A novel optical method providing for high-sensitivity and high-throughput biomolecular interaction analysis

We present a novel method for label-free detection of biomolecular interactions based on the surface plasmon resonance (SPR) phenomenon. The method enables simultaneous and extremely sensitive analysis of a large number of samples arranged in a 2D array format on the sensor surface. To realize the approach, a prototype of the optical sensor was constructed. With this sensor, interaction kinetics are sampled at a 10 Hz rate, and the dynamic range of the system extends from 1.32 to 1.38 refractive index units (RIU). While the fluidics for a highly multiplexed system are not yet developed, we optimized the prototype for simultaneous sensing of up to 110 interaction sites. In this configuration, extremely low root-mean-squared (RMS) noise, 2.6×10−8RIU/Hz, is obtained. This low noise level corresponds to sensitivity exceeding that of any commercial SPR instrument—even those with little or no multiplexing capability. Simple software changes allow the user to trade off dynamic range and multiplexing in exchange for additional sensitivity enhancement. This capability is demonstrated in experiments we perform characterizing the interaction of carbonic anhydrase II with a small molecule, carboxybenzenesulfonamide.