Nonlinear multi-photon laser wave-mixing optical detection in microarrays and microchips for ultrasensitive detection and separation of biomarkers for cancer and neurodegenerative diseases

Manna Iwabuchi; Marcel Hetu; Eric Maxwell; Jean Sebastien Pradel; Sashary Ramos; William G. Tong

doi:10.1117/12.2188797

3 September 2015 Nonlinear multi-photon laser wave-mixing optical detection in microarrays and microchips for ultrasensitive detection and separation of biomarkers for cancer and neurodegenerative diseases

Manna Iwabuchi, Marcel Hetu, Eric Maxwell, Jean Sebastien Pradel, Sashary Ramos, William G. Tong

Author Affiliations +

Proceedings Volume 9579, Novel Optical Systems Design and Optimization XVIII; 957904 (2015) https://doi.org/10.1117/12.2188797
Event: SPIE Optical Engineering + Applications, 2015, San Diego, California, United States

Abstract

Multi-photon degenerate four-wave mixing is demonstrated as an ultrasensitive absorption-based optical method for detection, separation and identification of biomarker proteins in the development of early diagnostic methods for HIV- 1, cancer and neurodegenerative diseases using compact, portable microarrays and capillary- or microchip-based chemical separation systems that offer high chemical specificity levels. The wave-mixing signal has a quadratic dependence on concentration, and hence, it allows more reliable monitoring of smaller changes in analyte properties. Our wave-mixing detection sensitivity is comparable or better than those of current methods including enzyme-linked immunoassay for clinical diagnostic and screening. Detection sensitivity is excellent since the wave-mixing signal is a coherent laser-like beam that can be collected with virtually 100% collection efficiency with high S/N. Our analysis time is short (1-15 minutes) for molecular weight-based protein separation as compared to that of a conventional separation technique, e.g., sodium dodecyl sulfate-polyacrylamide gel electrophoresis. When ultrasensitive wavemixing detection is paired with high-resolution capillary- or microchip-based separation systems, biomarkers can be separated and identified at the zepto- and yocto-mole levels for a wide range of analytes. Specific analytes can be captured in a microchannel through the use of antibody-antigen interactions that provide better chemical specificity as compared to size-based separation alone. The technique can also be combined with immune-precipitation and a multichannel capillary array for high-throughput analysis of more complex protein samples. Wave mixing allows the use of chromophores and absorption-modifying tags, in addition to conventional fluorophores, for online detection of immunecomplexes related to cancer.

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Manna Iwabuchi, Marcel Hetu, Eric Maxwell, Jean Sebastien Pradel, Sashary Ramos, and William G. Tong "Nonlinear multi-photon laser wave-mixing optical detection in microarrays and microchips for ultrasensitive detection and separation of biomarkers for cancer and neurodegenerative diseases", Proc. SPIE 9579, Novel Optical Systems Design and Optimization XVIII, 957904 (3 September 2015); https://doi.org/10.1117/12.2188797

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