Mechanical Stress Analysis of Microfluidic Environments Designed for Isolated Biological Cell Investigations

Abstract

Advancements in technologies for assessing biomechanics at the cellular level have led to discoveries in mechanotransduction and the investigation of cell mechanics as a biomarker for disease. With the recent development of an integrated optical tweezer with micron resolution particle image velocimetry, the opportunity to apply controlled multiaxial stresses to suspended single cells is available (Nève, N., Lingwood, J. K., Zimmerman, J., Kohles, S. S., and Tretheway, D. C., 2008, "The µPIVOT: An Integrated Particle Image Velocimetry and Optical Tweezers Instrument for Microenvironment Investigations," Meas. Sci. Technol., 19(9), pp. 095403). A stress analysis was applied to experimental and theoretical flow velocity gradients of suspended cell-sized polystyrene microspheres demonstrating the relevant geometry of nonadhered spherical cells, as observed for osteoblasts, chondrocytes, and fibroblasts. Three flow conditions were assessed: a uniform flow field generated by moving the fluid sample with an automated translation stage, a gravity driven flow through a straight microchannel, and a gravity driven flow through a microchannel cross junction. The analysis showed that fluid-induced stresses on suspended cells (hydrodynamic shear, normal, and principal stresses in the range of 0.02-0.04 Pa) are generally at least an order of magnitude lower than adhered single cell studies for uniform and straight microchannel flows (0.5-1.0 Pa). In addition, hydrostatic pressures dominate (1-100 Pa) over hydrodynamic stresses. However, in a cross junction configuration, orders of magnitude larger hydrodynamic stresses are possible without the influence of physical contact and with minimal laser trapping power.

Engineering of a synthetic quadrastable gene network to approach Waddington landscape and cell fate determination

“…Then, the supplied media was switched to the media added with Arabinose, AHL and aTc for another 18 hr. Media switching was controlled by adjusting the heights of the medium syringes relative to one another.However, cells treated with the three inducers demonstrate symptoms of significant stress and cell death, presumably due to photo toxicity compounded with flow-induced sheer stress and other mechanical stresses in the microenvironment (Kohles et al, 2009; Shen et al, 2014; Shemesh et al, 2015). Lower concentrations of three inducer combinations were also tested but yield no significant improvement of cells viability.…”

Two-Dimensional Modeling of Nanomechanical Strains in Healthy and Diseased Single-Cells During Microfluidic Stress Applications

“…Experimental stresses were recently applied to suspended, nonadhered microspheres and biological cells (radius, a=~10 μ m) [10,11]. The original stress analysis was applied to three separate flow conditions: (1) a uniform flow field generated by moving the fluid sample with a translation stage (500 μ m/ s freestream), (2) a gravity driven flow through a straight microchannel (460 μ m/ s freestream), and (3) a gravity driven flow through a microchannel cross-junction (750 μ m/s freestream and a shear rate of γ̇ =12.4 strain/ s).…”

“…A recent stress analysis was applied to experimental and theoretical flow velocity gradients around suspended cell-sized polystyrene microspheres in microfluidic environments representing the relevant spherical geometry of nonadhered, suspended osteoblasts, chondrocytes, and fibroblasts [10,11] as well as chondrons observed in situ [12]. That analysis identified very low levels of applied stresses available during creeping laminar flow within straight and cross-junction microfluidic channel arrangements with uniform and extensional flows, respectively.…”

Finite-Element Modeling of Viscoelastic Cells During High-Frequency Cyclic Strain

“…These investigations may involve cyclic stimulation with oscillating shear in microfluidic chambers [27,28,29,30], cyclic compression [31,32], vibration [24,33,34], or cyclic strain [23,35]. Strain is commonly introduced by stretching cell monolayers on flexible membranes, introducing either uniaxial [36,37,38,39], biaxial [40,41,42,43], or equibiaxial ( i.e.…”