Implantable Ultra-low Power VO2 MEMS Scanner based Surface-enhanced Raman Spectroscope for Wide-field Tumor Imaging in Free Moving Small Animals

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Every year, over 200,000 women are diagnosed with breast cancer which causes more than 40,000 deaths per year in the US. Tumor-targeting surface enhanced Raman scattering nanoparticles based multiplexed Raman spectroscopy has recently demonstrated great potentials to promote early and accurate cancer detection, which significantly impact patient's survival rates. Spectral fingerprints of Raman nanoparticles make it possible to study multiple cell surface biomarkers and analyze targeted drug delivery in breast cancer rat models. With long scanning time in slow speed, conventional Raman spectroscopy can only image ex-vivo tissue specimens or monitor small animals under anesthesia, which behave differently from free moving ones. There is an unmet need for an implantable Raman system, which performs in-vivo multiplexed wide-field imaging and longitudinal study on tumor, monitoring the dynamic response after drug delivery, and quantitatively study targeted nanoparticles for multiple biomarkers. This project will be focused on implantable thermal micro-scanner based Raman spectroscope for wide-field tumor-imaging in free moving breast cancer rat model. Societal impact will be significant, not only on scientific communities (cancer biology), but also on broader communities of energy science (solar cell inspection), pharmaceutical industry (drug screening). The scientific impact is to generate knowledge that will be significance to researchers in the field of implantable micro-system. The outcomes will yield next generation transformative devices to enable a comprehensive understanding of tumor development and targeted drug delivery. This project will provide educational opportunities for students to learn different disciplines and develop multiple skill sets. Outreach events will transform state-of-the-art technologies to educational resources that are more accessible to local K-12 schools and broader communities in greater Lansing area. The goal of this project is to overcome the fundamental limitations in miniaturized ultra-low power surface-enhanced Raman spectroscopy aimed for in-vivo wide-field tumor imaging in free moving rat. The research plan will be focused on developing an implantable microelectromechanical system based Raman spectroscopy for in-vivo monitoring and longitudinal study of tumor growth and nanoparticles based targeted drug delivery. To achieve this goal, an ultra-low power vanadium dioxide based self-sensing thermal monolithic micro-scanner will be developed for fast beam steering with large mirror deflection in two-dimensional raster scan manner, which enables wide-field spectroscopic imaging with large field-of-view. Novel micro-scale electroplating and molding techniques based mass-producible integration process will be developed for ultra-thin opto-mechanical devices, including the implantable Raman scan-head. In addition, an ultra-compact ultra-low power micro-scanner based Raman spectrometer will be developed based on single element near infra-red photomultiplier tube and a vanadium dioxide micro-scanner with on-chip grating. For interconnecting the scan-head with spectrometer and providing physiological recording, a compact small animal backpack with integrated physiology sensors on conformal surface, will be developed using stereolithography three-dimensional printing process. Finally, the platform will be characterized on free moving breast cancer rat model for acquiring Raman spectra from nanoparticles conjugated with anti-bodies specifically targeting over-expressed biomarkers. Although significant progress has been made in the Raman spectroscopy on biological tissue samples, molecularly targeted wide-field in-vivo multiplexed Raman imaging of tumor in free moving rat has not been demonstrated yet. Miniaturization of the scan-head and spectrometer with ultra-low power consumption is critical to implantable Raman system. The proposed implantable ultra-low power thermal micro-scanner enabled Raman imaging strategy will overcome the fundamental limitation in current Raman imaging modality that has urgent and unmet needs, such as higher sensitivity, scalable resolution, deeper penetration, shorter integration time.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.