The goal of this proposal is to design a novel surface that could significantly enhance rare cell capture efficacy and selectivity through synergistic research activities between Lehigh University and University of Pennsylvania, including a novel multi-scale computational model, fabrication of a 3D hierarchical surface, and a microfluidic testing platform. Specifically, we will design and fabricate a hierarchical surface consisting of patterned structures at two difference length scales: a micro-scale surface of ripples or herringbone structure and an array of nanoparticles or nanopillars. The micro-scale sinusoidal ripples and herringbone structures will generate micro-vortices to enhance cell-wall collision, provide larger adhesion area, avoid non-specific cell adhesion and possible cell damage, and enable accurate cell counting; the nanostructures will complement microvilli on cell membranes, thus, improve both interaction specificity and cell capturing efficiency.
Through a combined computational and experimental approach we expect that the proposed study will provide important insights for clinical isolation of rare cells from a blood sample. The multiscale computational modeling will be applied for the first time to guide the study of cell capture on various 3D surfaces with consideration of both hydrodynamics and adhesion dynamics. Various unique hierarchical surface designs will be integrated into a microfluidic device to validate the computational prediction and significantly improve rare cell capture performance. Specifically, we plan to: (1) Develop a multi-scale transport and adhesion dynamics model for cell capture process and perform cell capture analysis on surfaces of various designs. Characterize how various surface designs influence cell capture efficiency, throughput, and selectivity. (2) Fabricate a library of 3D hierarchical surface consisting of microscale wavy patterns (1D ripples and 2D herringbone structures) and an array of nanopillars or nanoparticles. (3) Perform microfluidic test on particle and cell capture using the fabricated hierarchical surface. Benchmark various surface designs in terms of capture efficiency, throughput, and selectively (Cheng and Liu). (4) Compare the experimental results with the computational model; optimize the model and re-engineer the hierarchical surface and the rare cell capture device.
The synergistic approach across diverse disciplines, including bioengineering, materials science, nanofabrication, and BioMEMS brings about a novel biomimetic approach to construct a lab-on-the-chip device for early cancer detection, thus making the project transformative. The research outcome will create a significant opportunity to excite the general public in bio-nanotechnology, thereby provoking and engaging their interest Science, Technology, Engineering, and Mathematics (STEM). In addition, this work will offer an effective tool to recruit and train students at all levels in a highly-integrated research and educational environment. The research outcome will be disseminated through a dedicated website and tool sharing at nanoHub for posting new discoveries in cell science, materials fabrication, and computational modeling frameworks developed from this project, as well as outreach to K-12 students.
