# Recognition, Signal Transduction, and Amplification of Nucleic Acids Under Isothermal Condition

## TL;DR

This paper reviews isothermal nucleic acid detection methods, focusing on how recognition, signal transduction, and amplification can be optimized for rapid and accessible diagnostics.

## Contribution

The paper introduces a modular framework for isothermal detection, emphasizing design principles for scalable and accurate diagnostics.

## Key findings

- Recognition strategies now include engineered proteins and synthetic modules beyond base pairing.
- Amplification methods now use catalytic cycles and cascade reactions to boost sensitivity.
- Integrated platforms are being developed for multiplexing and digital readouts in diagnostics.

## Abstract

Isothermal nucleic acid detection has become a compelling alternative to PCR, enabling rapid analysis with minimal instrumentation and strong potential for point‐of‐care use. Central to assay performance are three interconnected processes: recognition, signal transduction, and amplification. Recognition strategies now extend beyond base pairing to include engineered proteins, catalytic nucleic acids, and synthetic modules. Signal transduction has advanced through orthogonal chemistries and functional nanomaterials, converting molecular events into optical, electrical, or colorimetric outputs. Amplification encompasses not only nucleic acid replication but also catalytic cycles and cascade reactions that magnify signals across molecular and material scales. These innovations are converging toward integrated, programmable platforms that support multiplexing and digital readouts. In this Perspective, we highlight emerging mechanisms and design principles that define isothermal detection, and outline future opportunities to achieve accurate, scalable, and accessible diagnostics for clinical, environmental, and translational applications.

This Perspective outlines a modular framework for isothermal nucleic acid detection, highlighting recognition and signal transduction as central determinants of assay performance, with amplification strategies serving as sensitivity enhancers. Emerging design principles and future opportunities for scalable and accessible diagnostics are discussed.