A challenge of turning molecular biology knowledge into advance in disease detection to benefit patients is that most of available biomarkers are not powerful, lacking either sensitivity or specificity. Parallel to the effort of finding more specific biomarkers, one feasible way of providing better predictive value is to detect multiple low specificity biomarkers, and collectively analyze the response of multiple biomarkers contained in a sample. The multiplicity of thermal detection is reflected in simultaneous detection of rabbit immunoglobulin G (IgG) and human IgG, where lead–tin nanoparticles and tin nanoparticles are modified with anti-IgGs of the rabbit and human, respectively. Thermal biosensing is based on nanoparticles of solid–liquid nano-phase change materials, where each type of nanoparticles is conjugated with ligands of protein and DNA biomarkers, and immobilized on ligand-modified substrates by forming double helix DNA chain or sandwiched antibody–antigen complex.