Laser wave-mixing detectors for microfluidics are presented as compact systems for parts-per-quadrillion-level detection of biomedical and environmental samples. Wave mixing offers unique advantages including absorption-based detection of micrometer-thin samples, generation of coherent laser-like signal beams, and sensitive detection of both fluorescing and non-fluorescing samples. Biomarkers could be detected in their native forms without labels, or if labels are desired, one could use both fluorophores and chromophores as labels. By coupling low-power (mW) solid-state lasers and microfluidics and microarrays, one can design compact optical systems that can be battery powered and used in the field for real-time fingerprinting of chemicals.