Program Information

Biomarker Sensing

J Weaver*, X Zhang, D Reeves, I Perreard, W Kett, K Griswold, B Gimi, S Toraya-Brown, S Fiering, Dartmouth College, Hanover, NH

TH-A-WAB-1 Thursday 8:00AM - 9:55AM Room: Wabash Ballroom

Purpose:
To measure local biomarker concentrations longitudinally over time. Biomarker concentrations can be used to diagnose disease but the most promising application is in monitoring therapy. For example, the VEGF level provides a very direct evaluation of anti-angiogenic therapies or heat shock proteins provide a direct evaluation of thermal therapies. In this effort, the potential of the proposed technology was evaluated for sensitivity and specificity. The potential sensitivity was also estimated.

Methods:
Magnetic nanoparticles (NPs) can be detected remotely by measuring their magnetization induced by an alternating magnetic field. Magnetic spectroscopy of Brownian motion (MSB) characterizes the rotational Brownian motion from the shape of the magnetization. Rotational Brownian motion characterizes the local microenvironment surrounding the NPs: temperature, viscosity and chemical binding. We are reporting on a novel application of MSB that will allow the local concentration of biomarkers or drugs to be measured in vivo longitudinally over time.

Magnetic NPs in ~200 micron porous walled containers can be deposited in the vascular bed or into the extracellular space via injection in a lesions' blood supply or directly into the lesion. The NPs are decorated so that the target molecule (either biomarker or drug) binds the NPs together into an aggregate. The aggregate has a much longer relaxation time than the free NPs so the MSB signal changes dramatically. The MSB signal can be used to estimate the quantitative concentration of the biomarker.

Results:
The method has been explored in vitro for the following analytes (minimum sensitivities): 24 mer DNA (100 pM sensitivity); 20 mer DNA (2 nM); thrombin (4 nM); streptavidin (150 pM); VEGF (4 nM).

Conclusion:
These proof of concept experiments demonstrate that MSB methods are capable of measuring hormone concentrations of biomarkers and would require only reasonable increases in sensitivity to measure cytokine concentrations.

Funding Support, Disclosures, and Conflict of Interest: NIH-NCI 1U54CA151662-01 Hopeman Fund Grant: Norris Cotton Cancer Center

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