CN103323399B - A kind of micro-nano fiber biosensor - Google Patents
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Abstract
一种微纳光纤生物传感器，涉及光学领域，具体涉及一种生物传感器。它是为了解决现有对生物体布里渊谱的实时活体测量设备的结构复杂、稳定性差、准确性低的问题。它的激光器发出的激光入射至耦合器，经耦合器分为一号光束和二号光束，采用单边带调制器对一号光束进行调制并经微纳光纤入射至环行器的一号光输入端；电光调制器对二号光束的强度进行调制，并经掺铒光纤放大器放大后入射至环行器的二号光输入端；环行器的光输出端出射的光入射至光电探测器的感光端；光电探测器的电信号经锁相放大器输出至示波器。本发明适用于对生物体布里渊谱的实时活体测量。
A micro-nano optical fiber biosensor relates to the field of optics, in particular to a biosensor. It aims to solve the problems of complex structure, poor stability and low accuracy of existing real-time in vivo measurement equipment for Brillouin spectra of living organisms. The laser emitted by its laser enters the coupler, and is divided into No. 1 beam and No. 2 beam by the coupler. The No. 1 beam is modulated by a single-sideband modulator and is incident on the No. 1 light input of the circulator through a micro-nano fiber. The electro-optic modulator modulates the intensity of the No. 2 light beam, and after being amplified by the erbium-doped fiber amplifier, it enters the No. 2 light input port of the circulator; the light emitted from the light output port of the circulator enters the photosensitive end of the photodetector ; The electrical signal of the photodetector is output to the oscilloscope through the lock-in amplifier. The invention is suitable for the real-time living body measurement of the Brillouin spectrum of the living body.
Description
技术领域technical field
本发明涉及光学领域，具体涉及一种生物传感器。The invention relates to the field of optics, in particular to a biological sensor.
背景技术Background technique
自发布里渊散射是一种非弹性散射过程，它起源于介质中非相干的密度起伏或声子。布里渊光谱反映了散射过程中的光谱变化，并直接给出与介质弹光特性相关的声子信息。由布里渊频移可直接算出声速，由声速可以算出弹性常数，由声速的变化可以得到关于声速的各向异性，弛豫过程和相变的信息。由布里渊线宽(需用高分辨装置)可以研究声子衰减过程，得到物质的粘滞特性。根据强度的测量可以研究声子和电子态的耦合等。在生物医学领域，布里渊光谱学已成功应用于体外样品的弹光特性测量，这包括胶原纤维、骨头、眼角膜和晶状体，以及血液流变参数等。Spontaneous Brillouin scattering is an inelastic scattering process that originates from incoherent density fluctuations or phonons in a medium. The Brillouin spectrum reflects the spectral changes during the scattering process and directly gives the phonon information related to the elastic-optical properties of the medium. The sound velocity can be directly calculated from the Brillouin frequency shift, the elastic constant can be calculated from the sound velocity, and the information about the anisotropy of the sound velocity, the relaxation process and the phase transition can be obtained from the change of the sound velocity. From the Brillouin linewidth (requires a high-resolution device), the phonon attenuation process can be studied, and the viscosity characteristics of the material can be obtained. According to the measurement of intensity, the coupling of phonon and electronic state can be studied. In the field of biomedicine, Brillouin spectroscopy has been successfully applied to the measurement of elasto-optical properties of in vitro samples, including collagen fibers, bones, corneas and lenses, as well as blood rheological parameters.
传统测量布里渊光谱的办法是对自发布里渊散射进行直接测量，然而该技术的难点在于如何区分自发布里渊散射光和起源于瑞利散射和Mie散射的弹性散射光。在大多数生物物质和溶液中，弹性光散射的强度会比布里渊散射高几个量级，这势必会影响自发布里渊散射谱的测量精度。此外，布里渊频移非常小(只有GHz量级)，使用传统的光谱仪无法分辨。相比之下，基于泵浦-探测技术的受激布里渊散射光谱可以显著提高光谱分辨率和信噪比，并且该技术对背景光辐射不敏感，即测量光谱的零频移处没有瑞利散射信号，而且可以忽略由于角度偏差引起的布里渊频移和线宽的测量误差。但如果在自由空间中采用泵浦-探测技术测量生物物质液体的布里渊谱，则需要将泵浦光和探测光严格对准，致使结构复杂、稳定性差；而且在自由空间中无法长距离的保持较小的光斑，因此降低了布里渊增益和信噪比，此外这种复杂结构也无法实现对生物体的实时活体测量。The traditional way to measure the Brillouin spectrum is to directly measure the spontaneous Brillouin scattering. However, the difficulty of this technique lies in how to distinguish the spontaneous Brillouin scattered light from the elastic scattered light originating from Rayleigh scattering and Mie scattering. In most biological substances and solutions, the intensity of elastic light scattering will be several orders of magnitude higher than that of Brillouin scattering, which will inevitably affect the measurement accuracy of spontaneous Brillouin scattering spectroscopy. In addition, the Brillouin frequency shift is so small (only on the order of GHz) that it cannot be resolved using conventional spectrometers. In contrast, stimulated Brillouin scattering spectroscopy based on the pump-probe technique can significantly improve spectral resolution and signal-to-noise ratio, and this technique is insensitive to background light radiation, that is, there is no Ray at zero frequency shift of the measured spectrum. Scattering signals can be used, and the measurement errors of Brillouin frequency shift and line width caused by angle deviation can be ignored. However, if the pump-probe technique is used to measure the Brillouin spectrum of the biological material liquid in free space, it is necessary to strictly align the pump light and the probe light, resulting in a complex structure and poor stability; The light spot is kept small, so the Brillouin gain and signal-to-noise ratio are reduced. In addition, this complex structure cannot realize real-time in vivo measurement of organisms.
微纳光纤是纳米光子学中的一个重要研究领域，它以其卓越的性能成为未来光器件微型化、集成化的一种可供选择的基本单元。当光在微纳光纤中传输时，一部分能量分布于微纳光纤之外，形成倏逝波，利用倏逝波对周围介质折射率的敏感特性，可实现多种类型的微纳光纤生物传感器。Micro-nano fiber is an important research field in nanophotonics. It has become an optional basic unit for the miniaturization and integration of future optical devices due to its excellent performance. When light is transmitted in the micro-nano fiber, a part of the energy is distributed outside the micro-nano fiber, forming evanescent waves. Using the sensitivity of the evanescent wave to the refractive index of the surrounding medium, various types of micro-nano fiber biosensors can be realized.
发明内容Contents of the invention
本发明是为了解决现有对生物体布里渊谱的实时活体测量设备的结构复杂、稳定性差、准确性低的问题，从而提供一种微纳光纤生物传感器。The invention aims to solve the problems of complex structure, poor stability and low accuracy of the existing real-time living body measurement equipment for the Brillouin spectrum of the living body, thereby providing a micro-nano optical fiber biosensor.
一种微纳光纤生物传感器，它包括激光器1、耦合器2、微波源3、单边带调制器4、扰偏器5、储液设备6、微纳光纤7、环行器8、掺铒光纤放大器9、电光调制器10、函数发生器11、光电探测器12、锁相放大器13和示波器14，A micro-nano optical fiber biosensor, which includes a laser 1, a coupler 2, a microwave source 3, a single-sideband modulator 4, a polarization scrambler 5, a liquid storage device 6, a micro-nano optical fiber 7, a circulator 8, and an erbium-doped optical fiber amplifier 9, electro-optic modulator 10, function generator 11, photodetector 12, lock-in amplifier 13 and oscilloscope 14,
储液设备6内部充入待测溶液；微纳光纤7位于储液设备6内的溶液中；The liquid storage device 6 is filled with the solution to be tested; the micro-nano optical fiber 7 is located in the solution in the liquid storage device 6;
激光器1发出的激光入射至耦合器2，经耦合器2分为一号光束和二号光束，所述一号光束入射至单边带调制器4，微波源3驱动单边带调制器4对一号光束进行调制，获得探测光；所述探测光入射至微纳光纤7的一端；所述探测光在微纳光纤7的另一端射出并入射至环行器8的一号光输入端；The laser light emitted by the laser 1 is incident on the coupler 2, and is divided into the first beam and the second beam by the coupler 2, and the first beam is incident on the SSB modulator 4, and the microwave source 3 drives the SSB modulator 4 pairs The No. 1 light beam is modulated to obtain probing light; the probing light is incident on one end of the micro-nano fiber 7; the probing light is emitted from the other end of the micro-nano fiber 7 and is incident on the No. 1 light input end of the circulator 8;
二号光束入射至电光调制器10，函数发生器11驱动电光调制器10对二号光束的强度进行调制，获得斩波的泵浦光，所述斩波的泵浦光经掺铒光纤放大器9放大后入射至环行器8的二号光输入端；The second light beam is incident on the electro-optic modulator 10, and the function generator 11 drives the electro-optic modulator 10 to modulate the intensity of the second light beam to obtain chopped pump light, which passes through the erbium-doped fiber amplifier 9 Amplified and incident to the No. 2 light input end of the circulator 8;
环行器8的光输出端出射的光入射至光电探测器12的感光端；所述光电探测器12的电信号输出端与锁相放大器13的探测信号输入端连接；所述锁相放大器13的参考信号输入端与函数发生器11的参考信号输出端连接；所述锁相放大器13的信号输出端与示波器14的信号输入端连接。The light emitted by the light output end of the circulator 8 is incident on the photosensitive end of the photodetector 12; the electrical signal output end of the photodetector 12 is connected with the detection signal input end of the lock-in amplifier 13; the lock-in amplifier 13 The reference signal input terminal is connected to the reference signal output terminal of the function generator 11 ; the signal output terminal of the lock-in amplifier 13 is connected to the signal input terminal of the oscilloscope 14 .
本发明的有益效果：Beneficial effects of the present invention:
1、本发明利用微纳光纤束缚和传导泵浦光和探测光，使光场以倏逝波的形式大比例地渗透到其周围的液体介质中发生受激布里渊散射相互作用，然后再耦合到标准单模光纤中，全光纤的结构使系统结构简单、操作灵活；1. The present invention utilizes micro-nano optical fibers to confine and conduct the pump light and probe light, so that the light field penetrates into the surrounding liquid medium in a large proportion in the form of evanescent waves to interact with stimulated Brillouin scattering, and then Coupled to standard single-mode fiber, the all-fiber structure makes the system simple in structure and flexible in operation;
2、微纳光纤尺寸较小，可以很容易地埋入生物物质内部进行实时活体监测；2. The micro-nano optical fiber is small in size and can be easily embedded in biological matter for real-time live monitoring;
3、石英材料的微纳光纤具有无毒、结构稳定的特点，不会对生物物质造成污染和破坏。3. The micro-nano optical fiber of quartz material has the characteristics of non-toxicity and stable structure, and will not cause pollution and damage to biological substances.
附图说明Description of drawings
图1是本发明的结构示意图；Fig. 1 is a structural representation of the present invention;
图2是微纳光纤在溶液中的截面示意图；其中标记15为溶液；Fig. 2 is a schematic cross-sectional view of a micro-nano optical fiber in a solution; wherein the mark 15 is a solution;
图3是溶液中的微纳光纤的结构示意图；其中标记A是绝热锥形区；标记B是均匀微纳光纤。Fig. 3 is a schematic diagram of the structure of the micro-nano optical fiber in the solution; where mark A is an adiabatic tapered region; mark B is a uniform micro-nano optical fiber.
具体实施方式Detailed ways
具体实施方式一、结合图1至图3说明本具体实施方式，一种微纳光纤生物传感器，它包括激光器1、耦合器2、微波源3、单边带调制器4、扰偏器5、储液设备6、微纳光纤7、环行器8、掺铒光纤放大器9、电光调制器10、函数发生器11、光电探测器12、锁相放大器13和示波器14，Specific embodiments 1. This specific embodiment is described in conjunction with FIGS. 1 to 3 , a micro-nano optical fiber biosensor, which includes a laser 1, a coupler 2, a microwave source 3, a single sideband modulator 4, a polarization scrambler 5, Liquid storage device 6, micro-nano optical fiber 7, circulator 8, erbium-doped optical fiber amplifier 9, electro-optic modulator 10, function generator 11, photodetector 12, lock-in amplifier 13 and oscilloscope 14,
储液设备6内部充入待测溶液；微纳光纤7位于储液设备6内的溶液中；The liquid storage device 6 is filled with the solution to be tested; the micro-nano optical fiber 7 is located in the solution in the liquid storage device 6;
激光器1发出的激光入射至耦合器2，经耦合器2分为一号光束和二号光束，所述一号光束入射至单边带调制器4，微波源3驱动单边带调制器4对一号光束进行调制，获得探测光；所述探测光入射至微纳光纤7的一端；所述探测光在微纳光纤7的另一端射出并入射至环行器8的一号光输入端；The laser light emitted by the laser 1 is incident on the coupler 2, and is divided into the first beam and the second beam by the coupler 2, and the first beam is incident on the SSB modulator 4, and the microwave source 3 drives the SSB modulator 4 pairs The No. 1 light beam is modulated to obtain probing light; the probing light is incident on one end of the micro-nano fiber 7; the probing light is emitted from the other end of the micro-nano fiber 7 and is incident on the No. 1 light input end of the circulator 8;
二号光束入射至电光调制器10，函数发生器11驱动电光调制器10对二号光束的强度进行调制，获得斩波的泵浦光，所述斩波的泵浦光经掺铒光纤放大器9放大后入射至环行器8的二号光输入端；The second light beam is incident on the electro-optic modulator 10, and the function generator 11 drives the electro-optic modulator 10 to modulate the intensity of the second light beam to obtain chopped pump light, which passes through the erbium-doped fiber amplifier 9 Amplified and incident to the No. 2 light input end of the circulator 8;
环行器8的光输出端出射的光入射至光电探测器12的感光端；所述光电探测器12的电信号输出端与锁相放大器13的探测信号输入端连接；所述锁相放大器13的参考信号输入端与函数发生器11的参考信号输出端连接；所述锁相放大器13的信号输出端与示波器14的信号输入端连接。The light emitted by the light output end of the circulator 8 is incident on the photosensitive end of the photodetector 12; the electrical signal output end of the photodetector 12 is connected with the detection signal input end of the lock-in amplifier 13; the lock-in amplifier 13 The reference signal input terminal is connected to the reference signal output terminal of the function generator 11 ; the signal output terminal of the lock-in amplifier 13 is connected to the signal input terminal of the oscilloscope 14 .
具体实施方式二、本具体实施方式与具体实施方式一所述的一种微纳光纤生物传感器的区别在于，激光器1为窄线宽单频光纤激光器。Embodiment 2. The difference between this embodiment and the micro-nano optical fiber biosensor described in Embodiment 1 is that the laser 1 is a narrow-linewidth single-frequency fiber laser.
具体实施方式三、本具体实施方式与具体实施方式一或二所述的一种微纳光纤生物传感器的区别在于，耦合器2为50∶50耦合器。Embodiment 3. The difference between this embodiment and the micro-nano optical fiber biosensor described in Embodiment 1 or 2 is that the coupler 2 is a 50:50 coupler.
具体实施方式四、本具体实施方式与具体实施方式三所述的一种微纳光纤生物传感器的区别在于，探测光的频率低于二号光束的频率一个布里渊频移。Embodiment 4. The difference between this embodiment and the micro-nano optical fiber biosensor described in Embodiment 3 is that the frequency of the detection light is lower than the frequency of the second light beam by a Brillouin frequency shift.
具体实施方式五、本具体实施方式与具体实施方式一、二或四所述的一种微纳光纤生物传感器的区别在于，微纳光纤7的两端均为缓变的锥形结构。Embodiment 5. The difference between this embodiment and the micro-nano optical fiber biosensor described in Embodiment 1, 2 or 4 is that both ends of the micro-nano optical fiber 7 are tapered structures that gradually change.
工作原理：本发明采用窄线宽单频光纤激光器作为光源，输出波长为1550nm的连续光。泵浦-探测技术测量布里渊谱需要两个频率差锁定且可调的光源，为此把激光器输出的光分为两路，其中一路直接作为泵浦光，另一路经微波驱动单边带调制器调制后作为探测光，其频率比泵浦光频率低大约一个布里渊频移，通过改变微波源输出的微波频率可以方便地实现探测光频率的扫描。利用微波驱动单边带调制器获得探测光和泵浦光的方案除了具有调谐简单、结构紧凑的优点之外，由于泵浦光和探测光来自同一个光源，因此它们的频差本征稳定，不受激光频率漂移的影响，可以很好地解决二者之间的频差锁定问题。使用函数发生器驱动电光强度调制器对泵浦光进行强度调制获得斩波的泵浦光，同时函数发生器也为锁相放大器提供参考信号。函数发生器的型号为：泰克公司AFG3252。斩波后的泵浦光通过掺铒光纤放大器放大后再通过一个环行器进入微纳光纤区。由于布里渊放大过程的偏振相关性，泵浦光或探测光的偏振态变化会改变布里渊增益，为此使用一个光纤扰偏器随机地改变探测光的偏振态，用以避免偏振态变化导致的信噪比降低。放大后的探测光经光电探测器接收并转换，再经锁相放大器处理后提高信噪比，最后通过示波器记录放大信号。Working principle: the present invention uses a narrow-linewidth single-frequency fiber laser as a light source, and outputs continuous light with a wavelength of 1550nm. The measurement of Brillouin spectrum by pump-probe technology requires two frequency difference-locked and adjustable light sources. For this reason, the light output by the laser is divided into two paths, one of which is directly used as pump light, and the other is driven by microwave SSB After being modulated by the modulator, the frequency of the probe light is about one Brillouin frequency shift lower than that of the pump light. By changing the microwave frequency output by the microwave source, the frequency scanning of the probe light can be easily realized. In addition to the advantages of simple tuning and compact structure, the scheme of using a microwave-driven single-sideband modulator to obtain probe light and pump light, because the pump light and probe light come from the same light source, their frequency difference is intrinsically stable, Unaffected by laser frequency drift, it can well solve the problem of frequency difference locking between the two. A function generator is used to drive the electro-optic intensity modulator to modulate the intensity of the pump light to obtain chopped pump light, and the function generator also provides a reference signal for the lock-in amplifier. The model of the function generator is: Tektronix AFG3252. The chopped pump light is amplified by an erbium-doped fiber amplifier and then enters the micro-nano fiber region through a circulator. Due to the polarization dependence of the Brillouin amplification process, the polarization state of the pump light or the probe light will change the Brillouin gain. For this purpose, a fiber optic polarization scrambler is used to randomly change the polarization state of the probe light to avoid polarization. The change causes a decrease in the signal-to-noise ratio. The amplified detection light is received and converted by a photodetector, and then processed by a lock-in amplifier to improve the signal-to-noise ratio, and finally the amplified signal is recorded by an oscilloscope.
本发明具有以下的优点：The present invention has the following advantages:
1、本发明中利用微纳光纤束缚和传导泵浦光和探测光，使光场以倏逝波的形式大比例地渗透到其周围的液体介质中发生受激布里渊散射相互作用，然后再耦合到标准单模光纤中，全光纤的结构使系统结构简单、操作灵活；1. In the present invention, the micro-nano optical fiber is used to bind and conduct the pump light and the probe light, so that the light field penetrates into the surrounding liquid medium in a large proportion in the form of evanescent wave to generate stimulated Brillouin scattering interaction, and then Coupled to the standard single-mode fiber, the structure of the whole fiber makes the system structure simple and flexible;
2、微纳光纤尺寸较小，可以很容易地埋入生物物质内部进行实时活体监测；2. The micro-nano optical fiber is small in size and can be easily embedded in biological matter for real-time live monitoring;
3、石英材料的微纳光纤具有无毒、结构稳定的特点，不会对生物物质造成污染和破坏。3. The micro-nano optical fiber of quartz material has the characteristics of non-toxicity and stable structure, and will not cause pollution and damage to biological substances.
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