Sensitive Multi-Photon Nonlinear Laser Wave-Mixing Detection of Cancer and Heart Failure Biomarkers

摘要

Multi-photon nonlinear laser wave-mixing spectroscopy is presented as an ultrasensitive detection method for pancreaticcancer biomarkers, carbohydrate antigen 19-9 (CA 19-9) and carbohydrate antigen 242 (CA 242), and heart-failurebiomarkers, pro-atrial natriuretic peptide (proANP) and brain natriuretic peptide (BNP). Wave mixing is an ultrasensitiveoptical absorption-based detection method, and hence, it can detect both fluorescing and non-fluorescing biomarkers. Onecan detect biomarkers in their native form, label-free, without the use of time-consuming labeling steps. The wave-mixingsignal beam is strong, collimated and coherent (laser-like) and it can be collected using a simple photodetector with anexcellent signal-to-noise ratio (S/N). The wave-mixing signal has a quadratic dependence on the analyte concentration,and thus, small changes in analytes can be monitored more effectively (i.e., an ideal sensor). Compared to currentlyavailable detection methods, wave mixing offers inherent advantages such as short optical path length (micrometer-thinsamples), high spatial resolution, ultrasensitive detection limits comparable or better than those of fluorescence- or ELISAbasedmethods, and native label-free detection. Since laser wave-mixing probe volume is small (nanoliter to picoliter), itis intrinsically convenient to couple with microfluidics or capillary-based electrophoresis systems to enhance chemicalspecificity. Different biomarkers can be placed on a simple slide or flowed inside a capillary and then detected. Ournonlinear multi-photon detectors can be easily configured as portable battery-powered devices that are suitable for use inthe field. Potential real-world applications include detection of various biomarkers, cancer cells, and reliable earlydetection of diseases.