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Chip–NMR biosensor for detection and molecular analysis of cells

Abstract

Rapid and accurate measurement of biomarkers in tissue and fluid samples is a major challenge in medicine. Here we report the development of a new, miniaturized diagnostic magnetic resonance (DMR) system for multiplexed, quantitative and rapid analysis. By using magnetic particles as a proximity sensor to amplify molecular interactions, the handheld DMR system can perform measurements on unprocessed biological samples. We show the capability of the DMR system by using it to detect bacteria with high sensitivity, identify small numbers of cells and analyze them on a molecular level in real time, and measure a series of protein biomarkers in parallel. The DMR technology shows promise as a robust and portable diagnostic device.

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Figure 1: Principle of the assay and structure of the DMR system.
Figure 2: Accuracy and sensitivity of the DMR system.
Figure 3: Sensitive detection of bacteria.
Figure 4: Profiling of mammalian cells.

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Acknowledgements

The authors gratefully acknowledge N. Sergeyev for synthesizing CLIO, K. Kelly, K. Kristof and S. Thomas for cell culture and I. Koh for help in magnetic microparticle–based assay. We especially thank L. Josephson, J. Bradner and M. Cima for many helpful suggestions, R.M. Westervelt for generous support in device fabrication and D.S. Yun and A. Belcher for assistance in imaging bacteria with a transmission electron microscope.

Author information

Authors and Affiliations

Authors

Contributions

H.L. designed the device, built the DMR prototype, obtained measurements, analyzed data and wrote the manuscript. E.S. performed all chemical modifications of magnetic nanoparticles and assisted in measurements and data analysis. D.H. collaborated in the development of the NMR electronics of discrete components. R.W. conceived the project, provided overall guidance, designed experiments and targeted nanoparticles, analyzed the data and wrote the manuscript with contributions from all authors.

Corresponding author

Correspondence to Ralph Weissleder.

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Competing interests

R.W. is a shareholder of T2 Biosystems. H.L., D.H. and R.W. are listed on a patent application to the US Patent Office filed by Harvard University and Massachusetts General Hospital.

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Supplementary Figs. 1–5, Supplementary Tables 1–5 and Supplementary Methods (PDF 3354 kb)

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Lee, H., Sun, E., Ham, D. et al. Chip–NMR biosensor for detection and molecular analysis of cells. Nat Med 14, 869–874 (2008). https://doi.org/10.1038/nm.1711

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