Early detection and diagnosis of diseases and monitoring of treatment progress require ultrasensitive detection of biomarkers, proteins and small molecules. Currently available detection methods lack sensitivity or specificity or require time-consuming labeling steps.  We demonstrated nonlinear wave-mixing spectroscopy, an ultrasensitive optical absorption-based detection method, to yield zeptomole-level detection and high spatial resolution. Chemical selectivity is also significantly enhanced by interfacing to microfluidics or capillary-based electrophoresis systems. In a typical wave-mixing setup, two input beams are mixed inside the analyte and the resulting coherent laser-like signal can be collected with virtually 100% efficiency and excellent signal-to-noise ratio. The signal has a quadratic dependence on analyte concentration, and hence, wave mixing can monitor smaller changes more effectively. The wave-mixing probe volume is small (nanoliter to picoliter) and it is inherently suitable for interfacing to microfluidics or capillary systems, e.g., 20 μm microfluidic channels or 75 μm i.d. fused silica capillary. Biomarkers and proteins can be probed and detected label-free in their native form using a UV laser or by a visible label after using a label since wave mixing offers excellent detection limits for both fluorescing and non-fluorescing analytes. A standard protein ladder with a label can be generated to estimate expected retention times of the analytes. We obtained excellent preliminary results for CA15-3 antibody labeled with NBX and CEA antigen labeled with P-Chromeo 540 that are comparable or better than those reported for fluorescence-based detection methods.<br/>

Sensitive analysis of cancer biomarkers using nonlinear multi-photon laser wave mixing detector interfaced to micellar capillary electrophoresis

253rd National Meeting (2017)

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