Μm Polystyrene Microspheres Research Articles

A Zebrafish Embryo Model for In Vivo Visualization and Intravital Analysis of Biomaterial-associated Staphylococcus aureus Infection.

Biomaterial-associated infection (BAI) is a major cause of the failure of biomaterials/medical devices. Staphylococcus aureus is one of the major pathogens in BAI. Current experimental BAI mammalian animal models such as mouse models are costly and time-consuming, and therefore not suitable for high throughput analysis. Thus, novel animal models as complementary systems for investigating BAI in vivo are desired. In the present study, we aimed to develop a zebrafish embryo model for in vivo visualization and intravital analysis of bacterial infection in the presence of biomaterials based on fluorescence microscopy. In addition, the provoked macrophage response was studied. To this end, we used fluorescent protein-expressing S. aureus and transgenic zebrafish embryos expressing fluorescent proteins in their macrophages and developed a procedure to inject bacteria alone or together with microspheres into the muscle tissue of embryos. To monitor bacterial infection progression in live embryos over time, we devised a simple but reliable method of microscopic scoring of fluorescent bacteria. The results from microscopic scoring showed that all embryos with more than 20 colony-forming units (CFU) of bacteria yielded a positive fluorescent signal of bacteria. To study the potential effects of biomaterials on infection, we determined the CFU numbers of S. aureus with and without 10 µm polystyrene microspheres (PS10) as model biomaterials in the embryos. Moreover, we used the ObjectJ project file "Zebrafish-Immunotest" operating in ImageJ to quantify the fluorescence intensity of S. aureus infection with and without PS10 over time. Results from both methods showed higher numbers of S. aureus in infected embryos with microspheres than in embryos without microspheres, indicating an increased infection susceptibility in the presence of the biomaterial. Thus, the present study shows the potential of the zebrafish embryo model to study BAI with the methods developed here.

Effects of ingested polystyrene microplastics on brine shrimp, Artemia parthenogenetica

Microplastics are a contaminant of emerging concern which enter the marine environment from a variety of sources. The ingestion and toxic effects of microplastics on marine life, especially for filter feeders, are a cause of concern in view of their ubiquitous nature and their similar size as food sources. To assess the toxic effects of microspheres ingested by brine shrimp larvae, we exposed Artemia parthenogenetica to 10 μm polystyrene microspheres at different concentrations. These concentrations were approximate to the extrapolated marine aquatic environmentally relevant concentrations. The lowest polystyrene concentrations at which ingestion was visualized in A. parthenogenetica were 12 ± 0.57 particles/mL (6.7 ± 0.32 μg/L) and 1.1 ± 0.16 particles/mL (0.61 ± 0.088 μg/L), respectively. There were no significant impacts on the survival, growth or development in A. parthenogenetica occurring over the 14-d exposure across a range of polystyrene nominal concentrations (1–1000 particles/mL or 0.55–550 μg/L). However, abnormal ultrastructures of intestinal epithelial cells were observed upon exposure to polystyrene microspheres, including fewer and disordered microvilli, an increased number of mitochondrion and the appearance of autophagosome. These phenomena could affect nutrition absorption and energy metabolism. Although no major acute or chronic toxicity effects on A. parthenogenetica were observed over 24-h or 14-d exposures, this study provides evidence that the ingestion of polystyrene microplastics at extrapolated environmentally relevant concentrations can be visualized through a microscope to be causing a series of responses in intestinal epithelial cells.

A self-assembled metamaterial for Lamb waves

We report the design and characterization of a self-assembled, locally resonant acoustic metamaterial for Lamb waves, composed of a monolayer of 1.02 μm polystyrene microspheres adhered to a 1.27 μm thick free-standing silicon membrane. A laser-induced transient grating technique is used to generate Lamb waves in the metamaterial and to measure its acoustic response. The measurements reveal a microsphere contact resonance and the lowest frequency spheroidal microsphere resonance. The measured dispersion curves show hybridization of flexural Lamb waves with the microsphere contact resonance. We compare the measured dispersion with an analytical model using the contact resonance frequency as a single fitting parameter, and find that it well describes the observed hybridization. This study may lead to an improved understanding of microscale contact mechanics and to the design of new types of acoustic metamaterials.

Embolization of the first diagonal branch of the left anterior descending coronary artery as a porcine model of chronic trans-mural myocardial infarction

BackgroundAlthough the incidence of acute death related to coronary artery disease has decreased with the advent of new interventional therapies, myocardial infarction remains one of the leading causes of death in the US. Current animal models developed to replicate this phenomenon have been associated with unacceptably high morbidity and mortality. A new model utilizing the first diagonal branch of the left anterior descending artery (D1-LAD) was developed to provide a clinically relevant lesion, while attempting to minimize the incidence of adverse complications associated with infarct creation.MethodsEight Yucatan miniature pigs underwent percutaneous embolization of the D1-LAD via injection of 90 µm polystyrene micro-spheres. Cardiac structure and function were monitored at baseline, immediately post-operatively, and at 8-weeks post-infarct using transthoracic echocardiography. Post-mortem histopathology and biochemical analyses were performed to evaluate for changes in myocardial structure and extracellular matrix (ECM) composition respectively. Echocardiographic data were evaluated using a repeated measures analysis of variance followed by Tukey’s HSD post hoc test. Biochemical analyses of infarcted to non-infarcted myocardium were compared using analysis of variance.ResultsAll eight pigs successfully underwent echocardiography prior to catheterization. Overall procedural survival rate was 83% (5/6) with one pig excluded due to failure of infarction and another due to deviation from protocol. Ejection fraction significantly decreased from 69.7 ± 7.8% prior to infarction to 50.6 ± 14.7% immediately post-infarction, and progressed to 48.7 ± 8.9% after 8-weeks (p = 0.011). Left ventricular diameter in systole significantly increased from 22.6 ± 3.8 mm pre-operatively to 30.9 ± 5.0 mm at 8 weeks (p = 0.016). Histopathology showed the presence of disorganized fibrosis on hematoxylin and eosin and Picro Sirius red stains. Collagen I and sulfated glycosaminoglycan content were significantly greater in the infarcted region than in normal myocardium (p = 0.007 and p = 0.018, respectively); however, pyridinoline crosslink content per collagen I content in the infarcted region was significantly less than normal myocardium (p = 0.048).ConclusionSystolic dysfunction and changes in ECM composition induced via embolization of the D1-LAD closely mimic those found in individuals with chronic myocardial infarction (MI), and represents a location visible without the need for anesthesia. As a result, this method represents a useful model for studying chronic MI.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0547-4) contains supplementary material, which is available to authorized users.

Doxycycline Prevents Right Ventricular Dysfunction Induced by Pulmonary Embolism

Pulmonary embolism (PE) is commonly associated to right ventricular (RV) dysfunction, which predict poor outcome. Doxycycline pretreatment has been associated to beneficial effects after PE. However, no previous study has evaluated doxycycline posttreatment.Male Sprague‐Dawley rats (300‐350g) were anaesthetized with ketamine and xylazine. On day 1, the PE group received 85 µm polystyrene microspheres (221.000/100 g body wt, jugular vein) suspended in 0.01% Tween 20 and the Sham group received Tween only. Treatment animals received doxycycline (Doxy, 30mg/kg by gavage) and Controls received volume‐matched saline for 5 days after PE induction. Hearts were then extirpated from anesthetized animals on day 5 and perfused via the aorta using Langendorff technique with Krebs‐Henseleit buffer. We explored the Frank‐Starling relationship of RV contractile function (RV developed pressure, dP/dtmax and dP/dtmin) by increasing RV end diastolic pressures (from 0 to 40 mmHg). P<0.05 was considered significant.In the PE group (n=6), ex vivo RV function was decreased significantly after 5 days compared with the Sham group (n=6), including RV developed pressure (PE, from 14±3.5 to 68±5.1 mmHg) vs (Sham, from 38±1.2 to 88±2.4 mmHg), dP/dtmax (PE, from 516±114 to 1022±201 mmHg/s) vs (Sham, from 1442±113 to 1826±75 mmHg/s), and dP/dtmin (PE, from ‐401±76 to ‐667±108 mmHg/s) vs (Sham, from ‐992±71 to ‐1185±77 mmHg/s). When compared with PE group, Treatment animals (PE+Doxy, n=6) had significantly improved RV function (from 35±4.0 to 89±1.7 mmHg), (from 1411±198 to 2034±149 mmHg/s) and (‐852±126 to ‐1119±87 mmHg/s) respectively.Doxycycline improved the intrinsic RV contractile dysfunction caused by PE. Doxycycline may help preserve RV function and decrease morbidity after PE.

Assessment of Active Pharmaceutical Ingredient Particle Size in Tablets by Raman Chemical Imaging Validated using Polystyrene Microsphere Size Standards

Particle size is a critical parameter for controlling pharmaceutical quality. The aim of this study was to assess the size of the micrometer-scale active pharmaceutical ingredients (API) in tablets using Raman chemical imaging and to understand the effects of formulation on particle size. Model tablets containing National Institute of Standards and Technology traceable polystyrene microsphere size standards were developed to determine the binarization threshold value of Raman chemical images for API particle sizing in specific formulations and processes. Three sets of model tablets containing 5, 10, and 15 μm polystyrene microspheres, used to mimic API, were prepared using a commercial tablet formulation (Ebastel tablets, mean API particle size was about 5 μm). Raman mapping with a 50× objective (NA, 0.75) was applied to tablet cross-sections, and particle size of polystyrene microspheres was estimated from binary images using several binarization thresholds. Mean particle size for three sets of polystyrene microspheres showed good agreement between pre- and postformulation (the slope = 1.024, R = 1.000) at the specific threshold value ((mean + 0.5σ) of the polystyrene-specific peak intensity histogram), regardless of particle agglomeration, tablet surface roughness, and laser penetration depth. The binarization threshold value showed good applicability to Ebastel tablets, where the API-specific peak intensity histogram showed a pattern similar to that of polystyrene microspheres in model tablets. The model tablets enabled determination of an appropriate binarization threshold for assessing the mean particle size of micrometer-scale API in tablets by utilizing the unique physicochemical properties of polystyrene microspheres.

A multichannel acoustically driven microfluidic chip to study particle-cell interactions

Microfluidic devices have emerged as important tools for experimental physiology. They allow to study the effects of hydrodynamic flow on physiological and pathophysiological processes, e.g., in the circulatory system of the body. Such dynamic in vitro test systems are essential in order to address fundamental problems in drug delivery and targeted imaging, such as the binding of particles to cells under flow. In the present work an acoustically driven microfluidic platform is presented in which four miniature flow channels can be operated in parallel at distinct flow velocities with only slight inter-experimental variations. The device can accommodate various channel architectures and is fully compatible with cell culture as well as microscopy. Moreover, the flow channels can be readily separated from the surface acoustic wave pumps and subsequently channel-associated luminescence, absorbance, and/or fluorescence can be determined with a standard microplate reader. In order to create artificial blood vessels, different coatings were evaluated for the cultivation of endothelial cells in the microchannels. It was found that 0.01% fibronectin is the most suitable coating for growth of endothelial monolayers. Finally, the microfluidic system was used to study the binding of 1 μm polystyrene microspheres to three different types of endothelial cell monolayers (HUVEC, HUVECtert, HMEC-1) at different average shear rates. It demonstrated that average shear rates between 0.5 s(-1) and 2.25 s(-1) exert no significant effect on cytoadhesion of particles to all three types of endothelial monolayers. In conclusion, the multichannel microfluidic platform is a promising device to study the impact of hydrodynamic forces on cell physiology and binding of drug carriers to endothelium.

Giant resonant light forces in microspherical photonics

Resonant light pressure effects can open new degrees of freedom in optical manipulation with microparticles, but they have been traditionally considered as relatively subtle effects. Using a simplified two-dimensional model of surface electromagnetic waves evanescently coupled to whispering gallery modes (WGMs) in transparent circular cavities, we show that under resonant conditions the peaks of the optical forces can approach theoretical limits imposed by the momentum conservation law on totally absorbing particles. Experimentally, we proved the existence of strong peaks of the optical forces by studying the optical propulsion of dielectric microspheres along tapered microfibers. We observed giant optical propelling velocities ∼0.45 mm s−1 for some of the 15-20 µm polystyrene microspheres in water for guided powers limited at ∼43 mW. Such velocities exceed previous observations by more than an order of magnitude, thereby providing evidence for the strongly enhanced resonant optical forces. We analyzed the statistical properties of the velocity distribution function measured for slightly disordered (∼1% size variations) ensembles of microspheres with mean diameters varying from 3 to 20 µm. These results demonstrate a principal possibility of optical sorting of microspheres with the positions of WGM resonances overlapped at the wavelength of the laser source. They can be used as building blocks of the lossless coupled resonator optical waveguides and various integrated optoelectronics devices.

A soluble guanylate cyclase stimulator, BAY 41-8543, preserves right ventricular function in experimental pulmonary embolism

Pulmonary embolism (PE) increases pulmonary vascular resistance, causing right ventricular (RV) dysfunction, and poor clinical outcome. Present studies test if the soluble guanylate cyclase stimulator BAY 41-8543 reduces pulmonary vascular resistance and protects RV function. Experimental PE was induced in anesthetized, male Sprague–Dawley rats by infusing 25 μm polystyrene microspheres (1.95 million/100 g body wt, right jugular vein) producing moderate PE. Pulmonary artery vascular resistance, estimated as RVPSP/CO, increased 3-fold after 5 h of PE. Treatment with BAY 41-8543 (50 μg/kg, I.V.; given at the time of PE induction) normalized this index by reducing RVPSP and markedly increasing CO, via preservation of heart rate and stroke volume. Ex vivo RV heart function showed minimal changes at 5 h of PE, but decreased significantly after 18 h of PE, including peak systolic pressure (PSP, Control 39 ± 1 mmHg vs. 19 ± 3 PE), +dP/dt (1192 ± 93 mmHg/s vs. 444 ± 64) and −dP/dt (−576 ± 60 mmHg/s vs. −278 ± 40). BAY 41-8543 significantly improved all three indices of RV heart function (PSP 35 ± 3.5, +dP/dt 1129 ± 100, −dP/dt −568 ± 87). Experimental PE produced increased PVR and RV dysfunction, which were ameliorated by treatment with BAY 41-8543. Thus, there is vasodilator reserve in this model of experimental PE that can be exploited to reduce the stress upon the heart and preserve RV contractile function.

UV‐illuminated dielectrophoresis by two‐dimensional electron gas (2DEG) in AlGaN/GaN heterojunction

AbstractDielectrophoresis (DEP) induced by activating a patterned two‐dimensional electron gas (2DEG) at the interface of compound semiconductor AlGaN/GaN heterojunction has been demonstrated for the first time in our previous work. Briefly, with a peak voltage of ±10 V and a frequency from 100 kHz to 1 MHz, characteristics of both positive and negative DEP have been observed successfully manipulating 2 µm polystyrene microspheres in a drop of deionized (DI) water (pH ∼ 7 and conductivity 1 × 10−4 S m−1) over castellated 2DEG electrodes separated by critical dimensions 50 and 150 µm. This study reports a peculiar observation encountered when performing the DEP experiments under ultraviolet (UV) radiation: The microspheres have been repelled from the 2DEG electrodes yet remained on the surface during pDEP and then levitated upon switching to nDEP. This behavior is not observed in DEP with conventional microelectrodes and explained here by the UV‐induced electron–hole generation and the subsequent charge redistribution in the AlGaN/GaN heterostructure.

Using electrophoretic exclusion to manipulate small molecules and particles on a microdevice

Electrophoretic exclusion, a novel separations technique that differentiates species in bulk solution using the opposing forces of electrophoretic velocity and hydrodynamic flow, has been adapted to a microscale device. Proof-of-principle experiments indicate that the device was able to exclude small particles (1 μm polystyrene microspheres) and fluorescent dye molecules (rhodamine 123) from the entrance of a channel. Additionally, differentiation of the rhodamine 123 and polystyrene spheres was demonstrated. The current studies focus on the direct observation of the electrophoretic exclusion behavior on a microchip.

Microcapillary-assisted dielectrophoresis for single-particle positioning

Here, we demonstrate microcapillary-assisted dielectrophoresis (μC-DEP), a new capability for precise positioning of particles or biological cells in applications such as dynamic assays. The method largely derives from a need to evade the challenges faced with hydrodynamic trapping of particles or cells at microcapillaries typically realized through brief application of suction. Microcapillaries here serve a dual purpose by firstly squeezing field lines to define localized positive DEP traps and then establishing an exclusive access to the trapped cell for probing. Strength of the traps is presented through numerical results at various excitation frequencies. Their effectiveness is shown experimentally against relevant solution conductivities using 10 μm polystyrene microspheres. Usefulness of the method for positioning individual cells is demonstrated via experimental results on cell viability and single-cell impedance spectroscopy.

Microspheres as resistive elements in a check valve for low pressure and low flow rate conditions

In this paper we describe a microsphere-based check valve integrated with a micropump. The check valve uses Ø20 μm polystyrene microspheres to rectify flow in low pressure and low flow rate applications (Re < 1). The microspheres form a porous medium in the check valve increasing fluidic resistance based on the direction of flow. Three check valve designs were fabricated and characterized to study the microspheres' effectiveness as resistive elements. A maximum diodicity (ratio of flow in the forward and reverse direction) of 18 was achieved. The pumping system can deliver a minimum flow volume of 0.25 μL and a maximum flow volume of 1.26 μL under an applied pressure of 0.2 kPa and 1 kPa, respectively. A proof-of-concept study was conducted using a pharmaceutical agent, docetaxel (DTX), as a sample drug showing the microsphere check valve's ability to limit diffusion from the micropump. The proposed check valve and pumping concept shows strong potential for implantable drug delivery applications with low flow rate requirements.

Methods for the development and assessment of atrial fibrillation and heart failure dog models

ObjectiveTo report Medtronic experiences with the development of animal models for atrial fibrillation (AF) and chronic heart failure (CHF) using high-rate pacing for AF and microemboli for CHF.MethodsFor the AF model, an atrial lead was attached to a Medtronic Synergy™ neurostimulator, which was programmed to stimulate at 50 Hz in an on-off duty cycle. Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and N-terminal pro brain natriuretic peptide (NT-proBNP) were assayed at select time points. For CHF model, a serial injection of 90 µm polystyrene microspheres at 62,400 beads/mL (Polybead, Polysciences, Inc.) was performed to induce global ischemia, either with weekly monitoring and embolization schedule (group 1, n = 25) or with biweekly monitoring and emboliation schedule (group 2, n = 36 ). Echocardiograms were used along with ventriculograms and magnetic resonance imaging scans weekly to assess cardiac function and ANP, BNP and NT-proBNP were monitored.ResultsFor the AF model, the days to sustained AF for four animals following surgery were 7, 25, 21 and 19, respectively; For the CHF model, the days to meet CHF endpoints were 116 in group 1 and 89 in group 2. For both AF and CHF models, NT-proBNP correlated well with the development of disease states.ConclusionOur experience for the development and assessment of AF and CHF dog models may help researchers who are in search for animal model for assessing the safety and efficacy of a device-based therapy.

TOF-SIMS imaging of adsorbed proteins on topographically complex surfaces with Bi3+ primary ions

Although previous studies have demonstrated that TOF-SIMS is a powerful method for the characterization of adsorbed proteins due to its specificity and surface sensitivity, it was unclear from earlier work whether the differences between proteins observed on uniform flat surfaces were large enough to facilitate clear image contrast between similar proteins in small areas on topographically complex samples that are more typical of biological tissues. The goal of this study was to determine whether Bi(3) (+) could provide sufficiently high sensitivity to provide clear identification of the different proteins in an image. In this study, 10 μm polystyrene microspheres were adsorbed with one of three different proteins, human serum albumin (HSA), bovine serum albumin (BSA), and hemoglobin. Spheres coated with HSA were then mixed with spheres coated with either BSA (a very similar protein) or hemoglobin (a dramatically different protein), and deposited on silicon substrates. Fluorescent labeling was used to verify the SIMS results. With maximum autocorrelation factors (MAF) processing, images showed clear contrast between both the very different proteins (HSA and hemoglobin) and the very similar proteins (HSA and BSA). Similar results were obtained with and without the fluorescent labels. MAF images were calculated using both the full spectrum and only characteristic amino acid fragments. Although better image contrast was obtained using the full spectrum, differences between the spheres were still evident when only the amino acid fragments were included in the analysis, suggesting that we are truly observing differences between the proteins themselves. These results demonstrate that TOF-SIMS, with a Bi(3) (+) primary ion, is a powerful technique for characterizing interfacial proteins not only on large uniform surfaces, but also with high spatial resolution on the topographically complex samples typical in biological analysis.

Separation of mixtures of particles in a multipart microdevice employing insulator‐based dielectrophoresis

Dielectrophoresis is the electrokinetic movement of particles due to polarization effects in the presence of non-uniform electric fields. In insulator-based dielectrophoresis (iDEP) regions of low and high electric field intensity, i.e. non-uniformity of electric field, are produced when the cross-sectional area of a microchannel is decreased by the presence of electrical insulating structures between two electrodes. This technique is increasingly being studied for the manipulation of a wide variety of particles, and novel designs are continuously developed. Despite significant advances in the area, complex mixture separation and sample fractionation continue to be the most important challenges. In this work, a microchannel design is presented for carrying out direct current (DC)-iDEP for the separation of a mixture of particles. The device comprises a main channel, two side channels and two sections of cylindrical posts with different diameters, which will generate different non-uniformities in the electric field on the main channel, designed for the discrimination and separation of particles of two different sizes. By applying an electric potential of 1000 V, a mixture of 1 and 4 μm polystyrene microspheres were dielectrophoretically separated and concentrated at the same time and then redirected to different outlets. The results obtained here demonstrate that, by carefully designing the device geometry and selecting operating conditions, effective sorting of particle mixtures can be achieved in this type of multi-section DC-iDEP devices.

Synthesis and evaluation of heparin immobilized “side-on” to polystyrene microspheres coated with end-group activated polyethylene oxide

Thiol (–SH) groups were introduced into unfractionated heparin by reaction of carboxyl groups in its uronic acid residues with 3,3′dithiobis(propanoic)hydrazide. Thiolated heparin derivatives were then linked to pyridyl disulfide-activated polyethylene oxide–polypropylene oxide–polyethylene oxide triblocks, which had previously been coated onto the surfaces of 1.15 μm polystyrene microspheres. The heparin immobilization reaction was monitored spectrophotometrically as colored pyridine-2-thione was released. In addition, the zeta potentials of uncoated, triblock-coated, and heparin-containing microsphere suspensions were recorded to demonstrate the successful attachment of heparin on the surface. However this “side-on” attachment of heparin to pendant, polyethylene oxide chains did not significantly increase the anticoagulant or anti-Factor Xa activity of microsphere suspensions.

Optimizing Orthotopic Cell Transplantation in the Mouse Adrenal Gland

Orthotopic cell transplantation models are important for a complete understanding of cell-cell interactions as well as tumor biology. In published studies of orthotopic transplantation in the mouse adrenal gland, human neuroblastoma cells have been shown to invade and occupy the adrenal, but in these investigations a true orthotopic model was not established. Here we show an orthotopic model in which transplanted cells are retained within the adrenal gland by formation of a fibrin clot. To establish an appropriate technique, we used brightly fluorescent 10 microm polystyrene microspheres injected into the mouse adrenal gland. In the absence of fibrinogen/thrombin for clot formation, much of the injected material was extruded to the outside of the gland. When the microspheres were injected in a fibrinogen/thrombin mixture, fluorescence was confined to the adrenal gland. As a model neoplastic cell originating from the cortex of the gland, we used a tumorigenic bovine adrenocortical cell line. When 3 x 10(5) cells were implanted orthotopically, by 16 days the cell mass had expanded and had invaded the cortex, whereas when 1 x 10(5) cells were used, tumor masses were much smaller. We therefore subsequently used 3 x 10(5) cells. When mice were sacrificed at different time points, we found that tumor growth resulting was progressive and that by 26 days cells there was extensive invasion into the cortex or almost complete replacement of the cortex with tumor cells. As a model neoplastic cell of neural crest origin, we used SK-N-AS human neuroblastoma cells. Orthotopic transplantation of 3 x 10(5) cells resulted in extensive invasion and destruction of the gland by 26 days. In summary, the present orthotopic model for intra-adrenal cell transplantation is valuable for investigation of growth of neoplastic cells of both cortical and medullary origin and should be useful for future studies of cortex-medulla interactions.

Design and Characterization of Randomly Speckled Spheres

We use the "particle lithography" technique to fabricate randomly speckled spheres. Parts of positively charged 3.3 microm polystyrene microspheres were masked off with negatively charged 0.9 microm silica particles, and the remaining portion was covered with negatively charged 60 nm polystyrene nanoparticles. The masking particles were then removed to leave speckles on the larger core particle. Images from electron microscope and confocal microscope show that the diameter of the circular speckles is predictable and reliable, following an estimate from simple geometry, and that the number of speckles formed on a particle can be altered by changing the concentration of silica particle masks. The process described in this paper can be adapted to a wide variety of materials, opening the door for applications where size-controlled patches of one chemistry can appear on core particles of another chemistry and where the precise placement of patches is of little importance.

A three mechanism model to describe fouling of microfiltration membranes

Mathematical modeling of flux decline during filtration plays an important role in both sizing membrane systems and in the understanding of membrane fouling. Protein fouling is traditionally modeled using one of three classical fouling mechanisms: pore blockage, pore constriction or cake filtration. Here, we have developed a mathematical model to describe flux decline behavior during microfiltration accounting for all three classical fouling mechanisms. Pore constriction was assumed to first reduce the size of internal pores. Pore blockage then occurs at the top of the membrane, preventing further fouling to the interior structure. Finally the foulants at the top of the membrane form a cake, which controls the late stages of the filtration. The model prediction shows excellent agreement with experimental data for 0.25 μm polystyrene microspheres filtered through 0.22 μm Isopore membranes (where pore constriction is expected to be minimal) as well as non-aggregated bovine serum albumin solution through hydrophobic Durapore membranes (where pore constriction is expected to dominate). The effects of different fouling mechanisms on the flux decline were characterized by the ratio of characteristic fouling times of the different mechanisms. In this way the model can provide additional insights into the relative importance of different fouling mechanisms as compared to an analysis by a single mechanism model or by derivative plots, and it can be used to provide important insights into the flux decline characteristics.