Bridging the Invasiveness–Precision Gap: Autonomous Biohybrid Nanoelectronics Enable Surgery-Free Focal Neuromodulation
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yadav-shyadav-PhD-MAS-2025-thesis.pdf
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Author(s)
Yadav, Shubham
Advisor(s)
Sarkar, Deblina
Date Issued
February 2026
Publisher
Massachusetts Institute of Technology
Abstract
Neural stimulation represents a crucial tool for diagnosis, monitoring, and therapeutics in modern medicine, enabling researchers to decipher neural connections and advance our understanding of brain function. However, existing neuromodulation technologies face a fundamental trade-off between invasiveness and precision: highly precise methods require invasive surgery, while non-invasive approaches suffer from poor spatial resolution and off-target effects. This dissertation introduces a novel technological platform that bridges this invasiveness-precision gap through the development of novel nanoelectronic devices for surgery-free focal neuromodulation.
The foundational technology comprises subcellular wireless electronic devices (SWEDs) based on organic photovoltaic platforms. These devices, approximately 10 micrometers in diameter and 250-400 nanometers in thickness, are fabricated using a back-end-of-line CMOS-compatible process that enables mass production of untethered, mechanically flexible nanoelectronics. Comprehensive photovoltaic characterization demonstrated efficient wireless power conversion, scalability to subcellular dimensions, and reliable operation in physiological environments, including transcranial operation through intact brain tissue.
Building upon this foundation, the Circulatronics platform was developed to overcome the surgical barrier entirely. This system leverages cell-electronics hybrids created by covalently conjugating SWEDs to immune cell surfaces using biorthogonal chemistry. In vivo experiments in rodent models demonstrated that intravenously injected cell-electronics hybrids autonomously navigate the circulatory system, home to inflammation sites in the deep brain, and achieve self-implantation. Subsequent wireless activation with transcranial near-infrared light produced focal neuromodulation with subcellular spatial precision, validated through c-Fos mapping and direct electrophysiological recordings. Extensive biocompatibility studies confirmed the safety of both platforms, showing no adverse effects on motor function, cognition, or tissue integrity over extended periods. The devices demonstrated natural clearance pathways and biocompatible tissue integration.
This demonstrated ability to achieve surgery-free, focal neuromodulation through self-implantation of nanoelectronics represents a fundamental advancement in treating neurological and psychiatric disorders while providing powerful new tools for neuroscience research.
MIT Department
Program in Media Arts and Sciences (Massachusetts Institute of Technology)
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