Studies On High Sensitivity And Label-free Quantitative Biosensing Of Optical Microfiber Coupler

The realization of ultra-low concentration detection of cancer markers plays a key role in the early screening and diagnosis of cancer,which will greatly reduce the incidence and mortality of cancer.The optical microfiber coupler is a attractive high-sensitivity optical sensing structure,which provides a potential platform for realizing the high-sensitivity and label-free quantitative detection of clinical cancer markers.On the one hand,the repeatability of optical microfiber couplers is a problem in batch production.On the other hand,the label-free quantitative detection of cancer markers in the serum environment has the problems of non-specific adsorption and individual differences of human serum.To solve the above problems,this paper conducts in-depth theoretical and experimental research on the repeatability preparation of optical microfiber couplers,the ultra-high sensitivity characteristics of the micro/nano-fiber dispersion turning point,the specific standard-free biosensing in the serum environment,and the label-free quantitative detection.The main research contents are as follows:(1)For the micro/nano-fiber cladding-environmental double-layer structure,the influence of the refractive index of the external environment on the mode transmission was studied;the mode coupling phenomenon of the non-adiabatic fiber and and the appearance mechanism of dispersion turning point due to the coupling of high-order mode and fundamental mode were studied;the model of the micro-nano fiber coupler in strong melting state and the dispersion turning point phenomenon based on the optical microfiber coupler were studied.(2)For the problem of the poor repeatability of the optical microfiber coupler,a composite processing method combining the the fusion elongation and the etching method was proposed.The output spectral curve of the optical microfiber coupler is monitored real time online to accurately control the position of the dispersion turning point,and then the diameter of the fiber was controlled.The repeatability problem is solved by preparing the optical microfiber coupler with the same dispersion turning point position.The detection of 2pg/m L carcinoembryonic antigen(CEA)in phosphate buffer saline(PBS)can be achieved by using the optical microfiber coupler with a dispersion turning point near 1300 nm.(3)For the requirement of high-sensitivity sensing for cancer marker detection,the ultrasensitivity phenomenon of two micro/nano-fiber structures with dispersion turning points based on mode coupling were studied.The ultra-low concentration(2fg/m L)of cardiac troponin I(c Tn I)in PBS buffer was detected by using a optical microfiber coupler with a dispersion turning point;and a single S-tapered micro/nano-fiber structure with dispersion turning point was proposed and studied.Based on the asymmetric structure,the higher order mode(LP₁₁)is excited first,and when the phase matching condition is met,the LP₀₁and LP₁₁modes interfere.When their group effective refractive index difference is 0,the dispersion turning point would appears.Utilizing the ultra-high sensitivity characteristic of its chromatic dispersion turning point,the ultra-high refractive index sensitivity detection of the external environment near the refractive index of 1.33300 is realized,which is 1.46×10⁵±0.09×10⁵nm/RIU.(4)For the non-specific adsorption problem of the optical microfiber coupler label-free immunosensing in the serum environment,the strategy of serum pre-adsorption is adopted and optimized.The anti-adsorption capacity of two different serums,fetal bovine serum and human serum were studied.And the high sensitivity,wide dynamic range,and specificity label-free detection of cancer markers in the serum environment by optical microfiber couplers were realized.(5)For the problem of individual differences in human serum,a label-free quantitative detection method based on optical microfiber coupler biosensors was proposed.The wavelength shift of standard serum is used as a reference to reduce the influence of individual differences of human serum.The influence of different concentrations of standard serum on the correction of individual differences in human serum and the dissociation and regeneration of the optical microfiber coupler were studied.The concentration of CEA in serum samples of different cancer patients were quantitative detection,the detection results were in good agreement with clinical examinations,and further promote the practical application of optical microfiber coupler biosensors.