Isothermal Strand Displacement Amplification for Chemical Sensing: From Molecular Design to Integrated and...

Strand displacement amplification (SDA) provides a versatile isothermal framework for chemical and biosensing, coupling polymerase-driven strand displacement with programmable nucleic-acid signal generation. Its analytical scope now extends beyond direct nucleic-acid detection because aptamers, DNAzymes, antibodies, and responsive probes can convert diverse recognition events into amplifiable DNA triggers. This review develops a unified view of SDA from molecular design to practical implementation, with particular emphasis on programmable amplicon generation, recognition-to-DNA transduction, interfacial confinement, cascaded amplification, and CRISPR coupling. The review follows SDA across biomedical, food, and environmental applications, including RNA biomarkers, liquid biopsy, genetic and epigenetic targets, proteins, enzymes, small molecules, and viruses. It also considers how these assays are being transferred into microfluidic, paper-based, lateral-flow, self-powered, regenerative, and intelligent systems. The important distinction is that analytical sensitivity does not necessarily predict practical performance. Extremely low detection limits often depend on cascaded processing beyond SDA itself, whereas real samples expose weaknesses in matrix tolerance, background suppression, reagent stability, fluid control, assay duration, and manufacturing reproducibility. Comparison with commercially established isothermal methods further shows that wider adoption will depend on converting flexible molecular chemistry into robust, standardized, sample-to-answer systems.