Sttr phase I: development of an ultra-low concentration amino acid sensor for use in protein sequencing

Primary Bioscience, Inc. received a $305,000 Small Business Technology Transfer (STTR) Phase I award from the National Science Foundation (NSF) Technology, Innovation, and Partnerships program (CFDA 47.084) effective July 15, 2025, with a completion date of June 30, 2026. The company is developing an ultra-sensitive biosensor capable of single-molecule protein analysis and sequencing. The technology integrates a nanopatterned chip with a proprietary amino acid and protein scaffold material, leveraging surface-enhanced Raman spectroscopy (SERS) detection to achieve orders of magnitude signal enhancement. This innovation enables identification and characterization of low-abundance proteins, proteoforms, and post-translational modifications without requiring protein fragmentation, reference databases, or prior sample knowledge.

The project addresses critical gaps in proteomics by advancing molecular biosensing precision and accuracy for applications in biomarker discovery, diagnostics, drug development, and personalized medicine. The technology's ability to perform accurate full-length protein analysis at the individual molecular level has potential commercial applications in accelerated drug development, identification of novel therapeutic targets, and tailored treatment design based on precise proteomic profiling. Work is being performed in Seattle, Washington.

Abstract

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.- subawards are planned for this award.