Most of existing techniques cannot be used to detect molecular biomarkers (i.e., protein and DNA) contained in complex body fluids due to issues such as enzyme inhibition or signal interference. This thesis describes a nanoparticle-based thermal detection method for the highly sensitive detections of multiple DNA biomarkers or proteins contained in different type of fluids such as buffer solution, cell lysate and milk by using solid-liquid phase change nanoparticles as thermal barcodes. Besides, this method has also been applied for thrombin detection by using RNA aptamer-functionalized phase change nanoparticles as thermal probes. Furthermore, using nanostructured Si surface that have higher specific area can enhance the detection sensitivity by four times compared to use flat aluminum surfaces. The detection is based on the principle that the temperature of solid will not rise above its melting temperature unless all solid is molten, thus nanoparticles will have sharp melting peak during a linear thermal scan process. A one-to-one correspondence can be created between one type of nanoparticles and one type of biomarker, and multiple biomarkers can be detected simultaneously using different type nanoparticles. The melting temperature and the heat flow reflect the type and the concentration of biomarker, respectively. The melting temperatures of nanoparticles are designed to be over 100°C to avoid interference from species contained in fluids. The use of thermal nanoparticles allows detection of multiple low concentration DNAs or proteins in a complex fluid such as cell lysate regardless of the color, salt concentration, and conductivity of the sample.