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Reagentless biomolecular analysis using a molecular pendulum


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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Fig. 1: Modelling the dynamics of the MP tethered to an electrode surface.
Fig. 2: Modulation of MP dynamics by protein binding.
Fig. 3: Panel of proteins and biofluids that can be monitored using MPs.
Fig. 4: MP-based monitoring of a cardiac marker in living animals.

Data availability

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 ( and PhosphoSitePlus ( Source data are provided with this paper.

Code availability

The code corresponding to the theoretical model for the MP can be accessed at


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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 were used in the main text figures. All correspondence and requests for materials should be made to S.O.K.

Author information




J.D., S.G., E.H.S. and S.O.K. conceived the experiments. J.D. and S.G. designed and performed the experiments. S.G. conceived the theoretical model. J.B.C. fabricated the chips. J.D. and A.M. fabricated electrodes. H.Y. and W.Z. performed conjugation of ferrocence to oligo and antibody to oligo. S.A., J.D. and S.G. performed experiments with the animal model and J.D., S.G., E.H.S. and S.O.K. co-wrote the manuscript.

Corresponding authors

Correspondence to Edward H. Sargent or Shana O. Kelley.

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The authors declare no competing interests.

Additional information

Peer review information Nature Chemistry thanks Netz Arroyo and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

Supplementary Tables 1 and 2 and Figs. 1–26.

Reporting Summary

Supplementary Data 1

Statistical source data used to generate Supplementary figures.

Source data

Source Data Fig. 1

Statistical source data used to generate Fig. 1.

Source Data Fig. 2

Statistical source data used to generate Fig. 2.

Source Data Fig. 3

Statistical source data used to generate Fig. 3.

Source Data Fig. 4

Statistical source data used to generate Fig. 4.

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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).

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