Analysis and design optimization of an integrated micropump-micromixer operated for bio-MEMS applications

A generic microfluidic system composed by two single chamber valveless micropumps connected to a simple T-type channel intersection is examined numerically. The characteristics of a feasible valveless micropump have been used in the design, where efficient mixing is produced due to the pulsating flow generated by the micropumps. The advantages of using time pulsing inlet flows for enhancing mixing in channels have been harnessed through the activation of intrinsic characteristics of the pumps required to achieve the periodic flows. A parametric study is carried out on this microfluidic system using Computational Fluids Dynamics (CFD) on a design space defined by a Design-of-Experiments (DOE) technique. With this approach, the frequency f and the phase difference of the periodic fluid velocities (operation parameters) and the angle formed by the inlet channels at the intersection (geometric parameter) are used as design parameters, whereas mixing quality, pressure drop and maximum shear strain rate in the channel are the performance parameters. The study identifies design features for which the pressure drop and shear strain in the channel are reduced whereas the mixing quality is increased. The proposed microfluidic system achieves high mixing quality with performance parameters that enable manipulation of biological fluids in microchannels.Peer reviewedFinal Accepted Versio

Electromagnetic Actuated Stiring in Microbioreactor Enabling Easier Multiplexing and Flexible Device Design

The development of a novel electromagnetically (EM) actuated stirring method, for use in microbioreactors, is reported. Mixing in microbioreactors is critical to ensure even distribution of nutrients to microorganisms and cells. Magnetically driven stirrer bars or peristaltic mixing are the most commonly utilised mixing methods employed in completely liquid-filled microbioreactors. However the circular reactor shape required for mixing with a stirrer bar and frequently used for peristaltically mixed microbioreactors presents difficulties for bubble-free priming in a microfluidic bioreactor. Moreover the circular shape and the hardware required for both types of mixing reduces the potential packing density of multiplexed reactors. We present a new method of mixing, displaying design flexibility by demonstrating mixing in circular and diamond-shaped reactors and a duplex diamond reactor and fermentation of the gram-positive bacteria S. carnosus in a diamond-shaped microbioreactor system. The results of the optimisation of this mixing method for performing fermentations alongside both batch and continuous culture fermentations are presentedPeer reviewe

Dean flow focusing and separation of small microspheres within a narrow size range.

Copyright The Author(s) 2014. This article is published with open access at Springerlink.com. This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are creditedRapid, selective particle separation and concentration within the bacterial size range (1–3 μm) in clinical or environmental samples promises significant improvements in detection of pathogenic microorganisms in areas including diagnostics and bio-defence. It has been proposed that microfluidic Dean flow-based separation might offer simple, efficient sample clean-up: separation of larger, bioassay contaminants to prepare bioassay targets including spores, viruses and proteins. However, reports are limited to focusing spherical particles with diameters of 5 μm or above. To evaluate Dean flow separation for (1–3 μm) range samples, we employ a 20 μm width and depth, spiral microchannel. We demonstrate focusing, separation and concentration of particles with closely spaced diameters of 2.1 and 3.2 μm, significantly smaller than previously reported as separated in Dean flow devices. The smallest target, represented by 1.0 μm particles, is not focused due to the high pressures associated with focussing particles of this size; however, it is cleaned of 93 % of 3.2 μm and 87 % of 2.1 μm microparticles. Concentration increases approaching 3.5 times, close to the maximum, were obtained for 3.2 μm particles at a flow rate of 10 μl min−1. Increasing concentration degraded separation, commencing at significantly lower concentrations than previously predicted, particularly for particles on the limit of being focused. It was demonstrated that flow separation specificity can be fine-tuned by adjustment of output pressure differentials, improving separation of closely spaced particle sizes. We conclude that Dean flow separation techniques can be effectively applied to sample clean-up within this significant microorganism size range.Peer reviewedFinal Published versio

Novel strategies for targeting innate immune responses to influenza.

We previously reported that TLR4(-/-) mice are refractory to mouse-adapted A/PR/8/34 (PR8) influenza-induced lethality and that therapeutic administration of the TLR4 antagonist Eritoran blocked PR8-induced lethality and acute lung injury (ALI) when given starting 2 days post infection. Herein we extend these findings: anti-TLR4- or -TLR2-specific IgG therapy also conferred significant protection of wild-type (WT) mice from lethal PR8 infection. If treatment is initiated 3 h before PR8 infection and continued daily for 4 days, Eritoran failed to protect WT and TLR4(-/-) mice, implying that Eritoran must block a virus-induced, non-TLR4 signal that is required for protection. Mechanistically, we determined that (i) Eritoran blocks high-mobility group B1 (HMGB1)-mediated, TLR4-dependent signaling in vitro and circulating HMGB1 in vivo, and an HMGB1 inhibitor protects against PR8; (ii) Eritoran inhibits pulmonary lung edema associated with ALI; (iii) interleukin (IL)-1β contributes significantly to PR8-induced lethality, as evidenced by partial protection by IL-1 receptor antagonist (IL-1Ra) therapy. Synergistic protection against PR8-induced lethality was achieved when Eritoran and the antiviral drug oseltamivir were administered starting 4 days post infection. Eritoran treatment does not prevent development of an adaptive immune response to subsequent PR8 challenge. Overall, our data support the potential of a host-targeted therapeutic approach to influenza infection

Age at first birth in women is genetically associated with increased risk of schizophrenia

Prof. Paunio on PGC:n jäsenPrevious studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.Peer reviewe

Semi-automated assembly of high-quality diploid human reference genomes

The current human reference genome, GRCh38, represents over 20 years of effort to generate a high-quality assembly, which has benefitted society. However, it still has many gaps and errors, and does not represent a biological genome as it is a blend of multiple individuals. Recently, a high-quality telomere-to-telomere reference, CHM13, was generated with the latest long-read technologies, but it was derived from a hydatidiform mole cell line with a nearly homozygous genome. To address these limitations, the Human Pangenome Reference Consortium formed with the goal of creating high-quality, cost-effective, diploid genome assemblies for a pangenome reference that represents human genetic diversity. Here, in our first scientific report, we determined which combination of current genome sequencing and assembly approaches yield the most complete and accurate diploid genome assembly with minimal manual curation. Approaches that used highly accurate long reads and parent-child data with graph-based haplotype phasing during assembly outperformed those that did not. Developing a combination of the top-performing methods, we generated our first high-quality diploid reference assembly, containing only approximately four gaps per chromosome on average, with most chromosomes within ±1% of the length of CHM13. Nearly 48% of protein-coding genes have non-synonymous amino acid changes between haplotypes, and centromeric regions showed the highest diversity. Our findings serve as a foundation for assembling near-complete diploid human genomes at scale for a pangenome reference to capture global genetic variation from single nucleotides to structural rearrangements

A microfluidics-based instrument for cytomechanical studies of blood

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Increasing pumping efficiency in a micro throttle pump by enhancing displacement amplification in an elastomeric substrate

'This is an author-created, un-copyedited version of an article accepted for publication in Journal of Micromechanics and Microengineering. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The definitive publisher authenticated version is available online at: http://iopscience.iop.org/0960-1317'Fluid transport is accomplished in a micro throttle pump (MTP) by alternating deformation of a micro channel cast into a polydimethylsiloxane (PDMS) elastomeric substrate. The active deformation is achieved using a bimorph PZT piezoelectric disc actuator bonded to a glass diaphragm. The bimorph PZT deflects the diaphragm as well as alternately pushing and pulling the elastomer layer providing displacement amplification in the PDMS directly surrounding the micro channel. In order to improve pumping rates we have embedded a polymethylmethacrylate (PMMA) ring into the PMDS substrate which increases the magnitude of the displacement amplification achieved. FEM simulation of the elastomeric substrate deformation predicts that the inclusion of the PMMA ring should increase the channel deformation. We experimentally demonstrate that inclusion of a PMMA ring, having a diameter equal to that of the circular node of the PZT/glass/PDMS composite, increases in the throttle resistance ratio by 40% and the maximum pumping rate by 90% compared to an MTP with no ringPeer reviewe

Multi-Channel Patterning of Antibodies on a Sensor Surface for Simultaneous Detection of Pathogens and Toxins

This poster describes the development of a micro-engineered, PDMS/PMMA composite patterning device for the flow immobilisation of up to 16 separate antibody stripes on a single sensor chip surface. Results for a preliminary six channel version of the device will be described with antibodies immobilised on a commercially available BIAcore (TM) surface plasmon resonance chip. Testing was carried out using a range of bacteria, viruses and proteins using a Light-Scattering SPR instrument. The ultimate aim is to use the device to pattern multiplex sensor chips with antibodies for application in the rapid detection of a range of pathogenic microorganisms and toxins in the field.Non peer reviewe