Fig. 2. Strategies for amplifying biomolecular interactions.

a, Intracellular sensing allows access to new, high-concentration biomarkers. b, Surrogate biomarkers can provide alternative detection pathways for trace analytes. c, Synthetic biomarkers can be introduced to the body to amplify biomolecular processes and enable their detection. d, Nanozymes and DNAzymes provide alternative catalytic routes for analyte monitoring. e, Mass transport advances, including analyte-guiding nanochannels, superhydrophobic transport metamaterials and analyte mixing micromotors increase the rate of interaction between an analyte and its recognition element. f, Organic electrochemical transistors serve as powerful amplifiers for biomolecular interactions. g, Reporter multimerization enhances the signal output from affinity interactions. h, Debye length-manipulating approaches, including structure-switching receptors, nanostructure-mediated electron transfer and membrane-mediated Debye extension bypass traditional Debye limitations to extend transducer influence and increase signal generation. i, Computational approaches, combined with multiplexed analysis, may allow health state amplification for predictive medicine. Part c is adapted from ref. ²², Springer Nature Limited. Part e (analyte-guiding nanochannel) is adapted from ref. ³⁹, Springer Nature Limited. Part e (superhydrophobic transport metamaterials) is adapted from ref. ⁴⁰, Springer Nature Limited. Part f is adapted from ref. ⁴⁴, Springer Nature Limited. Part h (structure-switching receptor) from Nakatsuka, N. et al. Aptamer-field-effect transistors overcome Debye length limitations for small-molecule sensing. Science 362, 319–324 (2018)⁵¹. Adapted with permission from AAAS. Part h (nanostructure-mediated electron transfer) is adapted from ref. ⁵³, CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Part h (membrane-mediated Debye extension) is adapted from ref. ⁵⁴, Springer Nature Limited.