Intrinsically Fluorescent,Stealth Polypyrazoline Nanoparticles with Large Stokes Shift for In Vivo Imaging

Recent advances in super‐resolution microscopy and fluorescence bioimaging allow exploring previously inaccessible biological processes. To this end, there is a need for novel fluorescent probes with specific features in size, photophysical properties, colloidal and optical stabilities, as well as biocompatibility and ability to evade the reticuloendothelial system. Herein, novel fluorescent nanoparticles are introduced based on an inherently fluorescent polypyrazoline (PPy) core and a polyethylene glycol (PEG) shell, which address all aforementioned challenges. Synthesis of the PPy‐PEG amphiphilic block copolymer by phototriggered step‐growth polymerization is investigated by NMR spectroscopy, size‐exclusion chromatography, and mass spectrometry. The corresponding nanoparticles are characterized for their luminescent properties and hydrodynamic size in various aqueous environments (e.g., cell culture media). PPy nanoparticles particularly exhibit a large Stokes shift (Δλ = 160 nm or Δν > 7000 cm^?1) with visible light excitation and strong colloidal stability. While clearance by macrophages and endothelial cells is minimal, PPy displays good biocompatibility. Finally, PPy nanoparticles prove to be long circulating when injected in zebrafish embryos, as observed by in vivo time‐lapse fluorescence microscopy. In summary, PPy nanoparticles are highly promising to be further developed as fluorescent nanodelivery systems with low toxicity and exquisite retention in the blood stream.     

Poly(vinyl alcohol) and poly(vinyl amine) blend membranes for isopropanol dehydration

Blended membranes of hydrophilic polymers poly(vinyl alcohol) (PVA) and poly(vinyl amine) (PVAm) were prepared and crosslinked with glutaraldehyde. The prepared membranes were characterized using infrared (attenuated total reflection mode) spectroscopy, differential scanning calorimetry, X‐ray diffractometry, and scanning electron microscopy measurements. Pervaporation performances of the membranes were evaluated for the separation of water‐isopropanol (IPA) mixtures. As the PVAm content increased from PVAm0 to PVAm1.5, the flux through a 70 μm film increased from 0.023 to 0.10 kg/m² h at an IPA/water feed ratio of 85/15 at 30 °C. The driving force for permeation of water increased due to the temperature but it has no effect on IPA permeation. Activation energies for the permeation of IPA and water were calculated to be 17.11 and 12.46 kJ/mol, respectively. Controlling the thickness of the blend membrane could improve the permeation flux with only a marginal reduction in the separation factor. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45572.     

Electrophysiological and Structural Remodeling of the Atria in a Mouse Model of Troponin-I Mutation Linked Hypertrophic Cardiomyopathy: Implications for Atrial Fibrillation

Hypertrophic cardiomyopathy (HCM) is an inherited cardiac disorder affecting one in 500 of the general population. Atrial fibrillation (AF) is the most common arrhythmia in patients with HCM. We sought to characterize the atrial electrophysiological and structural substrate in young and aging Gly203Ser cardiac troponin-I transgenic (HCM) mice. At 30 weeks and 50 weeks of age (n = 6 per strain each group), the left atrium was excised and placed on a multi-electrode array (MEA) for electrophysiological study; subsequent histological analyses and plasma samples were analyzed for biomarkers of extracellular matrix remodeling and cell adhesion and inflammation. Wild-type mice of matched ages were included as controls. Young HCM mice demonstrated significantly shortened atrial action potential duration (APD), increased conduction heterogeneity index (CHI), increased myocyte size, and increased interstitial fibrosis without changes in effective refractory periods (ERP), conduction velocity (CV), inflammatory infiltrates, or circulating markers of extracellular matrix remodeling and inflammation. Aging HCM mice demonstrated aggravated changes in atria electrophysiology and structural remodeling as well as increased circulating matrix metalloproteinases (MMP)-2, MMP-3, and VCAM-1 levels. This model of HCM demonstrates an underlying atrial substrate that progresses with age and may in part be responsible for the greater propensity for AF in HCM.     

Numerical analysis of electrokinetic transport in micro-nanofluidic interconnect preconcentrator in hydrodynamic flow

The phenomenon of enrichment of charged analytes due to the presence of an electric field barrier at the micro-nanofluidic interconnect can be harnessed to enhance sensitivity and limit-of-detection in sensor instruments. We present a numerical analysis framework to investigate two critical electrokinetic phenomena underlying the experimental observation in Plecis et al. (Micro Total Analysis Systems, pp 1038–1041, 2005b): (1) ion transport of background electrolytes (BGE) and (2) enrichment of analytes in the micro-nanofluidic devices that operate under hydrodynamic flow. The analysis is based on the full, coupled solution of the Poisson–Nernst–Planck (PNP) and Naviér–Stokes equations, and the results are validated against analytical models of simple canonical geometry. Parametric simulation is performed to capture the critical effects of pressure head and BGE ion concentration on the electrokinetics and ion transport. Key findings obtained from the numerical analysis indicate that the hydrodynamic flow and overlapped electrical double layer induce concentration–polarization at the interfaces; significant electric field barrier arising from the Donnan potential forms at the micro–nano interfaces; and streaming potential and overall potential are effectively established across the micro-nanofluidic device. The simulation to examine analyte enrichment and its dependence on the hydrodynamic flow and analyte properties, demonstrates that order-of-magnitude enrichment can be achieved using properly configured hydrodynamic flow. The results can be used to guide practical design and operational protocol development of novel micro-nanofluidic interconnect-based analyte preconcentrators.     

System-level modeling and simulation of biochemical assays in lab-on-a-chip devices

We present a “mixed-methodology” based system-level modeling and simulation for biochemical assays in lab-on-a-chip (LoC) devices. The methodology uses a combination of numerical schemes and analytical approaches to simulate biological and physicochemical processes, specifically, an integral approach for fluid flow and electric field, method of lines (MOL) and two-compartment models for biochemical reactions, and Fourier series-based model for analyte mixing. The solution procedure begins with decomposing the LoC device into a system of inter-connected components (e.g., channels and junctions) and the models are solved in a network fashion. Models are developed to accurately capture the multi-physics (e.g., flow, mixing, and reaction) behavior of individual components. The assembly of the components is facilitated via exchange of fluid flux and Fourier series coefficients (or average concentration) of analytes between various components, which enables network solution of the models. The system models are validated against both experimental and numerical models on various biochemical assays (e.g. immunoassays and enzymatic reactions), showing significant computational speedup (100–10,000-fold depending on the assay) without appreciably compromising accuracy (<10% error relative to numerical analysis).