# Inverse sensitivity of plasmonic nanosensors at the single-molecule limit

## TL;DR

This paper critically examines the concept of inverse sensitivity in plasmonic nanosensors, questioning its consistency with established chemical principles and suggesting alternative explanations for observed phenomena.

## Contribution

It provides a detailed critique of recent claims about inverse sensitivity, highlighting inconsistencies with known chemistry and proposing the need for alternative explanations.

## Key findings

- Reported spectral changes likely require vastly more silver atoms than produced
- The assay's mechanism appears incompatible with the law of mass action
- Alternative explanations for the observed sensitivity are necessary

## Abstract

Recent work using plasmonic nanosensors in a clinically relevant detection assay reports extreme sensitivity based upon a mechanism termed 'inverse sensitivity', whereby reduction of substrate concentration increases reaction rate, even at the single-molecule limit. This near-homoeopathic mechanism contradicts the law of mass action. The assay involves deposition of silver atoms upon gold nanostars, changing their absorption spectrum. Multiple additional aspects of the assay appear to be incompatible with settled chemical knowledge, in particular the detection of tiny numbers of silver atoms on a background of the classic 'silver mirror reaction'. Finally, it is estimated here that the reported spectral changes require some 2.5E11 times more silver atoms than are likely to be produced. It is suggested that alternative explanations must be sought for the original observations.