Concept: Shear stress
We investigate the influences of expansion-contraction microchannels on droplet breakup in capillary microfluidic devices. With variations in channel dimension, local shear stresses at the injection nozzle and focusing orifice vary, significantly impacting flow behavior including droplet breakup locations and breakup modes. We observe transition of droplet breakup location from focusing orifice to injection nozzle, and three distinct types of recently-reported tip-multi-breaking modes. By balancing local shear stresses and interfacial tension effects, we determine the critical condition for breakup location transition, and characterize the tip-multi-breaking mode quantitatively. In addition, we identify the mechanism responsible for the periodic oscillation of inner fluid tip in tip-multi-breaking mode. Our results offer fundamental understanding of two-phase flow behaviors in expansion-contraction microstructures, and would benefit droplet generation, manipulation and design of microfluidic devices.
Biological microorganisms swim with flagella and cilia that execute nonreciprocal motions for low Reynolds number (Re) propulsion in viscous fluids. This symmetry requirement is a consequence of Purcell’s scallop theorem, which complicates the actuation scheme needed by microswimmers. However, most biomedically important fluids are non-Newtonian where the scallop theorem no longer holds. It should therefore be possible to realize a microswimmer that moves with reciprocal periodic body-shape changes in non-Newtonian fluids. Here we report a symmetric ‘micro-scallop’, a single-hinge microswimmer that can propel in shear thickening and shear thinning (non-Newtonian) fluids by reciprocal motion at low Re. Excellent agreement between our measurements and both numerical and analytical theoretical predictions indicates that the net propulsion is caused by modulation of the fluid viscosity upon varying the shear rate. This reciprocal swimming mechanism opens new possibilities in designing biomedical microdevices that can propel by a simple actuation scheme in non-Newtonian biological fluids.
Tissue and biological fluids are complex viscoelastic media with a nanoporous macromolecular structure. Here, we demonstrate that helical nano-propellers can be controllably steered through such a biological gel. The screw-propellers have a filament diameter of about 70 nm and are smaller than previously reported nano-propellers as well as any swimming microorganism. We show that the nano-screws will move through high viscosity solutions with comparable velocities to that of larger micro-propellers, even though they are so small that Brownian forces suppress their actuation in pure water. When actuated in viscoelastic hyaluronan gels, the nano-propellers appear to have a significant advantage, as they are of the same size range as the gel’s mesh-size. Whereas larger helices will show very low or negligible propulsion in hyaluronan solutions, the nano-screws actually display significantly enhanced propulsion velocities that exceed the highest measured speeds in Newtonian fluids. The nano-propellers are not only promising for applications in the extracellular environment, but are small enough to be taken up by cells.
The blood-brain barrier (BBB) is a unique feature of the human body, preserving brain homeostasis and preventing toxic substances to enter the brain. However, in various neurodegenerative diseases, the function of the BBB is disturbed. Mechanisms of the breakdown of the BBB are incompletely understood and therefore a realistic model of the BBB is essential. We present here the smallest model of the BBB yet, using a microfluidic chip, and the immortalized human brain endothelial cell line hCMEC/D3. Barrier function is modulated both mechanically, by exposure to fluid shear stress, and biochemically, by stimulation with tumor necrosis factor alpha (TNF-α), in one single device. The device has integrated electrodes to analyze barrier tightness by measuring the transendothelial electrical resistance (TEER). We demonstrate that hCMEC/D3 cells could be cultured in the microfluidic device up to 7 days, and that these cultures showed comparable TEER values with the well-established Transwell assay, with an average (± SEM) of 36.9 Ω.cm(2) (± 0.9 Ω.cm(2)) and 28.2 Ω.cm(2) (± 1.3 Ω.cm(2)) respectively. Moreover, hCMEC/D3 cells on chip expressed the tight junction protein Zonula Occludens-1 (ZO-1) at day 4. Furthermore, shear stress positively influenced barrier tightness and increased TEER values with a factor 3, up to 120 Ω.cm(2). Subsequent addition of TNF-α decreased the TEER with a factor of 10, down to 12 Ω.cm(2). This realistic microfluidic platform of the BBB is very well suited to study barrier function in detail and evaluate drug passage to finally gain more insight into the treatment of neurodegenerative diseases.
Bone fragility depends on its post-yield behavior since most energy dissipation in bone occurs during the post-yield deformation. Previous studies have investigated the progressive changes in the post-yield behavior of human cortical bone in tension and compression using a novel progressive loading scheme. However, little is known regarding the progressive changes in the post-yield behavior of bone in shear. The objective of this short study was to address this issue by testing bone specimens in an inclined double notch shear configuration using the progressive loading protocol. The results of this study indicated that the shear modulus of bone decreased with respect to the applied strain, and the rate of degradation was about 50% less than those previously observed in compression and tension tests. In addition, a quasi-linear relationship between the plastic and applied strains was observed in shear mode, which is similar to those previously reported in tension and compression tests. However, the viscous responses of bone (i.e. relaxation time constants and stress magnitude) demonstrated slight differences in shear compared with those observed in tension and compression tests. Nonetheless, the results of this study suggest that the intrinsic mechanism of plastic deformation of human cortical bone may be independent of loading modes.
We demonstrate an innovative technique for the direct measurement on the shear modulus of an individual nanorod. This measurement is based on atomic force microscopy (AFM) and micro-fabrication techniques. A nanorod is first aligned along the edge of a small trench in a silicon substrate, and then one end of the nanorod is fixed on the substrate. When an AFM tip scans over the nanorod in contact mode, the nanorod will be twisted by the comprehensive action from the force of the AFM tip, confinement from the trench edge and the fixing end. The shear deformation and the corresponding force that caused the deformation can be retrieved from topography and lateral force image respectively. By small angle approximation, the shear modulus of the ZnO NR, which has a radius of 166nm and a length of 4 µm, is measured to be 8.1 ± 1.9 GPa. This method can be applied directly to characterize the shear modulus of any nanowire/nanorod that possesses a polygon cross section.
Background:Most posture problems encountered in persons who use wheelchairs in a seated posture for extended periods are related to sacral sitting due to posterior pelvic tilt. Posterior pelvic tilt places pressure and shearing force on the sacrococcygeal area that can lead to pressure ulcers, but the relationship between pelvic tilt and force applied to the sacrococcygeal and ischial tuberosity areas has not yet been investigated.Objective:To investigate the relationships of posterior pelvic tilt in a seated posture with vertical force and horizontal force on the sacrococcygeal and ischial tuberosity areas.Study Design:Repeated measures design.Methods:Thirty male and female subjects aged ≥60 years sat in a measurement chair at varying pelvic tilt angles, and force on the sacrococcygeal and ischial tuberosity areas was measured.Results:The pressure on the sacrococcygeal area increased with pelvic tilt in all subjects, with vertical force averaging 19% of the body weight at a pelvic tilt angle of 30°. The horizontal force on the sacrococcygeal area increased in 93% of the subjects, with an average increase equal to 3% of the body weight.Conclusions:We confirmed changes in vertical and horizontal forces on the sacrococcygeal and ischial tuberosity areas with a change in seated posture (pelvic tilt).Clinical relevance:We propose guidelines for rehabilitation practitioners working with wheelchair users to suggest improved ways of sitting in wheelchairs that avoid pelvic tilt angles that might promote pressure ulcers on the buttocks.
This study compared the ground reaction forces (GRF) and plantar pressures between unloaded and occasional loaded gait. The GRF and plantar pressures of 60 participants were recorded during unloaded gait and occasional loaded gait (wearing a backpack that raised their body mass index to 30); this load criterion was adopted because is considered potentially harmful in permanent loaded gait (obese people). The results indicate an overall increase (absolute values) of GRF and plantar pressures during occasional loaded gait (p < 0.05); also, higher normalized (by total weight) values in the medial midfoot and toes, and lower values in the lateral rearfoot region were observed. During loaded gait the magnitude of the vertical GRF (impact and thrust maximum) decreased and the shear forces increased more than did the proportion of the load (normalized values). These data suggest a different pattern of GRF and plantar pressure distribution during occasional loaded compared to unloaded gait.
Acquired von-Willebrand syndrome (AVWS) is described in patients with Waldenström macroglobulinemia (WM). Assessment of ristocetin cofactor activity (VWF:RCo) and von-Willebrand factor (VWF) antigen (VWF:Ag) in 72 consecutive WM patients demonstrated a negative relationship between VWF levels <130 U/dL and both monoclonal immunoglobulin M concentration (mIgMC) and viscosity. Ten patients with VWF:RCo <50 U/dL (<40 for group O patients) fulfilled the AVWS criteria. They had higher mIgMC and viscosity. Reduction in mIgMC was associated with increase in VWF levels. The low VWF:RCo/VWF:Ag ratio suggested that high viscosity might be associated with increased shear force and cleavage of multimers. Surprisingly, 43 patients (59%) presented with high VWF:Ag (>110 U/dL). They had higher bone marrow (BM) microvessel density and vascular endothelial growth factor expression on BM mast cells. Five-year survival rates of patients with VWF:Ag <110, between 110 and 250 and >250 U/dL were 96%, 71%, and 44% respectively (p<0.0001). High VWF:Ag was also a significant adverse prognostic factor for survival after first-line therapy (p<0.0001), independently of the international scoring system. These results support systematic assessment of VWF in WM patients. The adverse prognostic value of high VWF levels raises issues on interactions between lymphoplasmacytic cells, mast cells and endothelial cells in WM.
A great deal of effort has been invested in the design and characterization of systems which spontaneously assemble into nanofibers. These systems are interesting for their fundamental supramolecular chemistry and have also been shown to be promising materials, particularly for biomedical applications. Multidomain peptides are one such assembler, and in previous work we have demonstrated the reversibility of their assembly under mild and easily controlled conditions, along with their utility for time-controlled drug delivery, protein delivery, cell encapsulation, and cell delivery applications. Additionally, their highly compliant criteria for sequence selection allows them to be modified to incorporate protease susceptibility and biological-recognition motifs for cell adhesion and angiogenesis. However, control of their assembly has been limited to the formation of disorganized nanofibers. In this work, we expand our ability to manipulate multidomain-peptide assembly into parallel-aligned fiber bundles. Albeit this alignment is achieved by the shearing forces of syringe delivery, it is also dependent on the amino acid sequence of the multidomain peptide. The incorporation of the amino acid DOPA (3,4-dihydroxyphenylalanine) allows the self-assembled nanofibers to form an anisotropic hydrogel string under modest shear stress. The hydrogel string shows remarkable birefringence, and highly aligned nanofibers are visible in scanning electronic microscopy. Furthermore, the covalent linkage induced by DOPA oxidation allows covalent capture of the aligned nanofiber bundles, enhancing their birefringence and structural integrity.