UC Berkeley

Although cancer immunotherapy has become a cornerstone of oncology, most patients fail to respond to treatment. For these non-responders, early identification of resistance mechanisms is critical for effective second-line interventions. However, current clinical imaging is limited to a single biomarker with millimeter resolution at month-long intervals, rendering the dynamic interplay between cancer and the immune system largely opaque.  Therefore, we present a miniaturized, implantable fluorescence imager designed for real-time monitoring of immune activity within a tumor. In this thesis, we take this idea from a concept to a bench-top demonstration of the full wireless system and, finally, to a fully packaged implant that we verify in mice. First, we describe an optical frontend design combining an interference filter with a fiber optic plate that enables fluorescent imaging of three biomarkers at 125-μm resolution without bulky lenses. Then, we introduce a wireless imaging chip, which harnesses ultrasound power harvesting and communication to achieve an operating depth of up to 5 cm in tissue. Finally, we present in vivo results using a wired implant with co-packaged waveguides and micro-laser diodes, tracking the CD8+ T cell response to immune checkpoint inhibitors over a week in tumor-bearing mice. Overall, these results represent significant progress toward a technology capable of providing rapid, real-time insight into therapeutic response and resistance to guide precision cancer immunotherapy.