High-speed microfluidic differential manometer for cellular-scale hydrodynamics

Abstract

We propose a broadly applicable high-speed microfluidic approach for measuring dynamical pressure-drop variations along a micrometer-sized channel and illustrate the potential of the technique by presenting measurements of the additional pressure drop produced at the scale of individual flowing cells. The influence of drug-modified mechanical properties of the cell membrane is shown. Finally, single hemolysis events during flow are recorded simultaneously with the critical pressure drop for the rupture of the membrane. This scale-independent measurement approach can be applied to any dynamical process or event that changes the hydrodynamic resistance of micro-or nanochannels.pressure measurement ͉ microcirculation ͉ hemolysis ͉ red blood cell ͉ membrane properties F luid motions at the micrometer scale are at the heart of many recent developments in microfabrication (1), separation processes (2), cellular-scale identifications (3), DNA sequencing (4), protein crystallization (5) and many basic transport pathways in plants (6), in the microcirculation (7), and specific to industrial processes. The main characteristics of these advances lie in the manipulation and understanding of the dynamics of ''soft'' objects such as polymers (8) (e.g., DNA), drops (9, 10), microemulsions (11), microfoams (12), cells (13), vesicles and microcapsules (14). In fact, the interaction of the flow with these deformable entities is a tool to further investigate the details of their mechanical properties and their structural features (e.g., the entropic elasticity of a polymer, the viscoelastic properties of a capsule, or the rheology of the liquid film between microbubbles in a foam). For the case of strong confinement offered by microchannels, the flow and shape of any close-fitting soft object is controlled by a competition among the properties of the objects, the fluid pressure, and the viscous stresses acting on the boundaries that resist the motion. The hydrodynamic resistance resulting from this fluid-structure interaction is reflected in a dynamical variation of the pressure drop along the channel during the flow and hence represents a crucial parameter to be measured.Nevertheless, rapid variations of pressure are very difficult to measure at the micrometer scale and below. Indeed, the difficulties do not originate from the lack of precision sensors commercially available or those described in the research literature (15). The problem is a subtle mix of pragmatism and technological limits. In addition to issues of dead volumes in standard pressure-measurement techniques (16-18) and those associated with interfacing microelectromechanical system devices to standard pressure gauges (19), existing techniques are simply difficult to implement [lasers, quadrant diodes, deformable membranes, multistep process of production (16-18)] and are unable to measure at millisecond rates the pressure changes in micrometer-scale flows. For instance, when a single red blood cell (RBC) enters a channel of 5 ϫ 5 m, the volume variation produced b...

Using a Multijunction Microfluidic Device To Inject Substrate into an Array of Preformed Plugs without Cross-Contamination: Comparing Theory and Experiments

“…Equation 3 predicts a maximum flow rate of substrate at which ΔP flow can still be overcome by P cap and formation of substrate droplets is prevented, Q max (m 3 /s). Similar to the largest working flow rate of the multiphase separation device, 1 this maximum flow is given by Q max = ( πR 3 γ ) ∕ (4μL ) (4) when cos θ = 1. We tested the influence of the μ and γ parameters on Q max in a device with R = 50 μm and L = 14000 μm (Figure 3).…”

Recent advances in microfluidic techniques for single-cell biophysical characterization

“…With the use of high-speed imaging or electrical impedance measurements, constriction-channel devices are capable of achieving a higher throughput than most other deformability measurement approaches. Due to these merits, constriction channels have been used to measure the deformability of RBCs, 22,23,[39][40][41][42][43][44] leukocytes 45 and cancer cells. 46,47 Due to the human capillary-like environment and the physiological relevance of RBC deformability, RBCs are mostly studied in the majority of existing constriction channel-based devices.…”

“…44 Despite the advantages of the constriction channel technique, cell volume and adhesion between the cell membrane and channel walls are coupled with cell deformability. Consequently, a longer transit time does not necessarily mean lower deformability since larger and stickier cells can also lead to a longer transit time.…”

A membrane-based microfluidic device for mechano-chemical cell manipulation

“…Despite the fact that conventional macroscopic assays for drug development are still widely used, microfluidic technology has attracted increasing interest in the past years (Nguyen et al 2013;Abkarian et al 2006;Dai et al 2010;Adamo et al 2012;Mao et al 2012;Ma et al 2009). …”