CN101750280A - Whispering-gallery-mode fiber optic biosensor - Google Patents
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Abstract
本发明公开了一种回音壁模式的光纤生物传感器,具有至少一条光纤以及至少一个微谐振腔,该回音壁模式的光纤生物传感器可以将光纤内的光耦合进微谐振腔并激发出回音壁模式,光纤生物传感器还具有一个可插入待测物质中的基板,光纤为Y形,Y形光纤的一个分支为可连接光源的光线入射端,另一个分支为可连接检测器的光线出射端,Y形光纤下端固定在基板上且其末端固定有反射镜,微谐振腔固定在基板上与Y形光纤下端耦合。本发明使用时,光源和检测仪器位于微谐振腔的同一侧,利于检测和移动,实现不对检测物标记,且实时地对待测分析物进行检测,也可以将这种光纤生物传感器的基板插入待测分析物,这样,检测比较方便、安全、稳定,也可实现野外检测。同时,该技术方案可使光波两次耦合进入微谐振腔,使这种回音壁模式的传感器的精度、灵敏度进一步提高。
The invention discloses a whispering gallery mode optical fiber biosensor, which has at least one optical fiber and at least one micro-resonant cavity, and the whispering gallery mode optical fiber biosensor can couple the light in the optical fiber into the micro-resonant cavity and excite the whispering gallery mode , the optical fiber biosensor also has a substrate that can be inserted into the substance to be measured, the optical fiber is Y-shaped, one branch of the Y-shaped optical fiber is the light incident end that can be connected to the light source, and the other branch is the light output end that can be connected to the detector, Y The lower end of the Y-shaped optical fiber is fixed on the substrate and a reflector is fixed at the end thereof, and the micro-resonant cavity is fixed on the substrate and coupled with the lower end of the Y-shaped optical fiber. When the present invention is used, the light source and the detection instrument are located on the same side of the micro-resonator cavity, which is convenient for detection and movement, and realizes the real-time detection of the analyte to be measured without marking the detection object. The substrate of this optical fiber biosensor can also be inserted into the In this way, the detection is more convenient, safe and stable, and field detection can also be realized. At the same time, this technical solution can couple light waves into the micro-resonator cavity twice, so that the accuracy and sensitivity of this whispering gallery mode sensor can be further improved.
Description
技术领域technical field
本发明涉及光纤传感器,尤其是一种采用微谐振腔的光纤生物传感器。The invention relates to an optical fiber sensor, in particular to an optical fiber biosensor using a micro-resonant cavity.
背景技术Background technique
如图1所示,回音壁模式的光纤生物传感器包括光纤以及可产生光学谐振的微谐振腔,这种微谐振腔一般是微球、微盘或微环。As shown in Figure 1, the whispering gallery mode optical fiber biosensor includes an optical fiber and a micro-resonant cavity that can generate optical resonance, such a micro-resonant cavity is generally a microsphere, a microdisk or a microring.
以微球谐振腔为例,微球谐振腔是半径从几微米到几百微米的球形光学谐振腔。通过在微球内表面不断地发生全反射,微球腔将光约束在赤道平面附近并沿大圆绕行,激发出特有的回音壁模式(whisperinggallery mode,简称WGM或WG)。由于全反射的作用,球外光场为倏逝场,这种光波是非传播波,因此渗出微球以外的光是及其微弱的,所以它能够将光约束在很小的体积内很长时间而几乎没有任何损失,故微球谐振腔以其拥有能够将能量长时间储存在很小的体积内的能力而备受关注。正因为微球谐振腔具有极高的品质因子(达到1010)和极小的模式体积,使它在非线性光学、腔体量子电动力学、低阈值激光器及量子光学等研究领域独具优势。Taking the microsphere resonator as an example, the microsphere resonator is a spherical optical resonator with a radius ranging from several microns to hundreds of microns. Through continuous total reflection on the inner surface of the microsphere, the microsphere cavity confines the light near the equatorial plane and orbits along the great circle, which excites a unique whispering gallery mode (WGM or WG for short). Due to the effect of total reflection, the light field outside the sphere is an evanescent field, and this light wave is a non-propagating wave, so the light that leaks out of the microsphere is extremely weak, so it can confine the light in a small volume for a long time Therefore, microsphere resonators have attracted much attention for their ability to store energy in a small volume for a long time. Because of the extremely high quality factor (up to 10 10 ) and the extremely small mode volume of the microsphere resonator, it has unique advantages in the research fields of nonlinear optics, cavity quantum electrodynamics, low-threshold lasers and quantum optics.
微球谐振腔应用于传感器领域,主要应用了微球谐振腔自身内部或者自身与外界相互作用的灵敏反应,诸如频率或光谱的变化。一般地说,很多外部因素可对其造成影响,如改变耦合器件与谐振腔的距离,或让微小物体接近球外的倏逝场影响谐振腔的模式;从内部造成影响的方法则有改变腔内光程,例如球体的形变或者折射率的改变等。由于微球谐振腔的作用,使得生物传感器、温度传感器和加速度传感器的精度和灵敏度等性能指标大大提高,甚至可以测定单分子物质。The microsphere resonator is used in the field of sensors, and mainly uses the sensitive response of the microsphere resonator itself or the interaction between itself and the outside world, such as changes in frequency or spectrum. Generally speaking, many external factors can affect it, such as changing the distance between the coupling device and the resonant cavity, or allowing the tiny object to approach the evanescent field outside the sphere to affect the mode of the resonant cavity; the internal method of affecting it is to change the cavity Internal optical path, such as the deformation of the sphere or the change of the refractive index, etc. Due to the role of the microsphere resonant cavity, the performance indicators such as the accuracy and sensitivity of the biosensor, temperature sensor and acceleration sensor are greatly improved, and even single molecular substances can be determined.
微球谐振腔在生物传感器方面的运用,是通过外界微小粒子在微球表面附近与球外的倏逝场相互作用引起本征模式的微小变化,使得激光波长变化而产生可观察效果。通常采用锥形光纤耦合,最基本的耦合方式是棱镜耦合(如图2),一束光从玻璃达到界面上,当i>ic时,将发生全反射现象。根据电动力学的推导结论,在空气介质方有一个倏逝场。将微球置于该倏逝场的适当位置,使之与微球腔的本征模式相匹配,外部的光就从外界的传播波耦合进入微球,在微球腔中激发出回音壁模式。现在,一般采用锥形光纤实现高效率的耦合。The application of microsphere resonators in biosensors is to cause small changes in eigenmodes through the interaction of external tiny particles near the surface of the microspheres with the evanescent field outside the sphere, so that the laser wavelength changes to produce observable effects. Usually tapered fiber coupling is used, and the most basic coupling method is prism coupling (as shown in Figure 2). When a beam of light reaches the interface from the glass, when i>ic, total reflection will occur. According to the derivation conclusion of electrodynamics, there is an evanescent field in the air medium. The microsphere is placed in the appropriate position of the evanescent field to match the eigenmode of the microsphere cavity, and the external light is coupled into the microsphere from the external propagating wave, and the whispering gallery mode is excited in the microsphere cavity . Now, tapered optical fibers are generally used to achieve high-efficiency coupling.
但是,由于微球谐振腔要设置在光纤的中间段,光纤的两端分别与光源、检测仪器相连接,探测部分体积较大,需要特殊仪器固定,固定不稳固,仪器分别位于微谐振腔的两侧,不利于检测和移动,现有的回音壁模式的传感器不能做成探针形状,因此,不能直接插入待测分析物,难以实现野外现场实时监测,也不能直接插入小的微腔内(如血管内)。However, since the microsphere resonant cavity should be set in the middle section of the optical fiber, the two ends of the optical fiber are respectively connected with the light source and the detection instrument. On both sides, it is not conducive to detection and movement. The existing whispering gallery mode sensor cannot be made into a probe shape. Therefore, it cannot be directly inserted into the analyte to be measured, and it is difficult to realize real-time monitoring in the field, and it cannot be directly inserted into a small microcavity. (eg intravascular).
发明内容Contents of the invention
本发明要解决的技术问题是,提供一种回音壁模式的光纤生物传感器,它可以实现不对检测物标记,且实时地对待测分析物进行检测,也可以方便安全地移动回音壁模式的光纤生物传感器。The technical problem to be solved by the present invention is to provide a fiber optic biosensor in whispering gallery mode, which can detect the analyte in real time without marking the detection object, and can also move the fiber optic biosensor in whispering gallery mode conveniently and safely. sensor.
为达到上述目的,本发明的技术方案为:一种回音壁模式的光纤生物传感器,具有至少一条光纤以及至少一个微谐振腔,该微谐振腔可以将光纤内的光耦合进微谐振腔并激发出回音壁模式,光纤生物传感器还具有一个可插入待测物质中的基板,光纤为Y形,Y形光纤的一个分支为可连接光源的光线入射端,另一个分支为可连接检测器的光线出射端,Y形光纤下端固定在基板上且其末端固定有反射镜,微谐振腔固定在基板上与Y形光纤下端耦合。由于设置了Y形的光纤以及固定光纤一端的基板,光源和检测仪器位于微谐振腔的同一侧,利于检测和移动,实现不对检测物标记,且实时地对待测分析物进行检测,也可以将这种光纤生物传感器的基板插入待测分析物,这样,检测比较方便、安全、稳定,也可实现野外检测。同时,该技术方案中,由于光波被反射镜反射,可使光波两次耦合进入微谐振腔,从而使这种回音壁模式的传感器的精度、灵敏度进一步提高。In order to achieve the above object, the technical solution of the present invention is: a whispering gallery mode optical fiber biosensor, which has at least one optical fiber and at least one micro-resonant cavity, and the micro-resonant cavity can couple the light in the optical fiber into the micro-resonant cavity and excite In the whispering gallery mode, the optical fiber biosensor also has a substrate that can be inserted into the substance to be measured. The optical fiber is Y-shaped. One branch of the Y-shaped optical fiber is the light incident end that can be connected to the light source, and the other branch is the light that can be connected to the detector. At the output end, the lower end of the Y-shaped optical fiber is fixed on the substrate and a reflector is fixed at the end thereof, and the micro-resonant cavity is fixed on the substrate and coupled with the lower end of the Y-shaped optical fiber. Due to the Y-shaped optical fiber and the substrate that fixes one end of the optical fiber, the light source and the detection instrument are located on the same side of the micro-resonator cavity, which is convenient for detection and movement, and realizes real-time detection of the analyte to be measured without marking the detection object. The substrate of the optical fiber biosensor is inserted into the analyte to be tested, so that the detection is relatively convenient, safe and stable, and field detection can also be realized. At the same time, in this technical solution, since the light wave is reflected by the mirror, the light wave can be coupled into the micro-resonator twice, so that the accuracy and sensitivity of the whispering gallery mode sensor are further improved.
Y形光纤由两条光纤组成,这两条光纤的一个末端相接组成Y形光纤的下端。The Y-shaped optical fiber is composed of two optical fibers, and one end of the two optical fibers is connected to form the lower end of the Y-shaped optical fiber.
基板为金属探针状,基板上开有放置光纤的凹槽,Y形光纤的下端设置在凹槽中。采用金属探针状的基板,可以更方便地将金属探针插入待测分析物,尤其是插入人体,基板和光纤的外部还可以设置保护物连接,以防基板滑脱和增加稳固性。The substrate is in the shape of a metal probe, and a groove for placing an optical fiber is opened on the substrate, and the lower end of the Y-shaped optical fiber is arranged in the groove. The use of metal probe-like substrates makes it easier to insert the metal probes into the analyte to be measured, especially into the human body, and a protective connection can be set on the outside of the substrate and the optical fiber to prevent the substrate from slipping and increase stability.
微谐振腔外附着能够对分析物起反应的敏感层。敏感层为抗体、抗原、细胞、核酸、蛋白质或分子印痕物质。在微谐振腔和敏感层之间还有纳米金属层,纳米金属层镀在微谐振腔上。A sensitive layer capable of reacting to the analyte is attached to the outside of the microresonator. The sensitive layer is antibody, antigen, cell, nucleic acid, protein or molecular imprinted substance. There is also a nano-metal layer between the micro-resonant cavity and the sensitive layer, and the nano-metal layer is plated on the micro-resonant cavity.
基板上设置有光纤的保护板,该保护板与基板的凹槽部分相扣合并将Y形光纤的下端包在其中,在保护板上与基板的凹槽相对的区域具有多个通孔。具有了保护板,使得本传感器方便保存,延长使用寿命。An optical fiber protective plate is arranged on the base plate, the protective plate is fastened with the groove part of the base plate and wraps the lower end of the Y-shaped optical fiber in it, and there are multiple through holes on the area opposite to the groove of the base plate on the protective plate. With a protective plate, the sensor is convenient for storage and prolongs its service life.
Y形光纤的数量为一条以上。光纤为锥形光纤。The number of Y-shaped optical fibers is one or more. The optical fiber is a tapered optical fiber.
附图说明Description of drawings
图1是作为本发明基础的现有技术示意图;Fig. 1 is the prior art schematic diagram as the basis of the present invention;
图2是微球谐振腔耦合原理图;Figure 2 is a schematic diagram of microsphere resonator coupling;
图3是本发明的示意图;Fig. 3 is a schematic diagram of the present invention;
图4是另一种Y形光纤的的示意图;Fig. 4 is the schematic diagram of another kind of Y-shaped optical fiber;
图5是基板与保护板的剖视示意图;5 is a schematic cross-sectional view of the substrate and the protective plate;
图6是微谐振腔与光纤的一种耦合图;Fig. 6 is a kind of coupling figure of microresonator and optical fiber;
图7是本发明的运用示意图。Fig. 7 is a schematic diagram of the application of the present invention.
具体实施方式Detailed ways
如图3所示,本发明回音壁模式的光纤生物传感器,具有光纤1、微谐振腔2和基板7,光纤1为Y形,Y形光纤1的一个分支为可连接光源的光线入射端3,另一个分支为可连接检测器的光线出射端4,Y形光纤的下端5固定在基板7上且其末端固定有反射镜6,微谐振腔2也固定在基板7上与Y形光纤下端5耦合,并可激发出回音壁模式,与微谐振腔耦合处的光纤采用锥形光纤。基板7具有一定的机械强度可插入待测分析物中。由于设置了Y形的光纤1以及固定光纤一端的基板7,就可以将这种光纤生物传感器的基板插入待测分析物,Y形光纤下端的反射镜6可以将由光纤入射端3进入的光线反射回,在光纤的出射端4可以用检测器检测到反射回的光线,它的运用如图7所示。这样使光源和检测仪器位于微谐振腔的同一侧,利于检测和移动,实现不对检测物标记,且实时地对待测分析物进行检测,可以将这种光纤生物传感器的基板插入待测分析物,这样,检测比较方便、安全、稳定,也可实现野外检测。也方便保存,延长使用寿命。As shown in Figure 3, the optical fiber biosensor of the whispering gallery mode of the present invention has an optical fiber 1, a
如图4所示,Y形光纤由两条光纤组成,这两条光纤的一个末端相接组成Y形光纤的下端5,反射镜6可以将一条光纤的入射光反射到另一条光纤中。As shown in Figure 4, the Y-shaped optical fiber is composed of two optical fibers, one end of the two optical fibers is connected to form the
如图3、5所示,基板7为金属探针,基板7上开有放置光纤的凹槽8,Y形光纤的下端5设置在凹槽8中。基板7上还可以设置光纤的保护板9,该保护板9与基板7的凹槽8部分相扣合并将Y形光纤的下端5包在其中,在保护板9上与基板7的凹槽8相对的区域具有多个通孔10。采用金属探针状的基板,可以更方便地将金属探针插入待测分析物,尤其是插入人体,如血管、脑积液。保护板对金属探针上的光纤起保护作用,保护板上开设的通孔使得待测分析物可以进入到金属探针的凹槽中与微谐振腔接触。As shown in Figures 3 and 5, the
微谐振腔2外部附着能够对分析物起反应的敏感层,敏感层为抗体、抗原、细胞、核酸、蛋白质或分子印痕物质,敏感层通过抗凝处理。在微谐振腔和敏感层之间还有纳米金属层,纳米金属层镀在微谐振腔上,敏感层附着在纳米金属层上。敏感层的物质可以结合与之相应的待测定分析物,结合了分析物的微谐振腔,它的光谱性能就发生改变,设置了特定物质的敏感层的传感器就可以检测特定的分析物。敏感层的物质为多种时,传感器就可以检测一种以上的待测物。A sensitive layer capable of reacting to the analyte is attached to the outside of the
光纤通常具有包覆层,在与微谐振腔2耦合处,应将包覆层剥离。如图6所示,为加强微谐振腔2的耦合效果,光纤的纤核通过腐蚀使之直径达到1~5μm。The optical fiber usually has a cladding layer, and the cladding layer should be stripped at the coupling position with the
光纤上的反射镜可以采取在光纤上镀金属的方式制作。Y形光纤的数量为一条以上。The mirror on the optical fiber can be made by plating metal on the optical fiber. The number of Y-shaped optical fibers is one or more.
图7示出了本发明的运用,本发明光纤生物传感器的光线入射端3与光源12连接,光线出射端4与检测器13连接,将本发明置于待测溶液中11,即可对待测分析物进行检测。Fig. 7 shows the application of the present invention, the
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US20070114477A1 (en) * | 2005-11-18 | 2007-05-24 | Iwao Teraoka | Enhanced sensitivity of a whispering gallery mode microsphere sensor by a high-refractive index surface layer |
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