# Energy–Biosensor Synergy: Intrinsic Catalytic Reactions as Label-Free Signal Pathways

## TL;DR

This review explores how energy-driven reactions can replace traditional labels in biosensors, simplifying detection and improving performance for various applications.

## Contribution

The paper introduces energy-based electrochemical reactions as a novel, label-free alternative to conventional electroactive labels in biosensing.

## Key findings

- Energy-based reactions like HER and ORR provide intrinsic electrochemical signals without synthetic redox mediators.
- These reactions simplify assay design and improve compatibility with diverse target molecules.
- Energy-driven approaches offer faster operation and lower costs compared to traditional methods.

## Abstract

The selection of appropriate signal labels is a central consideration in electrochemical biosensing as it directly determines the achievable detection limits, dynamic range, and overall analytical performance. Conventional electroactive labels require low operating potentials, fast electron-transfer kinetics, and reliable attachment to electrode surfaces or recognition elements. Despite their extensive use, these labels present notable challenges for point-of-care applications, particularly in the detection of small molecules where target binding does not inherently generate a measurable electrochemical output. As a result, most sensing architectures depend on externally added redox reporters, introduced either freely into solution or covalently linked to recognition structures, which increases assay complexity and limits scalability. These limitations have motivated the transition toward energy-based electrochemical signal pathways, such as the hydrogen evolution reaction (HER), oxygen reduction reaction (ORR), and water-splitting reactions. These reactions provide intrinsic electrochemical outputs that eliminate the need for synthetic redox mediators and can operate as built-in catalytic signal sources. Their integration into biosensing platforms simplifies assay design, enhances robustness, and broadens compatibility with diverse target molecules. This review outlines the mechanistic basis connecting HER/ORR/water-splitting reactions to signal generation in biosensors and highlights material design principles that enable their use as reagentless and label-free transduction strategies. Compared with traditional electroactive labels, energy-driven approaches offer simplicity, reduced cost, faster operation, and improved suitability for commercial translation. By establishing a unified framework for energy-based electro-recording mechanisms, this review aims to promote the development of next-generation bioanalytical methods that operate without electroactive labels and expand the applicability of electrochemical biosensing across various domains.