Multiplexed detection of molecular biomarkers with phase-change nanoparticles

This review describes a new biosensing method based on nanoparticles of solid-to-liquid phase-change materials, in which a panel of metallic nanoparticles (metals and eutectic alloys) that have different compositions and melting temperatures are used as thermal reporters. Each type of nanoparticle will be conjugated to a ligand that can specifically bind to one type of molecular biomarker (protein or DNA) and then immobilized onto a substrate that is comodified with multiple ligands by forming sandwiched antibody-antigen complexes or DNA double helices. After removing unbound nanoparticles by washing, the nature and concentration of the biomarkers are determined by detecting the melting temperature and fusion enthalpy of the nanoparticles using differential scanning calorimetry. Furthermore, an even larger panel of thermal barcodes can be formed by encapsulating selected phase-change nanoparticles inside non-melting shells, such as silica, where each microparticle will have a characteristic signature that can be determined from its thermal signatures.