Increasing the speed of sample throughput and the desire to conduct analysis at the point of sampling be it in the field, factory or surgery are two of the major trends driving measurement science today. Helen Parkes and Derek Craston report.
High throughput genetic analysis has been essential in the human genome mapping project and is applied in the sensitive and specific detection of single nucleotide polymorphisms (SNPs).
SNPs are single nucleotide base differences in the DNA sequence that can be observed between individuals in the population, and are the basis of many genetic variations including the ability to respond to particular clinical drugs a science known as apharmacogenetics'.
Minimising side effects
Advances in pharmacogenetics will enable pharmaceutical prescription to be informed by the individual genotype thus enhancing the efficacy of drugs while minimising side effects.
The emerging importance of SNPs as markers to identify genetic traits, such as drug response, has resulted in a great effort in recent years to develop commercially viable methods that are rapid, accurate, easily interpretable, robust and inexpensive to detect SNPs.
The technological challenge in meeting such criteria should not be underestimated, particularly when combined with the emerging demand for more complex, multivarient analysis in multigene systems.
Genetic diagnostics
Recent developments in DNA measurement technologies will, however, have an impact on the future of genetic diagnostics through addressing these analytical demands.
One such important technology is that of high-density measurement arrays DNA chips which provide miniature platforms for characterising many genetic sequences in parallel.
The power of miniature platforms extends well beyond genetic testing. From the wealth of related scientific publications and the recent launch of a number of high-tech companies, it is now clear that miniaturising analytical processes in general can create fast, flexible and portable measurement systems that achieve the key objectives of high throughput and local point of analysis delivery.
Miniaturisation has been made possible by technologies developed, in the first instance, for the microelectronics industry.
These technologies have been adapted to produce complex topography and physical microstructures on the surface of planar substrate materials, all with extraordinarily high precision.
Simultaneous measurement
As a result it is now possible to micro fabricate arrays of sensing elements to provide simultaneous measurement of multiple components or compound discrimination through pattern recognition.
Similarly microfluidic systems, separation columns, detectors and sample pre-treatment modules can be produced in on-chip formats and, by combining these, it should be possible to provide high-speed integrated analysis using established laboratory procedures. Both the miniature sensor and laboratory-based system constitute examples of what is now often referred to as a laboratory-on-a-chip.
An integrated genotyping platform is thus one form of laboratory-on-a-chip and should allow, for example, the future development of SNP pharmacogenetic diagnostic assays as point-of-care devices to obtain rapid genotype information in the doctor's surgery.
To realise the opportunities offered by miniaturisation, a diverse range of skills and expertise needs to be drawn from their traditional spheres of operation into a truly collaborative environment.
Parallel validation
In addition to developing the technology, there is a requirement for parallel validation of these miniature analytical systems, and the development of tools to enhance validity such as suitable reference materials and quality assurance schemes. Only then can gaps in the process of technology transfer to implementation be bridged.
Efforts are already underway on these fronts: for example, a major UK initiative (the Foresight LINK programme) involving widespread partnership between large corporates, SMEs and academia has been created to develop and mould some of these new technologies to address specific market-focussed, product-focussed ends. The pharmaceutical, healthcare and chemical sectors are all set to benefit from revolutionary new products within the next decade.
In the world of measurement science, small would indeed appear to be beautiful.
ENQUIRY No 65
Helen Parkes is Life Sciences manager and Derek Craston is head of Investigative Analysis at analytical laboratory LGC, Teddington, Middlesex, UK. www.lgc.co.uk
