Simultaneous detection of multiple biomarkers with over three orders of concentration difference using phase change nanoparticles.

A big challenge for multiplexed detection of cancer biomarkers is that biomarker concentrations in body fluid differs several orders of magnitude. Existing techniques are not suitable to detect low- and high-concentration biomarkers (protein and DNA) at the same time, and liquid chromatography or electrophoresis is used to separate or purify target biomarkers before analysis. This paper describes a new broad-range biomarker assay using solid to liquid phase change nanoparticles, where a panel of metallic nanoparticles (i.e., metals and eutectic alloys) are modified with a panel of ligands to establish a one-to-one correspondence and attached onto ligand-modified substrates by forming sandwiched complexes. The melting peak and fusion enthalpy of phase change nanoparticles during thermal analysis reflect the type and concentration of biomarkers, respectively. The thermal readout condition can be adjusted in such a way that multiple biomarkers with concentration difference over 3 orders of magnitude have been simultaneously detected under the same condition.