Sensitive Analysis of Biomarkers for Neurodegenerative Diseases by Laser Wave-Mixing Detection and Capillary Electrophoresis

Nonlinear multi-photon laser wave-mixing spectroscopy is presented as a highly sensitive optical absorption-based detection method for biomedical applications including early diagnosis of neurodegenerative diseases including α-synuclein for early-stage detection of Parkinson’s disease.  Laser wave-mixing offers inherent advantages over conventional methods including zeptomole-level or parts-per-quadrillion-level detection sensitivity, small sample requirements, compact portable designs, and high spatial resolution.  In a typical wave-mixing setup, two laser beams are focused and mixed inside a capillary flow cell, creating interference gratings.  The wave-mixing signal is a coherent laser-like beam, and hence, one can collect it efficiently with minimal background.  Wave-mixing detection sensitivity levels are comparable or better than those of popular fluorescent detection methods, and yet wave-mixing can detect biomolecules in their native form without using labels since it is an absorption based-method.  Using a UV laser, one can detect α-synuclein without a label or one can detect it with a 514 nm laser after using a Rhodamine label.  Capillary electrophoresis is used to separate and identify the proteins.  Our studies have shown wave mixing to be a sensitive detection technique for a wide range of analytes.  Laser wave mixing offers many desirable features including better sensitivity levels compared to conventional methods.  Potential applications include early disease diagnosis, and sensitive detection of biomarkers and bio agents.

Acknowledgments: We gratefully acknowledge NIH NIGMS SDSU MARC 5T34GM008303-23 (Linda Honaker), National Institutes of Health (R01), National Science Foundation, U.S. Department of Defense and U.S. Department of Homeland Security.