Intrinsic cytometry based on computational microscopy

Abstract

With the goal of understanding cells, we propose to study the intrinsic properties of individual cells by combining visual observation from large field-of-view computational microscopy with separation of cells via an integrated label-free microfluidic platform. This intrinsic cytometry will benefit from the parallel and gentle separation of label-free cells via a microfluidic platform and parallel tracking of multiple cells via a large field-of view microscopy in contrast to the gold standard, flow cytometry, which is able to rapidly and singly identify multiple cell properties via scattering of external fluorescent cell markers. In this thesis, a prototype of this integrated platform was designed and fabricated. The prototype consisted of a large field-of-view digital in-line holographic microscopy system and a microfluidic deterministic lateral displacement array which separated particles based on size. Each system was first characterized separately and later integrated such that individual cells inside the deterministic lateral displacement array could be recorded and tracked with the large field-of-view digital in-line holographic microscopy system, showing the promise of our proposed intrinsic cytometry. In future studies, if a microfluidic platform can be designed to investigate multiple intrinsic properties of individual cells on the same platform, the intrinsic cytometer will enable a large pool of quantitative measurement data of cell intrinsic properties that can potentially be used for cell characterization and diagnostics.