Imaging

We are developing miniaturized ultrasound sensor array based on Fabry-Perot interferometer made of thin Parylene-C and gold layers. They have potential advantages in higher signal to noise ratio, smaller element sizes and wavelength-dependent transparency over the array formed by conventional piezoelectric sensors with similar sub-millimeter dimensions. They will be used to develop miniaturized photoacoustic imaging probe for small animal imaging.

Molecular probes - Peptides have high diversity, and can achieve high specificity with binding affinities on the nanomolar scale. This probe platform has flexibility to be labeled with a broad range of fluorophores, and is inexpensive to produce in large quantities. We used topical application to deliver the peptides to the mucosal surface in high concentration to maximize target interactions and achieve rapid binding with minimal risk for toxicity. Compared with systemic delivery, this approach localizes distribution of the exogenous imaging agent to the target tissues only, minimizes background, and maximizes image contrast. These features of peptides are well suited for clinical use in high volume procedures.

Imaging platforms - Optical imaging techniques can provide the speed and resolution needed to observe cellular and molecular events in real time. Other methods of in vivo imaging, including ultrasound, CT, MRI, and PET lack the spatial resolution and temporal speed needed to visualize lesions that are flat in appearance and patchy in distribution. Non-optical imaging modalities have limited ability to visualize multiple targets concurrently in real time. New method of optical imaging that can image in multiple fluorescence channels simultaneously (multiplexing) can significantly improve our ability to image the epithelium for early detection of disease in hollow organs, including biliary tract, colon, esophagus, lung, pancreas, and stomach.

Peptide specific for FGFR2 - Chemical structure is shown for 12 amino acid (aa) peptide sequence (black) found to be specific for FGFR2. Cy5.5 is used as NIR label, and is attached via a GGGSK linker to prevent steric hindrance.

Structural model - Cy5.5-labeled peptide (arrow) was found using a structural model (1EV2) to bind to the extracellular domain (ECD) of FGFR2c (147-366 aa).

Bivalent peptide heterodimer - Chemical structure for heptapeptide monomers specific for EGFR and ErbB2 arranged in a heterodimer configuration and labeled with Cy5.5 using an E3 linker.