Ultra-sensitive DNAzyme-based optofluidic biosensor with liquid crystal-Au nanoparticle hybrid amplification for molecular detection

Due to the specific cofactor dependence and the potent catalytic capability, DNAzymes have shown great promise in the application of biosensors. However, it poses significant challenges for researchers to enhance the sensitivities of DNAzyme-based biosensing platforms. In this work, an ultra-sensitive, label-free, and quick-responsive DNAzyme biosensor is developed based on whispering gallery mode (WGM) optofluidic resonator with a hybrid amplification from liquid crystals (LCs) and Au nanoparticles (AuNPs). When a DNAzyme is cleaved by biotargets, the event of DNA hybridization is triggered and will result in the orientation transition of LC molecules (in the resonator core). According to the quadruple amplification from the disturbance of AuNPs, the excess polarizability of adhering biomolecules, the orientation variation of LC molecules, and the WGM resonance, the spectral wavelength shift can be employed as the sensing parameter to indicate the information of biotarget. L-histidine molecules are applied as the analyte. An ultra-low detection limit at a sub-femtomole level (~ 5×10-16 M) has been achieved using this highly-selective biosensor, which is eight orders of magnitude lower compared to the reported LC-based L-histidine sensor. In addition to L-histidine, this proposed optofluidic scheme with LC-AuNP hybrid amplification can also extend the applicability of DNAzyme-based biosensors for the detection of various molecules