Project Summary Guigen Liu, Ph.D., is a mechanical and optical engineer whose overarching career goal is to develop and translate optical fiber based biomedical optical imaging and sensing technologies. The research, entitled “Four- dimensional multi-modality microimaging-microdevice system for high throughput drug screening in vivo”, combines the advanced optical microimaging system with an emerging microdevice, which has the huge potential impact on drug development, individualized health care, and fundamental biomedical research. Candidate: Dr. Liu is an Instructor at the Radiology Department of Brigham and Women’s Hospital, Harvard Medical School. During his previous postdoctoral training, he and colleagues pioneered a silicon-tipped fiber- optic sensing platform featuring high speed and high resolution, which earned the 2015 Alan Berman Research Publication Award from the U.S. Naval Research Laboratory. While Dr. Liu has shown a successful track of record in engineering, his training in biomedical research is limited. Through the career development plans: 1) Gain more experience in two-photon fluorescence and Raman microimaging; 2) Learn to design and implement the microimaging-microdevice system; 3) Establish in vivo drug delivery and tissue response testing skills; and 4) Enhance leadership and career development skills, Dr. Liu will launch his independent career in the new field. Mentors/Environment: Dr. Liu has assembled a strong team of mentors to guide him through the proposed training and research activities. The proposed career development plan includes the rich resources available through Brigham & Women’s Hospital and Harvard Medical School, the Tearney Laboratory at the Wellman Center for Photomedicine, and the Laser Biomedical Research Center at Massachusetts Institute of Technology. Research: The research seeks to build an in situ multi-modality optical histological laboratory for the biomedical microdevice, through four specific research aims: 1) To implement quantitative 4D multi-color two-photon fluorescence microimaging; 2) To test drug efficacy in vivo using the 4D two-photon fluorescence MI-MD system; 3) To develop label-free MI-MD system using Raman microscopy; and 4) To investigate microimaging through long and flexible GRIN probes. Completion of these aims will push the microdevice a big step toward potential clinical adoptions in the future. Summary: Innovation of the proposed research is the integration of 3D microimaging and microdevice for 4D testing of drug efficacy and tissue response in vivo, which will meet the pressing needs of high throughput drug screening. The candidate has identified a group of experts who provide complementary training and mentoring on all the aspects for him to complete the proposed research and develop an independent research career.

Project Narrative The standard-of-care way in clinical oncology to evaluate the drug response of a tumor is through in vitro and ex vivo protocols done on cells or tissues excised from the live tumor, which is incapable of investigating many important and often critical events that only occur in vivo. The proposed multi-modality microimaging-microdevice (MI-MD) system provides such a technology for high throughput testing of drug response in vivo, without the need to excise any tissues from the native tumor. The MI-MD system to be developed in this project will have high potential impacts on drug development, individualized health care, and fundamental biomedical research.