STTR Phase I: Development of an Ultra-Low Concentration Amino Acid Sensor for Use in Protein Sequencing

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is an advancement to single-molecule biosensing technology. This innovation aims to enable accurate analysis of full-length proteins and identification of post-translational modifications (PTMs) at the individual molecular level independently without prior knowledge of the sample. The ability to sequence proteins and quantify protein abundance poses advances to biomarker discovery, diagnostics, and systems biology. The technology also enables accelerated drug development by identifying new targets and facilitating personalized medicine through precise proteomic profiling, enabling researchers the ability to design tailored therapies optimized for individual patients. By advancing ultrasensitive biosensors and proteomics tools, this technology has the potential to significantly advance molecular biosensing precision and accuracy, creating opportunities for growth in molecular biology research for addressing health care challenges. This Small Business Innovation Research (SBIR) Phase I project aims to develop an ultra-sensitive biosensor capable of protein analysis at single-molecule resolution. The biosensor consists of a nanopatterned chip overlayed with a proprietary material that acts as a scaffold for amino acids and proteins. The scaffold binds and immobilizes molecular targets that are detected with surface-enhanced Raman spectroscopy (SERS). The SERS detection signal is enhanced orders of magnitude by the chip nanopatterning, resulting in a biosensor capable of detecting single molecules. These components will enable the identification of low-abundance proteins, proteoforms, and co-occurring modifications that are inaccessible with existing technologies. The technology aims to eliminate the need for reference databases, protein fragmentation, and proxy sequencing methods, this approach will deliver direct, unbiased analysis of any protein sample, including full-length sequences. This ultrasensitive biosensor will transform proteomics research and applications in diagnostics, toxicology, microbiology, drug discovery, and personalized medicine while paving the way for scalable next-generation tools to advance biomedical research. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.