From Thermal Cycling PCR to Isothermal RPA: Vibrational Strong Coupling as a New Physical Control Axis for DNA Amplification

Abstract

The emergence of vibrational strong coupling (VSC) strategy has reshaped how biochemical reactions are regulated-not by chemical additives or thermal cycling, but through vacuum-field-mediated restructuring of solvent dynamics and energy landscapes. This Perspective bridges fundamental developments in cavity-modified enzymatic catalysis with the unique biochemical architecture of recombinase polymerase amplification (RPA), a low-temperature, hydration-regulated nucleic acid amplification system. Earlier enzyme-specific VSC studies established that coupling the O-H stretching manifold of water to Fabry-Pérot (FP) modes reorganizes hydrogen bond topology, alters activation barriers, and selectively accelerates or suppresses catalytic turnover depending on vibrational mode alignment. These mechanistic principles translate directly to multi-enzyme amplification: recent experiments demonstrate that tuning cavity length to water's O-H stretching band modulates RPA product yield, with on-resonance coupling suppressing amplification efficiency and off-resonance conditions restoring activity. Because RPA relies on hydration-assisted strand invasion, Mg²⁺-mediated recombinase filament formation, and solvent-regulated polymerase elongation, it represents a particularly responsive platform for cavitycontrolled biochemical amplification. We further outline how dielectric engineering, microfluidic confinement, and multimode photonic architectures may enable deterministic control of amplification kinetics and selectivity. This work recasts optical cavities as active thermodynamic variables capable of sculpting biochemical free-energy landscapes, enabling enzyme systems that respond to field structure rather than bulk chemistry.