SUMMARY

Quantitative oblique back-illumination microscopy (qOBM) is a novel tomographic, label-free, non-invasive, real-time, and affordable quantitative phase imaging (QPI) microscopy technique. The objective of the proposed research is to explore the unique imaging capabilities of qOBM applied to cerebral tissues and to develop new qOBM-based optical and computational methods to analyze qOBM data. qOBM operates in epi-mode, and thus, the microscope is able to provide the high-contrast, high-resolution quantitative phase information seen with QPI microscopy; however, unlike QPI, it can image in thick tissue. This allows access to valuable morphological and biophysical information about the imaged specimen.

In this work, we first apply qOBM to analyze and characterize cell samples non-invasively during the cell manufacturing process. In this, we analyze and segment T-cells during in-line imaging through dynamic analysis focused on the subcellular movement of the T-cells. This provides feedback in real time without the need for endpoint assays. Secondly, we use qOBM for long-term imaging of cerebral organoids as they grow. This includes studying particular disease models such as glioblastoma and tuberous sclerosis complex organoids. We can also introduce treatment to the organoids and study the effectiveness of that treatment. Lastly, we apply qOBM for the study bulk brain. This aim involves the development of a qOBM probe for use as a real-time surgical tool to find and remove invasive brain tumor. We also use qOBM as a tool to study sickle cell disease vasculature in whole mouse brains.

We expect this work to demonstrate that qOBM is a tool capable of providing novel insights into the human brain, diseases affecting the brain, and the treatments used for those diseases. We hope that qOBM will pave the way for the development of novel label-free platforms for clinical and biomedical purposes.