Tara Dalton

Development of interferometric temperature measurement procedures for microfluid flow

In order to understand heat transfer processes at the microscale, detailed temperature measurements are required. This article begins with a review of the current state-of-the art in fluid temperature measurement at the microscale. At present, fluid temperature profiles are not measured, with verification of predicted heat transfer performance being based on global measurements. The article describes a potential full-field technique based on micro-interferometry. The accuracy of extracting temperature data from small phase difference intensity maps is discussed, with particular reference to the high levels of signal to noise as would be found in a microscale flow. Benchmark optical experiments quantifying the effect of noise on phase evaluation are described and the article concludes with an outline of the achievable resolution for a given channel length and fluid.

Microfluidic droplet-based PCR instrumentation for high-throughput gene expression profiling and biomarker discovery

PCR is a common and often indispensable technique used in medical and biological research labs for a variety of applications. Real-time quantitative PCR (RT-qPCR) has become a definitive technique for quantitating differences in gene expression levels between samples. Yet, in spite of this importance, reliable methods to quantitate nucleic acid amounts in a higher throughput remain elusive. In the following paper, a unique design to quantify gene expression levels at the nanoscale in a continuous flow system is presented. Fully automated, high-throughput, low volume amplification of deoxynucleotides (DNA) in a droplet based microfluidic system is described. Unlike some conventional qPCR instrumentation that use integrated fluidic circuits or plate arrays, the instrument performs qPCR in a continuous, micro-droplet flowing process with droplet generation, distinctive reagent mixing, thermal cycling and optical detection platforms all combined on one complete instrument. Detailed experimental profiling of reactions of less than 300 nl total volume is achieved using the platform demonstrating the dynamic range to be 4 order logs and consistent instrument sensitivity. Furthermore, reduced pipetting steps by as much as 90% and a unique degree of hands-free automation makes the analytical possibilities for this instrumentation far reaching. In conclusion, a discussion of the first demonstrations of this approach to perform novel, continuous high-throughput biological screens is presented. The results generated from the instrument, when compared with commercial instrumentation, demonstrate the instrument reliability and robustness to carry out further studies of clinical significance with added throughput and economic benefits.

High-resolution vibration measurements using wavelength-demultiplexed fibre Fabry-Perot sensors

A fibre-optic system based upon fibre Fabry-Perot strain sensors, capable of measuring deformations and modes of vibration of a composite panel, is presented. Wavelength-division signal demultiplexing allows for the simultaneous interrogation of the strain sensors.

Friction Factors and Nusselt Numbers in Microchannels With Superhydrophobic Walls

The thermal management of electronics is becoming an increasing concern as industry continues to simultaneously push performance while shrinking the size of electronic devices. Microchannel cooling is a promising technology to accommodate the heat dissipation rates and associated fluxes projected for future generations of electronics while also satisfying the need for a reduced footprint to accommodate ever-shrinking device sizes. One shortfall of microchannel cooling, however, is the large pressure drop associated with pumping liquids through microchannels, i.e., channels in which the smallest dimension is between about 1 micron and 1 mm. Superhydrophobic surfaces combine roughness features with low surface energy coatings to create materials with substantially decreased wettability and drag resistance in laminar flows and represent a promising technology for reducing the flow resistance of microchannels. The presence of an (insulating) air layer that is trapped within the superhydrophobic surface, and which separates the microchannel wall from the working fluid, gives rise to a low shear-stress region responsible for the observed reduction in flow resistance. There have been a limited number of studies on the fluid mechanics in superhydrophobic microchannels and, to our knowledge, heat transfer has not been examined. Quantifying the trade-off between the enhanced heat transfer due to pressure drop reduction versus the insulating characteristics of the air layer is of paramount importance for determining the viability of superhydrophobic surfaces as a technology for enhancing microchannel heat transfer. In this work we compute friction factors and Nusselt numbers for the fully-developed (with respect to energy and momentum) flow of a fluid in a parallel-plane microchannel with different heat flux and momentum boundary conditions at the upper and lower channel walls. Two approximations are taken for modeling the superhydrophobic microchannel. In the first case we study the single-phase flow of a fluid in a microchannel where one or both microchannel walls is assumed to be superhydrophobic and where the superhydrophobicity is modeled via application of Navier’s slip model at the microchannel wall. Solutions for the velocity profiles are then employed to calculate theoretical friction factors and Nusselt numbers for the constant heat flux condition. This analysis is then extended to examine the implications on the thermal resistance of a superhydrophobic surface due to the presence of a purely conductive air layer. In the second case we model the fluid flow in the presence of a recirculating air layer that separates the fluid from the microchannel wall. In this instance the low-viscosity air layer gives rise to apparent fluid slip for the working fluid which is dependant on the thickness of the air layer and the viscosity ratio of the two working fluids. This case represents an upper apparent-slip limit as the characteristic spacing of the surface roughness becomes large relative to the channel height and air-layer thickness.Copyright

Liquid Diffusion Measurement in Micro/Mini Channels From Full-Field Digital Phase Measurement Interferometry (PMI)

This paper considers division of amplitude interferometry as a means to extract fluid information from micro-systems. Initially the phase measurement technique is analysed and the measurement limitations of mixing measurement are assessed. Accurate phase measurements are then made of the concentration in a 3 dimensional channel flow. A mini sized channel with tow fluid flows at Reynolds numbers of 0.848 and 0.0848 is numerically analysed. The same channel is experimentally tested and the results for the mixing concentration gradients in channel flow are compared with those obtained numerically. The requirement for experimental measurement for accurate measurement of binary liquid diffusion is observed by the variation between experimental and numerical results. The diffusion coefficient measurement verifies PMI as a means of mixture measurement, or more broadly as a phase measurement technique for small-scale, or micro scale, fluidic analysis. PMI’s potential is finally discussed as a measurement technique for concentration, and hence fluidic analysis of micro channel mixing.Copyright

Protein kinase C beta II suppresses colorectal cancer by regulating IGF-1 mediated cell survival

Despite extensive efforts, cancer therapies directed at the Protein Kinase C (PKC) family of serine/threonine kinases have failed in clinical trials. These therapies have been directed at inhibiting PKC and have, in some cases, worsened disease outcome. Here we examine colon cancer patients and show not only that PKC Beta II is a tumour suppressor, but patients with low levels of this isozyme have significantly decreased disease free survival. Specifically, analysis of gene expression levels of all PKC genes in matched normal and cancer tissue samples from colon cancer patients revealed a striking down-regulation of the gene coding PKC Beta in the cancer tissue (n = 21). Tissue microarray analysis revealed a dramatic down-regulation of PKC Beta II protein levels in both the epithelial and stromal diseased tissue (n = 166). Of clinical significance, low levels of the protein in the normal tissue of patients is associated with a low (10%) 10 year survival compared with a much higher (60%) survival in patients with relatively high levels of the protein. Consistent with PKC Beta II levels protecting against colon cancer, overexpression of PKC Beta II in colon cancer cell lines reveals that PKC Beta II reverses transformation in cell based assays. Further to this, activation of PKC Beta II results in a dramatic downregulation of IGF-I-induced AKT, indicating a role for PKCs in regulating IGF-1 mediated cell survival. Thus, PKC Beta II is a tumour suppressor in colon cancer and low levels serve as a predictor for poor survival outcome.

Direct Comparison between Five Different Microchannels, Part 2: Experimental Description and Flow Friction Measurement

Abstract Part one of this paper [1] investigates the manufacture of five types of microchannels produced by wet and dry etching in silicon and precision mechanical sawing in silicon and thermoset plastic. This paper describes the experimental equipment and methods used to measure the pressure flow characteristics of the manufactured channels. A test system has been built to test each sample using the same inlet and outlet manifolds, pressure tappings, pumping system, and instrumentation. The measured pressure flow behavior was compared with theoretical values calculated from macroscale theory. Error analysis was carried out in order to determine the overall accuracy of the experimental work and determine the significance of any experimental deviation from theoretical values. An area compensation term is introduced to account for the difference in cross-section between the measured actual channels and the rectangles/trapeziums that share their overall dimensions.

Rapid identification of antibiotic resistance using droplet microfluidics

ABSTRACT Culturing bacteria and monitoring bacterial cell growth is a critical issue when dealing with patients who present with bacterial infections. One of the main challenges that arises is the time taken to identify the particular strain of bacteria and consequently, decide the correct treatment. In the majority of cases, broad spectrum antibiotics are used to target infections when a narrow spectrum drug would be more appropriate. The efficient monitoring of bacterial growth and potential antibiotic resistance is necessary to identify the best treatment options for patients. Minturising the reactions into microfluidic droplets offers a novel method to rapidy analyze bacteria. Microfluidics facilitates low volume reactions that provide a unique system where each droplet reaction acts as an individual bioreactor. Here, we designed and built a novel platform that allowed us to create and monitor E.coli microfluidic droplet cultures. Optical capacity was built in and measurements of bacterial cultures were captured facilitating the continuous monitoring of individual reactions. The capacity of the instrument was demonstrated by the application of treatments to both bacteria and drug resistant strains of bacteria. We were able to detect responses within one hour in the droplet cultures, demonstrating the capacity of this workflow to the culture and rapid characterization of bacterial strains.

Challenges in using nano-textured surfaces to reduce pressure drop through microchannels

Advances in silicon processing and micro-machining now allow the consistent manufacture of micro- and nanoscale features necessary for the production of controlled roughness superhydrophobic surfaces. Superhydrophobic surfaces combine roughness features with low surface energy to create materials with substantially decreased wettability and, subsequently, reduced hydrodynamic drag. Thus, they represent a promising technology for reducing microchannel flow resistance; a major technical issue in microfluidic systems. In there, however, limits to the pressure a superhydrophobic surface can support before irreversible wetting transition occurs, leading to a loss of the drag-reducing effect. Of greater importance are preliminary observations that, even before a superhydrophobic surface wets irreversibly, the drag reduction over a superhydrophobic surface may be compromised by subtle changes in the three-phase contact line position. The positive impact of micro-geometries on heat transfer is well known. Coupling this phenomenon with superhydrophobic surfaces to reduce flow resistance, could represent a significant step forward in areas such as electronics cooling. However, theoretical models of superhydrophobic surfaces are complex due to the requirement for high resolution on multiple scales. This paper aims to present current results and discuss issues in implementing superhydrophobic surfaces, specifically nano-structured posts, in a microchannel

Extracellular matrix gene expression profiling using microfluidics for colorectal carcinoma stratification

In cancer, biomarkers have many potential applications including generation of a differential diagnosis, prediction of response to treatment, and monitoring disease progression. Many molecular biomarkers have been put forward for different diseases but most of them do not possess the required specificity and sensitivity. A biomarker with a high sensitivity has a low specificity and vice versa. The inaccuracy of the biomarkers currently in use has led to a compelling need to identify more accurate markers with diagnostic and prognostic significance. The aim of the present study was to use a novel, droplet-based, microfluidic platform to evaluate the prognostic value of a panel of thirty-four genes that regulate the composition of extracellular matrices in colorectal carcinoma. Our method is a novel approach as it uses using continuous-flowing Polymerase Chain Reaction for the sensitive detection and accurate quantitation of gene expression. We identified a panel of relevant extracellular matrix genes whose expression levels were measured by real-time quantitative polymerase chain reaction using Taqman® reagents in twenty-four pairs of matched colorectal cancer tumour and associated normal tissue. Differential expression patterns occurred between the normal and malignant tissue and correlated with histopathological parameters and overall surgical staging. The findings demonstrate that a droplet-based microfluidic quantitative PCR system enables biomarker classification. It was further possible to sub-classify colorectal cancer based on extracellular matrix protein expressing groups which in turn correlated with prognosis.