High-speed sorting is an essential process in a number of clinical and research applications, where single cells, droplets and particles are segregated based on their properties in a continuous flow. ...With recent developments in the field of microscale actuation, there is increasing interest in replicating the functions available to conventional fluorescence activated cell sorting (FACS) flow cytometry in integrated on-chip systems, which have substantial advantages in cost and portability. Surface acoustic wave (SAW) devices are ideal for many acoustofluidic applications, and have been used to perform such sorting at rates on the order of kHz. Essential to the accuracy of this sorting, however, is the dimensions of the region over which sorting occurs, where a smaller sorting region can largely avoid inaccurate sorting across a range of sample concentrations. Here we demonstrate the use of flow focusing and a highly focused SAW generated by a high-frequency (386 MHz), 10 μm wavelength set of focused interdigital transducers (FIDTs) on a piezoelectric lithium niobate substrate, yielding an effective sorting region only ~25 μm wide, with sub-millisecond pulses generated at up to kHz rates. Furthermore, because of the use of high frequencies, actuation of particles as small as 2 μm can be realized. Such devices represent a substantial step forward in the evolution of highly localized forces for lab-on-a-chip microfluidic applications.
Concentration and separation of particles and biological specimens are fundamental functions of micro/nanofluidic systems. Acoustic streaming is an effective and biocompatible way to create rapid ...microscale fluid motion and induce particle capture, though the >100 MHz frequencies required to directly generate acoustic body forces on the microscale have traditionally been difficult to generate and localize in a way that is amenable to efficient generation of streaming. Moreover, acoustic, hydrodynamic, and electrical forces as typically applied have difficulty manipulating specimens in the submicrometer regime. In this work, we introduce highly focused traveling surface acoustic waves (SAW) at high frequencies between 193 and 636 MHz for efficient and highly localized production of acoustic streaming vortices on microfluidic length scales. Concentration occurs via a novel mechanism, whereby the combined acoustic radiation and streaming field results in size-selective aggregation in fluid streamlines in the vicinity of a high-amplitude acoustic beam, as opposed to previous acoustic radiation induced particle concentration where objects typically migrate toward minimum pressure locations. Though the acoustic streaming is induced by a traveling wave, we are able to manipulate particles an order of magnitude smaller than possible using the traveling wave force alone. We experimentally and theoretically examine the range of particle sizes that can be captured in fluid streamlines using this technique, with rapid particle concentration demonstrated down to 300 nm diameters. We also demonstrate that locations of trapping and concentration are size-dependent, which is attributed to the combined effects of the acoustic streaming and acoustic forces.
HIV-1 Vif, Vpu, and Vpr Adapt Cellular Ubiquitin Ligase Adaptors to Counteract Host Antiviral Responses Ubiquitination is a post-translational protein modification that regulates protein ...degradation and trafficking.\n Recent studies have expanded the role of BST-2 to include viral sensing and signal transduction to activate NF-κB-dependent pro-inflammatory signals (reviewed in 23). ...the precise role of UNG2 remains controversial as it has both positive and negative effects on HIV-1 replication (reviewed in 26). Because the interaction with UNG2 does not appear to explain all of Vpr's activities, it is likely that Vpr targets additional cellular proteins that have not yet been identified.
The segregation of solutes at dislocations in a polycrystalline and a single crystal nickel-based superalloy is studied. Our observations confirm the often assumed but yet unproven diffusion along ...dislocations via pipe diffusion. Direct observation and quantitative, near-atomic scale segregation of chromium and cobalt at dislocations within γ' precipitates and at interfacial dislocations leading to the partial or complete dissolution of γ' precipitates at elevated temperatures is presented. Our results allow us to elucidate the physical mechanism by which pipe diffusion initiates the undesirable dissolution of γ' precipitates.
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Despite increasing demand in the manipulation of nanoscale objects for next generation biological and industrial processes, there is a lack of methods for reliable separation, concentration and ...purification of nanoscale objects. Acoustic methods have proven their utility in contactless manipulation of microscale objects mainly relying on the acoustic radiation effect, though the influence of acoustic streaming has typically prevented manipulation at smaller length scales. In this work, however, we explicitly take advantage of the strong acoustic streaming in the vicinity of a highly focused, high frequency surface acoustic wave (SAW) beam emanating from a series of focused 6 μm substrate wavelength interdigital transducers patterned on a piezoelectric lithium niobate substrate and actuated with a 633 MHz sinusoidal signal. This streaming field serves to focus fluid streamlines such that incoming particles interact with the acoustic field similarly regardless of their initial starting positions, and results in particle displacements that would not be possible with a travelling acoustic wave force alone. This streaming-induced manipulation of nanoscale particles is maximized with the formation of micro-vortices that extend the width of the microfluidic channel even with the imposition of a lateral flow, occurring when the streaming-induced flow velocities are an order of magnitude larger than the lateral one. We make use of this acoustic streaming to demonstrate the continuous and differential focusing of 100 nm, 300 nm and 500 nm particles.
HIV infection can be effectively treated by lifelong administration of combination antiretroviral therapy, but an effective vaccine will likely be required to end the HIV epidemic. Although the ...majority of current vaccine strategies focus on the induction of neutralizing antibodies, there is substantial evidence that cellular immunity mediated by CD8
T cells can sustain long-term disease-free and transmission-free HIV control and may be harnessed to induce both therapeutic and preventive antiviral effects. In this Review, we discuss the increasing evidence derived from individuals who spontaneously control infection without antiretroviral therapy as well as preclinical immunization studies that provide a clear rationale for renewed efforts to develop a CD8
T cell-based HIV vaccine in conjunction with B cell vaccine efforts. Further, we outline the remaining challenges in translating these findings into viable HIV prevention, treatment and cure strategies.
ABSTRACT We derive an analytic expression for the transitional column density value ( ) between the lognormal and power-law form of the probability distribution function (PDF) in star-forming ...molecular clouds. Our expression for depends on the mean column density, the variance of the lognormal portion of the PDF, and the slope of the power-law portion of the PDF. We show that can be related to physical quantities such as the sonic Mach number of the flow and the power-law index for a self-gravitating isothermal sphere. This implies that the transition point between the lognormal and power-law density/column density PDF represents the critical density where turbulent and thermal pressure balance, the so-called "post-shock density." We test our analytic prediction for the transition column density using dust PDF observations reported in the literature, as well as numerical MHD simulations of self-gravitating supersonic turbulence with the Enzo code. We find excellent agreement between the analytic and the measured values from the numerical simulations and observations (to within 1.2 AV). We discuss the utility of our expression for determining the properties of the PDF from unresolved low-density material in dust observations, for estimating the post-shock density, and for determining the H i-H2 transition in clouds.
In single-cell analysis, cellular activity and parameters are assayed on an individual, rather than population-average basis. Essential to observing the activity of these cells over time is the ...ability to trap, pattern and retain them, for which previous single-cell-patterning work has principally made use of mechanical methods. While successful as a long-term cell-patterning strategy, these devices remain essentially single use. Here we introduce a new method for the patterning of multiple spatially separated single particles and cells using high-frequency acoustic fields with one cell per acoustic well. We characterize and demonstrate patterning for both a range of particle sizes and the capture and patterning of cells, including human lymphocytes and red blood cells infected by the malarial parasite Plasmodium falciparum. This ability is made possible by a hitherto unexplored regime where the acoustic wavelength is on the same order as the cell dimensions.
Sorting of extracellular vesicles has important applications in early stage diagnostics. Current exosome isolation techniques, however, suffer from being costly, having long processing times, and ...producing low purities. Recent work has shown that active sorting via acoustic and electric fields are useful techniques for microscale separation activities, where combining these has the potential to take advantage of multiple force mechanisms simultaneously. In this work, we demonstrate an approach using both electrical and acoustic forces to manipulate bioparticles and submicrometer particles for deterministic sorting, where we find that the concurrent application of dielectrophoretic (DEP) and acoustophoretic forces decreases the critical diameter at which particles can be separated. We subsequently utilize this approach to sort subpopulations of extracellular vesicles, specifically exosomes (<200 nm) and microvesicles (>300 nm). Using our combined acoustic/electric approach, we demonstrate exosome purification with more than 95% purity and 81% recovery, well above comparable approaches.
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