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INSITE 1
INSITE 2
The INSITE Concept
Motivation
Immunotherapy is a powerful approach to unlock the immune system to fight cancer that is fundamentally changing treatment for the 1.7 million people diagnosed with cancer each year in the U.S. For instance, immune checkpoint inhibitors (ICIs) nearly doubled survival rates for melanoma and metastatic lung cancer. While these therapies promise broad impact—more than 40% of U.S. cancer patients are estimated to be eligible for ICIs—they face a significant challenge: across cancer types, less than 30% of patients respond to treatment. For non-responders, time spent on ineffective therapies allows for disease progression while incurring unnecessary toxicity and financial burdens. Thus, there is a critical need for diagnostic technologies that rapidly reveal the underlying mechanisms of therapeutic resistance, empowering clinicians to rationally choose and combine second-line therapies to generate a response.
However, clinical imaging lacks the contrast and resolution to capture the complex and dynamic interplay between immune cells and cancer that determines response: MRI and CT image changes in tumor size that take months to manifest and immuno-PET is fundamentally limited to a single biomarker at millimeter resolution. Our aim is provide real-time in vivo visualizations of the tumor micro-environment as it responds to immunotherapy with an implantable fluorescence microscope-on-a-chip, equipping clinicians with an understanding of resistance that is actionable within days rather than months.
Our Solution
Our device images immune cells—labeled with injected fluorescence probes—from within the tumor itself, avoiding the scattering of light by tissue, which precludes optical imaging outside the body. To create a miniaturized device suitable for long-term implantation, we harness several key technologies:
(1) A 5 × 2.5 mm2 IC integrates the image sensor with readout electronics, a power harvesting unit, laser driver, and digital control system on a single chip.
(2) Wireless power harvesting and bi-directional communication through ultrasound7 allows for chronic operation 5 cm deep in tissue.
(3) In place of bulky lenses, we have designed a 520-mm-thick optical frontend combining a fiber-optic plate and a multi-bandpass interference filter. This innovation enables 100-um-resolution images of 3 different fluorescent colors, each corresponding to a distinct immune cell type.
Progress
We have successfully designed two versions of the IC: INSITE 1 (CICC 2022) and INSITE 2 (ISSCC 2024). INSITE 2 claimed the title of the 'first fully wireless, implantable imager.' Both works have been expanded into journal publications (TBioCAS 2024 and JSSC 2024) where we show the full operation of the entire system with relevant ex vivo samples from preclinical cancer models. Check out the linked publications!
Current and Future Work
This project is accepting new students and we are currently working on several new exciting directions. Join the INSITE team!
Implant design: We are currently building a fully functional, biocompatible packaged version of INSITE 2.
Translational animal experiments: We currently working on implanting INSITE 2 in mice to record the immune response to cancer immunotherapy. Stay tuned for some exciting results!
Image sensor design: We are exploring new image sensor architectures and processes to improve SNR and resolution.
Wireless power harvesting and communication: How can we maximize power harvesting efficiency and robustly communicate data to and from the INSITE?
Towards continuous monitoring: One of our overarching goals is to create an 'untethered' system that takes images autonomously. The current version of INSITE requires an external US transducer to operate.
Optics for lensless imaging: How can we efficiently couple light from micro-laser diodes on the implant to take uniform images? We are also exploring lens-less imaging techniques for capturing single-shot 3D images.
Publications on INSITE
M. Roschelle,* R. Rabbani*, S. Gweon, R. Kumar, A. Vercruysse, N. Cho, M. Spitzer, A. Niknejad, V. Stojanovic, M. Anwar, "A Wireless, Multicolor Fluorescence Image Sensor Implant for Real-Time Monitoring in Cancer Therapy," in IEEE Journal of Solid-State Circuits, 2024. (*co-first authors) 🔗
R. Rabbani, H. Najafiaghdam, M. Roschelle, E. P. Papageorgiou, B. Zhao, M. M. Ghanbari, R. Muller, V. Stojanovic, M. Anwar, "Towards A Wireless Image Sensor for Real-Time Fluorescence Microscopy in Cancer Therapy" in IEEE Transactions on Biomedical Circuits and Systems, 2024. 🔗
R. Rabbani*, M. Roschelle*, S. Gweon, R. Kumar, A. Vercruysse, N. Woo Cho, M. Spitzer, A. Niknejad, V. Stojanovic, M. Anwar. "A Fully Wireless, Miniaturized, Multicolor Fluorescence Image Sensor Implant for Real-Time Monitoring in Cancer Therapy", 2024 IEEE International Solid-State Circuits Conference-(ISSCC), IEEE. (*co-first authors) 🔗
R. Rabbani, M. Roschelle, E. P. Papageorgiou, H. Zhang, V. Stojanovic and M. Anwar, “Towards Real-Time Monitoring of the Immune Response in ICI Immunotherapy with a Wireless Fluorescence Microscope-on-Chip” World Molecular Imaging Conference (WMIC) (2022).
R. Rabbani, H. Najafiaghdam, B. Zhao, M. Zeng, V. Stojanovic, R. Muller, M. Anwar. "A 36×40 Wireless Fluorescence Image Sensor for Real-Time Microscopy in Cancer Therapy" 2022 IEEE Custom Integrated Circuits Conference (CICC). 🔗
R. Rabbani, H. Najafiaghdam, M. M. Ghanbari, E. P. Papageorgiou, B. Zhao, M. Roschelle, V. Stojanovic, R. Muller, M. Anwar, "Towards an Implantable Fluorescence Image Sensor for Real-Time Monitoring of Immune Response in Cancer Therapy," 2021 43rd Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC), Mexico. 🔗
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