(568w) Microfluidic Organic Synthesis System with Automated Two-Dimensional UV Absorbance Imaging Detection for Online Process Optimization

Microreactor technology has recently received great attention because it offers advantages over conventional batch reactor technology, such as large surface-to-area ratio for enhanced heat and mass transfer, continuous flow operation for better yields and selectivity, and potential to integrate with analytical units for real-time, online reaction monitoring and optimization. However, integration of suitable analytical methods onto the microreactor still remains challenging because of the dead volume between the analytical unit and the microreactor, and very small sample volume for detection during the run. As a result, most microfluidic organic reactions are monitored by offline, off-chip analysis. Enough volume of the sample is first collected with the reaction quenched and then analyzed with macroscale instruments, such as GC, HPLC, or GC-MS, etc. This significantly limits the usefulness of microreactors in rapid process research and development.

UV absorbance-based detection is a good candidate for sample analysis on microfluidic devices because it is a label-free, nondestructive technique and is widely used in many commercially available capillary electrophoresis and chromatography systems. Unfortunately, UV absorbance-based detection on microfluidic devices does not reach the same level of sensitivity and reliability when compared to its counterpart in the capillary format due to the short optical pathlength (generally between 5 and 50 µm) of typical microchannels. Additional difficulty comes from the need of UV-transparent material, usually quartz or fused silica, to construct microfluidic devices compatible with UV absorbance-based detection. This results in a significant increase in the cost and complexity of the device fabrication process.

In this work, we designed and fabricated a high-aspect-ratio microreactor chip using simple soft lithographic techniques and integrated it with a two-dimensional UV absorbance imaging detector. As a proof of concept, we used this system to perform real-time, online monitoring and optimization of a model synthesis reaction, i.e., the Paal-Knorr pyrrole synthesis (Figure 1). The UV imaging detection technique we use here allows simultaneous detection of analytes in multiple microchannels on a single device with a high level of spatial and temporal resolution and enables us to visualize the corresponding concentration profile of the product, 2-(2,5-Dimethyl-pyrrol-1-yl)ethanol, across the whole microchannel in real time when we change such reaction parameters as reaction time, temperature, and reactant ratios, for process optimization.

Figure 1. Paal-Knorr pyrrole synthesis; 1 = ethanolamine, 2 = acetonylacetone, and 3 = 2-(2,5-Dimethyl-pyrrol-1-yl)ethanol.