Single cell rheometry with a microfluidic constriction: Quantitative control of friction and fluid leaks between cell and channel walls

Abstract

We report how cell rheology measurements can be performed by monitoring the deformation of a cell in a microfluidic constriction, provided that friction and fluid leaks effects between the cell and the walls of the microchannels are correctly taken into account. Indeed, the mismatch between the rounded shapes of cells and the angular cross-section of standard microfluidic channels hampers efficient obstruction of the channel by an incoming cell. Moreover, friction forces between a cell and channels walls have never been characterized. Both effects impede a quantitative determination of forces experienced by cells in a constriction. Our study is based on a new microfluidic device composed of two successive constrictions, combined with optical interference microscopy measurements to characterize the contact zone between the cell and the walls of the channel. A cell squeezed in a first constriction obstructs most of the channel cross-section, which strongly limits leaks around cells. The rheological properties of the cell are subsequently probed during its entry in a second narrower constriction. The pressure force is determined from the pressure drop across the device, the cell velocity, and the width of the gutters formed between the cell and the corners of the channel. The additional friction force, which has never been analyzed for moving and constrained cells before, is found to involve both hydrodynamic lubrication and surface forces. This friction results in the existence of a threshold for moving the cells and leads to a non-linear behavior at low velocity. The friction force can nevertheless be assessed in the linear regime. Finally, an apparent viscosity of single cells can be estimated from a numerical prediction of the viscous dissipation induced by a small step in the channel. A preliminary application of our method yields an apparent loss modulus on the order of 100 Pa s for leukocytes THP-1 cells, in agreement with the literature data. V C 2013 AIP Publishing LLC [http://dx

Constriction Channel Based Single-Cell Mechanical Property Characterization

“…To address this issue, a few studies have been conducted to model the cellular entry process into the constriction channel which can translate these raw parameters into intrinsic cellular mechanical parameters such as Young's Modulus and Cortical Tension [35,36,[45][46][47]51,52]. Ma et al, are pioneers in this field and they used a Newtonian liquid drop to model a RBC where the cell deformability is indicated by a persistent cortical tension of the cell membrane (see Figure 6) [35,46].…”

“…By combining measured instantaneous aspiration length and transitional aspiration length with these obtained from numerical simulations, Einstantaneous of these two cells types were quantified as 3.48 ± 0.86 kPa (A549 cells, n = 199) and 2.99 ± 0.38 kPa (95C cells, n = 164) (see Figure 7b). In addition, Theodoly et al, modelled the cellular entry process into the constriction channel with the effects of friction and leakage taken into consideration [51]. As a follow-up study, Chen et al, used a visco-hyperelastic solid to model a tumor cell using ABAQUS based numerical simulations where cell-channel wall frictions were modeled using a simple Coulomb law (see Figure 7) [47].…”

Trends in characterizing single cell's stiffness properties

“…Since the concept of MA is well translated into microfluidic, there are many previous works reported on studying of kinetic of cell shape deformation during entry, cell contour tracking [58] and nucleus deformation [59]. Works by Preira et al in 2013 implemented successive constrictions whereby the first constriction used only to clog the leukocytes without the presence of driving fluid and the second narrower gauge was used for quantitative measurement of force, deformation, and velocity [60]. In 2012, Guo et al proposed a ratchet mechanism to study asymmetry in the force required to deform single cells.…”

Influence of hydrodynamics on the growth kinetics of glass-adhering Pseudomonas putida cells through a parallel plate flow chamber

“…For instance, and among existing works, Preira et al 5 designed a microfluidic device to a) Author to whom correspondence should be addressed. measure the rheological properties of cells submitted to a flow-induced shear stress.…”