Optothermophoretic flipping method for biomolecule interaction enhancement in biosensing

Abstract 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 level or single-molecule analysis. To break this limitation, we developed an all-optical active method termed optothermophoretic flipping (OTF). The biomolecules were first enriched to aggregation and then 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. We achieved 36.9-fold sensitivity enhancement in this first temporal modulated approach that manipulates biomolecules for interaction enhancement. This method promises to be widely adopted in various biosensing platforms that require ultrasensitivity in colloidal sciences and biochemical studies.