Optothermophoretic flipping method for biomolecule interaction enhancement

The widely used surface-based biomolecule sensing scheme has greatly facilitated the investigation of protein-protein interactions in lab-on-a-chip microfluidic systems. However, in most biosensing schemes, the interactions are driven in a passive way: The overall sensing time and sensitivity are totally dependent on the Brownian diffusion process, which has greatly hindered their efficiency, especially at low concentration levels or single-molecule analysis. To break this limitation, we developed an all-optical active method termed optothermophoretic flipping (OTF). It is the first temporal modulated method that biomolecules were enriched and pushed to their counterparts for effective contact via a flipped thermophoresis. As a proof-of-concept experiment, we tested its performance via antibody-antigen binding on a surface plasmon resonance imaging (SPRi) platform. Compared with the interaction solely based on Brownian diffusion, we achieved a 23.6-fold sensitivity increment in biomolecule interactions sensing. This method has opened new opportunities for various biosensing platforms that require high-sensitivity in colloidal sciences and biochemical studies.