This Small Business Innovation Research (SBIR) Phase I project proposes to develop a handheld sub-cellular confocal microscope using Micro-Electro-Mechanical systems (MEMS) technologies for non-invasive and early detection of cancers. 85% of cancers arise in epithelium and occur in the topmost 200 microns of tissues, including oral, skin, cervical, and many other cancers. Epithelial cancers such as oral cancer at early stages are rarely painful and hard to detect without invasive biopsy or radiation-based imaging like CT scan. The proposed handheld microscope, consisting of confocal MEMS imaging scanners with mechanically tunable resolution and field-of-view (FOV), allows doctors to closely exam epithelial layers at multiple depths without mechanical cutting, and identify early signs of cancers through morphologic changes and alternations in tissue architectures. The tunability of the resolution and FOV is achieved by active micro-mechanical adjustment on-chip. A handheld prototype will be built to test the diagnostic capabilities by utilizing ex vivo tissue samples and measuring tissue morphology and used in future clinical trials to identify pre-cancer in vivo relative to the gold standard of histo-pathology.
The broader impact/commercial potential of this project is to enable a new class of clinical micro-imaging tools that can significantly improve early diagnosis of epithelial cancers leading towards individualized, minimally invasive treatment and improves long-term survival rates. Current diagnostic methods require recurring surgical biopsy of benign lesions and often detect malignant change too late for restorative treatment. The key innovation of this technology is that it translates confocal microscopy into in vivo application using miniature optics, optical fibers, tunable MEMS design and robust packaging technologies to provide clinicians and researchers a real-time 3D view of tissue cellular structure, without removal of tissue. This technology offers a potential breakthrough in non-invasive and radiation-free cancer diagnostics. The handheld scanner can not only be used to spot tumors at a very early stage and determine how far the cancer has progressed, it also can be used to monitor the tumor during treatment, and track the efficiency of therapy adopted, thus opening up a whole new opportunity to conquer cancers. The core technology builds on the strengths of the well-developed semiconductor industry and can potentially bring more intelligence to cancer imaging and lower healthcare cost.
The objective of this SBIR Phase I project was to develop a handheld sub-cellular confocal endoscope using Micro-Electro-Mechanical systems (MEMS) technologies for non-invasive and early detection of epithelial cancers. We have successfully executed the research tasks outlined in this Phase I project. We have developed high-reflectivity MEMS imaging scanners with mechanically tunable resonant frequency, and therefore the field-of-view (FOV) and frame rate tuning when applying the scanning in optical imaging. A novel design of the tunable MEMS scanner using localized heating of the torsion beam has been designed and fabricated. 10% of resonant frequency tuning was achieved which shows the effectiveness of the electrical current induced thermal tuning mechanism. A handheld confocal imaging handheld probe has been designed and fabricated for in-vivo imaging. For such miniaturized confocal system, significant software improvements have also been made to achieve high-quality imaging results. Through collaboration with the University of Texas Health Science Centerat San Antonio, we also conducted early clinical trials to test the diagnostic capabilities by utilizing ex vivo tissue samples, i.e. glass slides and gross tissues. The key findings resulting from our project include: Innovative design and feasibility testing of tunable scanner results in improved field-of-view (FOV) and frame rate tuning. Our miniaturized confocal imaging systems powered by the MEMS scanner proved to have imaging quality comparable to Olympus microscope, highlighting the potential of our technology to provide a more cost-effective confocal imaging system than those are currently on the market. Clinical trials and expert interviews suggested that applying our technology in surgical guide for breast and skin cancer surgery can yield in significant clinical value to improve quality of care, and position us with a promising commercialization pathway. This NSF SBIR project has not only successfully driven further innovation in MEMS technology, but also opened up opportunities to potentially improve cancer treatment and diagnostics and contribute to the efficiency of the healthcare system.
