Handheld quantitative phase imaging probe for in-vivo brain tumor margin assessment

Abstract

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.