Size-selective Filtration Research Articles

PODO/TERT256 – A promising human immortalized podocyte cell line and its potential use for in vitro research at different oxygen levels

Podocytes are of key interest for the prediction of nephrotoxicity as they are especially sensitive to toxic insults due to their central role in the glomerular filtration apparatus. However, currently, prediction of nephrotoxicity in humans remains insufficiently reliable, thus highlighting the need for advanced in vitro model systems using human cells with improved prediction capacity. Recent approaches for refining in vitro model systems focus on closely replicating physiological conditions as observed under the in vivo situation typical of the respective nephron section of interest. PODO/TERT256, a human immortalized podocyte cell line, were employed in a semi-static transwell system to evaluate its potential use as a human podocyte in vitro system for modelling potential human glomerular toxicity. Furthermore, the impact of routinely employed excessive oxygen tension (21 % - AtmOx), when compared to the physiological oxygen tensions (10 % - PhysOx) observed in vivo, was analyzed. Generally, cultured PODO/TERT256 formed a stable, contact-inhibited monolayer with typical podocyte morphology (large cell body, apical microvilli, finger-like cytoplasmic projections (reminiscent of foot processes), and interdigitating cell-cell junctions) and developed a size-selective filtration barrier. PhysOx, however, induced a more pronounced in vivo like phenotype, comprised of significantly larger cell bodies, significantly enhanced filtration barrier size-selectivity, and a remarkable re-localization of nephrin to the cell membrane, thus suggesting an improved in vitro replication of in vivo characteristics. Preliminary toxicity characterization with the known glomerulotoxin doxorubicin (DOX) suggested an increasing change in filtration permeability, already at the lowest DOX concentrations tested (0.01 μM) under PhysOx, whereas obvious changes under AtmOx were observed as of 0.16 μM and higher with a near all or nothing effect. The latter findings suggested that PODO/TERT256 could serve as an in vitro human podocyte model for studying glomerulotoxicity, whereby culturing at PhyOx tension appeared critical for an improved in vivo-like phenotype and functionality. Moreover, PODO/TERT256 could be incorporated into advanced human glomerulus systems in vitro, recapitulating microfluidic conditions and multiple cell types (endothelial and mesenchymal cells) that can even better predict human glomerular toxicity.

Nanoporous Atomically Thin Graphene Filters for Nanoscale Aerosols

Filtering nanoparticulate aerosols from air streams is important for a wide range of personal protection equipment (PPE), including masks used for medical research, healthcare, law enforcement, first responders, and military applications. Conventional PPEs capable of filtering nanoparticles <300 nm are typically bulky and sacrifice breathability to maximize protection from exposure to harmful nanoparticulate aerosols including viruses ∼20-300 nm from air streams. Here, we show that nanopores introduced into centimeter-scale monolayer graphene supported on polycarbonate track-etched supports via a facile oxygen plasma etch can allow for filtration of aerosolized SiO2 nanoparticles of ∼5-20 nm from air steams while maintaining air permeance of ∼2.28-7.1 × 10-5 mol m-2 s-1 Pa-1. Furthermore, a systematic increase in oxygen plasma etch time allows for a tunable size-selective filtration of aerosolized nanoparticles. We demonstrate a new route to realize ultra-compact, lightweight, and conformal form-factor filters capable of blocking sub-20 nm aerosolized nanoparticles with particular relevance for biological/viral threat mitigation.

Physiology assays in human kidney organoids.

Kidney organoids derived from human pluripotent stem cells constitute a novel model of disease, development, and regenerative therapy. Organoids are human, experimentally accessible, high throughput, and enable reconstitution of tissue-scale biology in a petri dish. Although gene expression patterns in organoid cells have been analyzed extensively, less is known about the functionality of these structures. Here, we review assays of physiological function in human kidney organoids, including best practices for quality control, and future applications. Tubular structures in organoids accumulate specific molecules through active transport, including dextran and organic anions, and swell with fluid in response to cAMP stimulation. When engrafted into animal models in vivo, organoids form vascularized glomerulus-like structures capable of size-selective filtration. Organoids exhibit metabolic, endocrine, injury, and infection phenotypes, although their specificity is not yet fully clear. To properly interpret organoid physiology assays, it is important to incorporate appropriate negative and positive controls, statistical methods, data presentation, molecular mechanisms, and clinical data sets. Improvements in organoid perfusion, patterning, and maturation are needed to enable branching morphogenesis, urine production, and renal replacement. Reconstituting renal physiology with kidney organoids is a new field with potential to provide fresh insights into classical phenomena.

Size-selective filtration of extracellular vesicles with a movable-layer device.

This paper presents a microfluidic device that can isolate extracellular vesicles (EVs) with multiple size intervals in a simple, effective, and automated manner. We accomplish this size-selective separation using a vertically movable plunger and a rotationally movable chip. The chip has open chambers with nanoporous filters that are sequentially connected by check valves. The plunger speed is adjusted to reduce chamber pressurization in order to prevent EV deformation, thereby achieving a high separation resolution. Herein, high-purity EVs with a purity ten times higher than that of ultracentrifugation were obtained by washing three times with a high EV recovery rate of 89%. For the analysis of device performance, we used polymer nanobeads, preformed liposomes, and canine blood plasma. To demonstrate the utility of the device, we applied size-selective isolation to EVs that were secreted by endothelial cells under shear flow. The results revealed that the cells secreted more EVs of larger size, the expression of CD63 protein was higher for EVs with a larger size, and a high amount of TSG101 protein was expressed under the condition of no shear flow. This device is envisioned to facilitate molecular analysis and EV-based biomarker discovery that use various biofluids, including blood plasma, urine, and cell culture supernatants. Our device automates size-selective EV filtration that requires laborious multiple washing and separation steps.

The podocyte-specific knockout of palladin in mice with a 129 genetic background affects podocyte morphology and the expression of palladin interacting proteins.

Proper and size selective blood filtration in the kidney depends on an intact morphology of podocyte foot processes. Effacement of interdigitating podocyte foot processes in the glomeruli causes a leaky filtration barrier resulting in proteinuria followed by the development of chronic kidney diseases. Since the function of the filtration barrier is depending on a proper actin cytoskeleton, we studied the role of the important actin-binding protein palladin for podocyte morphology. Podocyte-specific palladin knockout mice on a C57BL/6 genetic background (PodoPalldBL/6-/-) were back crossed to a 129 genetic background (PodoPalld129-/-) which is known to be more sensitive to kidney damage. Then we analyzed the morphological changes of glomeruli and podocytes as well as the expression of the palladin-binding partners Pdlim2, Lasp-1, Amotl1, ezrin and VASP in 6 and 12 months old mice. PodoPalld129-/- mice in 6 and 12 months showed a marked dilatation of the glomerular tuft and a reduced expression of the mesangial marker protein integrin α8 compared to controls of the same age. Furthermore, ultrastructural analysis showed significantly more podocytes with morphological deviations like an enlarged sub-podocyte space and regions with close contact to parietal epithelial cells. Moreover, PodoPalld129-/- of both age showed a severe effacement of podocyte foot processes, a significantly reduced expression of pLasp-1 and Pdlim2, and significantly reduced mRNA expression of Pdlim2 and VASP, three palladin-interacting proteins. Taken together, the results show that palladin is essential for proper podocyte morphology in mice with a 129 background.

Particle Collection in Imhoff Sedimentation Cones Enriches Both Motile Chemotactic and Particle-Attached Bacteria.

Marine heterotrophic microorganisms remineralize about half of the annual primary production, with the microbiomes on and around algae and particles having a major contribution. These microbiomes specifically include free-living chemotactic and particle-attached bacteria, which are often difficult to analyze individually, as the standard method of size-selective filtration only gives access to particle-attached bacteria. In this study, we demonstrated that particle collection in Imhoff sedimentation cones enriches microbiomes that included free-living chemotactic bacteria and were distinct from particle microbiomes obtained by filtration or centrifugation. Coastal seawater was collected during North Sea phytoplankton spring blooms, and the microbiomes were investigated using 16S rRNA amplicon sequencing and fluorescence microscopy. Enrichment factors of individual operational taxonomic units (OTUs) were calculated for comparison of fractionated communities after separation with unfractionated seawater communities. Filtration resulted in a loss of cells and yielded particle fractions including bacterial aggregates, filaments, and large cells. Centrifugation had the lowest separation capacity. Particles with a sinking rate of >2.4 m day–1 were collected in sedimentation cones as a bottom fraction and enriched in free-living chemotactic bacteria, i.e., Sulfitobacter, Pseudoalteromonas, and Vibrio. Subfractions of these bottom fractions, obtained by centrifugation, showed enrichment of either free-living or particle-attached bacteria. We identified five distinct enrichment patterns across all separation techniques: mechano-sensitive and mechano-stable free-living bacteria and three groups of particle-attached bacteria. Simultaneous enrichment of particle-attached and chemotactic free-living bacteria in Imhoff sedimentation cones is a novel experimental access to these groups providing more insights into the diversity, structure, and function of particle-associated microbiomes, including members of the phycosphere.

Floating Magnetic Membrane for Rapid Enrichment of Pathogenic Bacteria

Efficient separation and enrichment of pathogenic bacteria from complex matrices are crucial for the detection and downstream biomedical investigations. Herein, we report a floating magnetic membrane comprised of superparamagnetic nanoparticles and cationic polymer chains for rapid capture and enrichment of pathogenic bacteria under continuous flow. Magnetic nanoparticles combined with polymeric chains have shown affordable features to capture, release, and concentrate the pathogens by applying an external magnetic field. We have verified the modulated porous characteristics of the floating magnetic membrane depending on the molecular weight of cationic polymer chains and demonstrated rapid enrichment of pathogenic bacteria from aqueous fluid in the capillary glass tube (> 50-fold). Structural flexibility of the magnetic membrane allows the liquid and smaller species to pass through but efficiently induces binding of the bacteria on the antibody-functionalized magnetic nanoparticles of the floating virtual web. The magnetic membrane enables size-selective filtration and target-specific trapping through ionic exchange and immunomagnetic isolation. This study implies that spatiotemporal application of the magnetic membrane for rapid enrichment of biological targets in a large volume of continuous flow using microfluidic devices and biochips.

Aerosol Filtration Testing of Fabrics for Development of Reusable Face Masks

The ongoing outbreak of coronavirus disease of 2019 (COVID-19), triggered by the rapid community spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought forward the need for speedy testing and manufacturing of respiratory face masks for global use. Overwhelmed by the fast-growing demand for disposable face masks, many governments have recommended the use of, and elaborated design criteria for, reusable face masks that are meant to slow down the transmission of SARS-CoV-2 in the general population. Using aerosol particle size spectrometers, we performed particle size distribution measurements and calculated the fractional aerosol particle size-selective filtration efficiencies of over 300 fabrics and fabric-assemblies, including chiffon, cotton, synthetics, and various promising layered combinations. We suggest, and experimentally verify, a simple way for estimating the aerosol filtration efficiency of layered fabrics. The analysis herein investigates the relationship between the breathability and filtration properties of fabrics, assemblies of fabrics, and commercial reusable masks from various regions around the globe. In addition, we demonstrate how a hydrophobic coating can provide a statistically significant increase in the fabrics’ filtration efficiency. The insights of this work are crucial to developing non-woven, high-filtration-performance, reusable face masks that can be worn for extended periods of time. © The Author(s).

Size selective particle filtering on centimeter scale by frequency sweep type dynamic acoustic field

The objective of the study was to investigate and demonstrate the application of frequency-sweep dynamic acoustic fields for size-selective particle filtration on centimeter scale in a regulated continuous flow. The 3D-printed prototype of the acoustic separator has two inlets and two outlets, whereas the dynamic acoustic field is generated between a transducer, operating in the MHz range, and a reflector. The measured frequency response of the prototype was input to computer models, and simulations were carried out to explore the effects of the sweep period and the flow parameters on the filtration performance. A design-of-experiments study showed that the filtration performance is largely affected by the sweep period and the outlet flow rate. Lab experiments with model particle mixtures demonstrated the size selective filtration performance of the prototype with a total flow rate of 1Lh-1. A mixture with unknown properties was also used to demonstrate the selective filtration performance of the prototype.

Prolonged podocyte depletion in larval zebrafish resembles mammalian focal and segmental glomerulosclerosis.

Focal and segmental glomerulosclerosis (FSGS) is a histological pattern frequently found in patients with nephrotic syndrome that often progress to end-stage kidney disease. The initial step in development of this histologically defined entity is injury and ultimately depletion of podocytes, highly arborized interdigitating cells on the glomerular capillaries with important function for the glomerular filtration barrier. Since there are still no causal therapeutic options, animal models are needed to develop new treatment strategies. Here, we present an FSGS-like model in zebrafish larvae, an eligible vertebrate model for kidney research. In a transgenic zebrafish strain, podocytes were depleted, and the glomerular response was investigated by histological and morphometrical analysis combined with immunofluorescence staining and ultrastructural analysis by transmission electron microscopy. By intravenous injection of fluorescent high-molecular weight dextran, we confirmed leakage of the size selective filtration barrier. Additionally, we observed severe podocyte foot process effacement of remaining podocytes, activation of proximal tubule-like parietal epithelial cells identified by ultrastructural cytomorphology, and expression of proximal tubule markers. These activated cells deposited extracellular matrix on the glomerular tuft which are all hallmarks of FSGS. Our findings indicate that glomerular response to podocyte depletion in larval zebrafish resembles human FSGS in several important characteristics. Therefore, this model will help to investigate the disease development and the effects of potential drugs in a living organism.

100th Anniversary of Macromolecular Science Viewpoint: Integrated Membrane Systems.

Membranes fabricated from self-assembled materials are one recent example of how polymer science has been leveraged to advance membrane technology. Due to their well-defined nanostructures, the performance of membranes made from these materials is pushing the boundaries of size-selective filtration. Still, there remains a need for higher performance and more selective membranes. The advent of functional membrane platforms that rely on mechanisms beyond steric hindrance (e.g., charge-selective membranes and membrane sorbents) is one approach to realize improved solute-solute selectivity and further advance membrane technology. To date, the lab-scale demonstration of these platforms has often relied on fabrication schemes that require extended processing times. However, in order to translate lab-scale demonstrations to larger-scale implementation, it is critical that the rate of the functionalization scheme is reconciled with membrane manufacturing rates. In this viewpoint, it is postulated that substrates lined by reactive moieties that are amenable to postfabrication modification would enable the production of membranes with controlled nanostructures while providing access to a diverse array of pore wall chemistries. A comparison of reaction and manufacturing rates suggests that mechanisms that exhibit second-order reaction rate constants of at least 1 M-1 s-1 are needed for roll-to-roll processing. Furthermore, for mechanisms that exhibit rate constants greater than 300 M-1 s-1, it may be possible to integrate multiple functional domains over the membrane surface such that useful properties emerge. These multifunctional systems can expand the capabilities of membranes when the patterned chemistries interact at the heterojunctions between domains (e.g., Janus and charge-patterned mosaic membranes) or if they exhibit cooperative responses to external operating conditions (e.g., membrane pumps).

Size-selective filtration of the atrial wall estimated from the accumulation of tracers in the kidney of the mussel Mytilus galloprovincialis.

In order to determine the molecular weight cut-off (MWCO) for the atrial wall filtration into kidneys of the Mytilus galloprovincialis, we employed five magnetic resonance (MR) tracers: manganese chloride (Mn2+), gadolinium chloride (Gd3+), manganese-ethylenediaminetetraacetic acid (MnEDTA), gadolinium-diethylenetriamine pentaacetic acid (GdDTPA) and oligomer-based contrast agent (CH3-DTPA-Gd). After injection of the MR tracers (1 or 2 mmol l-1×0.1ml) into the visceral mass, T1-weighted MR imaging (T1w-MRI) and the longitudinal relaxation rates (1/T1=R1) were measured at 20°C. The MR tracers were distributed uniformly in the visceral mass within 1 h after injection. The T1w-MRI intensity and R1 of the kidney (R1K) were increased by Mn2+ and MnEDTA, with urine concentrations estimated at 210 and 65 µmoll-1, respectively. The rest of the tracers showed only minimal or no increase. When the mussels were additionally incubated in seawater with 10 µmoll-1 MnCl2, R1K was increased in the GdDTPA group, but not in the GdCl3 group. Therefore, Gd3+ might have inhibited renal accumulation of Mn2+ and Gd3+ Incubation in seawater with 10 µmoll-1 MnEDTA showed no increase in the R1K, but additional incubation with 10 µmoll-1 MnCl2 caused an increase in R1K It is suggested that injected MnEDTA was filtrated as MnEDTA per se, and not likely separated into free Mn2+ Thus, we concluded that the MWCO of the atrial wall of the M. galloprovincialis is around 0.5 kDa, which is almost 1/100 of that for vertebrate animals, and suggests a reduction in efforts to reabsorb metabolites and osmolytes from the urine.

Effects of Sample Preparation on Particle Size Distributions of Different Types of Silica in Suspensions.

The granulometric characterization of synthetic amorphous silica (SAS) nanomaterials (NMs) still demands harmonized standard operation procedures. SAS is produced as either precipitated, fumed (pyrogenic), gel and colloidal SAS and these qualities differ, among others, with respect to their state of aggregation and aggregate strength. The reproducible production of suspensions from SAS, e.g., for biological testing purposes, demands a reasonable amount of dispersing energy. Using materials representative for each of the types of SAS, we employed ultrasonic dispersing (USD) at energy densities of 8–1440 J/mL and measured resulting particle sizes by dynamic light scattering and laser diffraction. In this energy range, USD had no significant impact on particle size distributions of colloidal and gel SAS, but clearly decreased the particle size of precipitated and fumed SAS. For high energy densities, we observed a considerable contamination of SAS suspensions with metal particles caused by abrasion of the sonotrode’s tip. To avoid this problem, the energy density was limited to 270 J/mL and remaining coarse particles were removed with size-selective filtration. The ultrasonic dispersion of SAS at medium levels of energy density is suggested as a reasonable compromise to produce SAS suspensions for toxicological in vitro testing.

Incidental consumption of ephyrae of moon jellyfish Aurelia aurita s.l. by three filter-feeding sessile organisms: laboratory experiments

Moon jellyfish Aurelia aurita s.l. has been suggested to have high mortality during the ephyra stage, which potentially affects the population size of the later medusa stage. However, the mechanism behind the high mortality rate has still not been clarified. Ephyrae of A. aurita are liberated from the sessile strobila, which are usually surrounded by filter-feeding sessile organisms. In the present study, we carried out a series of feeding trials at 10 °C, offering A. aurita ephyrae to three potential predatory filter-feeding sessile organisms: the mussel Mytilus galloprovincialis, the ascidian Styela plicata, and the barnacle Amphibalanus eburneus. From the experiments, the mussel was estimated to have the highest ability to consume ephyrae among the sessile organisms. Size-selective filtration experiments showed that the mussel consumed newly liberated ephyrae [3 mm total body diameter (TBD)] at a significantly higher efficiency than larger (5 and 7 mm TBD) ephyrae. Our results demonstrate that filter-feeding sessile organisms, especially the mussel, are potential consumers of the early ephyra stage.

Fabrication of asymmetric and symmetric membranes based on PES/PEG/DMAc

Phase inversion is one of the main techniques for fabrication of asymmetric structural membranes and occasionally for the formation of a symmetric structure. Microporous membrane has been utilized for size-selective filtration in sample pre- or post-treatment applications. In this study, symmetrical or sponge-like membrane with highly interconnected pores based on polyethersulfone (PES) was fabricated via a combination of phase inversion techniques. The membrane pore sizes and distributions were controlled in the microfiltration range and the effects of humidity and polyethylene glycol (PEG) as a pore-forming agent on membrane morphology were investigated. Scanning electron microscopy (SEM) used to evaluate membrane cross section morphology, the porosity was calculated through the liquid immersion method, and pure water flux (PWF) was measured in a dead-end apparatus. We found that the humidity and pore-forming agent have a great impact on the formation of fully sponge-like structure in PES-based membrane. The results confirmed that by introducing PEG as pore-forming agent the sponge-like structure forms and molecular weight of additives as well as humidity alters the membrane morphology. Being located in a moist environment before immersion in non-solvent bath and after addition of PEG with different molecular weight (MW) will change the morphological structure of PES-based membrane, flux and retention properties. For nominal sample, the water permeability and porosity were 490.57 L/m2h and 90.39 %, respectively. Eventually the application of this membrane was investigated to determine the optimal potential in microorganisms filtration.

Preparation of Chemically-Tailored Copolymer Membranes with Tunable Ion Transport Properties.

Membranes derived from copolymer materials are a promising platform due to their straightforward fabrication and small yet tunable pore structures. However, most current applications of these membranes are limited to the size-selective filtration of solutes. In this study, to advance the utility of copolymer membranes beyond size-selective filtrations, a poly(acrylonitrile-r-oligo(ethylene glycol) methyl ether methacrylate-r-glycidyl methacrylate) (P(AN-r-OEGMA-r-GMA)) copolymer is used to fabricate membranes that can be chemically modified via straightforward schemes. The P(AN-r-OEGMA-r-GMA) copolymer is cast into asymmetric membranes using a nonsolvent induced phase separation technique. Then, the surface charge of the membrane is modified to tailor its performance for nanofiltration applications. The oxirane groups of the glycidyl methacrylate (GMA) moiety that line the pore walls of the membrane allows for both positively charged and negatively charged moieties to be introduced directly without any prior activation. Notably, the highly size-selective nanostructure of the copolymer materials is retained throughout the functionalization processes. Specifically, amine moieties are attached to the pore walls using the aminolysis of the oxirane groups. The resulting amine-functionalized membrane is positively charged and rejects up to 87% of the salt dissolved in a 10 mM magnesium chloride feed solution. Further modification of the amine-functionalized membrane with 4-sulfophenyl isothiocyanate results in pore walls lined by sulfonic acid moieties. These negatively charged membranes reject up to 90% of a 10 mM sodium sulfate feed solution. Throughout the modification scheme, the membrane permeability remains equal to 1.5 L m(-2) h(-1) bar(-1) and the rejection of neutral solutes (i.e., sucrose and poly(ethylene oxide)) is consistent with the membrane having a single well-defined pore diameter of ∼5 nm. The performance of the membrane as a function of ion valence number, solution pH, and ionic strength is investigated.

Circulating Epithelial Cells in Patients with Pancreatic Lesions: Clinical and Pathologic Findings

Circulating epithelial cell (CEC) isolation has provided diagnostic and prognostic information for a variety of cancers, previously supporting their identity as circulating tumor cells in the literature. However, we report CEC findings in patients with benign, premalignant, and malignant pancreatic lesions using a size-selective filtration device. Peripheral blood samples were drawn from patients found to have pancreatic lesions on preoperative imaging at a surgical clinic. Blood was filtered using ScreenCell devices, which were evaluated microscopically by a pancreatic cytopathologist. Pathologic data and clinical outcomes of these patients were obtained from medical records during a 1-year follow-up period. Nine healthy volunteers formed the control group and were found to be negative for CECs. There were 179 patients with pancreatic lesions that formed the study cohort. Circulating epithelial cells were morphologically similar in patients with a variety of pancreatic lesions. Specifically, CECs were identified in 51 of 105 pancreatic ductal adenocarcinomas (49%), 7 of 11 neuroendocrine tumors (64%), 13 of 21 intraductal papillary mucinous neoplasms (62%), and 6 of 13 patients with chronic pancreatitis. Rates of CEC identification were similar in patients with benign, premalignant, and malignant lesions (p = 0.41). In addition, CEC findings in pancreatic ductal adenocarcinoma patients were not associated with poor prognosis. Although CECs were not identified in healthy volunteers, they were identified in patients with benign, premalignant, and malignant pancreatic lesions. The presence of CECs in patients presenting with pancreatic lesions is neither diagnostic of malignancy nor prognostic for patients with pancreatic ductal adenocarcinoma.

Transport and deposition of stabilized engineered silver nanoparticles in water saturated loamy sand and silty loam

It is considered inevitable that the increasing production and application of engineered nanoparticles will lead to their release into the environment. However, the behavior of these materials under environmentally relevant conditions is still only poorly understood. In this study the transport and deposition behavior of engineered surfactant stabilized silver nanoparticles (AgNPs) in water saturated porous media was investigated in transport experiments with glass beads as reference porous medium and in two natural soils under various hydrodynamic and hydrochemical conditions. The transport and retention processes of AgNPs in the porous media were elucidated by inverse modeling and possible particle size changes occurring during the transport through the soil matrix were analyzed with flow field-flow fractionation (FlFFF). A high mobility of AgNPs was observed in loamy sand under low ionic strength (IS) conditions and at high flow rates. The transport was inhibited at low flow rates, at higher IS, in the presence of divalent cations and in a more complex, fine-grained silty loam. The slight decrease of the mean particle size of the AgNPs in almost all experiments indicates size selective filtration processes and enables the exclusion of homoaggregation processes.

Silver Nanoparticle-Mesoporous Oxide Nanocomposite Thin Films: A Platform for Spatially Homogeneous SERS-Active Substrates with Enhanced Stability

We introduce a nanoparticle-mesoporous oxide thin film composite (NP-MOTF) as low-cost and straightforward sensing platforms for surface-enhanced Raman Spectroscopy (SERS). Titania, zirconia, and silica mesoporous matrices templated with Pluronics F-127 were synthesized via evaporation-induced self-assembly and loaded with homogeneously dispersed Ag nanoparticles by soft reduction or photoreduction. Both methods give rise to uniform and reproducible Raman signals using 4-mercaptopyridine as a probe molecule. Details on stability and reproducibility of the Raman enhancement are discussed. Extensions in the design of these composite structures were explored including detection of nonthiolated molecules, such as rhodamine 6-G or salicylic acid, patterning techniques for locating the enhancement regions and bilayered mesoporous structures to provide additional control on the environment, and potential size-selective filtration. These inorganic oxide-metal composites stand as extremely simple, reproducible, and versatile platforms for Raman spectroscopy analysis.

The Podocyte as a Therapeutic Target in Proteinuric Kidney Disease

Kidney podocytes are highly differentiated cells with a complex cellular morphology. They are located inside the glomerulus, a corpuscle of capillaries through which blood is filtered hydrostatically through a high-volume/highdiscrimination filter. Neighboring podocyte Foot Processes (FP) is connected by a specialized cell-cell junction, the Slit Diaphragm (SD), which represents the main size selective filtration barrier in the kidney. The podocyte is an attractive cell for drug targeting due largely to its presence on the epithelial surface of one of the best vascularized organs in the body. Podocytes are exposed to 180 liters of filtered water and solutes each day, with the glomerular basement membrane and fenestrated glomerular endothelium not likely to be obstacles to small molecule passage. Though no podocyte-specific drugs are presently available, clinical nephrology has taken advantage of the pleitropic effects of a diverse array of therapeutic agents to treat glomerular disease. Glucocorticoids, retinoic acid, cyclosporine, abatacept, ACTH, thiazolidinedione, angiotensin converting enzyme inhibitors and rituximab have been successfully repurposed from other clinical indications to treat protein uric kidney disease. By different mechanisms these agents all nonspecifically target podocytes to promote their survival under disease conditions. This review summarizes the currently understood mechanistic basis for their use.