Characterization of a miniaturized liquid bridge for nL sample infusion: a comparative study of sample flush-out behavior using flow simulations and direct ESI-MS analysis

  • Volker Neu
  • Pablo Dörig
  • Christof Fattinger
  • Stephan Müller
  • Renato Zenobi
Research Paper


In this work we shed light on the microfluidics of a miniaturized liquid bridge that forms the central part of a so-called “capillary gap sampler,” a novel device for rapid and seamless injection of nanoliter sample volumes into an electrospray ionization mass spectrometer (ESI-MS). Parameters relevant for sample flush-out at the liquid bridge and in the spray capillary were identified by systematic variation of the capillary dimensions, the linear buffer flow rate (2.1–34 mm/s) and molecular weight of the analytes (0.5–30 kDa). We found that a reduction in capillary wall thickness by a factor of 1.6 significantly influences analyte peak shapes, leads to an inversion of the relationship between peak width and analyte molecular weight, and allows a fivefold decrease in peak width for large molecules down to 5 s. The results could be verified and explained by simulations, in which the presence of diffusion-controlled “dead zones” at the liquid bridge and dispersion in the spray tip that depend on analyte molecular weight were identified as key factors relevant for the sample flush-out process. The merging of simulations and experimental data gives useful hints toward the re-design of a spray tip as built-in ESI-MS interface for an optimized gap sampler performance.


Capillary gap sampler Flow injection analysis Molecule dispersion Peak profiles 



The authors would like to thank Janos Vörös for fruitful discussions.

Supplementary material

10404_2016_1732_MOESM1_ESM.docx (490 kb)
Supplementary material 1 (DOCX 490 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Volker Neu
    • 1
    • 4
  • Pablo Dörig
    • 2
    • 5
  • Christof Fattinger
    • 3
  • Stephan Müller
    • 3
  • Renato Zenobi
    • 1
  1. 1.Department of Chemistry and Applied BiosciencesETH ZurichZurichSwitzerland
  2. 2.Laboratory of Biosensors and BioelectronicsInstitute of Biomedical Engineering, ETH ZurichZurichSwitzerland
  3. 3.F. Hoffmann-La Roche AG, pRED, Pharma Research & Early Development, Discovery TechnologiesBaselSwitzerland
  4. 4.Competence Center Analytics, BASF SELudwigshafenGermany
  5. 5.Cytosurge AGGlattbruggSwitzerland

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