Clustered regularly interspaced short palindromic repeats (CRISPR) technology offers unprecedented precision in gene editing and nucleic acid detection. CRISPR/Cas systems are derived from bacterial adaptive immune responses and have been ingeniously adapted for the programmable recognition and cleavage of specific nucleic acid sequences. Their integration with either traditional nucleic acid amplification methods [e.g., polymerase chain reaction (PCR) and recombinase polymerase amplification (RPA)] or advanced nanotechnologies [e.g., surface plasmon resonance (SPR), surface-enhanced Raman scattering (SERS), and electrochemistry] enhances detection sensitivity and expands the applicability of these platforms, particularly in point-of-care testing and resource-limited environments. This review examines the convergence of CRISPR with traditional nucleic acid amplification techniques and its innovative integration with nanotechnology to showcase a significant leap in nucleic acid detection for disease diagnosis, pathogen examination, and food safety inspection.

This review investigates the mechanistic details of CRISPR/Cas9, CRISPR/Cas12, and CRISPR/Cas13 systems by illustrating the roles of these technologies in recognizing and cleaving specific nucleic acid sequences. Furthermore, the integration of CRISPR/Cas systems with traditional isothermal amplification techniques, such as PCR and RPA, has led to the development of rapid and portable detection platforms, such as SHERLOCK, thus demonstrating high sensitivity and specificity at reduced costs. In parallel, the convergence of CRISPR with nanotechnologies has opened new avenues for detection. For instance, the fusion of CRISPR with nanotechnologies, including SPR, SERS, and electrochemistry, has introduced novel detection modalities with improved sensitivity and speed. The combination of the specificity of CRISPR with the signal amplification properties of nanoparticles has resulted in the creation of biosensors with single-molecule detection capabilities and rapid, visual readouts.

The integration of CRISPR with both traditional and nanotechnology-based nucleic acid detection methods heralds a new era in diagnostics. The future of CRISPR-based detection technologies is likely to focus on enhancing specificity, reproducibility, and clinical adaptability while exploring new avenues in biomedical applications. The synergy between CRISPR and nanotechnology is anticipated to yield portable, highly sensitive diagnostic devices and integrate with smartphone technologies and artificial intelligence for real-time, on-site disease diagnosis. As research continues, the prospects for CRISPR-based nucleic acid detection are promising and could revolutionize clinical diagnostics, disease monitoring, and personalized medicine.