SEPARATION AND BEHAVIOR OF NONSPHERICAL PARTICLES IN SEDIMENTATION/STERIC FIELD-FLOW FRACTIONATION

Sedimentation/steric field-flow fractionation (Sd/StFFF) is an elution separation technique capable of measuring the size distribution of 0.3-100 µm spherical and near-spherical particles with advantages including high resolution, fast analysis, and the ready collection of narrow size fractions. In this study we investigate the applicability of Sd/StFFF to various nonspherical particles including the doublets of spheres, rod-shaped glass fibers, compressed latex discs, and quartz particles (BCR 67 and 70) with complex mixed shapes. Some fractionation, retention, and selectivity features of these particles are defined and measured in relationship to those of spheres (latex beads), which are better understood. While the relative behavior of these two particle types depends on many factors, especially the distance of the particle from the Sd/StFFF channel wall, in most cases the nonspherical particles are eluted before spheres of equal volume and they often display higher selectivity than spherical particles. However, when retention of nonspherical particles is compared with that for spheres whose diameter is equal to the particle length, elongated particles (doublets and rods) eluted after the sphere while flattened particles (discs) eluted earlier than spheres, an observation that might assist in shape discrimination by Sd/StFFF. Thus, when latex microspheres are used for calibration to obtain size distribution curves, the diameter obtained for any given subpopulation will be less than the length of rods but greater than the diameter of discs. For complex particles such as the quartz particles, the diameter of a particle provided by classical sedimentation using spherical calibration is less than the equivalent spherical diameter of the particle in question whereas Sd/StFFF yields a diameter somewhat greater than the particle length. Thus, these two techniques will yield size distribution curves displaced from one another along the diameter axis. The difference in diameters can be eliminated by using a diameter correction factor of 2.7, which brings the distribution curves for quartz obtained by these two techniques into concurrence.     

On-chip high-speed sorting of micron-sized particles for high-throughput analysis

A new design of particle sorting chip is presented. The device employs a dielectrophoretic gate that deflects particles into one of two microfluidic channels at high speed. The device operates by focussing particles into the central streamline of the main flow channel using dielectrophoretic focussing. At the sorting junction (T- or Y-junction) two sets of electrodes produce a small dielectrophoretic force that pushes the particle into one or other of the outlet channels, where they are carried under the pressure-driven fluid flow to the outlet. For a 40 microm wide and high channel, it is shown that 6 microm diameter particles can be deflected at a rate of 300/s. The principle of a fully automated sorting device is demonstrated by separating fluorescent from non-fluorescent latex beads.     

离心沉降场流分离技术用于纳米颗粒尺寸的准确表征

以名义粒径为240nm的聚苯乙烯标准纳米颗粒悬浮液为样品,利用离心沉降场流分离仪以0．1％FL-70的水溶液为流动相分离。测定检测器波长为254nm时,纳米颗粒在离心力场的作用下通过分离通道的保留时间,从而确定纳米颗粒的平均粒径,测定值为247nm。此外,还利用扫描电镜法测定了纳米颗粒标准物质的粒径,测定值为220nm,结果表明,离心沉降场流分离技术较扫描电镜法更接近于聚苯乙烯纳米颗粒标准的名义粒径,具有更高的准确度和精密度。该方法可望成为纳米尺度表征的一种参考方法。     

Particle size distribution by sedimentation/steric field-flow fractionation: development of a calibration procedure based on density compensation

Because of the important but mathematically complex role played by hydrodynamic lift forces in sedimentation/steric FFF, applied generally to particles greater than 1 micron in diameter, retention cannot readily be related to particle diameter on the basis of simple theory. Consequently, empirical calibration is needed. Unfortunately, retention is based on particle density as well as size so that a purely size-based calibration (e.g., with polystyrene latex standards) is not generally valid. By examining the balance between driving and lift forces, it is concluded that equal retention will be observed for equal size particles subject to equal driving forces irrespective of particle density. Therefore by adjusting the rotation rate to exactly compensate for density, retention can be brought in line with that of standards, a conclusion verified by microscopy. Linear calibration plots of log (retention time) versus log (diameter) can then be used. This approach is applied to two glass bead samples (5-30 and 5-50 microns) using both a conventional and a pinched inlet channel. The resulting size distribution curves are self consistent and in good agreement with results obtained independently.     

Single-particle fritting technology for capillary electrochromatography

Large perfusive silica beads (particle size 110 microm, through pore approximately 2 microm) held in place by the keystone effect were used as single-particle frits for the manufacture of particulate packed capillary columns. High-quality capillary electrochromatographic separations of a standard test mixture of alkylbenzenes were obtained over the full voltage range of 5-30 kV, with no requirement for pressurization. Excellent robustness was demonstrated by the reproducibility of migration times, peak efficiencies, and resolution during 100 consecutive runs at the highest voltage (30 kV) without thermostating and pressurization. Superior performance relative to traditional sinter-fritted columns is ascribed to the heat-free fritting process and short frit length of approximately 110 microm.     

Effect of carrier fluid viscosity on retention time and resolution in gravitational field-flow fractionation

Gravitational field-flow fractionation (GrFFF) is a useful technique for fast separation of micrometer-sized particles. Different sized particles are carried at different velocities by a flow of fluid along an unobstructed thin channel, resulting in a size-based separation. They are confined to thin focused layers in the channel thickness where force due to gravity is exactly opposed by hydrodynamic lift forces (HLF). It has been reported that the HLF are a function of various parameters including the flow rate (or shear rate), the size of the particles, and the density and viscosity of the liquid. The dependence of HLF on these parameters offers a means of altering the equilibrium transverse positions of the particles in GrFFF, and hence their elution times. In this study, the effect of the viscosity of the carrier fluid on the elution behavior (retention, zone broadening, and resolution) of micrometer-sized particles in GrFFF was investigated using polystyrene (PS) latex beads as model particles. In order to change the carrier liquid viscosity without affecting its density, various amounts of (hydroxypropyl) methyl cellulose (HPMC) were added to the aqueous carrier liquid. It was found that particles migrate at faster rates as the carrier viscosity is increased, which confirms the dependence of HLF on viscosity. At the same time, particle size selectivity decreased but peak shape and symmetry for the more strongly retained particles improved. As a result, separation was improved in terms of both the separation time and resolution with increase of carrier viscosity. A theoretical model for plate height in GrFFF is also presented, and its predictions are compared to experimentally measured values.     

Ibuprofen Release from Beads Coated with an Experimental Latex: Effect of Certain Variables

The objective of this study was to evaluate the effect of factors such as drug loading, particle size, plasticizer type, antiadherent type, and annealing method on the release of ibuprofen from controlled-release beads coated with an experimental latex. Further, the in vitro release kinetics and mechanism of drug transport across the polymeric membrane have been investigated. Ibuprofen-loaded beads were coated with the experimental latex using a fluidized-bed coating machine (Uniglatt). The drug release from these spherical membrane reservoir systems appeared to be diffusion controlled. Evaluation of the effect of osmotic pressure by using dissolution media of various osmolal concentrations indicated that it has no significant effect on the drug release. To further elucidate the mechanism of release from these polymeric membranes, the permeation of drug through free films was studied.     

Integrated label-free protein detection and separation in real time using confined surface plasmon resonance imaging

We demonstrate a label-free protein detection and separation technology for real-time monitoring of proteins in micro/nanofluidic channels, confined surface plasmon resonance imaging (confined-SPRi). This was achieved by fabricating ultrathin fluidic channels (500 nm high, 500 microm wide) directly on top of a specialized SPRi sensor surface. In this way, SPRi is uniquely used to detect proteins deep into the fluidic channel while maintaining high lateral accuracy of separated products. The channel fluid and proteins were driven electrokinetically under an external electric field. For this to occur, the metallic SPR sensor (46 nm of Au on 2 nm of Cr) was segmented into an array of squares (each 200 microm x 200 microm in size and spaced 8 microm apart) and coated with 30 nm of CYTOP polymer. In this work, we track label-free protein separation in real time through a simple cross-junction fluidic device with an 8-mm separation channel length under 30 V/cm electric field strength.     

Using channel depth to isolate and control flow in a micro free-flow electrophoresis device

A multiple-depth micro free-flow electrophoresis chip (mu-FFE) has been fabricated with a 20-microm-deep separation channel and 78-microm-deep electrode channels. Due to the difference in channel heights, the linear velocity of buffer in the electrode channels is approximately 15 times that of the buffer in the separation channel. Previous mu-FFE devices have been limited by electrolysis product formation at the electrodes. These electrolysis products, manifested as bubbles, decreased the electric field and disrupted the buffer flow profile, limiting performance and preventing continuous operation. Using channel depth to control buffer flow over the electrodes and in the separation channel effectively removes electrolysis products, allowing continuous operation. The linear velocities in the channels were confirmed using particle velocimetry and compared well with values predicted using lubrication theory. A separation potential of 645 V could be applied before significant Joule heating was observed. This corresponded to an electric field of 586 V/cm in the separation channel, a 4-fold increase over our previous design. A separation of fluorescent standards was demonstrated using the new mu-FFE device. Resolution increased by a factor of 1.3 over our previous design, even when operated under similar conditions, suggesting that effective removal of electrolysis products is more important than originally thought.     

Continuous dielectrophoretic size-based particle sorting

Continuous-flow dielectrophoretic (DEP) particle separation based on size is demonstrated in a microfluidic device. Polystyrene microspheres suspended in a neutrally buoyant aqueous solution are used as model particles to study DEP induced by an array of slanted, planar, interdigitated electrodes inside of a soft-lithography microchannel. The E-field gradients from the slanted electrodes impart a net transverse force component on the particles that causes them to "ratchet" across the channel. Over the length of the device, larger particles are deflected more than smaller particles according to the balance of hydrodynamic drag and DEP forces. Consequently, a flow-focused particle suspension containing different-sized particles is fractionated as the beads flow and separate down the length of the device. The flow behavior of spherical particles is modeled, and the total transverse particle displacement in the microfluidic device predicts fourth-order size and voltage and second-order inverse flow rate dependences. The model is verified experimentally for a range of flow rates, particle sizes, and E-field strengths.     

Size separation of supermicrometer particles in asymmetrical flow field-flow fractionation. Flow conditions for rapid elution

The performance of lift-hyperlayer asymmetrical flow field-flow fractionation using rapid elution conditions was tested through the separation of standard polystyrene latex particles of diameters from 2 to 20 microm. Optimization of flowrates was studied not only in order to obtain efficient and rapid separation, but also to work under conditions of various shape and steepness of the axial flow velocity gradient. Using extreme flow conditions, the five widely spaced particle sizes, 20.5-, 15.0-, 9.7-, 5.0-, and 2.0-microm diameter, could be resolved in 6 min, whereas for the narrower size range of 20.5-5.0 microm, 1 min was enough. The size selectivity in the size range 9.7-2.0 microm was studied as a function of flowrates and particle size and was found to be constant. A particle trapping device made it possible to separate particles of sizes > 10 microm, which has previously proven to be difficult in asymmetrical channels.     

Dual-field and flow-programmed lift hyperlayer field-flow fractionation.

Field and flow programming and their combination, dual programming, are shown to extend the particle size range to which a single flow/hyperlayer field-flow fractionation (FFF) run is applicable to approximately 1-50 microns. The rationale for programming flow/hyperlayer FFF (or other forms of lift hyperlayer FFF) is to expand the diameter range of micron size particles that can be resolved in a single run. By contrast, the reason for programming normal-mode FFF, the only kind of programming previously realized in FFF, is to reduce the analysis time of submicron particle samples of considerable size variability. These differences are explained in detail in relationship to the basic mechanisms governing retention in normal, steric, and lift hyperlayer FFF. Experiments are described in which field, flow, and dual programming are used to expand the accessible diameter range of flow/hyperlayer FFF. An example is shown in which 11 sizes of latex microspheres in the 2-48-microns diameter range are separated by dual programming in 11 min.     

Sheathless focusing of microbeads and blood cells based on hydrophoresis

This paper presents a microfluidic device for sheathless focusing of microbeads and blood cells based on a hydrophoretic platform comprising a V-shaped obstacle array (VOA). The VOA generates lateral pressure gradients that induce helical recirculations. Following the focusing flow particles passing through the VOA are focused in the center of the channel. In the device, the focusing pattern can be modulated by varying the gap height of the VOA. To achieve complete focusing within 4.4% coefficient of variation, the relative size differences between the gap and the particle were 3 and 4 microm for 10 and 15 microm beads, respectively. Red blood cells were used to study the hydrophoretic focusing pattern of biconcave, disk-shaped particles.     

Correction for particle-wall interactions in the separation of colloids by flow field-flow fractionation

In the characterization of materials by field-flow fractionation (FFF), the experienced analyst understands the importance of incorporating additives in the carrier liquid that minimize or eliminate interactions between the analyte and accumulation wall, particularly in aqueous systems. However, as FFF is applied to more difficult samples, such as those with high surface energies, it is increasingly difficult to find additives that completely eliminate particle-wall interactions. Furthermore, the analyst may wish to use specific conditions that preserve the high surface energy of particles, to study their interaction with other materials through their behavior in the FFF channel. With this in mind, Williams and co-workers developed a model that quantifies the effect of particle-wall interactions in FFF using an empirically determined interaction parameter. In this work, the model is evaluated for the application of flow FFF in carrier liquids of low ionic strength, where particle-wall interactions are magnified. The retention of particles ranging in size from 64 to 1000 nm is measured using a wide range of field strengths and retention levels. The model is found to be generally valid over the entire range, except for minor discrepancies at lower levels of retention. Although retention levels are dramatically affected by particle-wall interactions, the point of steric inversion (500 nm), where the size-based elution order reverses, is not affected. When particle-wall interactions are not accounted for, they lead to a bias in particle sizes calculated from standard retention theory of up to 70%. The model can also be used to refine the measurement of channel thickness, which is important for the accurate conversion of retention parameters to particle sizes. In this work, for example, errors in channel thickness led to systematic errors on the order of 10% in particle diameter.     

Scattering and absorption property database for nonspherical ice particles in the near- through far-infrared spectral region

The single-scattering properties of ice particles in the near- through far-infrared spectral region are computed from a composite method that is based on a combination of the finite-difference time-domain technique, the T-matrix method, an improved geometrical-optics method, and Lorenz-Mie theory. Seven nonspherical ice crystal habits (aggregates, hexagonal solid and hollow columns, hexagonal plates, bullet rosettes, spheroids, and droxtals) are considered. A database of the single-scattering properties for each of these ice particles has been developed at 49 wavelengths between 3 and 100 microm and for particle sizes ranging from 2 to 10,000 microm specified in terms of the particle maximum dimension. The spectral variations of the single-scattering properties are discussed, as well as their dependence on the particle maximum dimension and effective particle size. The comparisons show that the assumption of spherical ice particles in the near-IR through far-IR region is generally not optimal for radiative transfer computation. Furthermore, a parameterization of the bulk optical properties is developed for mid-latitude cirrus clouds based on a set of 21 particle size distributions obtained from various field campaigns.     

Palladium film decoupler for amperometric detection in electrophoresis chips

Demonstrated in this article is that a palladium metal film can be applied to decouple the electric circuitry of electrochemical detection from that of the electrophoretic separation in an electrophoresis chip. The Pd solid-state field decoupler, as well as the working electrodes, is thermally evaporated onto the plastic chip and oriented vertically across the separation channel. After the sample zones flow over the Pd decoupler, their electrochemical response is measured at working electrodes in the downstream pathway. Because the electrodes are on the separation channel, the electrode channel alignment is no longer a problem. For a separation channel of roughly 200 microm in width and 75 microm in depth in 10 mM phosphate (pH 5.1), the noise level at the working electrode is < 15 pA at an electric field of 570 V/cm.     

Simple solution phase synthesis of 3-D assembly of ZnO nanoneedles and its efficient field emission

Three dimensional (3-D) assemblies of ZnO nanoneedles have been synthesized on silicon substrate by a unique chemical process. Each nanoneedle in the assemblies was hexagonal faceted having [001] growth direction and tip diameter approximately 20 nm. The growth of 3-D assemblies was governed by the initial nuclei formation, followed by their aggregation and subsequently nanoneedle formation from each nucleus. Room temperature photoluminescence (PL) spectrum of the assemblies showed two prominent peaks, one narrow peak in the ultraviolet region (385 nm) and another broad peak in the visible region (440 nm-600 nm). The 3-D assemblies of ZnO nanoneedles showed very good field emission property with turn-on voltages 390 V, 530 V and 680 V for the anode-emitter distances of 100 microm, 200 microm and 300 microm respectively. The turn-on voltages showed a linear relationship with the anode-emitter distance. Field enhancement factor (beta) for the nanostructure was calculated to be 2873. The high beta value and the low turn-on field are attributed to the sharp needle like structure and their interesting three dimensional assemblies.     

Fabrication and characterization of nano-channel field effect transistors patterned by AFM anodic oxidation

We report a top-down approach based on atomic force microscope (AFM) local anodic oxidation (LAO) for the fabrications of the nanowire and nano-ribbon field effect transistors (FETs). In order to investigate the transport characteristics of nano-channel, we fabricated simple FET structures with channel width W approximately 300 nm (nanowire) and 10 microm (nano-ribbon) on 20 nm-thick silicon-on-insulator (SOL) wafers. In order to investigate the transport behavior in the device with different channel geometries, we have performed detailed two-dimensional simulations of nanowire and reference nano-ribbon FETs with a fixed channel length L and thickness t but varying channel width W from 300 nm to 10 microm. By evaluating the charge distributions, we have shown that the increase of 'on state' conduction current in SiNW channel is a dominant factor, which consequently result in the improved on/off current ratio of the nanowire FET.     

Electroosmotic flow control of fluids on a capillary electrophoresis microdevice using an applied external voltage

Independent control of electroosmosis is important for separation science techniques such as capillary zone electrophoresis and for the movement of fluids on microdevices. A capillary electrophoresis microdevice is demonstrated which provides more efficient control of electroosmosis with an applied external voltage field. The device is fabricated in a glass substrate where a 5.0 cm separation channel (30 microm wide) is paralleled with two embedded electrodes positioned 50 microm away in the substrate. With this structure, greatly reduced applied external potentials (< or = 120 V compared to tens of kilovolts) still effectively altered electroosmosis. The efficiency for the control of electroosmosis by the applied external field is improved by approximately 40 times over published values.     

Influence of the size of micronized active pharmaceutical ingredient on the aerodynamic particle size and stability of a metered dose inhaler

Pharmaceutical inhalers are often used to treat pulmonary diseases. Only active pharmaceutical ingredient (API) particles from these inhalers that are less than approximately 5 microm are likely to reach the lung and be efficacious. This study was designed to investigate the impact of micronized API particle size on the aerodynamic particle size distribution (PSD) profile and the particle size stability of a suspension metered dose inhaler (MDI) containing propellant HFA-227 (1,1,1,2,3,3,3 heptafluoropropane) and a corticosteroid. The median API particle size ranged from 1.1 microm to 1.8 microm (97% to 70% of particles <3 microm, respectively). This study showed that increasing the particle size of the API used to manufacture a suspension MDI product increased the aerodynamic PSD of the MDI product. Furthermore, upon storage of the MDI product under temperature cycling conditions, samples containing larger-size API particles were less stable with respect to their aerodynamic PSD than those with smaller-size API particles. It was found that size-dependent particle growth and/or aggregation of the suspended API may be occurring as a result of temperature cycling. In conclusion, this study has shown that the particle size of the raw API impacts the properties and stability of the emitted aerosol spray. Based on the findings from this study, it is recommended that the API particle size be carefully controlled in order to meet specifications set for the finished MDI product.