Non-aqueous electrophoresis integrated with electrospray ionization mass spectrometry on a thiol-ene polymer–based microchip device

Abstract

Non-aqueous capillary electrophoresis (NACE) on microfluidic chips is still a comparatively little explored area, despite the inherent advantages of this technique and its application potential for, in particular, lipophilic compounds. A main reason is probably the fact that implementation of NACE on microchips largely precluded the use of polymeric substrate materials. Here, we report non-aqueous electrophoresis on a thiol-ene-based microfluidic chip coupled to mass spectrometry via an on-chip ESI interface. Microchips with an integrated ESI emitter were fabricated using a double-molding approach. The durability of thiolene, when exposed to different organic solvents, was investigated with respect to swelling and decomposition of the polymer. Thiol-ene exhibited good stability against organic solvents such as methanol, ethanol, N-methylformamide, and formamide, which allows for a wide range of background electrolyte compositions. The integrated ESI emitter provided a stable spray with RSD% of the ESI signal ≤8%. Separation efficiency of the developed microchip electrophoresis system in different non-aqueous buffer solutions was tested with a mixture of several drugs of abuse. Ethanol-and methanol-based buffers provided comparable high theoretical plate numbers (≈ 6.6 × 10 4 -1.6 × 10 5 m −1 ) with ethanol exhibiting the best separation efficiency. Direct coupling of non-aqueous electrophoresis to mass spectrometry allowed for fast analysis of hydrophobic compounds in the range of 0.1-5 μg mL −1 and 0.2-10 μg mL −1 and very good sensitivities (LOD ≈ 0.06-0.28 μg mL −1 ; LOQ ≈ 0.20-0.90 μg mL −1 ). The novel combination of non-aqueous CE on a microfluidic thiol-ene device and ESI-MS provides a mass-producible and highly versatile system for the analysis of, in particular, lipophilic compounds in a wide range of organic solvents. This offers promising potential for future applications in forensic, clinical, and environmental analysis.

Concepts and recent advances in microchip electrophoresis coupled to mass spectrometry: Technologies and applications

“…It has been indicated that the thiol–ene, in comparison to other common micro‐fabrication materials, provides greater flexibility in terms of chip fabrication (mechanical stiffness/rigidity and possibility for low‐cost, non‐clean room replication), improved material stability against alcohols, and more opportunities to tune both the surface chemistry and the bulk properties toward the desired applications, without significantly affecting the ESI–MS performance. Later, another thiol–ene‐based ME coupled to MS was applied in aqueous and nonaqueous BGEs for the separation of a drug mixture [73], in which the integrated ESI emitter provided a stable spray with RSD% of the ESI signal ≤8%.…”