A highly integrated nanoliter dispensing system for fast liquid handling R. Steger, B. Bohl, C. Moosmann, G. Birkle, R. Zengerle, P. Koltay IMTEK - University of Freiburg, Laboratory for MEMS Applications, Georges-Koehler-Allee 103, 79110 Freiburg, Germany; www.imtek.de/anwendungen ; e-mail: steger@imtek.de Summary The final aim of the presented work is to speed up the liquid handling process in high-throughput screening (HTS) by providing a new method for parallel and contact-free dispensing. Therefore a dosage system called Dispensing Well Plate (DWP) has been developed. This device is able to dispense up to 1536 different liquids in the range of 10 to 200 nL within a few milliseconds into micro well plates. In contrast to other micro dispensers [1-4] the DWP consists of up to 1.536 individual microfluidic dispensing units arranged closely on a pitch according to the wells of a microtiterplate. Thus a multitude of different liquids can be handled simultaneously which is of major importance e.g. for ultra high-throughput screening in pharmaceutical industry. The presented prototype with 24 parallel dispensing elements comprising a fixed dosage volume of 50 nL each. It has been manufactured using a production process based on SU-8. Function and fabrication method of this type of DWP are described. The dispensing performance evaluated by experimental results is discussed and design rules for further improvement are given. The idea of a full plastic DWP is especially interesting for the application in HTS when a concept of a plastic disposable is requested. As the microtiterplate itself the DWP should fulfil the same requirements of cleanness and easy handling on one side and commercial success on the other. Therefore we present the first full-plastic prototype of the DWP made by mechanical micromachining. Introduction Pharmaceutical research experiences an increasing need for highly parallel dispensing technologies to speed up drug development. The automated equipment allows for the testing of several 100.000 chemicals per day stored in standardized containments termed well plates. To bring these compounds to the reaction vessels about 1.000 dispensing cycles per minute are required. At the same time accurate dispensing in the nanoliter range is also necessary to reduce reagent costs and to improve overall performance. It has been shown that the DWP dispensing technology [5] is able to meet these requirements. Fig. 1 Photograph of a DWP with 24 dispensing units manufactured in SU-8 hybrid technology 1 System Description and Chip Fabrication 1.1 System Description The complete dispensing unit consists of a pneumatic actuation unit driving the DWP. The DWP itself consists of numerous dispensing elements arranged very closely at conventional well plate spacing. The array of dispensing elements is surrounded by a unstructured border enabling better handling and sealing of the upper surface if the DWP chip is loaded into the actuation unit (cf. fig. 1). Each dispensing element of the DWP consists of three basic elements: a reservoir, a connection channel and a nozzle (cf. fig. 2a). For the experiments reported here we have chosen a pitch of 4,5 mm corresponding to the 384 - well plate format. When the reservoirs are filled with liquid capillary forces lead to self priming of the nozzles via the connection channels when the contact angle of the liquid related to the channel surface is below 90°. By applying a pressure pulse to the whole upper surface of the DWP the liquids contained in the nozzles (50 nL each) are driven out generating free liquid jets (fig. 2 b-c). So one pressure pulse empties all nozzles of the complete DWP simultaneously. Due to the pressure gradient is negligible across the connection channels, no considerable flow from the reservoirs occurs during that time. After switching off the driving pressure the nozzle chambers refill again by capillary forces (fig. 2d).