Quantitative phase microscopy via optimized inversion of the phase optical transfer function.

Abstract

Although the field of quantitative phase imaging (QPI) has wide-ranging biomedical applicability, many QPI methods are not well-suited for such applications due to their reliance on coherent illumination and specialized hardware. By contrast, methods utilizing partially coherent illumination have the potential to promote the widespread adoption of QPI due to their compatibility with microscopy, which is ubiquitous in the biomedical community. Described herein is a new defocus-based reconstruction method that utilizes a small number of efficiently sampled micrographs to optimally invert the partially coherent phase optical transfer function under assumptions of weak absorption and slowly varying phase. Simulation results are provided that compare the performance of this method with similar algorithms and demonstrate compatibility with large phase objects. The accuracy of the method is validated experimentally using a microlens array as a test phase object. Lastly, time-lapse images of live adherent cells are obtained with an off-the-shelf microscope, thus demonstrating the new method's potential for extending QPI capability widely in the biomedical community.