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Recent work with cyclical electrical field-flow fractionation systems has shown promise for the technique as a separation and analysis tool, but little is understood about how the carrier composition in the system affects its capabilities. The electrical properties of microscale CyElFFF systems change when the carrier ionic conditions are altered, and it is well known that the effects of increasing ionic strength carriers on retention in normal ElFFF systems are severe. Specifically, retention levels fall significantly. Accordingly, this work seeks to understand the effect that increasing carrier ionic strength in CyElFFF has on nanoparticle retention in the channels. The retention of polystyrene particles in the CyElFFF microsystem is reported at various ionic strengths of ammonium carbonate and at a variety of pH levels. The experiments are compared to the theory of CyElFFF available in the literature. The results indicate that the ionic strength of the carrier has a significant impact on retention and that high ionic strength carrier solutions lead to poor performance of the CyElFFF system. These results have significant impact on the possible uses of the technique and its applications, especially in the biomedical arena.

Stenosis-induced thrombosis and abandonment of the hemodialysis synthetic graft is an important cause of morbidity and mortality. The graft vascular circuit is a unique low-resistance shunt that has not yet been systematically evaluated. In this study, we developed a mathematical model of this circuit. Pressure losses ΔPs were measured in an in vitro experimental apparatus and compared with losses predicted by equations from the engineering literature. We considered the inflow artery, arterial and venous anastomoses, graft, stenosis, and outflow vein. We found significant differences between equations and experimental results, and attributed these differences to the transitional nature of the flow. Adjustment of the equations led to good agreement with experimental data. The resulting mathematical model predicts relations between stenosis, blood flow, intragraft pressure, and important clinical variables such as mean arterial blood pressure and hematocrit. Application of the model should improve understanding of the hemodynamics of the stenotic graft vascular circuit.

Platelet function is suggestive of pathological conditions in cardiovascular diseases. With current insufficient prognostic devices, the need exists for a device to assess complete platelet function. This work presents a preliminary microfluidic device for such analysis based on platelet adhesion under shear flow conditions. In this novel device, polydimethylsiloxane (PDMS) microchannels were coated using a layer-by-layer self-assembly technique to provide controlled nanometer-thick layers of fibrinogen. Anticoagulated platelet rich plasma labeled with a fluorescein isothiocynate-tagged anti-glycoprotein IIb/IIIa-antibody and acridine orange was passed through these micro-channels at various time-averaged shear rate values. Fluorescence assays confirmed shear-dependent adhesion of platelets in the microchannels. Control experiments showed that the extent of adhesion on bare PDMS surfaces was less than on the surfaces coated with fibrinogen at similar shear rates. Fluorescent microscopy demonstrated that the extent of platelet adhesion to the fibrinogen substrate depended on shear rate. The extent of adhesion was modeled as a third order polynomial in shear rate.

Previously reported theories for cyclical electrical field flow fractionation (CyElFFF) are severely limited in that they do not account for diffusion, steric, or electric double layer effects. Experiments have shown that these theories overpredict the retention of particles in CyElFFF. In this work, we present a model for prediction of steric, diffusion, and electrical effects. The electrical double layer effects are treated using a lumped electrical circuit model that accounts for the field shielding by the electrical double layer formed at the electrode–carrier interface. The electrical effects are shown to dominate retention times and outweigh the contributions of diffusion and particle size. Detailed results from the simulations are presented in this work, and a comparison between the theoretical and experimental results obtained from the retentions of polystyrene particle standards is presented in this paper. The models are shown to correctly predict the retention of the polystyrene standards in CyElFFF with a reasonable error, while existing models are shown to have significant failings.

Platelet function is suggestive of pathological conditions in heart related diseases. With current insufficient prognostic devices, we see the need for a device to assess complete platelet function. This work presents our preliminary microfluidic device for the analysis of shear-induced platelet activation, which is crucial in studying the pathological role of platelets. In our novel device, the polydimethylsiloxane microchannels were coated using a novel layer-by-layer self-assembly technique to provide controlled nanometer-thick layers of fibrinogen. Anticoagulated platelet rich plasma labeled with a fluorescein isothiocyanate-tagged anti-GpIIb/IIIa-antibody was passed through these microchannels and several experimental runs for different shear rates were carried out. Finally, fluorescence assays confirmed the activation of platelets in the microchannels for various shear rates. Control experiments showed that the extent of adhesion on bare PDMS surfaces was less than on the surfaces assembled with fibrinogen. Based on image processing, the extent of platelet adhesion to the fibrinogen substrate was determined for each of the shear rates. The extent of adhesion (/spl phi/) was modeled as a third order polynomial in shear rate for substrate fibrinogen.

Although platelets are small and simple in shape, they are complicated in their physiologhy. Their alpha granules and dense bodies secrete a large number of agents that are involved in haemostasis, and the glycoproteins on their surfaces form the linkages with proteins like fibrinogen, fibronectin, collagen and von Willebrand factor that are necessary for adhesion and aggregation (Frojmovic, 1998). Diseases such as heart attack (Meade, 1992), stroke (Harker, 1998) and eclampsia (Schindler et al., 1990), can be the result of pathologies in platelets. Although devices have been recently developed to diagnose platelet function (Nicholson et al., 1998), there is still a need for devices that can examine the multiple factors of platelet physiology that affect thrombus formation. Because fluid shear is a key factor in platelet adhesion and aggregation (Colantuoni et al., 1977), it is necessary to test platelet function under conditions of flow. Also, because of the large number of adhesion receptors and secreted agents that make up a platelet’s physiology, a complete diagnosis of platelet function should be performed on a variety of substrates.Copyright © 2002 by ASME

A microscale cyclical electrical field flow fractionation (CyElFFF) channel is characterized with regard to the effect of various operating parameters and comparison made to recent theoretical developments. Challenges associated with various operating conditions are reported along with some of the optimized operating parameters. The effect of retention wall choice, an offset voltage, relaxation steps, and flow rates, along with the basic operating parameters of voltage, frequency, and electrophoretic mobility are reported. Retention of polystyrene nanoparticle standards is accomplished and the first separations using this technique in a microscale system are also demonstrated. Relaxation steps and offset voltages are found to be effective in eliminating early peaks and in improving plate heights. Plate heights were also found to decrease with increasing flow rates, which is the opposite of the behavior seen in most existing chromatographic systems. The experimental results are compared to the analytical and empirical models of CyElFFF and found to be compatible. Suggestions are made for improving the separation and analysis methods used with CyElFFF.