SBIR Phase I: Enhanced Biomolecular Analysis Using Advanced Direct Detection Methods

This Small Business Innovation Research project will investigate enhanced measurements that can be made using a system that simultaneously reports mass capture during a biomolecular interaction along with changes in the structure of the capturing molecule. Current direct detection instruments are based on optical techniques that respond to changes in refractive index. To date, this response has been attributed strictly to mass capture as molecules are bound to the sensor surface. Using an optical fiber based grating technique, this project will show that conformational changes in derivatized proteins can create a transduction signal upon binding. Separating out these two effects will provide a more accurate picture of the molecular interaction, a better understanding of immobilization chemistries and the effect on protein response, and the potential for instruments with increased measurement sensitivity. The main commercial application of this project will be in the area of drug discovery research. Companies involved in drug discovery require an instrument able to detect and characterize protein interactions. Current direct detection biosensor instruments are limited to measuring bound mass. The proposed development effort will enable the characterization of conformational changes simultaneously with the measurement of bound mass and will be implemented in a high-throughput format.