Conical coreless optical fiber biosensor based on quantum measurement

Abstract

The utility model belongs to the technical field of quantum measurement and optical fiber sensing, and particularly relates to a conical coreless optical fiber biosensor based on quantum measurement. The conical coreless optical fiber biosensor is used for measurement of a photosensitive biological fragile system. The quantum entanglement source used in the utility model adopts a Sagnac interferometer structure, stable optical path configuration is provided, entanglement photon pairs generated through spontaneous parametric down-conversion (SPDC) have high quantum correlation, and a high signal-to-noise ratio can still be maintained under weak light detection. When the concentration of an analyte in a to-be-detected sample changes, the biological sensitive film on the conical surface captures the change of the analyte, so that the refractive index of the conical surface changes, the interference spectrum of the sensor moves, the light intensity at the wavelength position of signal light changes, and the number of signal photons changes; the photon counting of the first single-photon detector changes, and the second-order correlation measurement result of the signal photons and the reference photons on the coincidence counter changes, that is, the coincidence counting value changes. And establishing a proportional relation between the coincidence count value and the concentration of the to-be-measured sample, and measuring the concentration of the to-be-measured sample by monitoring the change of the coincidence count value.

Description

Technical Field

[0001] The utility model belongs to the technical field of quantum measurement and optical fiber sensing, and particularly relates to a conical coreless optical fiber biosensor based on quantum measurement for measuring photosensitive biological fragile systems. Background Art

[0002] A biosensor is an instrument that is sensitive to biological substances and converts observable biochemical reactions into measurable physical quantities. Biosensors are composed of biological sensitive elements (such as antibodies, aptamers, proteins, etc.), conversion elements (such as oxygen electrodes, photosensitive tubes, etc.) and signal amplification devices. The analyte enters the biological sensitive element through diffusion, is recognized by it and undergoes a biochemical reaction. The generated information is converted by the conversion element into quantifiable and processable sound, light, electricity and other signals, which are then amplified and output by the signal amplification device to obtain the response of the analyte, and then the analyte is qualitatively and quantitatively analyzed through data processing. Biosensors can be divided into thermal biosensors, piezoelectric biosensors, optical biosensors, mediator biosensors, etc. according to the detection principle. They are widely used in food testing, environmental pollution, clinical diagnosis, drug discovery and other aspects.

[0003] Quantum entanglement reveals the essence of quantum mechanics coherence, probability and spatial nonlocality, and is the most peculiar existence in quantum theory. At present, quantum entanglement has been widely used in many fields such as quantum communication, quantum metrology and quantum distance measurement. Quantum sensing uses the excellent low-noise performance of quantum to sense, which can greatly improve the accuracy of sensors and even break through the measurement limit of standard quantum in classical mechanics.

[0004] Ordinary biosensors usually use classical light sources to measure concentrations. When detecting low-concentration analytes, after removing all technical noise, the final estimated error is inversely proportional to the intensity of the light source. In theory, the only way to reduce the error is to increase the light intensity. However, for photosensitive fragile systems, blindly increasing the light intensity may seriously affect the vitality, function, structure and growth of the measured biological molecules. This reduces the detection sensitivity of the sensor to low-concentration analytes, limiting its wide application in ultrasensitive detection. Therefore, other strategies must be adopted to improve the sensitivity to detect samples without exposing them to higher light intensities and possible light damage. In response to the above problems, the utility model proposes a conical coreless optical fiber biosensor based on quantum measurement for the measurement of photosensitive biological fragile systems, combining quantum measurement with optical fiber sensing technology to effectively solve the problem of light damage when measuring photosensitive biological fragile systems. Under extremely low incident light, the high sensitivity and high resolution of the sensor can still be maintained, breaking through the measurement limit of the standard quantum of classical mechanics, solving the problems of classical biological sensing systems, and providing new ideas for bioengineering, disease detection and single-molecule label-free detection, with high practical value. Utility Model Content

[0005] In order to solve the problem of light damage when measuring photosensitive biological fragile systems and improve sensor sensitivity and resolution, the utility model provides a conical coreless optical fiber biosensor based on quantum measurement with extremely high sensitivity and practical value, breaking through the measurement limit of the standard quantum of classical mechanics and solving the problems of classical biological sensing systems.

[0006] The device adopted by the utility model to solve the technical problem:

[0007] Its features consist of 4 modules: entanglement module, sensor module, detection module, and coincidence counting module. The entanglement module includes a pump light source module and a Sagnac ring structure module. Entanglement module: semiconductor laser, polarization beam splitter (PBS), first and second quarter / half wave plate group (Q / HWP), dichroic mirror (DM), two-color polarization beam splitter (DPBS), two-color half-wave plate (DHWP), PPKTP crystal, parabolic mirror, spatial light to optical fiber coupler; sensor module: sensor, microfluidic tube, sample to be tested; detection module includes two single photon detectors (SPD); coincidence counting module is a coincidence counter (TDC).

[0008] The entanglement module includes a pump light source module and a Sagnac ring structure module.

[0009] The pump light source module mainly includes: semiconductor laser, polarization beam splitter (PBS), first quarter / half wave plate group (Q / HWP), dichroic mirror (DM), second quarter / half wave plate group (Q / HWP), and spatial light to optical fiber coupler. The semiconductor laser pump laser passes through the first quarter / half wave plate group (Q / HWP), polarization beam splitter (PBS), and second quarter / half wave plate group (Q / HWP) in sequence to adjust the phase and intensity of the pump laser. The pump light adjusted by the two wave plate groups is reflected by the dichroic mirror (DM) and enters the Sagnac ring structure module.

[0010] The Sagnac ring structure module mainly includes: a dual-color polarization beam splitter (DPBS), a dual-color half-wave plate (DHWP), a PPKTP crystal and a parabolic mirror group, and a spatial light to optical fiber coupler. After the pump laser is reflected by the dichroic mirror (DM), it enters the dual-color polarization beam splitter (DPBS) and is separated into horizontally polarized transmitted light and vertically polarized reflected light, and then pumped clockwise and counterclockwise along the Sagnac ring respectively. The vertically polarized reflected light in the counterclockwise direction is converted into horizontally polarized light by the dual-color half-wave plate (DHWP) set at 45°, and then reflected by the parabolic mirror and focused into the PPKTP crystal. The horizontally polarized transmitted light in the clockwise direction is directly reflected by another parabolic mirror and focused into the PPKTP crystal. The new light beams generated at the same time are output from both sides of the PPKTP crystal, and are acted upon by a two-color half-wave plate (DHWP) and a two-color polarization beam splitter (DPBS). One path is used as a signal path, in which the signal light is first coupled to the light transmitted by the optical fiber through a spatial light-to-optical fiber coupler, and then connected to the sensing device, and then connected to the first single-photon detector (SPD). The other path is used as a reference path, in which the reference light is coupled to the light transmitted by the optical fiber through a spatial light-to-optical fiber coupler, and then directly connected to the second single-photon detector (SPD).

[0011] The sensing module mainly includes: a sensor, a microfluidic tube, and a sample to be tested. The sensor includes: a first single-mode optical fiber (SMF), a second single-mode optical fiber (SMF), a coreless optical fiber (SPW), and a biosensitive membrane.

[0012] A beam of signal light from the quantum entanglement source is first coupled to the optical fiber through a spatial light to optical fiber coupler to couple the spatial light into optical fiber transmission light. Then, the first single-mode optical fiber (SMF) is fused with one end of the coreless optical fiber (SPW), and the other end of the coreless optical fiber (SPW) is fused with the second single-mode optical fiber (SMF). The coreless optical fiber (SPW) is tapered, and a specific biosensitive film is bonded to the surface of the tapered area. Then, the sensor is placed in a microfluidic tube, and the test samples of different concentrations are injected into the microfluidic tube through a microinjection pump.

[0013] The detection module includes two single photon detectors: a first single photon detector (SPD) and a second single photon detector (SPD), which are used to detect the number of single photons in the signal path and the reference path respectively.

[0014] The coincidence counting module includes a coincidence counter (TDC). The first and second single photon detectors (SPD) are respectively connected to the coincidence counter (TDC) to count the single photons detected by the reference path and the signal path.

[0015] The beneficial effects of the utility model are:

[0016] (1) Combining quantum optics with sensing technology, using weak light to measure photosensitive biological fragile systems to avoid light damage. For photosensitive fragile systems, avoid blindly increasing light intensity to seriously affect the vitality, function, structure and growth of the measured biological molecules. Using quantum optics to break through the standard quantum measurement limit of classical mechanics, use weak light to measure photosensitive biological fragile systems, and improve the detection sensitivity of sensors for low-concentration analytes.

[0017] (2) The Sagnac interferometer structure is used in the quantum entangled source, which provides a stable optical path configuration. The geometric superposition of the two paths minimizes the impact of external interference such as vibration or environmental changes. The quantum entangled source generated after spontaneous parametric down-conversion (SPDC) produces highly efficient entangled photon pairs through bidirectional pumping. It has a high quantum correlation, which reduces the quantum correlation noise between the signal light and the reference light, and produces a noise floor below the shot noise limit, so that the intensity change signal that was originally annihilated by the quantum noise can be detected.

[0018] (3) There is a good correlation between the signal light and the reference light generated by the quantum entangled light source. When performing second-order correlation measurement, it can effectively generate coincidence counts and improve measurement accuracy. For noise in the signal light or reference light, the second-order correlation measurement can effectively filter out its noise interference.

[0019] (4) The sensor has a simple structure, is lightweight, miniaturized, label-free, and easy to operate. It can perform rapid real-time monitoring and can detect small amounts of samples. It has ultra-high resolution and maintains the activity of the molecule. By changing the biosensitive membrane, it can be used for in situ and dynamic observation of the concentrations of multiple analytes. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 Schematic diagram of a tapered coreless optical fiber biosensor based on quantum measurement.

[0021] Figure 2 Schematic diagram of the structure of the tapered coreless optical fiber biosensor. DETAILED DESCRIPTION

[0022] The utility model is further described below in conjunction with the accompanying drawings.

[0023] like Figure 1As shown, it is a schematic diagram of a biosensor measurement system based on quantum measurement as a photon pair generation system. The pump light source module in the entanglement module 1 uses a semiconductor laser as a light source, and its output end passes through the first quarter / half wave plate group (Q / HWP) 101 and the polarization beam splitter 102 (PBS) to adjust the phase and light intensity of the pump laser, and then continues to pass through the second quarter / half wave plate group (Q / HWP) 103 to adjust the light intensity distribution in the Sagnac interference ring. After being reflected by the dichroic mirror 104 (DM), the pump laser enters the Sagnac ring structure module in the entanglement module 1, and is separated into horizontally polarized transmitted light and vertically polarized reflected light by the dual-color polarization beam splitter 201 (DPBS), and then pumped clockwise and counterclockwise along the Sagnac ring respectively. The vertically polarized reflected light in the counterclockwise direction is converted into horizontally polarized light by the two-color half-wave plate 202 (DHWP) set at 45°, and then reflected by the parabolic mirror 203 and focused into the PPKTP crystal 204. The horizontally polarized transmitted light in the clockwise direction is directly reflected and focused into the PPKTP crystal 204 by another parabolic mirror 205. The new light beams generated at the same time are output from both sides of the PPKTP crystal, and after the two-color half-wave plate (DHWP) 202 and the two-color polarization beam splitter (DPBS) 201, one path as signal light is first coupled to the light transmitted by the optical fiber through the spatial light to optical fiber coupler 206, and then connected to the sensor module 2, and then connected to the first single photon detector 402 (SPD). The other path of reference light is directly connected to the second single photon detector 401 (SPD) after the spatial light is coupled to the light transmitted by the optical fiber through the spatial light to optical fiber coupler 105. The change of the concentration of the analyte in the sample to be tested 306 in the sensing module 2 will change the capture of the analyte by the biosensitive membrane 304 on the surface of the conical area, thereby generating a change in the refractive index on the surface of the sensing area, causing the interference spectrum to move, and the light intensity at the signal light wavelength position to change, and the signal light intensity passing through the sensor to change. This causes the number of photons recognized by the first single photon detector 402 (SPD) in the detection module 3 to change, and the trigger time delay of the two single photon detectors 401 and 402 (SPD) is adjusted to make the arrival time of the signal path and the reference path the same, and the delay difference is 0, and the second-order correlation measurement of the signal photon and the reference photon is performed. In the coincidence counting module 4, the coincidence counter 403 (TDC) obtains the maximum coincidence count value. A proportional relationship between the coincidence count value and the concentration of the sample to be tested is established, and the concentration of the sample to be tested is measured by monitoring the change of the coincidence count value.

[0024] like Figure 2As shown, a schematic diagram of the structure of a tapered coreless fiber biosensor. In the sensing system, the first single-mode fiber 301 (SMF) is fused with one end of the coreless fiber 302 (SPW), and the other end of the coreless fiber 302 (SPW) is fused with the second single-mode fiber 303 (SMF). The coreless fiber 302 (SPW) is tapered, and a specific biosensitive membrane 304 is bonded to the surface of the tapered area. Then, the sensor is placed in a microfluidic tube 305, and a sample 306 to be tested is also encapsulated therein. The sample 306 to be tested of different concentrations is injected into the microfluidic tube 305 from the solution injection port 305-1 through a microinjection pump, and flows out from the solution output port 305-2.

[0025] The device can realize a conical coreless optical fiber biosensor based on quantum measurement for the measurement of photosensitive biological fragile systems. The key technologies are:

[0026] (1) The Sagnac interferometer structure is used in the quantum entanglement source, and bidirectional pumping produces highly efficient entangled photon pairs with stability and high quantum correlation.

[0027] (2) The sensor is taper-processed to achieve thermal insulation and reduce insertion loss.

[0028] (3) Prepare uniquely recognized biosensitive membranes to achieve high sensitivity and high selectivity in detecting targets.

[0029] (4) The sensor is placed in a special microfluidic tube. This measuring device can maintain the stability of the sensor and improve the accuracy of the measurement results by controlling the flow rate of the sample to be tested.

[0030] In a specific case of the utility model, a 795nm laser generated by a continuously adjustable power semiconductor laser is used to pump a periodically polarized potassium titanyl phosphate (PPKTP) crystal. The PPKTP crystal has a size of 1mm×1.8mm×20.14mm, a polarization period of 46.1μm, and a temperature set to 20°C. The PPKTP crystal parametrically down-converts a 1590nm signal light and a reference light when the pump light wavelength is 795nm. The conical area is coated with an antibody film of CD63 exosome transmembrane protein with a thickness of about 57nm, and is placed in a 0.3ml microfluidic tube made of acrylic glass for placing the sample exosome solution to be tested. The sensor surface has a biosensitive film, and different exosome solutions with concentrations of 0mg / mL, 0.5mg / mL, 1mg / mL, 1.5mg / mL, and 2mg / mL are immersed in the sensor through a microinjection pump. The cumulative time for coincidence counting is 100s, and the coincidence counting gate width is 3ns. The matching counts obtained were 20645, 16038, 12382, 8129, and 4706 respectively.

[0031] The basic principle and main features of the present invention are shown and described above. Without departing from the spirit and scope of the present invention, the present invention may be subject to various changes and improvements, which fall within the scope of the present invention to be protected.

Claims

1. A tapered coreless optical fiber biosensor based on quantum measurement, characterized in that: The invention is composed of four modules, including an entanglement module, a sensing module, a detection module, and a coincidence counting module; the entanglement module includes a pump light source module and a Sagnac ring structure module; the entanglement module includes a semiconductor laser, a polarization beam splitter, a first and a second quarter / half wave plate group, a dichroic mirror, a two-color polarization beam splitter, a two-color half-wave plate, a periodically polarized potassium titanyl phosphate crystal, a parabolic mirror, and a spatial light to optical fiber coupler; the sensing module includes a sensor, a microfluidic tube, and a sample to be tested; the detection module includes two single-photon detectors; the coincidence counting module is a coincidence counter; the pump light source module in the entanglement module uses a semiconductor laser as a light source, and its output end passes through the first quarter / half wave plate group and the polarization beam splitter. After the pump laser is reflected by the dichroic mirror, it enters the Sagnac ring structure module in the entanglement module, and is separated into horizontally polarized transmitted light and vertically polarized reflected light by the two-color polarization beam splitter, and then pumped and The method is pumped in a counterclockwise direction; the vertically polarized reflected light in the counterclockwise direction is converted into horizontally polarized light by a two-color half-wave plate set at 45°, and then reflected by a parabolic mirror and focused into a periodically polarized potassium titanyl phosphate crystal; the horizontally polarized transmitted light in the clockwise direction is directly reflected by another parabolic mirror and focused into a periodically polarized potassium titanyl phosphate crystal; at the same time, the light beams generated by spontaneous parametric down-conversion are output from both sides of the periodically polarized potassium titanyl phosphate crystal, and after the two-color half-wave plate and the two-color polarization beam splitter are used, one path as the signal light is first coupled to the light transmitted by the optical fiber through a spatial light-to-optical fiber coupler, and then connected to the sensor module, and then connected to the first single-photon detector; the other path of reference light is coupled to the light transmitted by the optical fiber through a spatial light-to-optical fiber coupler, and then directly connected to the second single-photon detector; the output ends of the two single-photon detectors are respectively connected to the two ports of the coincidence counter; the trigger time delay of the two single-photon detectors is adjusted, and the delay difference is 0, and the second-order correlation measurement of the two signals is performed on the coincidence counter.

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