We have carried out a detailed study of the motion of particles driven by a constant external force over a landscape consisting of a periodic potential corrugated by a small amount of spatial disorder. We observe anomalous behavior in the form of subdiffusion and superdiffusion and even subtransport over very long time scales. Recent studies of transport over slightly random landscapes have focused only on parameters leading to normal behavior, and while enhanced diffusion has been identified when the external force approaches the critical value associated with the transition from locked to running solutions, the regime of anomalous behavior had not been recognized. We provide a qualitative explanation for the origin of these anomalies. Solid state surfaces frequently present periodic potentials marred by some disorder. Herein we show that an overdamped particle moving over such a potential in one dimension (1D) may exhibit anomalous behavior in the form of superdiffusion, subdiffusion, and even subtransport. Although we cannot prove that these are steady state regimes, our numerical simulation data show them to be present over time spans of several orders of magnitude.That diffusion of particles over both periodic and random surfaces lead to some forms of anomalous behavior is of course well known and continues to attract a great deal of attention both theoretically and experimentally [1][2][3][4][5][6][7][8][9][10]. In periodic potentials with low friction, extremely long (in time) dispersionless transport regimes can be observed when forces exceed a critical force [6]. Moreover, in these same systems, in both overdamped and underdamped regimes, the diffusion coefficient versus the applied force presents a pronounced peak around the critical force that allows the coexistence of locked and running states [1,[4][5][6][7]. The The enhancement is quantitatively larger than the free particle diffusion coefficient. This behavior has been observed experimentally when tracking the motion of colloidal spheres through a periodic potential created with optical vortex traps [9].The enhancement of the diffusion coefficient is even more pronounced when disorder is also present [9]. This phenomenon has been tested by numerical simulations on a surface in which a small amount of spatial disorder in the form of a random potential is added to the periodic potential [10]. Dramatic diffusive enhancement occurs even for very small amounts of disorder, e.g., when the amplitude of the random contribution of the potential is as small as ∼ 5% of that of the periodic contribution.Although dramatic, diffusive enhancement turns out to be only a limited aspect of the story because it is not the only manifestation of disorder. Here we present a range of additional anomalous transport and diffusion phenomena arising from weak disorder that have not been previously noted. Our model and the behaviors it exhibits are inspired by [9,10]. We consider the overdamped motion of identical noninteracting Brownian particles moving in a 1D potential la...

Droplet based microfluidic systems have been shown to be most valuable in biology and chemistry research. However droplet modulation and manipulation requires still further improvement in order to make this technology feasible particularly for biological applications. On demand generation of droplets and droplet synchronization, which is crucial for coalescence, remain largely unanswered. The present study describes a simple and robust droplet generator based on a piezoelectric actuator which is integrated into a microfluidic device. The droplet generator is able to independently control the droplet size, rate of formation and distance between droplets. Moreover, the droplet uniformity is especially high, deviating from the mean value by less than 0.3%. The cross flow and T-junction configurations are tested and show no significant differences, yet the inlet to main channel ratio is found to be important. As this ratio increases, droplets tend to be generated in bursts instead of individually. The physical mechanisms involved are discussed, providing insight into optimized design of such systems.

The unlimited proliferative and differentiative capacities of embryonic stem cells (ESCs) are tightly regulated by their microenvironment. Local concentrations of soluble factors, cell-cell interactions and extracellular matrix signaling are just a few variables that influence ESC fate. A common method employed to induce ESC differentiation involves the formation of cell aggregates called embryoid bodies (EBs), which recapitulate early stages of embryonic development. EBs are normally formed in suspension cultures, producing heterogeneously shaped and sized aggregates. The present study demonstrates the usage of a microfluidic traps system which supports prolonged EB culturing. The traps are uniquely designed to facilitate cell capture and aggregation while offering efficient gas/nutrients exchange. A finite element simulation is presented with emphasis on several aspects critical to appropriate design of such bioreactors for ESC culture. Finally, human ESC, mouse Nestin-GFP ESC and OCT4-EGFP ESCs were cultured using this technique and demonstrated extended viability for more than 5 days. In addition, EBs developed and maintained a polarized differentiation pattern, possibly as a result of the nutrient gradients imposed by the traps bioreactor. The novel microbioreactor presented here can enhance future embryogenesis research by offering tight control of culturing conditions.

Complex biological systems in nature comprise cells that act collectively to solve sophisticated tasks. Synthetic biological systems, in contrast, are designed for specific tasks, following computational principles including logic gates and analog design. Yet such approaches cannot be easily adapted for multiple tasks in biological contexts. Alternatively, artificial neural networks, comprised of flexible interactions for computation, support adaptive designs and are adopted for diverse applications. Here, motivated by the structural similarity between artificial neural networks and cellular networks, we implement neural-like computing in bacteria consortia for recognizing patterns. Specifically, receiver bacteria collectively interact with sender bacteria for decision-making through quorum sensing. Input patterns formed by chemical inducers activate senders to produce signaling molecules at varying levels. These levels, which act as weights, are programmed by tuning the sender promoter strength Furthermore, a gradient descent based algorithm that enables weights optimization was developed. Weights were experimentally examined for recognizing 3 × 3-bit pattern.

Microfluidic bioreactors have been shown valuable for various cellular applications. The use of micro-wells/grooves bioreactors, in which micro-topographical features are used to protect sensitive cells from the detrimental effects of fluidic shear stress, is a promising approach to culture sensitive cells in these perfusion microsystems. However, such devices exhibit substantially different fluid dynamics and mass transport characteristics compared to conventional planar microchannel reactors. In order to properly design and optimize these systems, fluid and mass transport issues playing a key role in microscale bioreactors should be adequately addressed. The present work is a parametric study of micro-groove/micro-well microchannel bioreactors. Operation conditions and design parameters were theoretically examined via a numerical model. The complex flow pattern obtained at grooves of various depths was studied and the shear protection factor compared to planar microchannels was evaluated. 3D flow simulations were preformed in order to examine the shear protection factor in micro-wells, which were found to have similar attributes as the grooves. The oxygen mass transport problem, which is coupled to the fluid mechanics problem, was solved for various groove geometries and for several cell types, assuming a defined shear stress limitation. It is shown that by optimizing the groove depth, the groove bioreactor may be used to effectively maximize the number of cells cultured within it or to minimize the oxygen gradient existing in such devices. Moreover, for sensitive cells having a high oxygen demand (e.g., hepatocytes) or low endurance to shear (e.g., human embryonic stem cells), results show that the use of grooves is an enabling technology, since under the same physical conditions the cells cannot be cultured for long periods of time in a planar microchannel. In addition to the theoretical model findings, the culture of human foreskin fibroblasts in groove (30 microm depth) and well bioreactors (35 microm depth) was experimentally examined at various flow rates of medium perfusion and compared to cell culture in regular flat microchannels. It was shown that the wells and the grooves enable a one order of magnitude increase in the maximum perfusion rate compared to planar microchannels. Altogether, the study demonstrates that the proper design and use of microgroove/well bioreactors may be highly beneficial for cell culture assays.