Naked-eye thiol analyte detection via self-propagating, amplified reaction cycle

21 March 2023, Version 2
This content is a preprint and has not undergone peer review at the time of posting.


We introduce naked-eye thiol analyte detection through signal-triggered macroscopic degradation of a hydrogel scaffold using a molecular self-propagating amplification cycle. This system contains an allylic phosphonium salt coupled to a disulfide-crosslinked hydrogel, which is triggered by thiol-analytes to undergo physical degradation through chemical cascade reactions within the gel matrix. We constructed a numerical model to predict the behaviour of the signal-triggered amplification cycle applied to small molecules by varying the input concentration of thiol trigger. The model is validated using experimental data. Using the amplification system embedded within the hydrogel, multiple thiol analytes, including a small molecule probe, an amino acid, DNA and a protein, could be detected at concentrations ranging from 132 to 0.132 µM. Furthermore, we found that force-generated disulfide scission can initiate the cycle, enabling damage-triggered hydrogel destruction via the self-propagating amplification system.


signal amplification
chemical reaction network
chemical signal

Supplementary materials

supplementary information
synthetic details, control experiments, measurements


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