Nonlinear laser wave-mixing spectroscopy integrated to capillary electrophoresis has been demonstrated as a label-free antibody-free sensitive detection method for cancer biomarkers including carcinoembryonic antigen (CEA) and carbohydrate antigen (CA19-9). CEA and CA19-9 are the biomarkers for colorectal cancer and pancreatic cancer, respectively. Wave mixing offers advantages over current methods including label-free native detection, excellent sensitivity, small sample requirements, short optical path length, high spatial resolution and portable detector designs. A single laser is used to generate two input beams that are then focused and mixed inside the sample cell. The wave-mixing signal is generated when the two input beams are mixed inside the analyte and diffract incoming photons to produce two coherent laser-like signal beams. The stronger signal beam is collected by a photodetector with high collection efficiency and an excellent S/N. The wave-mixing signal has a quadratic dependence on analyte concentration, and hence, small changes in the analyte concentration can be monitored efficiently. Our preliminary cancer biomarker detection limit is comparable or better than those of ELISA or fluorescence-based techniques. Wave-mixing detection can be used for both fluorescing (labeled) and non-fluorescing (label-free) samples; it can also be easily adapted to a battery-powered portable detector that is suitable for use in the field. Potential applications include reliable detection of biomarkers, cancer cells, single cells, and viruses for early diagnosis of diseases.

Ultrasensitive detection of cancer biomarkers using multi-photon nonlinear laser wave-mixing spectroscopy

2019 Spring National Meeting

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