An optical device employing multiwavelength photoplethysmography for non-invasive in-vivo monitoring of optically active nanoparticles

Researchers employ increasingly complex sub-micron particles for oncological applications to deliver bioactive therapeutic or imaging compounds to known and unknown in vivo tumor targets. These particles are often manufactured using a vast array of compounds and techniques resulting in a complex architecture, which can be quantified ex vivo by conventional metrology and chemical assays. In practice however, experimental homogeneity using nanoparticles can be difficult to achieve. While several imaging techniques have been previously shown to follow the accumulation of nanoparticles into tumor targets, a more rapid sensor that provides a quantifiable estimate of dose delivery and short-term systemic response could increase the clinical efficacy and greatly reduce the variability of these treatments. We have developed an optical device, the pulse photometer, that when placed on an accessible location will estimate the vascular concentration of near-infrared extinguishing nanoparticles in murine subjects. Using a technique called multi-wavelength photoplethysmography, the same technique used in pulse oximetry, our pulse photometer requires no baseline for each estimate allowing it to be taken on and off of the subject several times during experiments employing long circulating nanoparticles. We present a formal study of our prototype instrument in which circulation half-life and nanoparticle concentration of gold nanorods is determined in murine subjects with the aid of light anesthesia. In this study, we show good agreement between vascular nanorod concentrations (given in optical density) as determined by our device and with UV-VIS spectrophotometry using low volume blood samples.