Monitoring On‐Chip Pictet–Spengler Reactions by Integrated Analytical Separation and Label‐Free Time‐Resolved Fluorescence

Abstract

High-throughput screening for optimal reaction conditions and the search for efficient catalysts is of eminent importance in the development of chemical processes and for expanding the spectrum of synthetic methodologies in chemistry. In this context we report a novel approach for a microfluidic chemical laboratory integrating organic synthesis, separation and time-resolved fluorescence detection on a single microchip. The feasibility of our integrated laboratory is demonstrated by monitoring the formation of tetrahydroisoquinoline derivatives by Pictet-Spengler condensation. After on-chip reaction the products and residual starting material were separated enantioselectively on the same chip. On-chip deep UV laser-induced fluorescence detection with time-correlated single photon counting was applied for compound assignment. The system was utilized to screen reaction conditions and various substrates for Pictet-Spengler reactions on-chip. Finally, the microlab was successfully applied to investigate enantioselective reactions using BINOL-based phosphoric acids as organocatalysts.

Integrated on-chip mass spectrometry reaction monitoring in microfluidic devices containing porous polymer monolithic columns

“…The integration of miniaturized chemical reactors 1 and analytical techniques 2,3 into single microfluidic devices 4,5 is attractive for process development. Continuous flow micro-systems can combine microflow reactors with a separation column.…”

“…To date, flow reactors have been typically combined with electrophoresis for downstream separation and fluorescence detection. 4,6 The immense potential of integrated devices to study stereoselective chemical conversions at the micro-and nanolitre scale was recently demonstrated in the context of whole cell enantioselective biocatalysis. 7 While the integration of electrophoretic separation into microfluidic channel networks is straightforward, electrophoresis has rather limited applications as the separation of typical uncharged small organic molecules poses a challenge.…”

Two‐photon excitation in chip electrophoresis enabling label‐free fluorescence detection in non‐UV transparent full‐body polymer chips

“…For deep UV‐illumination in chip devices usually laser systems are applied as it is more challenging to utilize potentially economic lamps such as mercury lamps, due to the lack of appropriate optical filter and UV‐transparent condenser systems in microscopic setups. Deep UV fluorescence detection has been employed for reaction monitoring and MCE of proteins, drugs, and other small aromatics . However, due to autofluorescence or even photodamage of both polymer and glass microfluidic devices caused by their opacity to deep UV light, label‐free fluorescence detection can hardly be realized in other device materials than fused silica .…”

An integrated microfluidic chip enabling control and spatially resolved monitoring of temperature in micro flow reactors

“…Because of the naturally limited volumetric throughput, the main motivation of such studies is to collect information rather than isolated chemical products [39][40][41][42][43][44][45].…”