(275f) Multiplexed Biomarker Detection Using Phase Change Nanoparticles

Many biomarkers are specific for early stage cancer detection, but no individual biomarker is ideal to distinguish lethal cancer from indolent ones due to lack of tumor specificity. Parallel to efforts of finding specific biomarkers, a feasible way of providing better predictive value is to detect multiple biomarkers from a sample and collectively assess response pattern of more biomarkers. But, existing techniques such as microarrays and nanoparticles are not suitable to detect multiple low concentration biomarkers in a tiny amount of sample due to low sensitivity, low multiplicity and extensive sample preparation. We have detected multiple DNA and protein biomarkers with a panel of phase change nanoparticles of metals and alloys. Nanoparticles attached on a substrate through ligand-biomarker interactions are readout using differential scanning calorimetry, where the peak position and area reflect presence and concentration of biomarkers. This research is innovative for several reasons. (1) It uses an unexplored phenomenon of solid materials, i.e., the temperature of a solid will not rise above its melting point until the entire solid is molten. (2) Sharp melting peak, large thermal scan range and wide choices of materials enhance multiplicity this detection without adding system complexity. (3) The surface grafting density of ligands on nanoparticles is controlled to detect multiple biomarkers with concentrations differing several orders of magnitude.

We have identified ten different metals that form binary eutectic alloys among any two of them are identified from phase diagram database. These metals (i.e., aluminum, bismuth, cadmium, copper, gadillium, indium, lead, magnesium, palladium, silver) can form 45 binary eutectic alloys, 120 ternary eutectic alloys, 210 quaternary eutectic alloys, and so on. The total number of metals and eutectic alloys are 1,023. Pandat 8 software (CompuTherm) has been used to derive compositions of ternary and higher order eutectic alloys formed by these ten metals. Two thermophysical properties (melting temperature and latent heat of fusion at eutectic composition) had been extracted from data. After obtaining eutectic compositions, nanoparticles had been made by thermally decomposing of organometallic precursor in a high boiling point solvent (ethylene glycol) by using polyvinyl alcohol (PVA) as surfactant. We have used these nanoparticles to detect proteins and single strand DNA (ssDNA).