Printable molecule-selective core–shell nanoparticles for wearable and implantable sensing

Creators: Wang, Minqiang¹; Ye, Cui¹; Yang, Yiran¹; Mukasa, Daniel¹; Wang, Canran¹; Xu, Changhao¹; Min, Jihong¹; Solomon, Samuel A.¹; Tu, Jiaobing¹; Shen, Guofang²; Tang, Songsong¹; Hsiai, Tzung K.³; Li, Zhaoping³; McCune, Jeannine S.²; Gao, Wei (Corresponding)¹

1. California Institute of Technology
2. City Of Hope National Medical Center
3. University of California, Los Angeles

Abstract

Wearable and implantable biosensors are pioneering new frontiers in precision medicine by enabling continuous biomolecule analysis for fundamental investigation and personalized health monitoring. However, their widespread adoption remains impeded by challenges such as the limited number of detectable targets, operational instability and production scalability. Here, to address these issues, we introduce printable core–shell nanoparticles with built-in dual functionality: a molecularly imprinted polymer shell for customizable target recognition, and a nickel hexacyanoferrate core for stable electrochemical transduction. Using inkjet printing with an optimized nanoparticle ink formulation, we demonstrate the mass production of robust and flexible biosensors capable of continuously monitoring a broad spectrum of biomarkers, including amino acids, vitamins, metabolites and drugs. We demonstrate their effectiveness in wearable metabolic monitoring of vitamin C, tryptophan and creatinine in individuals with long COVID. Additionally, we validate their utility in therapeutic drug monitoring for cancer patients and in a mouse model through providing real-time analysis of immunosuppressants such as busulfan, cyclophosphamide and mycophenolic acid.

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Acknowledgement

This project was supported by National Science Foundation grant 2145802, National Institutes of Health grants R01HL155815, R21DK13266, U01CA239373 and R01GM129863, American Cancer Society Research Scholar Grant RSG-21-181-01-CTPS, Office of Naval Research grants N00014-21-1-2483 and N00014-21-1-2845, Army Research Office grant W911NF-23-1-0041, NASA Cooperative Agreement 80NSSC20M0167, Heritage Medical Research Institute, and Caltech-City of Hope Biomedical Initiative Pilot Grant. We gratefully acknowledge critical support and infrastructure provided for this work by the Kavli Nanoscience Institute at Caltech. Research reported in this publication includes work performed in the Analytical Pharmacology Core supported by the National Cancer Institute of the National Institutes of Health under grant P30CA033572. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Contributions

These authors contributed equally: Minqiang Wang, Cui Ye.

W.G. and M.W. initiated the concept and designed the studies. M.W., C.Y., Y.Y., D.M., C.W., C.X., S.A.S., J.T. and S.T. performed sensor characterization, validation and sample analysis. J.M. contributed to the signal processing and app development. T.K.H., Z.L., G.S. and J.S.M contributed to the sensor evaluation in human subjects. W.G. and M.W. co-wrote the paper. All authors contributed to the data analysis and provided the feedback on the paper.

Supplemental Material

Supplementary Information: Supplementary figures, tables, references and video captions.
Supplementary Video 1: Inkjet-printable core–shell nanoparticles for wearable and implantable sensing.

Data Availability

The main data supporting the results in this study are available within the paper and its Supplementary Information. Source data are provided with this paper.

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