Frequency-induced morphology alterations in microconfined biological cells.

Low-intensity therapeutic ultrasound has demonstrated an impetus in bone signaling and tissue healing for decades now. Though this technology is clinically well proven, still there are breaches in studies to understand the fundamental principle of how osteoblast tissue regenerates physiologically at the cellular level with ultrasound interaction as a form of acoustic wave stimuli. Through this article, we illustrate an analysis for cytomechanical changes of cell membrane periphery as a basic first physical principle for facilitating late downstream biochemical pathways. With the help of in situ single-cell direct analysis in a microfluidic confinement, we demonstrate that alteration of low-intensity pulse ultrasound (LIPUS) frequency would physically perturb cell membrane and establish inherent cell oscillation. We experimentally demonstrate here that, at LIPUS resonance near 1.7 MHz (during 1-3 MHz alteration), cell membrane area would expand to 6.85 ± 0.7% during ultrasound exposure while it contracts 44.68 ± 0.8% in post actuation. Conversely, cell cross-sectional area change (%) from its previous morphology during and after switching off LIPUS was reversibly different before and after resonance. For instance, at 1.5 MHz, LIPUS exposure produced 1.44 ± 0.5% expansion while in contrast 2 MHz instigates 1.6 ± 0.3% contraction. We conclude that alteration of LIPUS frequency from 1-3 MHz keeping other ultrasound parameters like exposure time, pulse repetition frequency (PRF), etc., constant, if applied to a microconfined biological single living cell, would perturb physical structure reversibly based on the system resonance during and post exposure ultrasound pulsing. We envision, in the near future, our results would constitute the foundation of mechanistic effects of low-intensity therapeutic ultrasound and its allied potential in medical applications. Graphical Abstract Frequency Dependent Characterization of Area Strain in Cell Membrane by Microfluidic Based Single Cell Analysis.

Formation of Blood Droplets: Influence of the Plasma Proteins.

Blood is a complex multiphase fluid exhibiting pronounced shear-thinning and viscoelastic behavior. By studying the formation of blood droplets through simple dripping, we observe blood-drop detachment following a neck formation and subsequent thinning until breakup, similar to that of other liquids. Our experimental findings reveal that it exhibits two distinct modes of neck evolution characteristics; one mode corresponds to incessant collapsing of the liquid neck, whereas the other mode correlates thinning of an extended long thread leading to the breakup. We show that the two modes of neck evolution closely follow the theory of pinch-off for shear-thinning and viscoelastic fluids independent of hematocrit concentration in the range of healthy individuals. Furthermore, we observe that the relaxation time scales are very similar to that of plasma; this explains the key role of plasma proteins to blood rheology. We envision that our results are likely to bear far-reaching implications in understanding the contribution of plasma proteins to the rheology of blood and theory of drop formation of complex non-Newtonian fluids.

Droplet migration characteristics in confined oscillatory microflows.

We analyze the migration characteristics of a droplet in an oscillatory flow field in a parallel plate microconfinement. Using phase field formalism, we capture the dynamical evolution of the droplet over a wide range of the frequency of the imposed oscillation in the flow field, drop size relative to the channel gap, and the capillary number. The latter two factors imply the contribution of droplet deformability, commonly considered in the study of droplet migration under steady shear flow conditions. We show that the imposed oscillation brings an additional time complexity in the droplet movement, realized through temporally varying drop shape, flow direction, and the inertial response of the droplet. As a consequence, we observe a spatially complicated pathway of the droplet along the transverse direction, in sharp contrast to the smooth migration under a similar yet steady shear flow condition. Intuitively, the longitudinal component of the droplet movement is in tandem with the flow continuity and evolves with time at the same frequency as that of the imposed oscillation, although with an amplitude decreasing with the frequency. The time complexity of the transverse component of the movement pattern, however, cannot be rationalized through such intuitive arguments. Towards bringing out the underlying physics, we further endeavor in a reciprocal identity based analysis. Following this approach, we unveil the time complexities of the droplet movement, which appear to be sufficient to rationalize the complex movement patterns observed through the comprehensive simulation studies. These results can be of profound importance in designing droplet based microfluidic systems in an oscillatory flow environment.

Scaling regimes of thermocapillarity-driven dynamics of confined long bubbles: Effects of disjoining pressure.

During thermocapillary transport of a confined long bubble, we unveil the existence of a contrary-to-the-conventional disjoining-pressure-dominant scaling regime characterizing the dynamics of the thin liquid film engulfed between the bubble interface and the channel surface. Such a regime is realized for the limitingly small magnitude of the Marangoni stress (surface tension gradient) when the separating liquid region reaches an ultrathin dimension. Over this regime, we witness a severe breakdown of the seemingly intuitive scaling arguments based on the balance of viscous and capillary forces. Starting from competent balance criteria, we uncover the characteristic length scales involved, leading towards obtaining the new consistent scaling laws of the disjoining-pressure-dominant regime, in a simple closed form analytical fashion. Our scaling estimations are substantiated by full-scale numerical simulations of the pertinent thin-film equations. These new scaling laws appear to be convenient for implementing as a fundamental design basis for multiphase microfluidic systems.

Spreading of a droplet over a nonisothermal substrate: multiple scaling regimes.

We envisage the spreading behavior of a two-dimensional droplet under a thin-film-based paradigm, under a perfect wetting condition, while the droplet is placed over a nonisothermal substrate. Starting from the onset of thin-film behavior (or equivalently beyond the inertia-dominated initial stage), we identify the existence of mutually contrasting multiple scaling regimes defining the spreading behavior at different time scales. This is attributable to the time-stage-wise upsurge of capillarity or thermocapillarity over the other. In particular, the spreading behavior is characterized by the foot-width (w) evolution with time (t) in a power-law fashion w ∼ t(α), with α being the spreading exponent, defining the rate of spreading. Following pertinent thin-film and subsequent similarity analysis, we identify different asymptotes of α over disparate temporal scales, leading to the characterization of different scaling regimes over the entire spreading event starting from the inception of thin-film behavior. Reported literature data are found to correspond well to the present interpretations and estimations.

Influence of disjoining pressure on the dynamics of steadily moving long bubbles inside narrow cylindrical capillaries.

We study the influence of disjoining pressure for moving long bubbles inside cylindrical capillaries. Towards that end, consistent thin-film equations, for the annular region separating the bubble from the channel surface, are presented with specific emphasis on three different attributes: (a) the van der Waals interaction, formalized by the classical Lifshitz form of disjoining pressure; (b) the nonuniformity in film thickness, accommodated by the necessary corrections in the disjoining pressure; and (c) the electrostatic component of disjoining pressure, reminiscent of the electrostatic interactions in the presence of surface charges. The present thin-film analysis appositely uncovers the existence and the breakdown of the two-thirds power law for minimum film thickness behavior. This is attributed to the alteration in the characteristic length scales governing the underlying physics, as quantitatively established by our consistent scaling analysis. In the breakdown regimes, the characteristic length scales are found to be composed of the suitable combinations of the capillary number and the physics driven intrinsic length scales. The characteristics of the breakdown regime reported by us appear to match excellently with reported experimental data in the low capillary number regime. Towards unveiling the possible implications of slope and curvature dependence of disjoining pressure, our analysis reveals that the consequent correction term endorses an order two-thirds power of the capillary number contribution without alerting the governing length scales. The subsequent asymptotic analysis reveals that this correction may be neglected to the leading order approximation. Finally, we consider the electrostatic component of the disjoining pressure which may be realized in the presence of surface charges. Our analysis reveals that the significance of the electrostatic interaction is realized over a very small capillary number regime, leading towards the departure from the two-thirds power law type behavior. Reasonably good agreement is obtained with reported experimental data over this regime.

Transient dynamics of confined liquid drops in a uniform electric field.

We analyze the effect of confinement on the transient dynamics of liquid drops, suspended in another immiscible liquid medium, under the influence of an externally applied uniform dc electric field. For our analysis, we adhere to an analytical framework conforming to a Newtonian-leaky-dielectric liquid model in the Stokes flow regime, under the small deformation approximation. We characterize the transient relaxation of the drop shape towards its asymptotic configuration, attributed by the combined confluence of the charge-relaxation time scale and the intrinsic shape-relaxation time scale. While the former appears due to the charge accumulation process on the drop surface over a finite interval of time, the genesis of the latter is found to be intrinsic to the hydrodynamic situation under consideration. In an unbounded condition, the intrinsic shape-relaxation time scale is strongly governed by the viscosity ratio, defined as the ratio of dynamic viscosities of the droplet and the background liquid. However, when the wall effects are brought into consideration, the combined influence of the relative extent of the confinement and the intrinsic viscosity effects, acting in tandem, alter this time scale in a rather complicated and nontrivial manner. We reveal that the presence of confinement may dramatically increase the effective viscosity ratio that could have otherwise been required in an unconfined domain to realize identical time-relaxation characteristics. We also bring out the alterations in the streamline patterns because of the combinations of transient and confinement effects. Thus, our results reveal that the extent of fluidic confinement may provide an elegant alternative towards manipulating the transient dynamics of liquid drops in the presence of an externally applied electric field, bearing far-ranging consequences towards the design and functionalities of several modern-day microfluidic applications.

Controlled splitting and focusing of a stream of nanoparticles in a converging-diverging microchannel.

We demonstrate the potential of a converging-diverging microchannel to split a stream of nanoparticles towards the interfacial region of the dispersed and the carrier phases, introduced through the middle inlet and through the remaining two inlets respectively, while maintaining a low Reynolds number limit (<10) for the flow of both phases. In addition to the splitting of passive tracer particles, such as polystyrene beads as used herein, the present setup has the potential to be utilized for a controlled reaction and thereby the separation of products towards an intended location, as observed from the experimentation with silver-nanoparticles and hydrogen-peroxide solution. Moreover, the microscale dimension of the channel allows controlled deposition of the reaction product over the bottom surface of the channel, allowing the possibility of bottom-up fabrication of microscale features. We unveil the underlying hydrodynamics that lead to such behaviours through numerical simulations, which are consistent with the experimental observations. The phenomenological features are found to be guided by the splitting of the intrinsic streamlines conforming to the flow geometry under consideration.