Ultrasensitive Detection and Separation of Pancreatic Cancer Biomarker CA 19-9 Using a Multiphoton Laser Wave-Mixing Detector Interfaced to Capillary Electrophoresis

The carbohydrate antigen 19-9 (CA 19-9) is the most commonly used biomarker in the clinical diagnosis of pancreatic cancer. Multiphoton nonlinear laser wave-mixing spectroscopy is presented as an ultrasensitive detection method for CA 19-9. Wave mixing is an optical absorption-based method, and hence, one can detect CA 19-9 without labels in their native form using compact ultraviolet (UV) lasers or labeled samples using a visible laser. The wave-mixing signal exhibits a quadratic dependence on the sample concentration, and hence, it is an ideal sensor to monitor small changes in the sample. Wave mixing has inherent advantages over other absorption-based detection methods, including short optical path length (micrometer-thin samples instead of 1 cm cuvette) and excellent spatial resolution (micrometer probe). Since the laser wave-mixing probe volume is small (picoliter), it is convenient to interface to microfluidics or capillary-based electrophoresis systems to enhance chemical specificity. Our wave-mixing detectors could be configured as portable battery-powered devices suitable for field use. Laser wave-mixing spectroscopy offers enhanced selectivity levels for protein detection when coupled with capillary electrophoresis (CE). We report a concentration detection limit of 0.16 U/mL, and a corresponding mass detection limit of 1.2 x 10(-8) U, and these detection limits are better than those of chemiluminescence- or ELISA- based methods.

Automated summary

The carbohydrate antigen 19-9 (CA 19-9) serves as a commonly used biomarker for diagnosing pancreatic cancer. Multiphoton nonlinear laser wave-mixing spectroscopy is proposed as an extremely sensitive detection method for CA 19-9. This method allows for the detection of CA 19-9 without labels or with labeled samples, offering advantages such as short optical path length and high spatial resolution. The wave-mixing signal exhibits a quadratic dependence on sample concentration, making it an ideal sensor for monitoring small changes in the sample. When combined with capillary electrophoresis, laser wave-mixing spectroscopy provides enhanced selectivity levels for protein detection, surpassing the detection limits of chemiluminescence- or ELISA-based methods.