IDBR: Development of Higher Eigenmode Ultrasound Bioprobe for Sub-Cellular Biological Imaging

Northwestern University, Evanston IL

Investigators

Abstract

There is an acute and timely need for innovative and non-invasive imaging modalities in biology, especially to identify early manifestation of disease state, and efficacy of potential cell-based therapeutics. This project at Northwestern University will help develop higher eigenmode "Ultrasound Bioprobe" for sub-cellular biological imaging. The objective of this project is to develop Ultrasound Bioprobe with higher order harmonics capabilities to detect and track subcellular defects at nanoscale resolution under physiological conditions. Anticipated applications will investigate the dynamics of endothelial cells under cellular transfection to develop potential therapeutics for acute lung injuries in the early stage. It will further be extended to study the progression of tumorous cells at onset of their development. In Ultrasound Bioprobe, the cantilever monitors the perturbation to the surface acoustic waves, especially their phase, which carry information about embedded or buried sub-structures reflected in the scattering of specimen acoustic waves due to the difference in their respective viscoelastic properties. Variations in the amplitude and phase of the bulk wave due to the presence of the sub-surface nanostructures/defects as well as the variations in near surface affect the amplitude and the phase of the difference frequency signal (beats) which is detected by cantilever. These variations are used to create spatial mappings generated by subsurface and near-surface features/defects. To realize these efforts requires a way to combine scanning probe microscopy hardware,functional electronics and its integration into an FPGA (field programmable gate arrays) for simultaneous generation and detection of multiple harmonics in scan using labVIEW codes. By leveraging the nanoscale resolution of scanning probe microscope and use of higher order harmonics, this innovative approach may provide a new way to perform sub-cellular biological imaging of living cells in close to real-time, uninhibited by traditionally cited challenges in electron microscopy methods that require chemically fixing of the cells or cryo preservation and conventional confocal/fluorescent microscopies that require fluorescent tags to image and have micro scale resolutionThe ability of the Ultrasound Bioprobe to detect features at nanometer scale has important implications to study the nanomechanics of human pulmonary artery endothelial cells which are transfected with plasmid. It will help understand how to regulate endothelial cell structural arrangements that result in the barrier function properties of the pulmonary vasculature and to assist therapeutics targets. The Broader Impact of the project promises to open new vistas in high resolution non-destructive and non-invasive imaging of biological and soft structures under physiologically viable conditions. The ultrasound bioprobe will be positioned to provide abroad user base with exposure to the developed technology. Once developed, the technology will be accessible to other institutions, broadening their user base to include life sciences. In undergraduate course material, the PI?s will use examples from this research project to highlight how integration of engineering and physical principles is incorporated into real biological research. The PI?s will promote the active participation of women and other minorities in science and participation in classroom visits to elementary schools through the Science Chicago program in Midwest and Chicago public institutions for broader audience. The education plan focuses on development of a teaching module in sub-cellular imaging which includes hand-on-laboratory demo and classroom tutorials. The educational objectives will be achieved by (a) providing hand-on, team experience to promote active and collaborative learning; (b) exposing promising students at the undergraduate level to research opportunities in emerging field of sub-cellular biological imaging, and (c) to recruit and retain traditionally under-represented students though MIN (Minority Internships in Nanotechnology) programs which provide opportunities for undergraduates to participate in hands-on research in the area of nanotechnology. Thsi award is co-funded by CBET/Biophotonics Program, and Instrument Development for Biological Research (IDBR).