Ultrasensitive detection methods are needed to achieve reliable detection of proteins and small molecules for quantitative analysis and early disease detection. We have previously demonstrated sensitivity and specificity levels of laser wave-mixing spectroscopic methods. Portable and compact detectors that exploit this detection method would be ideal for field use and for providing reliable detection of small molecules in explosives and protein biomarkers in multiple sclerosis. The detection of explosives is essential for security applications while the detection of biomarker proteins can save many lives. In a typical laser wave-mixing setup, the input laser beam is split into two input beams and then focused and mixed inside the sample cell. Since the signal is a coherent laser-like beam, it can be collected by a simple photodetector with an excellent signal-to-noise ratio. Wave mixing only requires a small amount of sample (nanogram levels), and hence, it can be conveniently interfaced to the microarray, microfluidic, or chip-based capillary electrophoresis setups along with other multi-channel flow systems to yield excellent chemical specificity and detection sensitivity levels (pico- to femtomolar). Potential applications include on-site, real-time separation, detection, and monitoring of explosives traces. Preliminary studies have been performed for quick and selective methods to distinguish nitrate-based explosives from common interference and other explosive molecules. Early diagnosis of Multiple Sclerosis is challenging and MRI is still the gold standard to detect this debilitating disease. In addition to imaging techniques and lumbar puncture, there are a wide variety of proposed biomarkers that might provide an alternative to MRI, if there was a simple, inexpensive, and sensitive way to detect them. Previous studies in the Tong Lab have focused on detection of myelin basic protein (MBP) using capillary electrophoresis to obtain separation of different isoforms.This study aims to improve sensitivity in detecting myelin basic protein and IGG, both multiple sclerosis biomarkers, by immobilizing the specific antibodies on a glass surface using a 3D-printed custom-made microarray setup that is then analyzed using our degenerate four-wave mixing detection system.