Program Information
Theoretical Limits to Molecular Biomarker Detection Using Magnetic Nanoparticles
J Weaver1,2*, (1) Dartmouth-Hitchcock Medical Center, Lebanon, NH (2) Geisel School of Medicine, Dartmouth College, Hanover NH
Presentations
WE-H-207A-9 (Wednesday, August 3, 2016) 4:30 PM - 6:00 PM Room: 207A
Purpose:
Estimate the limits of molecular biomarker detection using magnetic nanoparticle methods like in vivo ELISA.
Methods:
Magnetic nanoparticles in an alternating magnetic field produce a magnetization that can be detected at exceedingly low levels because the signal at the harmonic frequencies is uniquely produced by the nanoparticles. Because the magnetization can also be used to characterize the nanoparticle rotational freedom, the bound state can be found. If the nanoparticles are coated with molecules that bind the desired biomarker, the rotational freedom reflects the biomarker concentration. The irreducible noise limit is the thermal noise or Johnson noise of the tissue and the contrast that can be measured must be larger than that limit. The contrast produced is a function of the applied field and depends strongly on nanoparticle volume. We have estimated the contrast using a Langevin function of a single composite variable to approximate the full stochastic Langevin equation for nanoparticle dynamics.
Results:
The thermal noise for a bandwidth reasonable for spectroscopy suggests mid zeptomolar (10-21) to low attomolar (10-18) concentrations can be measured in a volume that is 10cm in scale. The suggested sensitivity is far below the physiologically concentrations of almost all critical biomarkers including cytokines (picomolar), hormones (nanomolar) and heat shock proteins.
Conclusion:
The sensitivity of in vivo ELISA concentration measurements should be sufficient to measure physiological concentrations of critical biomarkers like cytokines in vivo. Further the sensitivity should be sufficient to measure concentrations of other biomarkers that are six to eight orders of magnitude lower in concentration than immune signaling molecules like cytokines.
Funding Support, Disclosures, and Conflict of Interest: NIH - 1U54CA151662-01 Department of Radiology
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