DNA sequencing costs have fallen more than 50-fold over the past decade, driven part by tools, technology and process improvements made during the Human Genome Project. However, it still costs around $10 million to sequence 3 billion base pairs - the amount of DNA found in the genomes of humans and other mammals. 1st generation sequencing platforms, which are based upon capillary electrophoresis and fluorescence detection, have been around since 1992. Due to poor price/performance parameters several initiatives have been launched to facilitate a replacement of this sequencing technology. Most notably is the US National Institute of Health with the goal of developing 2nd and 3rd generation technologies that can read a human genome for $100.000 and $1.000 respectively. To date four vendors have introduced 2nd generation platforms to the market and they have the capacities of sequencing between 0,5 to 2 Gb per 24 hours. The main limitation for improved price/performance of 2nd generation platforms is that they are based on an expensive CCD-camera set up. As a consequence new and radical approaches are required to meet the $1.000 genome goal. This proposal aims to develop a high-throughput low cost 3rd generation DNA sequencing instrument, by deploying novel DNA preparation methods and read-out technologies. The potential instrument output is 200-300Gbp raw sequence per run, which allows for whole genome sequencing on a mass scale. A consortium of five European partners with multidisciplinary expertise has been established to reach the overall objective of this ambitious project.