Ultra-sensitive and high-resolution microarray scanner

The goal of this project is the development of a compact fluorescence based microarray scanning device with single molecule sensitivity. The system is based on a technology that for the first time enables high-throughput scanning of large areas with single molecule sensitivity and diffraction limited resolution. With single molecule sensitivity and a total dynamic range of 8 orders of magnitude, the device will be superior to currently available microarray scanners and thus allow to reveal information currently not accessible in microarray-analysis. Microarrays permit the characterization of gene expression, DNA sequence variation, protein levels, tissues, cells and other biological and chemical molecules in a massively parallel format. The recent availability of advanced commercial RNA expression platforms and the milestone of over 5,000 published microarray papers demonstrate the rapid inroads made by this technology into basic and applied research. As a consequence of this enormous scientific potential the global market for microarrays is poised to grow rapidly (DNA-microarrays: from $596 million in 2003 to $937 million in 2010, protein microarrays: from $122 million in 2002 to more than $500 million in 2008). Without question, microarray technology offers an enormous potential. However, there are still limitations. In the case of DNA microarrays, error prone and time consuming amplification steps hinder obtaining fast and reliable results, in particular when only minute amounts of sample are available. For protein microarrays, the lack of an adequate amplification procedure to polymerase chain reaction even prohibits to obtain any results in case of small sample amounts. With the development of an ultra-sensitive compact scanner in this project, we provide the possibility to obtain reliable results from microarrays without the necessity for any amplification step. The system will allow to detect single hybridized biomolecules within a microarray spot and at the same time enable precise quantification of up to 108 molecules bound. By increasing the dynamic range by 5 orders of magnitude compared to currently available microarray scanners, the device will open up new perspectives in biomedical research and diagnostics.