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The accumulation of platelets near the blood vessel wall or artificial surface is an important factor in the cascade of events responsible for coagulation and/or thrombosis. In small blood vessels and flow channels this phenomenon has been attributed to the blood phase separation that creates a red blood cell (RBC)-poor layer near the wall. We hypothesized that blood soluble drag-reducing polymers (DRP), which were previously shown to lessen the near-wall RBC depletion layer in small channels, may consequently reduce the near-wall platelet excess. This study investigated the effects of DRP on the lateral distribution of platelet-sized fluorescent particles (diam. = 2 µm, 2.5 × 108/ml) in a glass square microchannel (width and depth = 100 µm). RBC suspensions in PBS were mixed with particles and driven through the microchannel at flow rates of 6–18 ml/h with and without added DRP (10 ppm of PEO, MW = 4500 kDa). Microscopic flow visualization revealed an elevated concentration of particles in the near-wall region for the control samples at all tested flow rates (between 2.4 ± 0.8 times at 6 ml/h and 3.3 ± 0.3 times at 18 ml/h). The addition of a minute concentration of DRP virtually eliminated the near-wall particle excess, effectively resulting in their even distribution across the channel, suggesting a potentially significant role of DRP in managing and mitigating thrombosis.

This paper reports a novel, physiologically significant, microfluidic phenomenon generated by nanomolar concen- trations of drag-reducing polymers (DRP) dissolved in flowing blood, which may explain previously demonstrated beneficial effects of DRP on tissue perfusion. In microfluidic systems used in this study, DRP additives were found to significantly mod- ify traffic of red blood cells (RBC) into microchannel branches as well as reduce the near-wall cell-free layer, which normally is found in microvessels with a diameter smaller than 0.3 mm. The reduction in plasma layer size led to attenuation of the so-called "plasma skimming" effect at microchannel bifurcations, increasing the number of RBC entering branches. In vivo, these changes in RBC traffic may facilitate gas transport by increasing the near vessel wall concentration of RBC and capillary hematocrit. In addition, an increase in near-wall viscosity due to the redirection of RBC in this region may potentially decrease vascular resistance as a result of increased wall shear stress, which promotes endothelium mediated vasodilation. These mi- crocirculatory phenomena can explain the previously reported beneficial effects of DRP on hemodynamics in vivo observed in many animal studies. We also report here our finding that DRP additives reduce flow separations at microchannel expansions, deflecting RBC closer to the wall and eliminating the plasma recirculation zone. Although the exact mechanism of the DRP effects on RBC traffic in microchannels is yet to be elucidated, these findings may further DRP progress toward clinical use.

Microscopic steps and crevices are inevitable features within prosthetic blood-contacting devices. This study aimed to elucidate the thrombogenicity of the associated microscopic flow features by studying the transport of fluorescent platelet-sized particles in a suspension of red blood cells (RBCs) flowing through a 100 microm:200 microm sudden expansion. Micro-flow visualization revealed a strong influence of hematocrit upon the path of RBCs and spatial concentration of particles. At all flow rates studied (Re = 8.3-41.7) and hematocrit 20% and lower, RBC streamlines were found to detach from the microchannel wall creating an RBC-depleted zone inside the step that was much larger than the cells themselves. However, the observed distribution of particles was relatively homogeneous. By contrast, the RBC streamlines of samples with hematocrit equal to or greater than 30% more closely followed the contour of the microchannel, yet exhibited enhanced concentration of particles within the corner. The corresponding size of the cell depletion layer was comparable with the size of the cells. This study implies that local platelet concentration in blood within the physiological range of hematocrit can be elevated within the flow separation region of a sudden expansion and implicates the role of RBCs in causing this effect.

About seven decades ago, it was discovered that special long-chain soluble polymers added to fluid at nanomolar concentrations significantly reduce resistance to turbulent flow (Toms effect). These so-called drag-reducing polymers (DRPs) do not affect resistance to laminar flow. While the flow parameters associated with the Toms effect do not occur in the cardiovascular system, many later studies demonstrated that intravenous injections of DRPs given to experimental animals produced significant hemodynamic effects, such as increasing tissue perfusion, suggesting potential clinical use of these polymers. Moreover, it was found that the specific viscoelastic properties of these polymers make them capable of modifying traffic of blood cells in microvessels and beneficially redistributing them in the blood capillary system—a phenomenon related to rheological properties of DRPs and not related to their specific chemistry. The domain of drag reducing polymers includes many organic and water-soluble, synthetic and natural long-chain molecules. The study presented here employed chemical and rheological methods, as well as macro and microfluidic tests, to characterize the DRP that we discovered in the Aloe vera plant, which was found to be a more powerful drag reducer and less fragile than many synthetic DRPs. The drag-reducing component of aloe gel was purified and chemically identified, which helped to standardize preparation and made this polymer a strong candidate for clinical use. Examples of successful testing of the aloe-derived DRP in animal models are described.

Advances in genomic research have revealed that each patient has their own unique tumor profile. While silencing RNA (siRNA) screening tests can identify which genes drive tumor cell growth, results obtained from these assays have been limited in their clinical translatability because they employ cell lines growing on flat surfaces. The Cancer BioChip System (CBCS) is a functional screening assay for identification of siRNA capable of inhibiting anchorage-independent three-dimensional (3D) cancer cell growth. Anchorage-independent growth assays are important in vitro predicators of regulators of cancer cell growth. Unique features of the CBCS include a Cancer BioChip, wherein cells incorporate different siRNAs in parallel and grow in a 3D matrix to form colonies that can be quantified using real-time imaging and an image analysis software. Thus, the CBCS can be developed as a tool for personalized identification of targeted cancer therapies.

The bulk properties and structural characteristics of emulsions arise substantially from their interfacial rheology, which depends strongly on surfactant mass transfer and its coupling to flow. Typical methods used to measure such properties often employ simpler flows and larger drops than those encountered in typical processing applications. Mass transfer mechanisms are governed by droplet size; therefore experimentation at length scales typical of those encountered in applications is desired. Utilizing a microfluidic approach allows high-throughput experimentation at relevant length scales and with adjustable flow dynamics. Using a microfluidic device that facilitates the measurement of interfacial tension in two-phase droplet flows, particle tracers are also used to determine the droplet internal circulation velocity as a measure of interfacial mobility. Combining these measurements in a single device, the coupling between interfacial tension, interfacial retardation, and surfactant mass transfer is explored and mass transfer coefficients and interfacial mobility are measured for a two-phase system containing a diffusing surfactant. Such a device is also used to probe the deformability of elastic capsules and viscoelastic biological cells.

Natural and synthetic soluble drag reducing polymers (DRP) have been shown to produce beneficial effects on blood circulation in various animal models and may represent a novel bioengineering way to treat cardiovascular disorders. These polymers are known to degrade when subjected to high shear stresses which could be a part of the process of their elimination from the vascular system. However, the relative rate of their degradation was not known especially in the presence of blood cells or particles. The hydrodynamic tests in this study demonstrated that DRP mechanical degradation was significantly increased by the presence of red blood cells (RBC) and even more so by the presence of rigid particles of similar size. Degradation rates increased with an increase in RBC or particle concentration. The natural DRP (derived from aloe) was shown to be much more resistant to flow-induced degradation than polyethylene oxide in the presence or absence of RBC.

Thrombosis is a common complication associated with blood contacting devices [1]. Platelets often (or preferably) deposit in specific regions which contain complex flow featuring separations, recirculation zones and stagnation points [2, 3].Copyright © 2007 by ASME

Water-soluble drag-reducing polymers (DRPs) were previously demonstrated to significantly increase blood flow, tissue perfusion, and tissue oxygenation when injected intravenously at nanomolar concentrations in various animal models. Turbulent flow drag-reducing ability was proven to be the most important factor defining the potential of polymers to favorably affect blood circulation. Several DRPs were applied in previous in vivo tests, but the search continues for suitable DRPs for biomedical applications. We demonstrated that poly(N-vinylformamide) (PNVF) with a molecular weight of 4.5 x 10(6) Da significantly reduced resistance to turbulent flow in a pipe and thus presents a DRP. We also found that the PNVF mechanical degradation is much slower than that of the most commonly used DRP, poly(ethylene oxide). PNVF is known to have low toxicity. Furthermore, our pilot in vivo study showed that PNVF had acceptable biocompatibility and hemodynamic effectiveness and thus could be considered as a DRP candidate for potential clinical use.

Various bis(2-hydroxy-3-chloropropyl)alkylamines were synthesized by coupling primary amine with epichlorohydrin and utilized as a monomer to react with ethylenediamine (EDA), N,N'-dimethylethylenediamine (DMEDA), or tetramethylethylenediamine (TMEDA) to generate a series of lipopolyhydroxylalkyleneamines. The number- and weight-average molecular weight (Mn and Mw) and polydispersity index (Mw/Mn) of the lipopolyhydroxylalkyleneamines were dependent on reactant solvent and reaction temperature. The compounds with EDA as backbone have better transfection activity and lower toxicity than those with DMEDA and TMEDA as backbone.