IDR: Nanoplasmonic sensing for dynamic cell-based biomolecular assays

Lehigh University, Bethlehem PA

Investigators

Abstract

1014957 Bartoli The successful differentiation and maturation of precursor cells is a major challenge in biomedicine, and is critical to the preparation of cells and tissue for transplantation. While traditional approaches to in vitro transformation have made many advances, progress towards engineering cells for transplantation is severely limited due to the inability to effectively mimic in vivo developmental conditions, including material substrates, dynamic sensing of metabolic changes, and feedback control that is characterized by up or down-regulation of critical genes required for successful maturation of cells. Developing "real-time" tools to sense and manipulate the dynamics of cell signaling processes through their secretome will open new research doors in a variety of areas, including tissue regeneration, in vivo cell therapeutics, pharmaceutical drug testing in vitro, and experimental cell biology. Intellectual Merit The long-term goal of this research is to create an integrated microfluidic biosensing system that is capable of highly sensitive, real-time, label-free, sensing of dynamic live-cell secretions, and that provides feedback-based cell stimulation to induce neuronal differentiation in the P19 cells and C17.2 neural progenitor cell lines selected for study. One of the fundamental features of this platform is a promising new class of nanoplasmonic interferometric biosensors under study here to achieve bold advances in on-chip surface plasmon resonance (SPR) bioaffinity sensing. Novel cell-culture interfaces will be designed to mimic in vivo cellular microenvironments, using in situ soluble signaling agents and immobilized biochemical cues such as surface-bound extracellular matrix ligands to stimulate cells and modulate neuronal differentiation. The novel nanoplasmonic sensing elements and cell-culture microenvironment will be integrated into a single microfluidic platform, and employed for real-time detection of dynamic secretion processes, for eventual in situ interactive cell stimulation, all key to cell fate control and neural tissue engineering. This interdisciplinary research should push the frontiers of multiple engineering disciplines in the areas of optical sensing, nanoplasmonics, biointerface design, nanofabrication, microfluidics, cell-based tissue engineering, and lab-on-a-chip technology. It will require the synergy of experts from several different engineering disciplines, including electrical engineering, bioengineering, materials science and engineering, and chemical engineering, and will significantly advance fundamental knowledge in multiple engineering areas. Ultimately, this research seeks to address a long-standing grand challenge in biomedicine, which if successfully met could have enormous long-term impact on health care and our national needs. This research has the potential to be transformative in creating unprecedented interactive sensing capabilities that can help overcome fundamental barriers to understanding the dynamics of cell differentiation. It provides a highly sensitive, integrated microfluidic sensing platform enabling real-time detection and control of dynamic secretion processes during neuronal differentiation. This understanding can lead to new advances in the area of cell transplantation, pharmaceutical research, and biomedical therapies, enormously impacting health care and society. Broader Impacts: Although this research will focus primarily on affinity-based nanoplasmonic biosensing of live-cell secretions, the eventual realization of an integrated platform for biosensing and actuation would have broad societal impact, and lead to new advances in diverse of engineering disciplines. This interdisciplinary research provides excellent opportunities for undergraduate and graduate student training, giving them experience in laboratories spanning several engineering disciplines. The research will contribute to new course development and directly impact the undergraduate curriculum. Findings will be broadly disseminated through publications in peer-reviewed journals, student presentations at national meetings, and web-based materials. The educational plan includes K-12 outreach programs to attract talented students to engineering and mentoring future scientists and engineers from underrepresented groups. This research directly impacts Lehigh's Bioengineering program, half of whose students are female, providing a promising venue for achieving a more diverse pool of talented students and meeting the nation's workforce needs.