Research

Peptides are promising for in vivo use to visualize overexpressed tumor targets, such as CD44. These protein fragments have been developed to bind cell surface targets with high affinity and fast kinetics. Peptides can achieve selective tumor uptake in vivo within 1-2 hours after intravenous administration, and are stable in serum with a half-life of several hours. This time scale is compatible with clinical use. These ligands clear quickly from the circulation to avoid toxicity to viable tissues, and minimize biodistribution to non-target tissues. Peptides by comparison with antibodies have smaller dimensions to better diffuse and extravasate through leaky vessels and achieve higher concentrations and deeper penetration in solid tumors. Also, these ligands have lower potential for immunogenicity, and can be used repetitively. Moreover, peptides can be scaled up for mass manufacture at relatively low cost for broad clinical translation.

Miniature scanners and actuators, including electrostatic, thin-film PZT, and electrothermal, can be fabricated using Micro-Electro-Mechanical-Systems (MEMS) technology. The small dimensions allow for placement in the distal end of endomicroscopes where greater control the focus can be achieved. The small size allows for placement in the post-objective position, which allows the optical design to be scaled down in diameter without loss of resolution. Also, a very large image field-of-view can be achieved by deflecting the beam at wide angles limited only by the scanning mechanism rather than by the objective. These devices can be batch fabricated using simple processes whereby hundreds of devices can be produced on a single silicon wafer to scale up production for mass manufacture. By comparison, conventional microscopes use bulky scanners, such as galvos, that are large in dimension and must be placed in the pre-objective position.