The research for this project came at an important time as advanced manufacturing is driving toward future products and medically useful approaches in the United States. Biomanufacturing is a rapidly evolving field that will enable exciting advances. The responses of multicellular biology systems were very related to manufacturing for developing future therapies and diagnostics. While traditional approaches have made some progress, addressing these challenges with logical yet novel ideas led to significant insights for biological approaches and responses in the future. One goal of this proposal was to develop high throughput cell analysis approaches that allowed for the controlled application of reagents to 3D tissues for targeted cell collection. This was a multidisciplinary project involving Carnegie Mellon University and the University of Pittsburgh. The team was uniquely qualified for this project by virtue of its diverse strengths in multi-cellular systems, microfluidics, and cell and molecular biology. While this project was multidisciplinary in nature, the principal discipline of the project was biomedical engineering and advanced manufacturing. The unique contribution of this project rested in its multidisciplinary approach to the advancement of the understanding of biology, manufacturing, engineering, and multicellular response. As opposed to employing separate approaches for these multidisciplinary problems, the team developed a hybrid approach, which used the skills of an engineer to build devices merged with answering biological questions. This will have implications beyond advanced manufacturing for the diagnosis, understanding, and treatment of disease. Furthermore, by providing fundamental understanding, this research targeted to ensure the successful implementation of these ideas in academia, government, and industry.

The intellectual merit of this proposal was the development of a generalizable approach that will enable microfluidic based analysis of cells from within complex 3D tissues. This project produced a significant advancement in the targeted analysis of cells from tissues with a high throughput technology to use cells in cellular biomanufacturing as building blocks for other applications including diagnostic and therapeutic approaches. In the long term this approach will also be adapted to isolating other cells types from a variety of 3D tissues. The proposed interdisciplinary research combines complementary skill sets and research infrastructure of the research groups with expertise in microfluidics, cell biology, biomaterials, and imaging.

The broader impact of these studies included building an education and training pipeline for preparing future leaders in engineering and science. This was accomplished through work with K-12 students, undergraduate students, and graduate students. One major focus here was to develop a successful minority PhD program building off of successes over the past decade for minority PhDs. These efforts also included work with academically challenged public schools in Pennsylvania. In addition, work was extended through appointments in the Sloan Foundation Minority PhD program in continuing to build on diversity efforts.

The results from the research over this 2 year grant have been presented in more than 10 peer-reviewed archival journal publications, and have provided support for 2 PhD students. The work has also been presented at a variety of conferences including the Biomedical Engineering Society, the Biophysical Society, and the American Society of Mechanical Engineers International Mechanical Engineering Congress and Exposition. Graduate students involved in this project developed a combined biology, manufacturing, engineering, and material science background that have made them highly valuable in industry and academics.  In addition, the research of this project was fundamental, yet required an intuitive, hands-on understanding of biomedical engineering merged with advanced manufacturing.  This combination of skills provided them a unique training for a graduate-level project. Students in this program also benefited greatly from interactions with engineering and biology faculty. The graduation of these students helped address the growing industry and scientific need for multidisciplinary engineers, who are comfortable working in teams of diverse technical background.

Last Modified: 11/15/2018
Modified by: Philip R Leduc