The development of high-performance photoacoustic (PA) probes that can monitor disease biomarkers in deep tissue has the potential to replace invasive medical procedures such as a biopsy. However, such probes must be optimized for in vivo performance and exhibit an exceptional safety profile. In this study, we have developed PACu-1, a PA probe designed for biopsy-free assessment (BFA) of hepatic Cu via photoacoustic imaging. PACu-1 features a Cu(I)-responsive trigger appended to an aza-BODIPY dye platform that has been optimized for ratiometric sensing. Owing to its excellent performance, we were able to detect basal levels of Cu in healthy wild-type mice as well as elevated Cu in a Wilson’s disease model and in a liver metastasis model. To showcase the potential impact of PACu-1 for BFA, we conducted two blind studies in which we were able to successfully identify Wilson’s disease animals from healthy control mice in each instance.

Photoacoustic imaging is a state-of-the-art technique that combines light excitation with ultrasound generation via the photoacoustic effect. Since sound waves at clinically relevant frequencies undergo minimal perturbation as they pass through the body, photoacoustic imaging is ideal for deep-tissue imaging applications in vivo. Despite its utility in the biomedical field, it is unlikely that undergraduate students will ever experience this technology firsthand in a classroom setting owing to the delicate and expensive nature of the instrumentation. Likewise, students will not be exposed to acoustogenic probes, which are specialized chemicals designed to detect biologically relevant analytes using photoacoustic imaging. With the goal of introducing new chemical analysis and imaging techniques to the undergraduate chemistry curricula, we present a simple and inexpensive setup (all materials were purchased for less than $48 USD) to demonstrate the photoacoustic effect through analyte sensing.

<p>The development of high-performance photoacoustic (PA) probes that can monitor disease biomarkers in deep-tissue has the potential to replace invasive medical procedures such as a biopsy. However, such probes must be highly optimized for <i>in vivo</i> performance and exhibit an exceptional safety profile. In this study, we have developed PACu-1, the first PA probe designed for biopsy-free assessment (BFA) of hepatic Cu via photoacoustic imaging. PACu-1 features a Cu(I)-responsive trigger appended to an aza-BODIPY dye platform that has been optimized for ratiometric sensing. Owing to its excellent performance, we were able to detect basal levels of Cu in healthy wildtype mice, as well as elevated Cu in a Wilson’s disease model and in a liver metastasis model. To showcase the potential impact of PACu-1 for BFA, we conducted a blind study where we were able to successfully identify a Wilson’s disease animal from a group of healthy control mice with greater than 99.7% confidence.</p>