A fiberoptic microneedle device, FMD, has been invented that can significantly enhance light penetration in tissue to enable a new regime of minimally-invasive and more selective photothermal therapy combining light and nanomedicine delivery. The device is comprised of one or more optically transparent glass fibers (~40 microns in diameter) which are guided into a patient's tissue by a novel support ferrule. For dermatological applications, the device may be placed against a patient's skin, and mechanical compression causes the fiber needles to slide through the ferrule and painlessly penetrate the skin, similar to the dynamics of a mosquito bite. The fiber tips may be positioned at desirable target positions (potentially >2mm deep) within tissue. Some fibers may be hollow, enabling delivery of drugs (chemotherapeutic agents, nanomaterials etc.) to specific tissue regions for targeted treatment. Subsequent application of laser energy into the solid fibers will be transmitted efficiently to the target tissue containing the light-absorbing nanomaterials, thereby inducing selective photothermal or photochemical damage. To achieve clinical translation of this device for cancer treatment a fundamental understanding of its optical, mechanical, and therapeutic capability must be performed. To demonstrate the potential of this technology the research team has organized the research goals in the following three objectives:
1) Mechanical Penetration: Design and fabricate a fiberoptic microneedle device (FMD) and evaluate its performance in penetrating ex vivo porcine skin using white light photographic imaging and load-cell testing 2) Optical/Fluid Delivery: Design and fabricate individual fiberoptic microneedles with solid cores to deliver light and hollow cores to deliver fluids containing nanoparticles, and evaluate their light/fluid delivery performance using brightfield and fluorescence imaging 3) Thermal/Therapeutic: Evaluate photothermal damage specificity of FMD light delivery alone or in combination with nanoparticles using thermal imaging and cell viability assays
All objectives will involve experimentation using cell-based tissue representative phantoms and ex vivo porcine skin. Each objective has associated milestones to be completed during each of the three years of this project. Completion of this work will provide preliminary results necessary to move forward with animal and eventually human clinical trials for cancer treatment using the FMD.
The proposed research will greatly advance development of FMD-mediated laser cancer therapies by providing an understanding of the optical, mechanical, and therapeutic capabilities of this technology. Using the FMD, nanoparticles and light may be delivered to specific target sites several millimeters beneath an epithelial surface via minimally-invasive fiberoptic microneedles. Due to selective absorption of optical radiation by the nanoparticles in the target tissue, the optical dose can be more precisely delivered, reducing unwanted collateral tissue damage and associated pain, and promoting faster wound healing. This project involves interdisciplinary experimentation and modeling of tissue mechanics (needle penetration), tissue optics (light transport), transport of nanomaterials, heat generation and transport, and cellular injury.
Long-range societal impact of this work will be improved quality of life for cancer patients. The FMD is an enabling technology for minimally-invasive detection and treatment of early stage, small epithelial cancers located a few millimeters under the tissue surface, such as melanoma, uterine, and esophageal cancer. Early stage detection and treatment of cancer is the key to enhanced survival and diminished morbidity. The FMD device is appropriately scaled for minimally invasive selective detection and treatment of early stage tumors. Furthermore, the FMD is well suited to deliver photosensitizing drugs or nanomaterials to increase the selective tumor destruction while maintaining the viability of the surrounding healthy tissue. The interdisciplinary nature of this project will provide opportunities for students from different scientific fields to gain experience in experimental design, engineering, imaging, and computational modeling. The PI is devoted to increasing the number of females and minorities within the engineering field through active participation in programs such as Multicultural Academic Opportunities Program (MAOP), and Center for the Enhancement of Engineering Diversity (CEED) at Virginia Tech. Funding from this proposal will allow recruitment of additional female and minority students to study in his biotransport and optics laboratory.
