Investigation of particle movement in irregularly shaped channels in inertial fluidics for scale up applications in bioprocessing

Particle separation is a vital step in many analytical chemistry, biomedical diagnosis, and environmental applications. Inertial microfluidics has emerged in recent years as a promising tool for a wide range of flow cytometric tasks including cell separation, cell counting and mechanical phenotyping. In inertial fluidics, a transverse inertia-induced lift force across streamlines is inherently accompanied with higher order of magnitude convection mass transfer (channel Reynolds number >10), in contrast to microdevices working mainly based on diffusion mass transport phenomenon (Stokes flow) or low-Re flows, increasing throughput significantly. Emerging inertial focusing technique as an alternative method to microfiltration has brought remarkable benefits such as a continuous and clog-free system with lower maintenance costs. These features along with its relative ease of scalability to reach a relevant industrial scale will facilitate its potential adoption in various industries such as waste water treatment and bioprocessing. Of particular interest, dealing with a broader range of particle sizes up to one order of magnitude larger than cell sizes (a > 50 µm) in bioprocessing requires scaled-up channels to avoid clogging. However, Dean-coupled inertial focusing has not been studied in detail when the channel hydraulic diameter is greater than DH ≈ 0.3 mm. Moreover, with the advancement of cell therapy industry in recent years, cell purification at downstream processing introduces some new challenges. While removing particulates from manufactured cell products, using routine membrane technologies similar to protein manufacturing industry do not work as well. This work focuses on the design and development of a membrane-less filtration and separation device using inertial focusing for a large range of particle sizes. To this end, inertial focusing is investigated in straight and mainly curved channels due to their scalability, throughput and efficiency. Inertial focusing is profoundly reliant on the cross-sectional shape of channel and it affects not only the shear field but also the wall-effect lift force near the wall region. The wall-effect lift force is known as a determining factor for cross-lateral migration that leads to a reduced number of equilibrium positions. In order to investigate this, a rectilinear channel with trapezoidal cross-section is designed to break down the symmetrical condition in conventional rectangular microchannels for a broad range of channel Re number (2050). Finally, a trapezoidal straight channel along with a bifurcation was designed and used for continuous filtration of a broad range of particle size (0.3<K<1) exiting through the longer wall outlet with ~99% efficiency (Re<100). Nonetheless, though the linear structure of channel can be scaled out relatively easy to reach higher volumetric throughput, it inherently suffers from low particle concentration. Thus, further investigations focused on a curvature-induced secondary flow in conjunction with inertial lift. The mechanism of Dean-coupled inertial focusing inside scaled-up rectangular and trapezoidal spiral channels (i.e., 5-10x bigger than conventional microchannels) is studied with an aim to develop a continuous and clog-free microfiltration system for bioprocessing. Scaling up channel hydraulic diameter one order of magnitude from ~0.1 mm (micron scale) to ~1 mm (millimeter scale) quenches the inertia of flow for a given channel Re number (Re≤500), resulting in deterioration of Dean-coupled inertial focusing (DH > ~1 mm). Accordingly, different scaled-up trapezoidal spirals are developed to (i) filter cell-microcarrier complex (retention device) and (ii) separate microcarriers from cell suspensions. Further biological experimentation validates the applicability of the developed devices. Since particulate contamination in GMP-grade biological products only exists at low concentrations, membrane-based filtration can eliminate large particulates without clogging. However, due to limitation on minimum screen size, particulates smaller than ~70 µm pass through the filter and end up in the manufactured cell products. To alleviate the particulates contamination, a scalable hybrid method using a combination of sieve and inertial-based separator is proposed as a generic method to remove particulates contamination larger than cell sizes ranging from visible to subvisible. Hence, a large-aspect-ratio trapezoidal spiral channel is established and then implemented to remove subvisible particles down to 25 µm from a mesenchymal stem cell suspension possessing a diverse cell size (10 µm ≤a<30 µm). Though the inertial-based separator can reduce the particulate burden in manufactured cell products, it is not a hundred percent reliable when the size of the particulate overlaps with that of cells. Thus, a combination of methods using inertial focusing together with active methods such as dielectrophoresis is needed to manipulate multi biophysical markers such as size and electrical properties.Doctor of Philosoph

Fabrication of poly phosphoric acid into polyacrilonitrile composite nanofibers

Poly phosphoric acid/ Polyacrilonitrile composite nanofibers (PPA/PAN composite nanofibers) has been fabricated by the electro-spinning of PAN solutions containing different amount of PPA. The prepared nanofibers have been characterized by the using of FT-IR, SEM and XRD techniques. © (2012) Trans Tech Publications, Switzerland

DAILY RUNNING PROMOTES SPATIAL LEARNING AND MEMORY IN RATS

Previous studies have shown that physical activity improves learning and memory. Present study was performed to determine the effects of acute, chronic and continuous exercise with different periods on spatial learning and memory recorded as the latency and length of swim path in the Morris water maze testing in subsequent 8 days. Four rat groups were included as follows: 1- Group C (controls which did not exercise). 2- Group A (30 days treadmill running before and 8 days during the Morris water maze testing period). 3- Group B (30 days exercise before the Morris water maze testing period only) and 4- Group D (8 days exercise only during the Morris water maze testing period). The results showed that chronic (30 days) and continuous (during 8 days of Morris water maze testing days) treadmill training produced a significant enhancement in spatial learning and memory which was indicated by decreases in path length and latency to reach the platform in the Morris water maze test (p < 0.05). The benefits in these tests were lost in three days, if the daily running session was abandoned. In group D with acute treadmill running (8 days exercise only) the difference between the Group A disappeared in one week and benefit seemed to be obtained in comparison with the controls without running program. In conclusion the chronic and daily running exercises promoted learning and memory in Morris water maze, but the benefits were lost in few days without daily running sessions in adult rat

The Effects of Cholestasis and Cirrhosis on Gastric Acid and Pepsin Secretions in Rat: Involvement of Nitric Oxide

Abstract Objective(s) The liver has major role in the organism homeostasis, interactions with other systems, synthesis and metabolism of bile production, drug detoxification and hormone inactivation. Cholestasis can be defined as an impairment of the bile flow which can lead to hepatocytes necrosis and finally cirrhosis. Some studies reported a gastric acid secretion reduction in cirrhotic subjects, while others reported normal production gastric acid secretion. Our aim was to evaluate the effects of cholestasis and cirrhosis on gastric acid and pepsin secretions and its possible mechanism in rat. Materials and Methods Male Wistar rats were randomly divided into five groups (n= 8): control, cholestasis, sham cholestasis, cirrhosis and sham cirrhosis. Laparatomy was done under general anesthesia and then bile duct ligation (BDL) was performed. After 2 and 4 weeks in cholestasis and cirrhosis groups respectively, gastric content was collected by wash-out technique. Basal and stimulated acid and pepsin secretions were measured by using titration and the Anson method respectively in all groups. In order to measure stimulated acid and pepsin secretions, pentagastrin (25 µg/kg, i.p.) was used. Nitric Oxide (NO) metabolites of gastric tissue were determined by Griess microassy method. Results Acid and pepsin secretions were significantly reduced in cholestatic and cirrhotic rats in comparison with control and sham groups (P&lt; 0.01). NO metabolite of gastric tissue was significantly increased in cholestatic and cirrhotic rats (P&lt; 0.01). Conclusion Reducing of gastric acid and pepsin output in cholestatic and cirrhotic rats may be due to increasing in NO content of gastric tissue

Evaluation of External Genital Anomalies and the Underlying Factors in Male Newborns

Background: External genital anomalies are the most common congenital disorders in male infants with unknown etiology in the majority of cases. According to recent reports, incidence rate of these anomalies is rising in different countries. This study aimed to evaluate the prevalence of external genital anomalies and possible underlying factors in male newborns. Methods: This cross-sectional study was conducted on all the male neonates born in Motahari Hospital of Urmia during October 2009-June 2010. Neonatal screening results and demographic data were recorded separately in a questionnaire for each neonate. Data analysis was performed in SPSS V.20 using descriptive statistics (mean, frequency, percentage, and standard deviation) and Chi-square test to evaluate the correlations between quantitative variables. Results: In this study, external genital anomalies were identified in 83 male neonates (8.3%). Moreover, 59 infants (5.9%) had cryptorchidism, 18 (1.8%) had hypospadias and 12 infants (1.2%) had microphallus. Moreover, a significant correlation was observed between the incidence of cryptorchidism and maternal comorbidities, low birth weight, prematurity, maternal gestational hypertension, and diabetes mellitus. Conclusion: According to the results of this study, cryptorchidism is the most prevalent external genital anomaly in male newborns, followed by hypospadias. Occurrence of these anomalies is associated with several risk factors, such as prematurity, low birth weight, maternal diseases (e.g., diabetes and hypertension), and use of medications during pregnancy. In addition, cryptorchidism had a significant correlation with smoking habits, and further studies with larger sample sizes are required in this regard