Oliver Gutmann

An improved 24 channel picoliter dispenser based on direct liquid displacement

For the first time we present a systematic study concerning the relation between nozzle diameter and ejected droplet volume of a highly parallel picoliter dispenser. Such dispensers are essential parts for the mass fabrication of microarrays and are able to dispense up to 96 different reagents at a pitch of 500 /spl mu/m simultaneously. In contrast to an earlier design we investigated different nozzle diameters. The change from 35 /spl mu/m to 60 /spl mu/m in nozzle diameter resulted in a doubling of dispensed volume for most used elastomers and irrespective of actuation parameters. Minimum and maximum of dispensed volumes have been determined to be 125 pl and 1700 pl. Those results are based on a new design, which also includes passive microstructures for droplet homogeneity as well as modified microchannels for improved priming and prevention of cross-contamination. Based on this, the CV of droplet velocity could be reduced from 50% down to less than 5%. The CV of droplet volume is clearly below the measurement error (8%).

Integrated process control for highly parallel and contact-free micro array printing

This paper reports for the first time on an integrated process control of a highly parallel non-contact dispenser for microarray production. Monitoring the fundamental process parameters has become indispensable because of significantly increased demands on high quality microarrays. We integrated a pressure sensor in our pneumatically actuated dispenser to acquire the transient pressure pulse during droplet ejection. This enables the total process control for the dispenser and with it the adoption of operation parameters for varying liquid properties, like viscosity, surface tension and density. We optimised pressure parameter and the geometry of the actuation chamber. This made it possible to dispense liquid viscosities up to 10.8 mPas (four fold improvement) at frequencies up to 30 Hz (15 fold improvement) for all tested liquids. In addition, the integrated pressure sensor allows to detect failure modes, like flooded actuation chamber or empty printhead nozzles, leading to a higher quality of the fabricated microarrays.

Microfluidics and Beyond – Devices for Applications in Biotechnology -

For the performance of certain analytical and diagnostic tasks in modern Life Science applications high throughput screening (HTS) methods are essential. Miniaturization, parallelization and automation allow to decrease consumption of expensive materials and lead to faster analyzing times. The miniaturization of total assay volumes by the use of microtiter plates as well as the microarray technology have revolutionized the field of biotechnology and Life Sciences. Neither printing of microarrays with droplet volumes of several picoliters, nor handling of precious enzymes in the upper nanoliter range can be accomplished with traditional liquid handling devices like air displacement pipettes. The development of novel low volume liquid handling devices, which are subject to current research, addresses the diverse requirements shifting steadily to lower volumes. Various novel non-contact dispensing methods in the nanoliter and picoliter range are presented and classified according to their working principles like air displacement and direct displacement methods (TopSpot ® , NanoJet TM , Dispensing Well Plate TM ). Properties of the various methods are compared in terms of flexibility, integration density, speed of operation, precision, addressable volume range and amenability to multi-parallel operation. By integrating processing steps of biological assays within these novel non-contact dispensing devices multifunctional Lab-on-a-chip (LOAC) devices can be developed. A prototype of such a flexible and modular application platform was developed. This platform enables to perform various processing steps (e.g. PCR, post-processing) in one chip with subsequent probe transfer into another chip with a different functionality (e.g. detection). This basically points into the direction to reach new functionalities by combining advantages of novel low volume liquid handling devices with LOAC functionality.

Dispensing of cells for highly parallel production of living cell microarrays

The growing new field of cell microarrays enables new biomedical assays. We present a unique parallel cell printing technique, which allows the fast production of living cell microarrays. A 24 nozzle printhead was used to spot vital cells in a non-contact manner. We used a cell suspension with 8/spl times/10/sup 7/ cells/ml to generate 100 microarrays containing 24 cell-spots each. Every spot contains between 80 and 100 living cells with extraordinary high survival rates of more than 90% after printing. Compared to other cell printing techniques, we achieved a four times higher cell number per spot and very evenly distributed cells within the spot.