Research On Fabrication And Characterization Of Skin-Simulating Phantoms For Biomedical Optical Imaging

Biomedical optical imaging has flourished for nearly half a century.Current innovations in optical imaging,measurement techniques and data analysis algorithms have placed a pressing need for reliable testing and calibration techniques.Optical phantoms are commonly used as a calibration standard for verification and validation of biomedical optical devices.However,most of the currently available optical phantoms are homogeneous phantoms without reflecting the actual structural and functional heterogeneties of biological tissue.Using an optical device calibrated by a homogeneous phantom to measure heterogeneous tissue will result in significant bias that can be reduced by using a calibration phantom that simulates tissue heterogeneity.Furthermore,the accuracy for optical measurements in biologic tissue can be further enhanced by using phantoms that simulate dynamic variations of tissue structural and functional characteristics.The emergence of three-dimensional(3D)printing processes offers a new avenue for freeform fabrication of phantoms with structural heterogeneity.To further enhance the fidelity of the tissue-simulating phantoms,it is important to study the 3D printing materials and fabrication processes that simulate tissue functional and dynamic characteristics.This thesis was based on our research in 3D printing and construction of optical phantoms.The 3D printed phantoms simulate structural,functional and optical characteristics of complex skin tissue at both macroscopic and microscopic scales.The selection of phantom materials and the process for phantom fabrication were investigated and optimized.The main contents of the thesis are listed as following:(1)Phantom was prepared for simulation of skin tissue surface textures.Skin textures of the volunteer’s back and forearm were reproduced with skin replica.The images of skin replica were segmented into texture features and simplified into a two-dimensional pattern.The texture features were copied onto the SU8 photoresist on the surface of a wafer by soft lithography.The SU8 negative mold was used to cast PDMS phantoms that simulate skin surface texture.The effects of phantom surface texture and roughness on optical scattering properties were studied.(2)Phantom was prepared for simulation of spectral characteristics for hemoglobin oxygen saturation.Hemoglobin was encapsulated in photocurable microcapsules by a coaxial flow focusing method in order to produce artificial red blood cells with the improved optical stability and the protected oxygen binding capability for hemoglobin.Different oxygenation levels within the physiologic range were achieved by adjusting oxygen partial pressure levels of the surrounding medium.With the long-term optical stability and the oxygen binding capability,the prepared artificial red blood cells can be used to construct phantoms that simulate tissue functional properties.(3)Integration of multiple three-dimensional(3D)printing processes for fabrication of multi-layered phantoms that simulate structural,optical,and functional properties of skin tissue.First,the "digital optical phantom" was established by defining the material ratios and process parameters for different positions of multi-layered tissue structure.Second,the structural and functional heterogeneities of multi-layered tissue-simulating phantoms were achieved by layer-by-layer fabrication using multiple 3D printing processes.Finally,the 3D printed skin-simulating phantoms were characterized in benchtop experiments.This research validated the technical feasibility of establishing traceable phantom standards that simulate structural and functional properties of biologic tissue for calibration and validation of biomedical optical devices.