Research On The Key Technology Of Optofluidic Laser Sensing And Its Application In Biomarker Detection

High-performance biomarker detection has an important role in early disease diagnosis,disease screening,and daily monitoring of diseases.Existing optical biosensors meet the following challenges:（1）traditional optical sensors suffer from low sensitivity.（2）The fine microcavities/microstructures of sensitive sensors are difficult to reproduce and difficult to handle due to weak structure strength.（3）Prior optical sensors are single-functional and without customized design for specific applications.Therefore,developing highly sensitive,disposable,and multifunctional biosensors is the bottleneck for optical biosensors.Aiming at the above challenges,in this thesis,sensing technologies such as zero-threshold optofluidic laser（ZT-OFL）method,disposable optofluidic laser with thick-walled capillary,and hollow-core Bragg fiber optofluidic laser are proposed.By means of gain offset,highly reproducible microcavity fabrication,and dual-band laser output,optofluidic lasers are developed and applied in highly sensitive,disposable,and multifunctional biomarker detection.The main achievements are as follows:（1）A highly sensitive optofluidic laser detection method with zero-threshold concentration is proposed.A gain offset instead of excessive analytes is pre-added to achieve the lasing threshold,which breaks the threshold limitation and lowers the LOD.Sensitive uric acid（a renal function biomarker）detection is achieved with a LOD of 3.63μM,lowered by one order of magnitude.Incorporating the amplification effect of the enzyme,a zero-threshold enzyme-amplified optofluidic laser（ZTEA-OFL）is proposed.Sensitive enzyme detection is achieved,showing 4 orders of magnitude decreasing compared with direct optofluidic laser detection.Applying the ZTEA-OFL method to a magnetic particles-based enzyme-linked immunosorbent assay（ELISA）,labeled homogeneous detection ofα-synuclein（a biomarker for Parkinson’s disease）is achieved with the LOD of 1 pg·m L^-1,2 orders of magnitude lower than the traditional ELISA.（2）Optofluidic laser based on thick-walled capillary is proposed for disposable biomarker detection,addressing the problem of fine microcavities lacking structure strength and difficulty in handling.Disposable detection of a biomarker for immunologic function is achieved.The thick-walled capillary can be mass-produced with high reproducibility at low cost,and it is used as a reproducible FP microcavity for disposable optofluidic laser（）.Disposable and fast（15 min）detection of immunological function biomarker with an LOD of 4 n M is demonstrated.In addition,taking advantage of the"cavity-less"property of random laser,it is exploited for disposable use.The structurally robust thick-walled capillary allows for secondary processing.A random laser is proposed with a polymer-scatterer thin film reproducibly（）coated on the inner wall of the thick-walled capillary.The path lengths of random laser output are analyzed against different analyte concentrations,which reveals a new sensing mechanism for optofluidic random laser sensors.The biomarker detection is realized with a low sample volume of～30 n L（1/67th of the traditional method）.（3）A multifunctional optofluidic laser based on a hollow-core Bragg fiber（HCBF）is proposed.The HCBF supports dual-band optofluidic lasing.Immunosensing of microalbumin（biomarker for renal disease）is realized by using the periodic resonant peaks in the band I(LOD=0.06 ngμL^-1).By encoding the random resonant peaks in band II and multiplexing in the spatial domain,a physically unclonable 2D laser tag is generated with a large and expandable encoding capacity(>2⁸⁵⁰⁰).The functions of biomarker sensing and 2D laser tag are integrated on the same 7.5-millimeter-long HCBF.