Chirality-Driven Photonic PCR Enables Label-Free Genetic Amplification
Haeun KangiD, Jeongmin ParkiD, Hyung Joo Lee, Jeong Hyun HaniD, Youngbi Kim, Dong-Il Won, Donghyun KimiD, Mijin Kwon, Dabin KimiD, Pil J. Yoo, Jeong Woo Han, Dongseok Suh, Ki Tae Nam, Dong Ha KIMiD, Luke P. LeeiD
Abstract
Photonic polymerase chain reaction (PCR) offers a rapid alternative to conventional thermal cycling for genetic amplification, but current platforms are limited by low photothermal conversion efficiencies and a dependence on bulky fluorescent monitoring systems. Here we report a chirality-driven photonic amplification paradigm that achieves both accelerated nucleic acid replication and direct, label-free detection. By leveraging chiral plasmonic nanoparticles, we exploit their elevated absorption cross-sections to achieve exceptional light-to-heat conversion and rapid thermal relaxation, significantly accelerating heating and cooling rates during cycling. We show that localized chiral near-fields generated by these chiral plasmonic nanoparticles optimize DNA polymerase conformational dynamics, lowering the activation energy barrier for synthesis and boosting amplification efficiency. Furthermore, by tracking the reaction with circular dichroism spectroscopy, we directly monitor the intrinsic chiroptical signature of amplifying DNA, completely eliminating the need for external fluorescent dyes or labeled probes. We validate this system using SARS-CoV-2 E-gene plasmid DNA templates, demonstrating rapid, label-free amplification and single-copy detection within clinically relevant timelines. By bridging asymmetric photothermal dynamics with chiral-field-induced enzymatic activation, this work translates chiroplasmonic materials from fundamental physics into high-performance, point-of-care molecular diagnostics.
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