Design of a Microarray Production Line

Volltext: Today in large laboratories analytical results with special requirements are obtained from patient probes successively. In some fields of application as in allergy and DNA diagnostics or blood banks parallel, fast and precise analytical systems could revolutionise the daily routine. For example in large blood banks up to 2500 blood samples per day have to be examined reliably on HIV and hepatitis. A parallel detection of various infectious deseases parameters could increase the safety in the use of blood conserves. The requirements of analytical technologies are: - fast analytical process (speed) - parallel processing of many different assays (parallelism) - very precise and reliable results (precision). Böhringer Mannheim developed in the last three years a technology where the central element is a Microspot chip, a highly precise but low-priced disposable component of injection moulded polystyrene. This chip has a tremendous potential: - The miniaturisation of the chemical reaction in tiny reaction areas results in shorter reaction times - Hundreds of different determinations can be done on one chip. - Higher sensitivity and specifity because of improved signal/noise ratio. On one chip reaction areas with a diameter of only 100mm the spots are deposited in square sections of about 200-300mm. Such a spot contains several hundred thousands of specific molecules, which are coupled to the plastic surface of the chip by a streptavidin-biotin binding chemistry. The production technology of this chip is a very complex procedure, because requirements for the deposition of tiny dots of 100mm must be produced in high quantities. In the realised production plant all 16 chips are picked up at once from parallel magazines and put on carriers. To ensure constant process periods and quality for all chips the carriers are timed through the whole plant. The core of the device is a special printing head which can deposit tiny droplets of a volume of 100-300pl precisely on to the surface of the chip. Later in the production process the chips are retreated several times. Different biochemical solutions are applied on the chips and taken off after defined incubation periods. Afterwards a 100% quality control of the spot pattern is carried out with a highly resolving vision system before the chips are automatically put in the magazines. The described production line was developed and put in operation in two years by the Fraunhofer IPA in cooperation with Boehringer Mannheim and build a plant manufacturer. This line makes it possible for the first time to produce 5000 Microspot chips per hour automatically.