Development and Evaluation of a Potentially Wearable Device for Circulating Cell Monitoring

Abstract

Monitoring circulating cells is crucial for assessing cancer metastasis and evaluating the efficacy of chimeric antigen receptor (CAR) T-cell therapies. Traditional blood-draw methods face challenges such as discontinuous monitoring and potential cell degradation, leading to inaccurate estimations. In vivo flow cytometry (IVFC), which measures real-time cellular response to laser illumination such as fluorescence, presents a viable alternative. However, its application in humans has been limited by the bulky design of existing devices and configurations unsuitable for larger organisms. This thesis introduces a novel, wearable fluorescence IVFC device tailored for human use, featuring a compact laser diode and silicon photomultiplier (SiPM) to enhance portability and functionality. The device includes a specialized optical system similar to a fluorescent microscope, which optimizes the signal- to-noise ratio by maximizing cellular fluorescence and minimizing background interference. Experimental determination of the limit of detection (LOD) for the SiPM and device establishes their detection capabilities and operational stability. Theoretical evaluations confirm that while the device can detect individual fluorescent cells in vitro, its current configuration does not support this sensitivity in vivo. The thesis also proposes strategies to improve the device’s sensitivity, aiming for reliable in vivo detection of single fluorescent cells.