Nonuniform evaporation from sessile droplets induces radial convection within the drop, which produces the well-known "coffee-ring" effect. The evaporation also induces a gradient in temperature and consequently a gradient in surface tension, generating a Marangoni flow. Here we investigate theoretically and experimentally the thermal Marangoni flow and establish criteria to gauge its influence. An asymptotic analysis indicates that the direction of the flow depends on the relative thermal conductivities of the substrate and liquid, k_{R} identical withk_{S}/k_{L}, reversing direction at a critical contact angle over the range 1.45

Adenosine triphosphate (ATP) is a regulatory molecule for many cell functions, both for intracellular and, perhaps less well known, extracellular functions. An important example of the latter involves red blood cells (RBCs), which help regulate blood pressure by releasing ATP as a vasodilatory signaling molecule in response to the increased shear stress inside arterial constrictions. Although shear-induced ATP release has been observed widely and is believed to be triggered by deformation of the cell membrane, the underlying mechanosensing mechanism inside RBCs is still controversial. Here, we use an in vitro microfluidic approach to investigate the dynamics of shear-induced ATP release from human RBCs with millisecond resolution. We demonstrate that there is a sizable delay time between the onset of increased shear stress and the release of ATP. This response time decreases with shear stress, but surprisingly does not depend significantly on membrane rigidity. Furthermore, we show that even though the RBCs deform significantly in short constrictions (duration of increased stress <3 ms), no measurable ATP is released. This critical timescale is commensurate with a characteristic membrane relaxation time determined from observations of the cell deformation by using high-speed video. Taken together our results suggest a model wherein the retraction of the spectrin-actin cytoskeleton network triggers the mechanosensitive ATP release and a shear-dependent membrane viscosity controls the rate of release. mechanotransduction ͉ microfluidic ͉ RBCsA s the central component of the human circulatory system, RBCs have evolved highly specific mechanisms for responding to variations in the local environment. One key but poorly understood response mechanism involves the release of ATP to the extracellular space, which occurs in response to small changes in pH (1), oxygen concentration (2) or osmotic pressure (3). Although ATP is well known as the energy source for intracellular functions, extracellular ATP plays an important role as a signaling molecule in a variety of physiological processes. For example, the ATP released from RBCs helps regulate vascular tone by binding with purigenic receptors on endothelial cells, which then respond by releasing nitric oxide, a potent vasodilator, into the surrounding smooth muscle cells (1, 4-6). In addition, a variety of diseases are linked to impaired ATP release from RBCs, including cystic fibrosis (7), pulmonary hypertension (8), and diabetes (9, 10). Furthermore, extracellular ATP is known to inhibit growth of breast and lung tumors (11,12) and plays a role in the inflammation response to wounds (13). Knowledge of the circumstances under which RBCs release ATP is crucial for designing effective therapeutic strategies.A fundamental characteristic of RBCs is that they regularly encounter variations in hydrodynamic shear stress, especially on entering or exiting arterioles and capillaries (14). A mounting body of evidence suggests that RBCs respond to these variations in shear stress b...

Dripping and jetting regimes in microfluidic multiphase flows have been investigated extensively, and this review summarizes the main observations and physical understandings in this field to date for three common device geometries: coaxial, flow-focusing and T-junction. The format of the presentation allows for simple and direct comparison of the different conditions for drop and jet formation, as well as the relative ease and utility of forming either drops or jets among the three geometries. The emphasis is on the use of drops and jets as templates for microparticle and microfiber syntheses, and a description is given of the more common methods of solidification and strategies for achieving complex multicomponent microparticles and microfibers.

The detection of single nuclear spins is an important goal in magnetic resonance spectroscopy. Optically detected magnetic resonance can detect single nuclear spins that are strongly coupled to an electron spin, but the detection of distant nuclear spins that are only weakly coupled to the electron spin has not been considered feasible. Here, using the nitrogen-vacancy centre in diamond as a model system, we numerically demonstrate that it is possible to detect two or more distant nuclear spins that are weakly coupled to a centre electron spin if these nuclear spins are strongly bonded to each other in a cluster. This cluster will stand out from other nuclear spins by virtue of characteristic oscillations imprinted onto the electron spin decoherence profile, which become pronounced under dynamical decoupling control. Under many-pulse dynamical decoupling, the centre electron spin coherence can be used to measure nuclear magnetic resonances of single molecules. This atomic-scale magnetometry should improve the performance of magnetic resonance spectroscopy for applications in chemical, biological, medical and materials research, and could also have applications in solid-state quantum computing.

Summary Energy production in the brain depends almost exclusively on oxidative metabolism. Neurons have small energy reserves and require a continuous supply of oxygen (O2). It is therefore not surprising that one of the hallmarks of normal brain function is the tight coupling between cerebral blood flow and neuronal activity. Since capillaries are embedded in the O2-consuming neuropil, we have here examined whether activity-dependent dips in O2 tension drive capillary hyperemia. In vivo analyses showed that transient dips in tissue O2 tension elicit capillary hyperemia. Ex vivo experiments revealed that red blood cells (RBCs) themselves act as O2 sensors that autonomously regulate their own deformability and thereby flow velocity through capillaries in response to physiological decreases in O2 tension. This observation has broad implications for understanding how local changes in blood flow are coupled to synaptic transmission.

RBCs are known to release ATP, which acts as a signaling molecule to cause dilation of blood vessels. A reduction in the release of ATP from RBCs has been linked to diseases such as type II diabetes and cystic fibrosis. Furthermore, reduced deformation of RBCs has been correlated with myocardial infarction and coronary heart disease. Because ATP release has been linked to cell deformation, we undertook a multiscale approach to understand the links between single RBC dynamics, ATP release, and macroscopic viscosity all at physiological shear rates. Our experimental approach included microfluidics, ATP measurements using a bioluminescent reaction, and rheology. Using microfluidics technology with high-speed imaging, we visualize the deformation and dynamics of single cells, which are known to undergo motions such as tumbling, swinging, tanktreading, and deformation. We report that shear thinning is not due to cellular deformation as previously believed, but rather it is due to the tumbling-to-tanktreading transition. In addition, our results indicate that ATP release is constant at shear stresses below a threshold (3 Pa), whereas above the threshold ATP release is increased and accompanied by large cellular deformations. Finally, performing experiments with well-known inhibitors, we show that the Pannexin 1 hemichannel is the main avenue for ATP release both above and below the threshold, whereas, the cystic fibrosis transmembrane conductance regulator only contributes to deformation-dependent ATP release above the stress threshold.

Piezo proteins (Piezo1 and Piezo2) are recently identified mechanically activated cation channels in eukaryotic cells and associated with physiological responses to touch, pressure, and stretch. In particular, human RBCs express Piezo1 on their membranes, and mutations of Piezo1 have been linked to hereditary xerocytosis. To date, however, physiological functions of Piezo1 on normal RBCs remain poorly understood. Here, we show that Piezo1 regulates mechanotransductive release of ATP from human RBCs by controlling the shear-induced calcium (Ca 2+ ) influx. We find that, in human RBCs treated with Piezo1 inhibitors or having mutant Piezo1 channels, the amounts of shear-induced ATP release and Ca 2+ influx decrease significantly. Remarkably, a critical extracellular Ca 2+ concentration is required to trigger significant ATP release, but membrane-associated ATP pools in RBCs also contribute to the release of ATP. Our results show how Piezo1 channels are likely to function in normal RBCs and suggest a previously unidentified mechanotransductive pathway in ATP release. Thus, we anticipate that the study will impact broadly on the research of red cells, cellular mechanosensing, and clinical studies related to red cell disorders and vascular disease. Previous studies have shown that the addition of chemicals that stiffen RBC membranes decreases the amount of ATP released (9, 16), indicating that deformation of the cell membrane is a necessary trigger. In addition, biological mediators, such as cystic fibrosis transmembrane conductance regulator (CFTR) and pannexin-1 hemichannels, are involved in the release pathways of mechanotransductive ATP release from RBCs (9,14,17,18). Inhibition of CFTR leads to an impaired ATP release from deformed RBCs (14). Recent studies, including our previous findings, suggest that interactions between membrane-associated actin and CFTR play important roles in the mechanotransductive ATP release from RBCs (9, 17). Pannexin-1, however, is a channel-forming protein and has been suggested as a mechanosensing ATP release channel (18). Under osmotic stress, for example, ATP released from RBCs was attenuated by carbenoxolone, a highly effective pannexin channel blocker, suggesting that pannexin-1 might be one of the conductance channels responsible for the mechanotransductive release of ATP (18). Although progress has been made in understanding mechanotransductive ATP release from RBCs, many questions remain about the signal transduction pathways. For example, how does mechanical force transduce signals to ATP release channels? Are there any stretch-activated ion channels on RBCs that may sense mechanical forces and activate ATP release? If so, are there any secondary messengers that could be generated by mechanical stimuli and regulate ATP release?Piezo proteins (Piezo1 and Pizeo2) are recently identified mechanically activated cation channels in mammals (19,20) and can be fully activated without involvement of additional proteins (20, 21). Piezo-induced cationic currents were first observe...

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