Microthermoforming of microfluidic substrates by soft lithography (μTSL): optimization using design of experiments

We present a detailed analysis of microthermoforming by soft lithography (mu TSL) for replication of foil-based microfluidic substrates. The process was systematically optimized by design of experiments (DOE) enabling fabrication of defect-free lab-on-a-chip devices. After the assessment of typical error patterns we optimized the process toward the minimum deviation between mold and thermoformed foil substrates. The following process parameters have most significant impact on the dimensional responses (p < 0.05): critical temperature before start of evacuation, molding temperature, pressure of pre-stretching and duration of pre-stretching as well as duration of molding pressure. The most relevant parameter is molding temperature with >40% relative impact. The DOE results in an empirical process model with a maximum deviation between the prediction and experimental proof of 2% for the optimum parameter set. Finally, process optimization is validated by the fabrication and testing of a microfluidic structure for blood plasma separation from human whole blood. The optimized process enabled metering of a nominal volume of 4.0 mu l of blood plasma with an accuracy deviation of 3% and a metering precision of +/- 7.0%. The mu TSL process takes about 30 min and easily enables the replication of 300 mu m wide microchannels having vertical sidewalls without any draft angles in a well-controllable way. It proves to be suitable for multiple applications in the field of microfluidic devices.