The overall project objectives are to (i) develop an Micro-Opto-Electro-Mechanical System (MOEMS) device for resolving and detecting fluorescence emission from biological tissues and cells; (ii) provide knowledge and strategies about how spectroscopic micro-devices can be integrated in existing diagnostic instruments; and (iii) enable advanced, fully integrated platforms for biochemical assays and minimally-invasive medical diagnosis and surgery. The device will have broad applicability including diagnosis, localization and staging of cancer and other diseases, monitoring of therapeutic effects, spectroscopy/image guided biopsy and surgery. Because fluorescence spectroscopy is very sensitive to changes in functional and structural properties of molecules and molecular complexes in biological systems, fluorescence spectroscopy plays a key role on a broad area of biological and medical applications. Advances proposed here, using micro-fabrication techniques, allow construction of integrated spectroscopy micro-devices capable of real-time fluorescence measurements from tissues and cells. This will enable advances in miniature multifunctional instrumentation and synergy of diagnostic technologies. For example, integrating such device in endoscopes, biopsy probes, and surgical/monitoring devices will provide simultaneously information about biochemical and functional changes at the investigated side, thus the diagnostic capability of these instruments will be enhanced without altering their function and basic form. We propose to develop a MOEMS device consisting of a micro-fabricated dispersive system and photomultiplier that will replace the conventional monochromator and detector in a fluorescence spectroscopy apparatus and allow both steady-state and time-resolved (lifetime) measurements.
Specific aims i nclude: (1) To design, micro-fabricate, integrate and test a micro-monochromator (MMC). This is to be a multi-chip system including a series of key elements (piezoelectrically actuated cantilever with diffraction grating, mirrors and lenses). (2) To design, microfabricate, and demonstrate functionability of a multichannel plate photomultiplier (MM-MCP-PMT). The results of this R21 application will be a basis of knowledge sufficient to permit continued integration of the proposed MMC and MM-MCP-PMT into a compact MOEMS device in a future R01 application. This work will provide information about the spectroscopic performance (spectral resolution, sensitivity) and limitations of the MMC; and develop design solutions for an optimal MM-MCP-PMT. The knowledge gained will be used to improve the MOEMS design and to investigate pathways for further miniaturization of the electronics associated with the spectroscopic device. The device will provide the initial kernel for development of fully integrated miniature fluorescence spectroscopy devices and fluorescence-guided surgical/diagnostic micro-systems. The device will widely be applied to various biomedical instruments that require wavelength differentiation and selection.
|Sun, Yinghua; Phipps, Jennifer E; Meier, Jeremy et al. (2013) Endoscopic fluorescence lifetime imaging for in vivo intraoperative diagnosis of oral carcinoma. Microsc Microanal 19:791-8|
|Sun, Yinghua; Sun, Yang; Stephens, Douglas et al. (2011) Dynamic tissue analysis using time- and wavelength-resolved fluorescence spectroscopy for atherosclerosis diagnosis. Opt Express 19:3890-901|
|Sun, Yang; Chaudhari, Abhijit J; Lam, Matthew et al. (2011) Multimodal characterization of compositional, structural and functional features of human atherosclerotic plaques. Biomed Opt Express 2:2288-98|
|Lo, Joe; Chen, Shih-Jui; Fang, Qiyin et al. (2009) Performance of a diaphragmed microlens for a packaged microspectrometer. Sensors (Basel) 9:859-68|
|Sun, Yinghua; Phipps, Jennifer; Elson, Daniel S et al. (2009) Fluorescence lifetime imaging microscopy: in vivo application to diagnosis of oral carcinoma. Opt Lett 34:2081-3|
|Sun, Yinghua; Liu, Rui; Elson, Daniel S et al. (2008) Simultaneous time- and wavelength-resolved fluorescence spectroscopy for near real-time tissue diagnosis. Opt Lett 33:630-2|