Browsing by Author "Larcombe, L. D."

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    Effects of channel surface finish on blood flow in microfluidic devices
    (Springer Science Business Media, 2010-01-12T00:00:00Z) Prentner, S.; Allen, David M.; Larcombe, L. D.; Marson, Silvia; Jenkins, Karl W.; Saumer, M.
    The behaviour of blood flow in relation to microchannel surface roughness has been investigated. Special attention was focused on the techniques used to fabricate the microchannels and on the apparent viscosity of the blood as it flowed through these microchannels. For the experimental comparison of smooth and rough surface channels, each channel was designed to be 10mm long and rectangular in cross-section with aspect ratios of ⠥100:1 for channel heights of 50 and 100μm. Polycarbonate was used as the material for the device construction. The shims, which created the heights of the channels, were made of polyethylene terephthalate. Surface roughnesses of the channels were varied from Rz of 60nm to 1.8μm. Whole horse blood and filtered water were used as the test fluids and differential pressures ranged from 200 to 5000Pa. The defibrinated horse blood was treated further to prevent coagulation. The results indicate that a surface roughness above an unknown value lowers the apparent viscosity of blood dramatically due to boundary effects. Furthermore, the roughness seemed to influence both water and whole blood almost equally. A set of design rules for channel fabrication is also presented in accordance with the experiments performed.
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    An in silico study of the differential effect of oxidation on two biologically relevant G-quadruplexes: Possible implications in oncogene expression
    (PLOS (Public Library of Science), 2012-08-22T00:00:00Z) Stebbeds, William Joshua David; Lunec, Joseph; Larcombe, L. D.
    G-quadruplex structures, formed from guanine rich sequences, have previously been shown to be involved in various physiological processes including cancer-related gene expression. Furthermore, G-quadruplexes have been found in several oncogene promoter regions, and have been shown to play a role in the regulation of gene expression. The mutagenic properties of oxidative stress on DNA have been widely studied, as has the association with carcinogenesis. Guanine is the most susceptible nucleotide to oxidation, and as such, G-rich sequences that form G-quadruplexes can be viewed as potential "hot-spots" for DNA oxidation. We propose that oxidation may destabilise the G-quadruplex structure, leading to its unfolding into the duplex structure, affecting gene expression. This would imply a possible mechanism by which oxidation may impact on oncogene expression. This work investigates the effect of oxidation on two biologically relevant G-quadruplex structures through 500 ns molecular dynamics simulations on those found in the promoter regions of the c-Kit and c-Myc oncogenes. The results show oxidation having a detrimental effect on stability of the structure, substantially destabilising the c-Kit quadruplex, and with a more attenuated effect on the c-Myc quadruplex. Results are suggestive of a novel route for oxidation-mediated oncogenesis and may have wider implications for genome stability.
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    Study of blood flow behavior in microchannels
    (2008-06-01T00:00:00Z) Marson, Silvia; Benade, M.; Attia, Usama M.; Allen, David M.; Kersaudy, Kerhoas M.; Hedge, J.; Morgan, S. L.; Larcombe, L. D.; Alcock, Jeffrey R.; van Brussel, H.; Brinksmeier, E.; Spaan, H.; Burke, T.
    Microfluidic (also known as lab-on-a-chip) devices offer the capability ofmanipulating very low volumes of fluids (of the order of micro litres) for severalapplications including medical diagnostics. This property makes microfluidicdevices very attractive when the fluid, such as blood, has a limited supply becausethe patients cannot easily and frequently provide a large sample. This is typically thecase for aged, diseased patients that do require frequent sampling during acute careor of older people that have the option of being treated and cared for at home [1].Prototype lab-on-a-chip devices for medical diagnostics comprise a number ofelements which separately perform different functions within the system. Activitywithin the research community is focusing on the better integration of devicefunctionalities with the long term goal of creating fully integrated, portable,affordable clinical devices. However, engineering these solutions for the largevolume production of lab-on-a-chip devices requires design rules which are not yetentirely available.This paper describes the results obtained from a set of experiments run to drawgeneric design rules for the manufacture of a cells/plasma micro separator [2]. Thecells/plasma micro separator was selected for investigation because it is a strategicelement required in the preparation of blood samples for many different analyticaldevices. The experiments focused on the study of the behaviour of whole bloodpassing through micro constrictions which are required for enhancing the separationeffect [3].The test microfluidic device was an aluminium specimen designed andmanufactured to incorporate micro constrictions of different width and length. The metallic aluminium test device was designed for manufacturing by micromilling anddiamond cutting processes in view of applying these techniques to the manufactureof micro-moulds for the high-volume production of plastic microfluidic devices viamicro-injection moulding.The widths of the constrictions were 23, 53 and 93µm and the lengths were 300 and700µm. The blood flow pattern and the level of haemolysis generated in the wholeblood were determined for flow rates between 0.2 and 1 ml/min. Initial resultssuggested that the above conditions generate a stable flow and do not cause bloodhaemolysis following passage through the narrow constrictions. This result impliesthat constrictions as narrow as 23 µm and as long as 700µm can be safely used inblood microfluidic devices under appropriate flow conditions without the risk ofdamaging the blood compone