A Wireless, Multicolor Fluorescence Image Sensor Implant for Real-Time Monitoring in Cancer Therapy

TL;DR

This work addresses the need for real-time, molecularly specific monitoring of cancer immunotherapy by delivering a fully wireless, three-color fluorescence image sensor implanted at millimeter scale. The system integrates micro-lasers, a multi-band optical frontend, a piezoelectric ultrasound link for power and uplink, and a CMOS ASIC that coordinates energy harvesting, imaging, and backscatter data transmission at a data rate of $13$ kbps with BER <$10^{-6}$. It demonstrates ex vivo imaging of CD8+ T-cells and neutrophils in tumor sections, revealing both therapeutic responses and resistance mechanisms, which are difficult to capture with conventional clinical imaging. The results show potential for real-time, chronic monitoring to guide personalized cancer therapy and to uncover immune dynamics at high spatial resolution beyond current modalities.

Abstract

Real-time monitoring of dynamic biological processes in the body is critical to understanding disease progression and treatment response. This data, for instance, can help address the lower than 50% response rates to cancer immunotherapy. However, current clinical imaging modalities lack the molecular contrast, resolution, and chronic usability for rapid and accurate response assessments. Here, we present a fully wireless image sensor featuring a 2.5$\times$5 mm$^2$ CMOS integrated circuit for multicolor fluorescence imaging deep in tissue. The sensor operates wirelessly via ultrasound (US) at 5 cm depth in oil, harvesting energy with 221 mW/cm$^{2}$ incident US power density (31% of FDA limits) and backscattering data at 13 kbps with a bit error rate <$10^{-6}$. In-situ fluorescence excitation is provided by micro-laser diodes controlled with a programmable on-chip driver. An optical frontend combining a multi-bandpass interference filter and a fiber optic plate provides >6 OD excitation blocking and enables three-color imaging for detecting multiple cell types. A 36$\times$40-pixel array captures images with <125 $μ$m resolution. We demonstrate wireless, dual-color fluorescence imaging of both effector and suppressor immune cells in ex vivo mouse tumor samples with and without immunotherapy. These results show promise for providing rapid insight into therapeutic response and resistance, guiding personalized medicine.

Figures (29)

• Figure 1: Concept of a fully wireless, multicolor, implantable imager for real-time monitoring of immune response.
• Figure 2: (a) To-scale diagram of the full system. (b) Mechanical assembly.
• Figure 3: Multicolor fluorescence imaging. (a) Each cell type is labeled with a different color fluorescent probe. (b,c) Fluorophores are excited near the absorption peak and emit light at a slightly longer wavelength. A multi-bandpass filter passes emissions while blocking excitation.
• Figure 4: Measured laser diode (a) PIV curves and (b) wall-plug efficiencies.
• Figure 5: (a) Normal incidence transmittance spectra of the multi-bandpass interference filter. (b,c) Measured transmittance through the FOP across AOIs. (d) Angular transmittance of the filter with and without the FOP measured at the excitation laser wavelengths.