Effect of Surface Nanotopography on Immunoaffinity Cell Capture in Microfluidic Devices

Abstract

Immunoaffinity microfluidic devices have recently become a popular choice to isolate specific cells for many applications. To increase cell capture efficiency, several groups have employed capture beds with nanotopography. However, no systematic study has been performed to quantitatively correlate surface nanopatterns with immunoaffinity cell immobilization. In this work, we controlled substrate topography by depositing close-packed arrays of silica nanobeads with uniform diameters ranging from 100 to 1150 nm onto flat glass. These surfaces were functionalized with a specific antibody and assembled as the base in microfluidic channels, which were then used to capture CD4+ T cells under continuous flow. It is observed that capture efficiency generally increases with nanoparticle size under low flow rate. At higher flow rates, cell capture efficiency becomes increasingly complex; it initially increases with the bead size then gradually decreases. Surprisingly, capture yield plummets atop depositions of some particle diameters. These dips likely stem from dynamic interactions between nanostructures on the substrate and cell membrane as indicated by roughness-insensitive cell capture after glutaraldehyde fixing. This systematic study of surface nanotopography and cell capture efficiency will help optimize the physical properties of microfluidic capture beds for cell isolation from biological fluids.

Effects of nanopillar array diameter and spacing on cancer cell capture and cell behaviors

“…In one previous study, dense silica bead (diameter ranges from 100 to1150 nm) were deposited closely onto a glass slide without any spacing, cell capture yield was only 1.2–1.6 times higher than that on a planar surface. 42 This result also indicates the spacing plays an important role in capture yield. On the contrary, increased nonspecific settlement may appear on sparse NP surface when the spacing is larger than 500 nm, i.e., diameter of filopodia.…”

Nanostructured substrates for isolation of circulating tumor cells

“…The finding indicates that anti-EpCAM coated surfaces cannot be used for capturing EpCAM − (negative) cancer cells. In another report, surface nanotopography of glass slides was carefully controlled over a large range by coating with silica beads and its influence on Jurkat cell capture was also studied [99]. Antibody modified silica beads ranging from 100 to 1150 nm in diameter were deposited on hydrophobically treated glass slides (Fig.…”

Synergistic Effects of Matrix Nanotopography and Stiffness on Vascular Smooth Muscle Cell Function

“…15,17,18 The ability to design and fabricate synthetic tissue scaffolds that can recapitulate the multiscale cellmatrix connections in vivo can (i) result in more biomimetic constructs for tissue repair and reconstruction, and (ii) create testbeds to perform molecular engineering and testing in more physiologically relevant platforms. This ability to alter the nanotopography of the fabricated surfaces, coupled with the integration of these surfaces with conventional multiwell plates, as in the current study, or in microfluidic platforms, [19][20][21] serves as an enabling tool for the development of nanolithography-based devices for multiscale, multipleinput, spatial control of cell homeostasis and function. While probing the ability of cells to respond to contact guidance has gained traction, 15,17,22 the mechanisms and pathophysiological consequences of such cues in various cell types are still under scrutiny.…”