A Study On Phase-sensitive OCT And Its Application In Biosensing

Optical coherence tomography(OCT)is a near-infrared tomography technique based on low coherence interference.With high spatial resolution,high sensitivity,low cost and compact system structure,it has been used to diagnose fundus,gastrointestinal tract,cardiovascular and skin diseases,etc.The diagnosis of these disease is based on the imaging of the structural morphology of biological tissues by OCT.In addition to imaging tissue structure,phase-resolved OCT can achieve sub-nanometer displacement resolution,so OCT has also been used to obtain functional information of biological tissues.In functional imaging,it is often necessary to extract multimodal information from tissue simultaneously.Thus,we have developed a phase-resolved OCT-based multimodal system for solving problems in the life sciences,such as biomolecular immunoassays and auditory function studies.We first built a phase-sensitive OCT based on a common path structure,and the experimentally measured displacement resolution is pm.The displacement resolution is much higher than the nano-scale thickness variation caused by the binding of single-layer protein molecules,so the system can be used for real-time detection of protein molecules and the study of protein-molecular interactions.Protein molecular immunoassay experiments demonstrate the potential of the system for biomolecular immunoassay and also demonstrate the high resolution of phase-sensitive OCT.We developed a dual-mode system based on phase-sensitive OCT and fluorescence microscopy for simultaneous detection of multiple analytes.In the method,the thickness of the glass microchip and the fluorescence intensity of the quantum dot are selected to encode the type of the analyte and quantify the concentration of the analyte,respectively.A dual-mode system incorporating a frequency domain phase microscopic OCT and a fluorescence microscopy imaging module is built to decode the signal.The coding method of selecting two different coded signals avoids signal interference and aliasing caused by a single fluorescent signal coding method,and improves detection sensitivity.Using the thickness of the glass microchip as the encoded signal,the stability of the thickness of the glass microchip can ensure the accuracy of the encoding.At the same time,the frequency domain phase difference OCT-based decoding system can guarantee sub-micron thickness resolution and millimeter-level decoding range,thus providing more coding numbers.We developed a dual-mode system combining time domain OCT and spectral domain OCT for the study of in situ vibration measurement of biological tissues.In the dual-mode system,the spectral domain OCT module is used to image the biological tissue topography and locate the measurement position,and the time domain OCT module is used for the in-situ vibration measurement.We used this system to measure the vibration of the tympanic membrane and the ossicle of the guinea pig in the sound stimulation,and to help study the hearing conduction function.