A droplet-based microfluidic device with seamless hyphenation to electrospray mass spectrometry was developed to rapidly investigate organic reactions in segmented flow providing a versatile tool for drug development. A chip-MS interface with an integrated counterelectrode allowed for a flexible positioning of the chip-emitter in front of the MS orifice as well as an independent adjustment of the electrospray potentials. This was necessary to avoid contamination of the mass spectrometer as well as sample overloading due to the high analyte concentrations. The device was exemplarily applied to study the scope of an amino-catalyzed domino reaction with low picomole amount of catalyst in individual nanoliter sized droplets.

An integrated lab‐on‐a‐chip enables the rapid analysis of heterogenized enantioselective organocatalysis at the microscale. A packed‐bed microreactor was seamlessly integrated with a downstream chiral high pressure liquid chromatography (HPLC) functionality to study enantioselective transformations on a single microfluidic glass chip. Hyphenation to mass spectrometry allows for the rapid investigation of the selectivity and the substrate scope of microgram amounts of catalyst beads. Optimization of reaction conditions is possible with minimal reagent consumption and instant analytical feedback.

We present a microfluidic system, seamlessly integrating microflow and microbatch synthesis with a HPLC/nano-ESI-MS functionality on a single glass chip. The microfluidic approach allows to efficiently steer and dispense sample streams down to the nanoliter-range for studying reactions in quasi real-time. In a proof-of-concept study, the system was applied to explore amino-catalyzed reactions, including asymmetric iminium-catalyzed Friedel-Crafts alkylations in microflow and micro confined reaction vessels.

The online hyphenation of chip-based high-performance liquid chromatography (chip-HPLC) with ion mobility spectrometry (IMS) via fully integrated electrospray emitters is introduced. A custom-built drift tube IMS with shifted potentials was developed in order to keep the IMS orifice electrically grounded, allowing for a robust coupling with chip-HPLC. Proof-of-concept studies with the newly developed analytical setup revealed the suitability of IMS as a promising and powerful detection concept for chip-based separation techniques. Comparison of IMS with fluorescence detection and electrospray ionization-mass spectrometry (ESI-MS) allowed a more detailed characterization of the IMS as a new detection method for chip-HPLC. Moreover, the analysis of a mixture consisting of three isobaric antidepressants demonstrated the performance of chip-HPLC/IMS as a miniaturized two-dimensional separation technique.

The investigation of stereoselective biocatalytic transformations at a single-cell level is to date an unsolved challenge. Here, we report the development of an integrated microfluidic device which enables the analytical characterization of enantioselective reactions at nanoliter scale by combining whole-cell catalyzed on-chip syntheses, chiral microchip electrophoresis, and label-free detection of enantiomers by deep UV time-resolved fluorescence. Using Escherichia coli expressing recombinant Aspergillus niger epoxide hydrolase as the model enzyme for various enantioselective reactions, we evaluated the approach for downscaling the reaction to a few hundred cells. Our work is thus an important step toward the analysis of single-cell stereoselective biocatalysis.