The development of reagentless sensors that can detect molecular analytes in biological fluids could enable a broad range of applications in personalized health monitoring. However, only a limited set of molecular inputs can currently be detected using reagentless sensors. Here, we report a sensing mechanism that is compatible with the analysis of proteins that are important physiological markers of stress, allergy, cardiovascular health, inflammation and cancer. The sensing method is based on the motion of an inverted molecular pendulum that exhibits field-induced transport modulated by the presence of a bound analyte. We measure the sensor’s electric field-mediated transport using the electron-transfer kinetics of an attached reporter molecule. Using time-resolved electrochemical measurements that enable unidirectional motion of our sensor, the presence of an analyte bound to our sensor complex can be tracked continuously in real time. We show that this sensing approach is compatible with making measurements in blood, saliva, urine, tears and sweat and that the sensors can collect data in situ in living animals.
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The main data supporting the findings of the current study are available within the paper and its Supplementary Information. Data for figures in the Supplementary Information are included as additional Supplementary files. Data for chemical and physical protein parameters were derived from UniProt (https://www.uniprot.org/) and PhosphoSitePlus (https://www.phosphosite.org/). Source data are provided with this paper.
The code corresponding to the theoretical model for the MP can be accessed at https://github.com/sgomis/MP-biosensor.
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This research is supported by the Canadian Institutes of Health Research (FDN-148415, CHRPJ 523597-18) and the Natural Sciences and Engineering Research Council of Canada (2016-06090, CHRPJ 523597-18). Assets from BioRender.com were used in the main text figures. All correspondence and requests for materials should be made to S.O.K.
The authors declare no competing interests.
Peer review information Nature Chemistry thanks Netz Arroyo and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
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Das, J., Gomis, S., Chen, J.B. et al. Reagentless biomolecular analysis using a molecular pendulum. Nat. Chem. 13, 428–434 (2021). https://doi.org/10.1038/s41557-021-00644-y
Nature Chemistry (2021)