HPLC-MS with Glass Chips Featuring Monolithically Integrated Electrospray Emitters of Different Geometries

Abstract

We present and evaluate an approach for coupling liquid chromatography in glass chips with mass spectrometry via fully integrated electrospray emitters. We developed an instrumental platform which allows a robust and reproducible operation of high performance chip chromatography coupled to mass spectrometry. A comparison of differently shaped emitters, from flat over edged to pulled geometries, revealed that all types performed equally well for typical nano-HPLC flow rates. At very low flow rates below 50 nL·min(-1) very sharp, pulled nanospray emitters turned out to be mandatory for the generation of a stable electrospray.

An Integrated Lab‐on‐a‐chip Approach to Study Heterogeneous Enantioselective Catalysts at the Microscale

“…The device was engineered based on our experience in designing glass chips incorporating HPLC columns . A more complex device was realized by interconnecting two different packed‐bed columns on a single microchip (see Supporting Information (SI) for details).…”

“…The device was engineered based on our experience in designing glass chips incorporating HPLC columns. [39][40][41][42] A more complex device was realized by interconnecting two different packed-bed columns on a single microchip (see Supporting Information (SI) for details). The integrated chip device, requires significantly reduced amounts of catalyst when compared to traditional tube or capillary-based packed bed reactors.…”

On-chip integration of organic synthesis and HPLC/MS analysis for monitoring stereoselective transformations at the micro-scale

“…The chip layout features an optional make-up flow channel, not used in this study, to facilitate mass spec detection with various eluents. 52 As a first proof-of-concept, the device was applied to study a catalyzed Knoevenagel condensation of an aldehyde and a 1,3-diketone followed by an intramolecular hetero-Diels-Alder reaction (Scheme 1). 56 Fig.…”

“…At such slow reactor flows peak broadening was observed, which can be explained by diffusion or migration of sample components onto the column. Due to the limitations of the current flow steering process based on earlier work, 51,52 we further developed the approach by effectively separating reactor fluid flow manipulations and the injection process to enable microbatch operation with stopped flow. For this purpose we redesigned and upgraded the outer chip periphery by the addition of pumps, valves and interconnecting tubing.…”

“…This can be overcome if the flows are steered hydraulically with valves and flow restrictors in the outer chip periphery. This concept was applied for on-chip low pressure sample injection [48][49][50][51][52] and more recently also for the connection of an external flow reactor via transfer capillaries to a 2D HPLC chip. 53 A true integration of micro-or nano-reactors and a HPLC column on the same device is very attractive as it would allow to monitor chemical processes at smallest dimensions in real-time.…”