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The CRISPR/Cas system serves as a robust biosensing platform owing to its programmable nature and precise targeting capability. The advancement of nanotechnology has enabled the synthesis of various nanostructures with precisely tunable nanoscale dimensions, which demonstrate distinctive nanoconfined physicochemical characteristics, including a high surface-to-volume ratio, enhanced electrochemical activity, and optimized signal transduction pathways─opening novel avenues for biosensor development. The integration of CRISPR/Cas systems with engineered nanoparticles significantly enhances biosensing performance through improved detection stability, heightened sensitivity, and refined accuracy, while simultaneously expanding available signal transduction modalities. Focusing on signal output modalities, this review comprehensively categorizes nanoparticle architectures in CRISPR/Cas biosensors while elucidating their functional mechanisms and performance characteristics through systematic analysis of representative systems. Moreover, we critically examine the emerging landscape of CRISPR/Cas-integrated nanobiosensors, analyzing their translational potential, existing challenges, and future opportunities to establish design principles for next-generation biosensors with enhanced stability and superior analytical capabilities.
Zhen et al. (Wed,) studied this question.