Inertial-Based Filtration Method for Removal of Microcarriers from Mesenchymal Stem Cell Suspensions

© 2018, The Author(s). Rapidly evolving cell-based therapies towards clinical trials demand alternative approaches for efficient expansion of adherent cell types such as human mesenchymal stem cells (hMSCs). Using microcarriers (100–300 µm) in a stirred tank bioreactor offers considerably enhanced surface to volume ratio of culture environment. However, downstream purification of the harvested cell product needs to be addressed carefully due to distinctive features and fragility of these cell products. This work demonstrates a novel alternative approach which utilizes inertial focusing to separate microcarriers (MCs) from the final cell suspension. First, we systematically investigated MC focusing dynamics inside scaled-up curved channels with trapezoidal and rectangular cross-sections. A trapezoidal spiral channel with ultra-low-slope (Tan(α) = 0.0375) was found to contribute to strong MC focusing (~300 < Re < ~400) while managing high MC volume fractions up to ~1.68%. Accordingly, the high-throughput trapezoidal spiral channel successfully separated MCs from hMSC suspension with total cell yield~94% (after two passes) at a high volumetric flow rate of ~30 mL/min (Re~326.5)

Synthesis, Characterization, and Application of Stabilized-Ni/Fe Bimetallic Nanoparticles for the Selective Elimination of Chlorate Impurity in Military Grade Ammonium Perchlorate

Ammonium perchlorate (AP) is used as the most common oxidizer in composite solid propellants. Control of chlorate impurity in military grade ammonium perchlorate is important, since it has an undesirable effect on the thermal decomposition of ammonium perchlorate. In this work stabilized Ni/Fe bimetallic nanoparticles (S-Ni/Fe NPs) were synthesized using the borohydride reduction method (BRM) in the presence of starch as a stabilizing agent, and they were characterized by field emission scanning electron microscopy (SEM), and their X-ray diffraction pattern (XRD). The results showed that the synthesized S-Ni/Fe bimetallic nanoparticles were spherical in shape and had nearly uniform distribution, with particle sizes of 20-50 nm. The prepared nanoparticles were then used for the selective elimination of chlorate impurity in ammonium perchlorate. The main factors controlling the elimination of chlorate, such as the initial pH of the solution, dosage of S-Fe/Ni NPs, initial chlorate and perchlorate concentrations, reaction temperature, and reaction time, were optimized by using an experimental design based on the Taguchi method. An L9 orthogonal array (L9-OA) was used to design experiments with four 4-level factors (34). Under the optimal conditions, i.e., pH 6.5, at 30 °C and a dosage of 50 mg S-Ni/Fe NPs, chlorate was eliminated with nearly 100% efficiency in 50 mL of a solution containing 2.0 μg·mL−1 and 100 μg·mL−1 of chlorate and perchlorate, respectively, without change in perchlorate concentration

Opportunistic Multi-Layer Transmission over Unknown Channels

We use the received bit information rate (RBIR) to analyze the performance of multi-layer transmission when combined with hybrid automatic repeat request (HARQ). The different layers are obtained from ordinary Gray-coded M-QAM and used for transmitting log2(M) codewords in parallel, exploiting that the different bits in Gray-coded M-QAM have very different reliability. The performance is analyzed when different layers are decoded in parallel (independently) as well as when successive decoding is used. In addition, we study how the RBIR can be used to select a suitable layer for a retransmission to further improve the performance. Simulation results based on a Wi-Fi like physical layer show that a significant gain compared to the standard approach can be achieved by using basic multilayer transmission, and also that using successive decoding and carefully selecting what layer to use for retransmission can give further gains

Predisposing role of Vitamin D receptor (VDR) polymorphisms in the development of multiple sclerosis: A case-control study

Multiple sclerosis (MS) is a chronic inflammatory, demyelinating, and neurodegenerative disease of the central nervous system (CNS) with a complex etiology. Given the Vitamin D receptor (VDR) gene, it is considered an outstanding risk component associated with MS. The aim of the present study has been to explore and emphasize the role of ApaI, BsmI, TaqI and FokI polymorphisms of VDR gene in susceptibility to MS in an Iranian case-control population including 160 patients and 150 healthy controls. All cases were clinically diagnosed with relapsing-remitting (RR) form, and the controls were age, gender, and race matched which were completely in agreement with the case group. PCR-R FLP was conducted for all the SNPs genotyping. The findings of the study showed a significant difference in allele frequency between the cases and controls for ApaI (p 0.0125). The results also showed that AA genotype polymorphism of ApaI and BsmI (OR = 4.6 and OR = 2.52, respectively), CC genotype of TaqI (OR = 2.41) and AC genotype of ApaI (OR = 1.79) are associated with the disease status. Nevertheless, the results revealed the protective role of TT genotype of TaqI (ORs < 1), CC genotype of Apal, and GG genotype of BsmI (ORs < 1). VDR polymorphisms seem to have a notable connection with MS pathogenesis, however, study of more big population and functional work on the gene structure and its function are recommended. © 2016 Published by Elsevier B.V

Inertial particle focusing dynamics in a trapezoidal straight microchannel: application to particle filtration

© 2018, Springer-Verlag GmbH Germany, part of Springer Nature. Inertial microfluidics has emerged recently as a promising tool for high-throughput manipulation of particles and cells for a wide range of flow cytometric tasks including cell separation/filtration, cell counting, and mechanical phenotyping. Inertial focusing is profoundly reliant on the cross-sectional shape of channel and its impacts on not only the shear field but also the wall-effect lift force near the wall region. In this study, particle focusing dynamics inside trapezoidal straight microchannels was first studied systematically for a broad range of channel Re number (20 OpenSPiltSPi Re OpenSPiltSPi 800). The altered axial velocity profile and consequently new shear force arrangement led to a cross-lateral movement of equilibration toward the longer side wall when the rectangular straight channel was changed to a trapezoid; however, the lateral focusing started to move backward toward the middle and the shorter side wall, depending on particle clogging ratio, channel aspect ratio, and slope of slanted wall, as the channel Reynolds number further increased (Re CloseSPigtSPi 50). Remarkably, an almost complete transition of major focusing from the longer side wall to the shorter side wall was found for large-sized particles of clogging ratio K ~ 0.9 (K = a/Hmin) when Re increased noticeably to ~ 650. Finally, based on our findings, a trapezoidal straight channel along with a bifurcation was designed and applied for continuous filtration of a broad range of particle size (0.3 OpenSPiltSPi K OpenSPiltSPi 1) exiting through the longer wall outlet with ~ 99% efficiency (Re OpenSPiltSPi 100)

Scaled-Up Inertial Microfluidics: Retention System for Microcarrier-Based Suspension Cultures

© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Recently, particle concentration and filtration using inertial microfluidics have drawn attention as an alternative to membrane and centrifugal technologies for industrial applications, where the target particle size varies between 1 µm and 500 µm. Inevitably, the bigger particle size (>50 µm) mandates scaling up the channel cross-section or hydraulic diameter (DH > 0.5 mm). The Dean-coupled inertial focusing dynamics in spiral microchannels is studied broadly; however, the impacts of secondary flow on particle migration in a scaled-up spiral channel is not fully elucidated. The mechanism of particle focusing inside scaled-up rectangular and trapezoidal spiral channels (i.e., 5–10× bigger than conventional microchannels) with an aim to develop a continuous and clog-free microfiltration system for bioprocessing is studied in detail. Herein, a unique focusing based on inflection point without the aid of sheath flow is reported. This new focusing mechanism, observed in the scaled-up channels, out-performs the conventional focusing scenarios in the previously reported trapezoidal and rectangular channels. Finally, as a proof-of-concept, the utility of this device is showcased for the first time as a retention system for a cell–microcarrier (MC) suspension culture

Alginate hydrogel co-loaded with cisplatin and gold nanoparticles for computed tomography image-guided chemotherapy

The biomedical applications of gold nanoparticles (AuNPs) have experienced rapid growth in recent years, due to their expected benefits in medical imaging and therapy. In this work, we report the development of a theranostic nanocomplex constructed from alginate hydrogel co-loaded with cisplatin and AuNPs (abbreviated as ACA) for simultaneous drug delivery and computed tomography imaging. CT26 cells derived from mouse colon adenocarcinoma were exposed to various concentrations of ACA nanocomplex (for 24 h) and the cytotoxicity was measured using MTT assay. Moreover, the cells treated with ACA nanocomplex were imaged in a computed tomography scanner and the contrast enhancement due to the presence of nanocomplex was assessed. The cytotoxicity results showed that ACA nanocomplex had a more potent chemotherapy efficacy than free cisplatin, so that ACA nanocomplex at the concentration of 5 µg/ml (per cisplatin) and 20 µg/ml of free cisplatin resulted in the same cytotoxicity (survival rate: 66). The computed tomography imaging study revealed that ACA nanocomplex increased the brightness of computed tomography images, the computed tomography number value, and contrast-to-noise ratio (CNR). ACA nanocomplex can be presented as a computed tomography-traceable nanocarrier that allows to monitor the delivery of therapeutics by assessing their localized accumulation and in vivo biodistribution. © The Author(s) 2018

Inductively powered wireless pacing via a miniature pacemaker and remote stimulation control system

Pacemakers have existed for decades as a means to restore cardiac electrical rhythms. However, lead-related complications have remained a clinical challenge. While market-released leadless devices have addressed some of the issues, their pacer-integrated batteries cause new health risks and functional limitations. Inductive power transfer enables wireless powering of bioelectronic devices; however, Specific Absorption Rate and size limitations reduce power efficiency for biomedical applications. We designed a remote-controlled system in which power requirements were significantly reduced via intermittent power transfer to control stimulation intervals. In parallel, the cardiac component was miniaturized to facilitate intravascular deployment into the anterior cardiac vein. Given size constraints, efficiency was optimal via a circular receiver coil wrapped into a half-cylinder with a meandering tail. The pacemaker was epicardially tested in a euthanized pig at 60 beats per minute, 2 V amplitude, and 1 ms pulse width, restoring mean arterial pressure from 0 to 37 mmHg. Power consumption was 1 mW at a range of &gt; 3 cm with no misalignment and at 2 cm with 45° displacement misalignment, 45° x-axis angular misalignment, or 45° y-axis angular misalignment. Thus, we demonstrated a remote-controlled miniaturized pacing system with low power consumption, thereby providing a basis for the next generation of wireless implantable devices