A Label-Free Analytical Method for Imaging Biomarker Distribution in Soft Tissues - PROJECT SUMMARY/ABSTRACT Advancing biomedical research and clinical translation requires practical approaches to spatially resolved monitoring of chemical biomarker distributions and dynamics in living tissues. Variations in pH, for example, are tightly coupled to physiological and pathological states, including ischemia, atherosclerotic plaque development, inflammation, and tumor growth. Current chemical imaging technologies face fundamental limitations. Optical methods, such as fluorescent dyes and genetically encoded sensors, enable spatiotemporal visualization but rely on exogenous labeling, suffer from photobleaching and phototoxicity, and lack long-term biocompatibility. Electrical approaches, such as microelectrodes and field-effect transistor arrays, are constrained by rigid geometries and limited adaptability, which restrict resolution and precision. There is a critical need for innovative biosensing strategies that combine high resolution, biocompatibility, and adaptability in real time. This project introduces a transformative platform—Silicon-based Light-Enabled Active Potentiometry (SiLEAP)—to address this unmet need. SiLEAP is a mechanically flexible, ultrathin electronic interface constructed from an unpatterned SiO₂/Si bilayer (<100 nm) transferred onto a polymer substrate (<20 μm total thickness) using a unique inverted fabrication process. SiLEAP operates through a label-free optoelectronic effect: under DC bias, photoexcitation generates transient photocurrents at the SiO₂/Si interface that are highly sensitive to local surface potentials, thereby enabling chemical concentration mapping in the microenvironment. Critically, spatially resolved, adaptive light addressing allows sensing at cellular-scale resolution (<10 μm). The platform further enables integration with compact or tissue-compatible light sources, including micro-LED chips, optical fibers, or deep-red light delivery systems. Our goals are to: (1) fabricate ultrathin, flexible SiLEAP devices using the “inverted fabrication” process; (2) integrate SiLEAP with an illumination system and evaluate key performance metrics; and (3) demonstrate spatially resolved biomarker imaging in vitro and in vivo using cardiac models, with pH sensing as the validation target. Myocardial ischemia and reperfusion are characterized by rapid, heterogeneous pH shifts that profoundly affect ion channel function, conduction, and cell survival. These fluctuations drive reperfusion injury and serve as early, sensitive indicators of metabolic stress. Current diagnostic approaches (pH electrodes, magnetic resonance spectroscopy, fluorescence imaging, PET tracers) lack the spatiotemporal resolution and adaptability required to capture these dynamic events. By providing continuous, real-time metabolic insight at cellular resolution, SiLEAP offers the potential to support early pathology detection, refine risk stratification, and guide precise therapies to preserve cardiac function. The proposed research program establishes a foundation for a new class of biocompatible, flexible, light- addressable sensors. Its impact spans fundamental discovery in tissue physiology, development of translational diagnostic tools, and alignment with the mission of the NIGMS Biomedical Technology Branch to drive innovation in bioanalytical technologies.
