Sensitive detection of surface-mounted micrometer-thin cancer biomarkers and viruses using laser wave-mixing...

We report laser wave-mixing spectroscopy as a highly sensitive and rapid absorption-based detection method for pancreatic and breast cancer biomarkers and viruses on surface-mounted micrometer-thin samples. Currently, cancer diagnosis is done mostly by imaging techniques such as magnetic resonance imaging (MRI) and computed tomography (CT), which typically are effective for detecting tumors only at later stages. Similarly, early viral detection, such as HIV, is challenged by the diagnostic window period. These limitations underscore the urgent need for more sensitive, rapid, and minimally invasive biomarker-based diagnostic tools. Our laser wave-mixing detection method offers significant advantages over existing techniques, including ultrasensitive detection, excellent chemical specificity, and high spatial resolution achieved through the use of small probe volumes (nL) and micrometer-thin samples that can be mounted on microscope slides and microarrays that can be reproducibly moved and controlled by piezo actuators. We achieved detection sensitivity for the pancreatic cancer biomarker CA 19-9 at micro-unit levels, and for HIV-1 p24 and HER-2 at zeptomole levels. Laser wave-mixing detection method provides excellent detection limits and high spatial resolution compared to traditional methods, making it an effective microchip-based detector for point-of-care diagnostics.