter 7 is used to transfer the image formed by the focusing objective to a CCD imaging device; a focusing objective 8 is used to couple the collimated laser light to a microbubble-integrated Fabry-Perot resonant cavity sensor chip 9, and is also used to collect the output light of the sensor chip and to image the sensor chip; the microbubble-integrated Fabry-Perot resonant cavity sensor chip 9 has openings at both ends of the microbubble, one end of which is connected to a microfluidic system such as a syringe or injection pump through a Teflon tube, and the other end... The analyte is connected to the Teflon tube; the output light signal collected by the focusing objective 10 is fully collected by the large-core fiber bundle and transmitted to the photodetector (or spectrometer) 12; the photodetector (or spectrometer) 12 receives the output light signal and converts it into an electrical signal, which is then transmitted to the oscilloscope (or the output spectrum is analyzed directly); the oscilloscope is used to display the emitted spectral signal collected by the photodetector; the CCD imaging device 14 is used to image the microbubble integrated Fabry-Perot resonant cavity sensor chip; the microfluidic system, including a syringe pump, syringe, and Teflon tube, is used to extract the analyte into the quartz microbubble; and the test tube is used to store the analyte.

[0027] Accordingly, the present invention also provides a detection method for a sensor chip, comprising: turning on a tunable laser (or a supercontinuum light source) to emit a detection laser; using a CCD imaging system and a five-dimensional adjustment frame to couple the incident laser to the microbubble region of the sensor chip; using a microfluidic system (including a syringe pump, a syringe, and a Teflon tube) to extract the analyte into the microbubble, wherein one end of the microfluidic system is connected to one port of a quartz microbubble, and the other port of the quartz microbubble is connected to a test tube containing the analyte through a Teflon tube; and using a photodetector (or a spectrometer) to collect the signal and display and store the data using an oscilloscope.

[0028] The technical principle achieved by this invention is as follows: the planar reflector is bonded to the upper and lower surfaces of the square tube to ensure the parallelism of the two planar reflectors. By integrating microbubbles, the additional optical loss introduced by the inability of the two reflectors to guarantee high parallelism is further reduced, and a microfluidic channel is naturally integrated.

[0029] In this invention, due to the lens effect of the hollow microbubble itself, the light field inside the cavity is effectively constrained to the optical axis position in the microbubble region. This not only greatly reduces the mode volume of the resonant mode and increases the light energy density, but also effectively overcomes the additional optical loss introduced by the inability of the two mirrors to guarantee high parallelism, thus increasing the quality factor of the sensor chip. Due to the high quality factor and high sensitivity, the sensor chip's ability to detect weak signals is enhanced, making its quality factor (quality factor = Q * sensitivity) at least one order of magnitude higher than that of traditional Fabry-Perot resonant cavity sensors.

[0030] This invention has the following characteristics:

[0031] (1) The key difference between this invention and conventional Fabry-Perot resonant cavity sensors. In this invention, quartz microbubbles are integrated into the conventional Fabry-Perot resonant cavity. Due to the lens effect of the quartz microbubbles, the mode volume of the resonant mode is reduced, the intensity of the light-matter interaction is enhanced, and the quality factor of the Fabry-Perot resonant cavity is greatly improved.

[0032] (2) The microbubble integrated Fabry-Perot structure resonant cavity sensing chip provided by the present invention overcomes the additional optical loss caused by the inability of the two planar mirrors to maintain high parallelism, and greatly improves the quality factor of the sensing chip.

[0033] (3) The quartz microbubble integrated in this invention is itself a microfluidic channel, so there is no need to make an additional analyte transport channel;

[0034] (4) The biomolecule detection mechanism achieved by the present invention is that the specific binding between biomolecules leads to a large change in refractive index. This process does not require labeling of biomolecules or chemical modification of the interior of quartz microbubbles, thus reducing the complexity of biomolecule detection.

[0035] (5) The microbubble integrated Fabry-Perot structure resonant cavity sensor chip provided in this invention has an extremely high quality factor, which enables the detection of signals of biochemical molecules (proteins, DNA, chemical gases, bacteria and viruses) and weak physical quantities (temperature, pressure, refractive index) at ultra-low concentrations and in minute volumes.

[0036] (6) The sensing chip provided in this invention can use different optical sensing bands according to the actual detection reagent requirements;

[0037] (7) The sensor chip fabrication method provided in this invention is simple, easy to operate, and can be reused multiple times;

[0038] (8) The sensor chip testing method provided in this invention is simple and has low requirements for the testing system, making it easy to apply in practice. Attached Figure Description

[0039] Figure 1 This is a schematic diagram of the microbubble integrated Fabry-Perot structure resonant cavity sensing chip structure of the present invention.

[0040] Figure 2 This is a diagram illustrating the fabrication method of the microbubble-integrated Fabry-Perot structure resonant cavity sensor chip based on the present invention.

[0041] Figure 3 This is a schematic diagram of a detection system based on the microbubble integrated Fabry-Perot structure resonant cavity sensing chip of this invention.

[0042] Figure 4 This is a transmission spectrum diagram of the microbubble integrated Fabry-Perot structure resonant cavity sensing chip based on the present invention.

[0043] Figure 5 is based on Figure 4 Enlarged image.

[0044] Figure 6 illustrates the sensitivity test results of the microbubble-integrated Fabry-Perot structure resonant cavity sensing chip based on the present invention.

[0045] In the diagram, the following labels are used: 1 is the quartz substrate; 2 is the reflective film for a specific wavelength band; 3 is the quartz microbubble; 4 is the square quartz tube; 5 is the tunable laser (or supercontinuum light source); 6 is the beam collimator; 7 is the beam splitter; 8 is the focusing objective; 9 is the microbubble integrated Fabry-Perot resonant cavity sensor chip; 10 is the focusing objective; 11 is the focusing objective or lens; 12 is the photodetector (or spectrometer); 13 is the focusing objective or lens; 14 is the CCD imaging device; 15 is the sensing optical path; and 16 is the imaging optical path. Detailed Implementation

[0046] The present invention will be further described in detail below with reference to the accompanying drawings and examples, but the present invention is not limited to these examples.

[0047] Example 1

[0048] In this embodiment, a microbubble-integrated Fabry-Perot resonant cavity sensing chip (see...) Figure 1 Specifically, it includes: two plane mirrors coated with a specific wavelength reflective film, with a reflectivity range of 80%-100%, and a quartz substrate 1 with a thickness of 300-500 μm; two square quartz tubes 4, the height of which does not exceed 1 mm, and the height of which is close to the diameter of the microbubble; a microtube 3 with quartz microbubbles, wherein the diameter of the quartz microbubbles does not exceed 1 mm, the wall thickness does not exceed 15 μm, and the microtube has openings at both ends; the square quartz tubes are bonded to the coated surfaces of the plane mirrors with UV adhesive; the two ends of the microtube with quartz microbubbles are fixed to the middle of the plane mirror with UV adhesive.

[0049] In this device, the fabrication method of the microbubble-integrated Fabry-Perot resonant cavity sensing chip is as follows: Figure 2 As shown, it includes:

[0050] (1) Select a section of quartz microtube and prepare one or more microbubbles with similar diameters on it by melt blowing;

[0051] (2) Apply a layer of UV adhesive evenly to the lower surface of the square quartz tube and lay it horizontally on the surface of a plane mirror. Use the UV adhesive to bond the side of the plane mirror coated with the reflective film to the square quartz tube, such as... Figure 2 As shown in (b);

[0052] (3) Use a five-dimensional adjustment frame to adjust the quartz microbubble to be parallel to the plane mirror, and fix its two ends to the surface of the plane mirror, such as Figure 2 As shown in (c);

[0053] (4) Apply a layer of UV adhesive to the upper surface of the square quartz tube, and place another reflector on the upper surface of the square quartz tube, wherein the side of the reflector coated with the reflective film is bonded to the square tube, such as... Figure 2 As shown in (d).

[0054] In this device, when laser light is incident on the aforementioned sensing chip, some of it passes through the mirrors and enters the Fabry-Perot cavity. Due to reflection from the two plane mirrors, only light that simultaneously satisfies the cavity resonance condition and light propagating parallel to the optical axis can undergo constructive interference, thus forming a stable resonance. For light that does not satisfy the resonance condition, destructive interference results in zero output light. For light with a certain angle to the optical axis, it is reflected multiple times by the mirrors and is ultimately reflected out of the cavity, failing to form resonance. The resonance condition of the Fabry-Perot cavity is:

[0055] (1)

[0056] in, n The effective refractive index within the cavity, L For cavity length, m The vertical modulus is a positive integer. λ This is the resonant wavelength. As can be seen from Equation 1, when the refractive index... n When changes occur, the resonant wavelength of the cavity also changes accordingly for the same longitudinal mode. For chemical liquids of different concentrations, their refractive index usually changes with the concentration. Therefore, when chemical liquids of different concentrations are introduced into the microbubble, the wavelength of the resonant mode will shift accordingly. Thus, by detecting the shift in wavelength, the analyte solution of a specific concentration can be tested, thereby realizing chemical molecule sensing.

[0057] Example 2

[0058] In this embodiment, based on the parameters of Example 1, the transmission spectrum of the sensor chip is tested. The specific process is as follows: the microbubble integrated Fabry-Perot structure resonant cavity sensor chip prepared in Example 1 is combined with microfluidic technology. That is, one end of the microtube with microbubbles is connected to a syringe or injection pump through a Teflon tube to extract the liquid to be tested; the other end of the microtube with microbubbles is connected to the liquid to be tested through a Teflon tube.

[0059] In this device, the testing system is as follows: Figure 3 As shown. A tunable laser (or supercontinuum source) is turned on to emit incident laser light. After collimation by a collimator, the incident laser passes through a beam splitter, and then a focusing objective lens focuses the incident laser onto the surface of the sensor chip. A CCD imaging system and a five-dimensional adjustment frame couple the incident laser to the microbubble region of the sensor chip. A microfluidic system (including a syringe pump, syringe, and Teflon tubing) is used to extract the analyte into the microbubble. A photodetector (or spectrometer) collects the signal and displays it on an oscilloscope. The transmission spectrum of the microbubble-integrated Fabry-Perot resonant cavity sensor chip is tested as shown below. Figure 4As shown. According to Formula 1 in Example 1, the wavelength that satisfies the resonance condition generates stable oscillations, which appear as sharp peaks in the transmission spectrum; at the same time, the resonant wavelength is different for different longitudinal modes, resulting in a series of approximately periodically arranged peaks in the transmission spectrum. The distance between two adjacent resonant modes is the Free Spectrum Range (FSR), which can be written as:

[0060] (2)

[0061] like Figure 4 As shown, the free spectral range of the transmission spectrum of the test sensor chip is 1.71 nm. Figure 5 for Figure 4 The magnified image shows that, through Lorentz fitting of the resonant modes in the spectrum, the quality factor of the sensor chip is 10. 5 The quality factor of the resonant cavity is related to the spectral linewidth of the resonant mode, and can be written as:

[0062] (3)

[0063] Where Δλ is the full width at half maximum (FWHM) of the resonant mode spectrum. According to Equation 3, the larger the quality factor of the sensor chip, the narrower the spectral linewidth of its resonant mode, the higher the resolution of the sensor, and the easier it is to detect weak signals.

[0064] Example 3

[0065] In this embodiment, the sensitivity of the sensor chip is tested based on the sensor chip parameters of Embodiment 1 and the test system and test method of Embodiment 2. Specifically, based on the test system of Embodiment 2, dimethyl sulfoxide (DMSO) solutions with concentrations of 0-1% are passed into microbubbles, and the shift of resonant modes in the spectrum is observed in real time using an oscilloscope. Figure 6 As shown in (a), the resonant wavelength red-shifts with increasing dimethyl sulfoxide solution concentration. The peak values ​​of the resonant modes are extracted to obtain the following results: Figure 6 (b) shows the curve of the resonant wavelength changing with the refractive index. Through linear fitting, the sensitivity of the sensor chip is found to be 594 nm / RIU.

[0066] This device also enables the specific detection of biomolecules while avoiding complex surface chemical modification processes. The specific binding of biomolecules (specific binding of probe proteins and corresponding antibody proteins) causes a significant change in the refractive index of the corresponding biomolecule solution. As the concentration of the probe protein changes, the refractive index of the solution also changes, resulting in a redshift of the resonant wavelength. By detecting the shift in the resonant wavelength, the concentration of the probe protein can be determined.

Claims

1. A detection system based on a microbubble-integrated Fabry-Perot structure resonant cavity sensing chip, characterized in that, include: A tunable laser or supercontinuum light source (5), a beam collimator (6), a beam splitter (7), a focusing objective (8), a microbubble-integrated Fabry-Perot resonant cavity sensing chip (9), a focusing objective (10), a focusing objective or lens (11), and a photodetector or spectrometer (12) are connected in sequence to form a sensing optical path; this also includes a focusing objective or lens (13) and a CCD imaging device (14) connected in sequence to the beam splitter (7) to form an imaging optical path; wherein: A tunable laser or supercontinuum light source (5) is used to emit a detection laser; the output laser of the laser is transmitted to a beam collimator (6) by a single-mode fiber; the beam collimator is used to collimate the diverging laser output from the fiber into parallel light; a beam splitter (7) is used to transmit the image formed by the focusing objective to a CCD imaging device; the focusing objective (8) is used to couple the collimated laser into a microbubble-integrated Fabry-Perot structure resonant cavity sensor chip (9), and is also used to collect the output light of the sensor chip and to image the sensor chip; the microbubble-integrated Fabry-Perot structure resonant cavity sensor chip (9) has openings at both ends of the microbubble. One end is connected to a microfluidic system such as a syringe or injection pump via a Teflon tube, and the other end is connected to the analyte via a Teflon tube; the output light signal collected by the focusing objective (10) is fully collected by the large-core fiber bundle and transmitted to the photodetector or spectrometer (12); the photodetector or spectrometer (12) receives the output light signal and converts it into an electrical signal to be transmitted to the oscilloscope or directly analyzes the output spectrum; the output spectrum signal collected by the photodetector is displayed on the oscilloscope; the CCD imaging device (14) is used to image the microbubble integrated Fabry-Perot structure resonant cavity sensor chip; The microbubble-integrated Fabry-Perot structure resonant cavity sensor chip (9) includes: two planar mirrors, one or more quartz microtubes with varying numbers of hollow microbubbles in the middle, and two square quartz tubes; wherein the two planar mirrors are placed parallel to each other on the top and bottom, and the two square quartz tubes are of the same height and are arranged parallel to each other on the left and right edges of the two planar mirrors; the two planar mirrors are respectively bonded and fixed to the upper and lower surfaces of the two square quartz tubes, and the two mirrors are kept parallel to each other; the hollow quartz microbubbles of the microtubes are arranged between the two planar mirrors and in the middle of the two square quartz tubes, and their upper and lower surfaces are respectively parallel to the two planar mirrors; the two ends of the microtubes are bonded and fixed to the planar mirrors to form a microbubble-integrated Fabry-Perot structure resonant cavity sensor chip; The plane mirror is based on a quartz plate, and its surface is coated with a metal thin film with a specific reflectivity or multiple layers of dielectric thin films with high and low refractive indices arranged periodically. The reflection band of the plane mirror ranges from near-ultraviolet light to mid-infrared light; The height of the square quartz tube shall not exceed 1 mm; The diameter of the quartz microbubbles does not exceed 1 mm and the wall thickness does not exceed 15 μm; The hollow microbubbles prepared on the quartz microtubes are elliptical in shape and number at least three. The plane mirror has a metal or dielectric film coated on one side surface, wherein the reflectivity ranges from 80% to 100%.

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