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

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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 thiol-ene, 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 × 104–1.6 × 105 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.

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Funding

The present study is supported financially by the Chinese Scholarship Council (CSC No. 201708210241).

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Authors and Affiliations

  1. Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark

    Nan Lu, Nickolaj J. Petersen, Andreas C. Kretschmann & Jörg P. Kutter

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  1. Nan Lu
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  2. Nickolaj J. Petersen
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Correspondence to Jörg P. Kutter.

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Lu, N., Petersen, N.J., Kretschmann, A.C. et al. Non-aqueous electrophoresis integrated with electrospray ionization mass spectrometry on a thiol-ene polymer–based microchip device. Anal Bioanal Chem 413, 4195–4205 (2021). https://doi.org/10.1007/s00216-021-03374-9

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