Implantable magnetic relaxation sensors measure cumulative exposure to cardiac biomarkers

Abstract

Molecular biomarkers can be used as objective indicators of pathologic processes. Although their levels often change over time, their measurement is often constrained to a single time point. Cumulative biomarker exposure would provide a fundamentally different kind of measurement to what is available in the clinic. Magnetic resonance relaxometry can be used to noninvasively monitor changes in the relaxation properties of antibody-coated magnetic particles when they aggregate upon exposure to a biomarker of interest. We used implantable devices containing such sensors to continuously profile changes in three clinically relevant cardiac biomarkers at physiological levels for up to 72 h. Sensor response differed between experimental and control groups in a mouse model of myocardial infarction and correlated with infarct size. Our prototype for a biomarker monitoring device also detected doxorubicin-induced cardiotoxicity and can be adapted to detect other molecular biomarkers with a sensitivity as low as the pg/ml range.

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Figure 1: Evidence of cardiac biomarker extravasation from serum to the subcutaneous space.
Figure 2: Use of functionalized MRSw particles, encapsulated within discrete sensors and calibrated in vitro, to measure cumulative exposure to analyte in vitro.
Figure 3: Sensor response differs markedly between MI and sham/control groups, and its magnitude correlates with the extent of infarction.
Figure 4: An implanted MRSw sensor device can detect the cardiotoxic effect of the chemotherapeutic drug doxorubicin in vivo.

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Acknowledgements

This work was supported by National Cancer Institute Centers of Cancer Nanotechnology Excellence no. 5 U54 CA119349-12 and CA151844 grants and National Science Foundation Division of Materials Research Award no. 0746264. Y.L. was supported by a National Defense Science and Engineering Graduate fellowship. T.P. was supported by an American Heart Association fellowship.

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Y.L. initiated the project, designed and performed experiments, analyzed data and wrote the manuscript. T.P. conceived experiments, designed and performed animal experiments, analyzed data and wrote the manuscript. C.C.V. contributed ideas, performed experiments, analyzed data and wrote the manuscript. P.L.H. contributed to the design experiments related to clinical relevance, doxorubicin toxicity and myocardial infarction model. M.J.C. was the principal investigator; he initiated the project, conceived experiments and obtained funding.

Corresponding author

Correspondence to Michael J Cima.

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Competing interests

M.J.C. is a director at T2 Biosystems, a company developing in vitro diagnostic assays.

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Ling, Y., Pong, T., Vassiliou, C. et al. Implantable magnetic relaxation sensors measure cumulative exposure to cardiac biomarkers. Nat Biotechnol 29, 273–277 (2011). https://doi.org/10.1038/nbt.1780

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