Modeling of on-chip (bio)-particle separation and counting using 3D electrode structures

This paper was presented at the 4th Micro and Nano Flows Conference (MNF2014), which was held at University College, London, UK. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute, ASME Press, LCN London Centre for Nanotechnology, UCL University College London, UCL Engineering, the International NanoScience Community, www.nanopaprika.eu.In lab-on-a-chip applications, manipulation and quantification of (bio)particles is required in a variety of biomedical applications such as drug screening, disease detection and treatment. For manipulation of particles, electrical techniques such as dielectrophoresis (DEP) is very suitable. For the quantification or counting of the bioparticles, flow cytometer, fluorescence-activated cell sorting (FACS) and magneticactivated cell sorting (MACS) are common techniques. In this study, modeling of microfluidic (bio)-particle separation based on dielectrophoresis and counting based on capacitance measurement using COMSOL Multiphysics have been presented. The device performance with planar and 3D electrode structures have been compared. Microfluidic devices with an asymmetric pair (for separation) and a symmetric pair (for counting) of electrodes are considered. The effects of the geometrical parameters, material properties, flow rate, particle size and applied voltage on the device performance have been discussed. The fabrication procedure of 3D electrode structures is also addressed

Analysis of heat transfer and entropy generation for a low-Peclet-number microtube flow using a second-order slip model: an extended-Graetz problem

Cataloged from PDF version of article.The classical Graetz problem, which is the problem of the hydrodynamically developed, thermally developing laminar flow of an incompressible fluid inside a tube neglecting axial conduction and viscous dissipation, is one of the fundamental problems of internal-flow studies. This study is an extension of the Graetz problem to include the rarefaction effect, viscous dissipation term and axial conduction with a constant wall temperature thermal boundary condition. The energy equation is solved to determine the temperature field analytically using general eigenfunction expansion with a fully developed velocity profile. To analyze the low-Peclet-number nature of the flow, the flow domain is extended from −∞ to +∞. To model the rarefaction effect, a second-order slip model is implemented. The temperature distribution, local Nusselt number, and local entropy generation are determined in terms of confluent hypergeometric functions. This kind of theoretical study is important for a fundamental understanding of the convective heat transfer characteristics of flows at the microscale and for the optimum design of thermal systems, which includes convective heat transfer at the microscale, especially operating at low Reynolds number

Autosomal recessive congenital ichthyosis: CERS3 mutations identified by a next generation sequencing panel targeting ichthyosis genes

There are at least 38 mutant genes known to be associated with the ichthyosis phenotypes, and autosomal recessive congenital ichthyosis (ARCI) is a specific subgroup caused by mutations in 13 different genes. Mutations in some of these genes, such as CERS3 with only two previous reports, are rare. In this study, we identified mutations in candidate genes in consanguineous families with ARCI with a next generation sequencing (NGS) array that incorporates 38 ichthyosis associated genes. We applied this sequencing array to DNA from 140 ichthyosis families with high prevalence of consanguinity. Among these patients we identified six distinct, previously unreported mutations in CERS3 in six Iranian families. These mutations in each family co-segregated with the ichthyosis phenotype. The patients demonstrated collodion membrane at birth, acrogeria, generalized scaling, and hyperlinearity of the palms and soles. The presence of a significant percentage of CERS3 mutations in our cohort depicts a marked difference between the etiology of ichthyoses in genetically poorly characterized regions and well-characterized western populations. Also, it shows that rare alleles are more prevalent in the gene pool of consanguineous populations and emphasizes the importance of these population studies for better understanding of ichthyosis pathogenesis

Mutational spectrum of autosomal recessive limb-girdle muscular dystrophies in a cohort of 112 Iranian patients and reporting of a possible founder effect

Background: Limb-girdle muscular dystrophies are a group of genetically heterogeneous diseases that are inherited in both autosomal dominant (LGMDD) and autosomal recessive forms (LGMDR), the latter is more common especially in populations with high consanguineous marriages like Iran. In the present study, we aimed to investigate the genetic basis of patients who are suspicious of being affected by LGMDR. DNA samples of 60 families suspected of LGMD were extracted from their whole blood. Four short tandem repeat (STR) markers for each candidate genes related to LGMD R1 (calpain3 related)- R6 (δ-sarcoglycan-related) were selected, and all these 24 STRs were applied in two sets of multiplex PCR. After autozygosity mapping, Sanger sequencing and variant analysis were done. Predicting identified variants' effect was performed using in-silico tools, and they were interpreted according to the American College of Medical Genomics and Genetics (ACMG) guideline. MLPA was used for those patients who had large deletions. Fresh muscle specimens were taken from subjects and were evaluated using the conventional panel of histochemical stains. Results: forty out of sixty families showed homozygote haplotypes in CAPN3, DYSF, SGCA, and SGCB genes. The exons and intron-exon boundaries of the relevant genes were sequenced and totally 38 mutations including CAPN3 (n = 15), DYSF (n = 9), SGCB (n = 11), and SGCA (n = 3) were identified. Five out of them were novel. The most prevalent form of LGMDs in our study was calpainopathy followed by sarcoglycanopathy in which beta-sarcoglycanopathy was the most common form amongst them. Exon 2 deletion in the SGCB gene was the most frequent mutation in this study. We also reported evidence of a possible founder effect in families with mutations in DYSF and SGCB genes. We also detected a large consanguineous family suffered from calpainopathy who showed allelic heterogeneity. Conclusions: This study can expand our knowledge about the genetic spectrum of LGMD in Iran, and also suggest the probable founder effects in some Iranian subpopulations which confirming it with more sample size can facilitate our genetic diagnosis and genetic counseling. © 2020 The Author(s)

Lessons of 10 years experience on CCHF in Iran

International audienceCrimean-Congo Hemorrhagic Fever (CCHF) is a viral zoonotic disease with high mortality rate in humans caused by CCHF virus (CCHFV) belonging to the genus Nairovirus, family Bunyaviridae, and congaing a three segment single-stranded RNA genome. The CCHFV is transmitted to humans by bite of infected ticks, by direct contact with blood or tissues of infected livestock and nosocomially. After Chaharmahal-va-Bakhtiari outbreak in 1999 whose serum samples was sent to South Africa for diagnosis, Arboviruses and Viral Hemorrhagic Fevers Laboratory (As National Reference Lab) was established in 2000 to precise and on time laboratory diagnosis of CCHF in the country. The Lab along with CDC of Iran (national health regulator) and Veterinary organization (control program of tick populations and livestock monitoring) are members of National Expert Committee on Viral Hemorrhagic Fevers (NECVHFs) for surveillance and control of CCHF in Ir

Evaluation of the relative contribution of meteorological and oceanic forces to the drift of ice islands offshore Newfoundland

On 29 April 2015, four beacons were deployed onto an ice island in the Strait of Belle Isle to record positional data. The ice island later broke up into many fragments, four of which were tracked by the beacons. The relative influences of wind drag, current drag, Coriolis force, sea surface height gradient and sea-ice force on the drift of the tracked ice island fragments were analyzed. Using atmospheric and oceanic model outputs, the sea-ice force was calculated as the residual of the fragments' net forces and the sum of all other forces. This was compared against the force obtained through ice concentration-dependent relationships when sea ice was present. The sea-ice forces calculated from the residual approach and concentration-dependent relationships were significant only when sea ice was present at medium-high concentrations in the vicinity of the ice island fragments. The forces from ocean currents and sea surface tilt contributed the most to the drift of the

Fabrication of continuous flow microfluidics device with 3D electrode structures for high throughput DEP applications using mechanical machining

Microfluidics is the combination of micro/nano fabrication techniques with fluid flow at microscale to pursue powerful techniques in controlling and manipulating chemical and biological processes. Sorting and separation of bio-particles are highly considered in diagnostics and biological analyses. Dielectrophoresis (DEP) has offered unique advantages for microfluidic devices. In DEP devices, asymmetric pair of planar electrodes could be employed to generate non-uniform electric fields. In DEP applications, facing 3D sidewall electrodes is considered to be one of the key solutions to increase device throughput due to the generated homogeneous electric fields along the height of microchannels. Despite the advantages, fabrication of 3D vertical electrodes requires a considerable challenge. In this study, two alternative fabrication techniques have been proposed for the fabrication of a microfluidic device with 3D sidewall electrodes. In the first method, both the mold and the electrodes are fabricated using high precision machining. In the second method, the mold with tilted sidewalls is fabricated using high precision machining and the electrodes are deposited on the sidewall using sputtering together with a shadow mask fabricated by electric discharge machining. Both fabrication processes are assessed as highly repeatable and robust. Moreover, the two methods are found to be complementary with respect to the channel height. Only the manipulation of particles with negative-DEP is demonstrated in the experiments, and the throughput values up to 105 particles / min is reached in a continuous flow. The experimental results are compared with the simulation results and the limitations on the fabrication techniques are also discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

A Radial Flow Microfluidic Device for Ultra‐High‐Throughput Affinity‐Based Isolation of Circulating Tumor Cells

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110045/1/smll201400719.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/110045/2/smll201400719-sup-0001-S1.pd

Effect of the mechanical activation on size reduction of crystalline acetaminophen drug particles

The decrease in particle size may offer new properties to drugs. In this study, we investigated the size reduction influence of the acetaminophen (C8H9O2N) particles by mechanical activation using a dry ball mill. The activated samples with the average size of 1 μm were then investigated in different time periods with the infrared (IR), inductively coupled plasma (ICP), atomic force microscopy (AFM), and X-ray diffraction (XRD) methods. The results of the IR and XRD images showed no change in the drug structure after the mechanical activation of all samples. With the peak height at full width at half maximum from XRD and the Scherrer equation, the size of the activated crystallite samples illustrated that the AFM images were in sound agreement with the Scherrer equation. According to the peaks of the AFM images, the average size of the particles in 30 hours of activation was 24 nm with a normal particle distribution. The ICP analysis demonstrated the presence of tungsten carbide particle impurities after activation from the powder sample impacting with the ball and jar. The greatest reduction in size was after milling for 30 hours