Scanning calorimetric detections of multiple DNA biomarkers contained in complex fluids

Most of the existing techniques cannot be used to detect molecular biomarkers contained in complex fluids due to issues such as enzyme inhibition or signal interference. We have developed a nanoparticle-based scanning calorimetric method for the highly sensitive detections of multiple DNA biomarkers contained in cell lysate and milk by using solid-liquid phase change nanoparticles as thermal barcodes. The detection is based on the principle that the temperature of solid will not rise above the melting temperature unless all solid is molten, thus nanoparticles have sharp melting peaks during the thermal scan process. A one-to-one correspondence can thus be created between one type of nanoparticles and one type of biomarker, i.e., multiple biomarkers can be detected at the same time using a combination of nanoparticles. The melting temperature and the heat flow reflect the type and the concentration of the biomarker, respectively. The target oligonucleotides at low concentration in cell lysate (80 pM) have been detected through thermal signal transduction. The melting temperature of nanoparticles can be designed to avoid interference from coexisting species contained in the fluids, bringing simultaneously high sensitivity and multiplicity, as well as sample preparation benefits to biomarker detections.