Revolutionizing biointerface analysis: nanoscale electrical insights from Kelvin probe force microscopy and their impact on biological science and industry

Abstract

Kelvin Probe Force Microscopy (KPFM) has emerged as a valuable tool in biological sciences by providing direct access to the nanoscale electrical landscape of living systems. This technology uniquely bridges a critical gap in biophysical characterization, enabling the noninvasive, label free mapping of surface potential distributions with nanoscale resolution under physiological conditions. The ability to directly correlate electrical properties with topographical and mechanical information across diverse biological interfaces, from cell membranes and proteins to biomaterials and extracellular vesicles, is revolutionizing our understanding of life's fundamental processes. This review comprehensively examines the principles, advancements, and far reaching applications of KPFM, highlighting how it reveals structure function relationships in biomolecules, quantifies drug induced cellular responses, guides the rational design of advanced biomaterials, and identifies novel disease biomarkers. Key technological innovations such as high speed and multimodal KPFM are overcoming traditional limitations, allowing dynamic monitoring of biological events and integration with complementary techniques. While challenges in absolute quantification and imaging speed persist, ongoing developments in probe technology, liquid phase operation, and data analysis are poised to further solidify KPFM's role. The insights driven by KPFM not only deepen our fundamental knowledge of electrophysiological mechanisms but also pave the way for groundbreaking advancements in biomedical engineering, targeted therapeutic development, and next generation diagnostic technologies, ultimately shaping the future of precision medicine.