Grant: Research Tools and Instruments - Category 1 (<$150,000)

An ultrafast tunable laser will be purchased as an excitation source for a new biomedical imaging technology called photocoustic microscopy. Previous work with photoacosutic microscopy has demonstrated breathtaking imaging of microvascular structures and is capable of seeing the smallest vessels in the body important for heath research and basic biology. This new tool is also capable of imaging blood oxygen levels. We aim to extend the capabilities of this exciting new technology to image the distribution of chemical bonds of proteins, lipids, nucleic acids, and other species, all non-invasively in the body. Other microscopy techniques can image these targets but typically require special dyes, many of which have undesirable levels of toxicity which limits their adaptation by some clinicans and biologists. Our proposed methods offer the promise of label-free imaging, meaning that no external dyes or other agents are needed. One of our proposed techniques promises to image cell nuclei, which are often enlarged in cancers and pre-cancers. Unique pump-probe photoacoustic methods are proposed that should enable quantitation of melanin species in melanomas to help improve diagnosis to distinguish between benign and malignant disease. The techniques will also help us image protein-protein interaction and may provide a glimpse of enzyme activity often upregulated in disease states. Because signals from many of our proposed target species are weak, we propose novel pump-probe and phase-sensitive lock-in techniques that have the potential to extract extremely weak signals from noise or other interfering signals. If sucessful, our pump-probe photoacoustic microscopy methods would break new ground to image important chemical-bond specific information non-invasively, in a label-free way, and to depths greater than is now possible with other microscopy techniques.