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CANCER DIAGNOSTICS
Background
The multi-stage theory of genetic abnormalities, leading to tumour development, has become widely accepted as an explanation for the observed development of many tumour types. It follows that many cancers can be diagnosed in their early stages by looking for gene-abnormalities. Genetic markers have now been developed for a number of cancer types and it is expected that the definition and scope of these will improve markedly over the next five years. Sequencing mammalian genomes has had an enormous impact on this process. The stage is therefore set for the genetic diagnosis of cancer to bring about a significant improvement in survivability.It is considerably easier to find diagnostic markers by looking at the transcriptome, measuring mRNA expression, than by addressing genetic DNA. This approach was found to work when transcriptome restructuring as a result of colon cancer was found to significantly change the level of expression of 289 mRNAs. Measuring these expression levels then becomes a diagnostic tool.
Challenge
The scientific challenge for the biofluidics team in the SRI is to develop a diagnostic methodology, based on gene expression, and to engineer a system that will perform such an analysis from sample to diagnosis swiftly, accurately and at low cost on very small tissue samples.
Approach
The scientific approach taken to the need for molecular diagnosis of cancers is to use the Polymerase Chain Reaction (PCR) method of amplification of genetic targets to characterise the disease. The PCR is ideally suited to this as it can theoretically determine the level of gene expression in a single cell. Using quantitative PCR, comparative levels of expression can be found for the genetic markers discovered in gene array analysis. PCR allows working with very small samples and offers the prospect of working with peripheral blood.
The engineering approach taken is to design an automated microfluidic Total Analysis System (mTAS).

The biofluidics group has projects in the following areas:
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Cell culturing for high throughput screening
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Nanolitre dispensing and mixing
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High throughput sample preparation
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Optical measurement
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Very significant funding has already been raised to support this programme of work.
The Stokes Institute collaborates with the Childhood Cancer Unit in Bart’s Hospital under the direction of Professor Vaskar Saha, the Oncology unit at the Regional Hospital Limerick, under the direction of Professor Rajnish Gupta and, finally, the Joint Research Centre, under the direction of Professor Maurice Whelan.
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