Paddlebots: Translation of Rotating Colloidal Assemblies near an Air/Water Interface.

Microbot propulsion requires unique strategies due to the dominance of viscosity and the reversible nature of microscale flows. To address this, swimmers of specific structure that translate in bulk fluid are commonly used; however, another approach is to take advantage of the inherent asymmetry of liquid/solid surfaces for microbots (µbots) to walk or roll. Using this technique, we have previously demonstrated that superparamagnetic colloidal particles can be assembled into small µbots, which can quickly roll along solid surfaces. In an analogous approach, here we show that symmetry can be similarly broken near air/liquid interfaces and µbots propelled at rates comparable to those demonstrated for liquid/solid interfaces.

Multimodal microwheel swarms for targeting in three-dimensional networks.

Microscale bots intended for targeted drug delivery must move through three-dimensional (3D) environments that include bifurcations, inclined surfaces, and curvature. In previous studies, we have shown that magnetically actuated colloidal microwheels (µwheels) reversibly assembled from superparamagnetic beads can translate rapidly and be readily directed. Here we show that, at high concentrations, µwheels assemble into swarms that, depending on applied magnetic field actuation patterns, can be designed to transport cargo, climb steep inclines, spread over large areas, or provide mechanical action. We test the ability of these multimodal swarms to navigate through complex, inclined microenvironments by characterizing the translation and dispersion of individual µwheels and swarms of µwheels on steeply inclined and flat surfaces. Swarms are then studied within branching 3D vascular models with multiple turns where good targeting efficiencies are achieved over centimeter length scales. With this approach, we present a readily reconfigurable swarm platform capable of navigating through 3D microenvironments.

An experimental design for the control and assembly of magnetic microwheels.

Superparamagnetic colloidal particles can be reversibly assembled into wheel-like structures called microwheels (µwheels), which roll on surfaces due to friction and can be driven at user-controlled speeds and directions using rotating magnetic fields. Here, we describe the hardware and software to create and control the magnetic fields that assemble and direct µwheel motion and the optics to visualize them. Motivated by portability, adaptability, and low-cost, an extruded aluminum heat-dissipating frame incorporating open optics and audio speaker coils outfitted with high magnetic permeability cores was constructed. Open-source software was developed to define the magnitude, frequency, and orientation of the magnetic field, allowing for real-time joystick control of µwheels through two-dimensional (2D) and three-dimensional (3D) fluidic environments. With this combination of hardware and software, µwheels translate at speeds up to 50 µm/s through sample sizes up to 5 × 5 × 5 cm3 using 0.75 mT-2.5 mT magnetic fields with rotation frequencies of 5 Hz-40 Hz. Heat dissipation by aluminum coil clamps maintained sample temperatures within 3 °C of ambient temperature, a range conducive for biological applications. With this design, µwheels can be manipulated and imaged in 2D and 3D networks at length scales of micrometers to centimeters.

Infliximab vs. adalimumab in Crohn's disease: results from 327 patients in an Australian and New Zealand observational cohort study.

BACKGROUND: Maintenance anti-tumour necrosis factor-α (anti-TNFα) treatment for Crohn's disease is the standard of care for patients with an inadequate response to corticosteroids and immunomodulators. AIM: To compare the efficacy and safety of infliximab and adalimumab in clinical practice and assess the value of concomitant immunomodulator therapy. METHODS: We performed an observational cohort study in consecutive patients with Crohn's disease qualifying for anti-TNFα treatment in Australia and New Zealand between 2007 and 2011. Demographic and clinical data were prospectively recorded to identify independent factors associated with induction and maintenance of response to infliximab or adalimumab, or to either anti-TNFα therapy. RESULTS: Three hundred and twenty-seven patients (183 infliximab, 144 adalimumab) successfully applied for treatment. Eighty-nine percent responded in all groups and median maintenance of response was similar for the two agents. Concomitant immunomodulator with infliximab, but not adalimumab, demonstrated a significantly longer response overall (P = 0.002), and significantly fewer disease and treatment-related complications (P = 0.017). Corticosteroids at baseline, and/or in the preceding 12 months, were associated with a 9-13 times greater risk of disease flare during maintenance treatment as compared to no corticosteroids (P < 0.0001). Maintenance of response was similar in the anti-TNF naïve and anti-TNF experienced subgroups. CONCLUSIONS: In this large, real-life study, we demonstrate infliximab and adalimumab to have similar response characteristics. However, infliximab requires concomitant immunomodulator to achieve optimal maintenance of response comparable to adalimumab monotherapy. The results of this study will assist clinicians in further optimising patient care in their day-to-day clinical practice.

Characterization of La1-xSrxMnO3 perovskite catalysts for hydrogen peroxide reduction.

We investigated the crystalline phase and electronic structure of perovskite-type La1-xSrxMnO3 (0.0 ≤ x ≤ 1.0) (LSMx) catalysts synthesized via the citric sol-gel route, for H2O2 reduction. The resulting materials were characterized by XRD, XANES, TR-XANES, and TPO and, after calcination, consisted of cubic perovskite for 0.0 ≤ x ≤ 0.8 and hexagonal perovskite for x = 1.0. Mn species in the precalcined catalysts were oxidized to Mn(3+) for x = 0.0 to 0.6 and to Mn(2+) for x = 0.8 and 1.0. After calcination, Mn species were present in a mixed oxidation state of Mn(3+)/Mn(4+), while Sr(2+) and La(3+) were not altered. TR-XANES and TPO showed that Mn species were oxidized at 210-220 °C and formed active perovskites LSM0.4 and LSM0.0 at 580 °C and 640 °C. This shows that Sr doping can reduce the oxidation temperature of LSMx with 0.2 ≤ x ≤ 0.4. However, the concentration of Mn(4+) in LSMx is increased which is useful for enhancing their catalytic activity and stability. When tested in an alkaline electrolyte, LSM0.6 containing the optimum Mn(4+)/Mn(3+) ratio promoted the formation of hydroxyl via the oxygen intercalation reaction and exhibited low polarization resistance and the highest catalytic activity for H2O2 reduction.

Surface-enabled propulsion and control of colloidal microwheels.

Propulsion at the microscale requires unique strategies such as the undulating or rotating filaments that microorganisms have evolved to swim. These features however can be difficult to artificially replicate and control, limiting the ability to actuate and direct engineered microdevices to targeted locations within practical timeframes. An alternative propulsion strategy to swimming is rolling. Here we report that low-strength magnetic fields can reversibly assemble wheel-shaped devices in situ from individual colloidal building blocks and also drive, rotate and direct them along surfaces at velocities faster than most other microscale propulsion schemes. By varying spin frequency and angle relative to the surface, we demonstrate that microwheels can be directed rapidly and precisely along user-defined paths. Such in situ assembly of readily modified colloidal devices capable of targeted movements provides a practical transport and delivery tool for microscale applications, especially those in complex or tortuous geometries.

Imaging of a linear diode bar for an optical cell stretcher.

We present a simplified approach for imaging a linear diode bar laser for application as an optical stretcher within a microfluidic geometry. We have recently shown that these linear sources can be used to measure cell mechanical properties; however, the source geometry creates imaging challenges. To minimize intensity losses and simplify implementation within microfluidic systems without the use of expensive objectives, we combine aspheric and cylindrical lenses to create a 1:1 image of the source at the stretcher focal plane and demonstrate effectiveness by measuring the deformation of human red blood cells and neutrophils.

FACS-style detection for real-time cell viscoelastic cytometry.

Cell mechanical properties have been established as a label-free biophysical marker of cell viability and health; however, real-time methods with significant throughput for accurately and non-destructively measuring these properties remain widely unavailable. Without appropriate labels for use with fluorescence activated cell sorters (FACS), easily implemented real-time technology for tracking cell-level mechanical properties remains a current need. Employing modulated optical forces and enabled by a low-dimensional FACS-style detection method introduced here, we present a viscoelasticity cytometer (VC) capable of real-time and continuous measurements. We demonstrate the utility of this approach by tracking the high-frequency cell physical properties of populations of chemically-modified cells at rates of ~ 1 s-1 and explain observations within the context of a simple theoretical model.

A simple microfluidic dispenser for single-microparticle and cell samples.

Non-destructive isolation of single-cells has become an important need for many biology research laboratories; however, there is a lack of easily employed and inexpensive tools. Here, we present a single-particle sample delivery approach fabricated from simple, economical components that may address this need. In this, we employ unique flow and timing strategies to bridge the significant force and length scale differences inherent in transitioning from single particle isolation to delivery. Demonstrating this approach, we use an optical trap to isolate individual microparticles and red blood cells that are dispensed within separate 50 µl droplets off a microfluidic chip for collection into microscope slides or microtiter plates.

Cell elongation via intrinsic antipodal stretching forces.

To probe the mechanical properties of cells, we investigate a technique to perform deformability-based cytometry that inherently induces normal antipodal surface forces using a single line-shaped optical trap. We show theoretically that these opposing forces are generated simultaneously over curved microscopic object surfaces with optimal magnitude at low numerical apertures, allowing the directed stretching of elastic cells with a single, weakly focused laser source. Matching these findings with concomitant experimental observations, we elongate red blood cells, effectively stretching them within the narrow confines of a steep, optically induced potential well.

Single-cell isolation using a DVD optical pickup.

A low-cost single-cell isolation system incorporating a digital versatile disc burner (DVD RW) optical pickup has been developed. We show that these readily available modules have the required laser power and focusing optics to provide a steady Gaussian beam capable of optically trapping micron-sized colloids and red blood cells. Utility of the pickup is demonstrated through the non-destructive isolation of such particles in a laminar-flow based microfluidic device that captures and translates single microscale objects across streamlines into designated channel exits. In this, the integrated objective lens focusing coils are used to steer the optical trap across the channel, resulting in the isolation of colloids and red blood cells using a very inexpensive off-the-shelf optical component.

In situ assembly of linked geometrically coupled microdevices.

Complex systems require their distinct components to function in a dynamic, integrated, and cooperative fashion. To accomplish this in current microfluidic networks, individual valves are often switched and pumps separately powered by using macroscopic methods such as applied external pressure. Direct manipulation and control at the single-device level, however, limits scalability, restricts portability, and hinders the development of massively parallel architectures that would take best advantage of microscale systems. In this article, we demonstrate that local geometry combined with a simple global field can not only reversibly drive component assembly but also power distinct devices in a parallel, locally uncoupled, and integrated fashion. By employing this single approach, we assemble and demonstrate the operation of check valves, mixers, and pistons within specially designed microfluidic environments. In addition, we show that by linking these individual components together, more complex devices such as pumps can be both fabricated and powered in situ.

Synthesis of colloidal aluminosilicate for light-scattering investigations.

To develop a binary colloidal system with a slight index of refraction mismatch suitable for light scattering studies, pure silica particles synthesized by the method of Stöber were mixed with aluminosilicate colloids synthesized using a novel approach. With this, index-matching for one component allowed extraction of the spatial distribution of the other. In addition, it was observed that by varying the solvent, interactions between colloids could be tuned from purely repulsive to weakly attractive.

Pollen dispersal in Yucca filamentosa (Agavaceae): the paradox of self-pollination behavior by Tegeticula yuccasella (Prodoxidae).

We investigated pollen dispersal in an obligate pollination mutualism between Yucca filamentosa and Tegeticula yuccasella. Yucca moths are the only documented pollinator of yuccas, and moth larvae feed solely on developing yucca seeds. The quality of pollination by a female moth affects larval survival because flowers receiving small amounts of pollen or self-pollen have a high abscission probability, and larvae die in abscised flowers. We tested the prediction that yucca moths primarily perform outcross pollinations by using fluorescent dye to track pollen dispersal in five populations of Y. filamentosa. Dye transfers within plants were common in all populations (mean ± 1 SE, 55 ± 3.0%), indicating that moths frequently deposit self-pollen. Distance of dye transfers ranged from 0 to 50 m, and the mean number of flowering plants between the pollen donor and recipient was 5 (median = 0), suggesting that most pollen was transferred among near neighbors. A multilocus genetic estimate of outcrossing based on seedlings matured from open-pollinated fruits at one site was 94 ± 6% (mean ± 1 SD). We discuss why moths frequently deposit self-pollen to the detriment of their offspring and compare the yucca-yucca moth interaction with other obligate pollinator mutualisms in which neither pollinator nor plant benefit from self-pollination.

Seed provisioning in gynodioeciousSilene acaulis (Caryophyllaceae).

In gynodioecious species, which contain females and hermaphrodites, the outcrossed seeds of females have been found to outperform the outcrossed seeds of hermaphrodites, in spite of the fact that their seeds are not larger in mass. Females do not make pollen. Hence the nutrients that hermaphrodites allocate to pollen, such as nitrogen, might be allocated to seeds by the females, such that individual seeds from females are better provisioned than those from hermaphrodites. Alternatively, females might make more seeds, rather than better provisioned seeds. We tested the hypothesis that seeds from females would be better provisioned for the gynodioecious species Silene acaulis, by comparing seed mass, embryo/endosperm mass, nitrogen and phosphorus content, and energy content for outcrossed seeds from females and hermaphrodites produced in a natural population. We also measured the proportion of flowers that set fruit in both morphs. Seeds from the two sexual morphs were not found to differ significantly for any of the measures of seed provisioning, with seeds from females containing either nonsignificantly less or equivalent amounts of each of the measures as compared to hermaphrodites. However, females set a significantly higher proportion of their flowers to fruit, as compared to hermaphrodites. These results indicate that females do not provision individual seeds more than hermaphrodites in S. acaulis, and alternative hypotheses will need to be examined to explain the difference in the performance of the seeds from the two sexual morphs.

HIV-specific cellular and humoral immune responses in primary HIV infection.

Primary human immunodeficiency virus (HIV) infection is characterized by a high-titer viremia that declines precipitously within weeks, most likely as a result of host immune responses. Peripheral blood mononuclear cells (PBMCs) and plasma of four recently HIV-infected individuals were examined to assess the humoral and cellular immune responses potentially involved in early suppression of viral replication. Neutralizing antibodies against autologous viral isolates were low or undetectable in three subjects studied. Cellular cytotoxicity was assayed using Epstein-Barr virus (EBV)-transformed B lymphoblastoid cell lines (B-LCLs) infected with recombinant vaccinia that express HIV-1 proteins. HIV envelope-specific cytotoxicity, which was not mediated by CD8+ cells nor human leukocyte antigen (HLA) class I restricted, developed in PBMCs of all four subjects early after primary infection, but was not correlated with declines in viremia. Gag-specific cytotoxic T lymphocyte (CTL) activity was observed in freshly isolated PBMCs of two subjects, and HIV-specific CTL cell lines were cultured from PBMCs of three subjects shortly after HIV infection. Antibody-dependent cellular cytotoxicity (ADCC) developed early in all four subjects, and was temporally correlated with declines in viremia in two subjects in whom viral load was well characterized. These data suggest that both CTL responses and ADCC may be critical to control of viral replication in acute HIV infection.

Accuracy of volume measurements of computed tomography and magnetic resonance imaging phantoms by three-dimensional reconstruction and preliminary clinical application.

RATIONALE AND OBJECTIVES: Using an independent three-dimensional workstation, the accuracy of volume measurements of phantoms was assessed using three-dimensional reconstruction of two-dimensional computed tomography (CT) and magnetic resonance (MR) images. METHODS: Round, cylindrical, and irregularly shaped high-contrast phantoms of known volume were imaged in a water bath. The effect of object contrast on volume estimation was tested using phantoms of known volume diluted serially with a contrast agent. The effect of changing field of view and slice thickness was assessed. A clinical application was performed, in which nine shoulders were injected with a known quantity of contrast material, to test the accuracy of the technique in vivo. RESULTS: A strong paired correlation (r = .99) between estimated and true volumes was obtained for high-contrast phantoms ranging from 17 to 128 mL. The weighted average absolute error was 1.42 mL (MR) and 3.50 mL (CT). Accuracy of the serially diluted 27-mL phantoms was essentially unaffected by contrast differences greater than 133 units (MR) and 102 units (CT). The weighted average absolute error was 1.33 mL (MR) and 1.56 mL (CT). Changing field of view had no effect on accuracy, but increasing the slice thickness resulted in over-estimation of volume. The mean error for the clinical application was 4.4% (range: 1.7%-8.3%). CONCLUSION: Under certain circumstances, three-dimensional reconstructive volume estimation can be a convenient and accurate method for volume determination.