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Oligonucleotide dna micro-array synthesis quality

To improve the quality of oligonucleotide dna micro-arrays produced with ink jet technology. It will be achieved with image processing software for control of oligonucleotide synthesis.

EURO GENOM is proposing the OLIGOSYNT project on the ink jet oligonucleotide synthesiser and micro-arrayer improvement. The main goal of the project is to improve the quality of DNA micro-arrays produced with an ink jet oligonucleotide synthesiser and micro-arrayer. An ink jet synthesiser and micro-arrayer employs the standard ink jet printing technology (which is used in low cost piezoelectric ink jet printers for printing ink on paper) for printing a DNA micro-array on a glass slide. The improvements of an ink jet synthesiser and micro-arrayer are directed into increased quality and efficiency of DNA micro-array printing. These improvements would allow the synthesiser to be more competitive than the established U.S. micro-array producers. The ink jet oligonucleotide synthesiser and micro-arrayer uses standard phosphoramidite DNA chemistry, which is widely used in column synthesisers for synthesis of DNA oligonucleotides. Instead of ink, the synthesiser and micro-arrayer delivers extremely small droplets (picoliters) of reagents needed for DNA synthesis on precisely determined spots on the glass substrate. The droplet forms a reaction well where synthesis reaction occurs. With each droplet of reagent, the oligonucleotide probes (that are synthesised this way) grow for one building unit (a nucleotide). A spot has hundreds or thousands of copies of particular oligonucleotide (or DNA probe). The array of spots (or features) includes thousands or even tens or hundreds of thousands of spots on a square centimetre. This array of oligonucleotide probes is called a DNA micro-array. The main improvement of quality of DNA micro-arrays produced with ink jet technology is a real-time sensor of nozzle flow control. Real-time monitoring of droplet firing would maximally reduce the mistakes in the DNA synthesis that arise due to the random nozzle clogging. Besides the improvement of quality, this would also increase the printing speed, as the double printing step that is used now to minimise the mistakes would not be necessary anymore. The oligonucleotides that would miss a nucleotide due to the clogging of the nozzle could be marked with a fluorescent marker or the missing base could be printed on that feature from another nozzle. This way the mistakes in the oligonucleotide synthesis would be minimal and if by any chance the mistakes are not corrected immediately with reprinting of the nucleotide, the failed oligonucleotides could be marked and disregarded during the data processing. The most technologically advanced and precise method for quality control is visual monitoring combined with image processing. An image capturing device takes a picture of the slide after each print and the image is processed by image processing software to detect the occurrence of droplets, their position and shape. This method offers a much broader range of information about a micro-array compared to other possible methods (for instance the combination of laser beam and diode sensor), thus enabling much better and real-time quality control. The market for the DNA micro-arrays has an immense growth potential because they can be used in all natural sciences that deal with living organisms (bacteria, fungi, plants, animals). DNA micro-arrays are used for instance in medicine, pharmacy, biotechnology, toxicology, veterinary science, ecology, food technology, agronomy and biology. In the near future a very large part of diagnostics in medicine will be based on the DNA micro-arrays. The analysis of gene expression is especially important in the treatment of cancer and neurological diseases. High prices of DNA micro-arrays are the main obstacle for their wider use, especially in countries with low science and health care budgets. But with increasing applications of DNA micro-arrays, the prices are slowly reducing, and the market is widening. With the development of specific DNA micro-arrays for diagnostics of various diseases and other specific purposes, their use will become even greater. Cost efficient technology for producing DNA micro-arrays, such as ink jet printing, is crucial for their wider application. Our final goal is to develop this technology to be more suitable for faster production of DNA micro-arrays and to produce DNA micro-arrays of higher quality but at lower prices than the prices of currently available DNA micro-arrays. This will give us some edge to compete with the acknowledged DNA micro-arrays producers from the U.S.A on the European market. Keywords: DNA micro-arrays, ink jet printing, quality control.
Acronym: 
OLIGOSYNT
Project ID: 
4 091
Start date: 
01-01-2008
Project Duration: 
36months
Project costs: 
960 000.00€
Technological Area: 
Cellular and Molecular Biology
Market Area: 
Recombinant DNA

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