Quantitative oblique back-illumination microscopy (qOBM) enables quantitative phase imaging (QPI) in thick samples using epi-illumination. While qOBM offers unprecedented access to refractive index (RI) information in arbitrarily thick scattering samples, QPI-based (or RI index based) imaging still suffers from low cell nuclear contrast, which important for disease detection, including cancer. In this work, we use the acetowhitening effect of acetic acid to enhance the nuclear phase contrast of thick fresh tissue samples. Imaging results from brain samples are presented. Acetic acid phase staining may have important implications for in-vivo QPI-based disease detection
Quantitative phase imaging (QPI) enables label-free optical-path-length measurement of biological samples with nanometer-scale sensitivity, which offers unparalleled access to important histological and biophysical properties of cells and tissues. However, traditional QPI methods require a transmission-based optical geometry and are thus restricted to thin samples, which prevents the use of QPI for in-vivo applications. In this work, we present the design, characterization, and experimental validation of a handheld rigid probe for QPI with epi-illumination, using an optimized lighting configuration to achieve high phase-contrast sensitivity. The approach is based on a recently developed technology called quantitative oblique back illumination microscopy (qOBM). We demonstrate the real-time operation of our system with the future goal of applying it to help guide human brain tumor margin assessment intraoperatively in vivo, among many other potential applications.
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