Analytical and Bioanalytical Chemistry

, Volume 410, Issue 29, pp 7679–7687 | Cite as

An integrated chip-mass spectrometry and epifluorescence approach for online monitoring of bioactive metabolites from incubated Actinobacteria in picoliter droplets

  • Konstantin Wink
  • Lisa Mahler
  • Julia R. Beulig
  • Sebastian K. Piendl
  • Martin Roth
  • Detlev BelderEmail author
Research Paper


We present a lab-on-a-chip approach for the analysis of secondary metabolites produced in microfluidic droplets by simultaneous epifluorescence microscopy and electrospray ionization mass spectrometry (ESI-MS). The approach includes encapsulation and long-term off-chip incubation of microbes in surfactant-stabilized droplets followed by a transfer of droplets into a microfluidic chip for subsequent analysis. Before the reinjected droplets are spaced and electrosprayed from an integrated emitter into a mass spectrometer, the presence of fluorescent marker molecules is monitored nearly simultaneously with a custom-made portable epifluorescence microscope. This combined fluorescence and MS-detection setup allows the analysis of metabolites and fluorescent labels in a complex biological matrix at a single droplet level. Using hyphae of Streptomyces griseus, encapsulated in microfluidic droplets of ~ 200 picoliter as a model system, we show the detection of in situ produced streptomycin by ESI-MS and the feasibility of detecting fluorophores inside droplets shortly before they are electrosprayed. The presented method expands the analytical toolbox for the discovery of bioactive metabolites such as novel antibiotics, produced by microorganisms.


Chip-mass spectrometry Lab-on-a-chip Droplet-based cultivation Droplet-based microfluidics Electrospray ionization Segmented flow Microdroplets 


Funding information

This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—FOR 2177—project number 275564491.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

216_2018_1383_MOESM1_ESM.pdf (771 kb)
ESM 1 (PDF 771 kb)

(MP4 3081 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute of Analytical ChemistryUniversity of LeipzigLeipzigGermany
  2. 2.Leibniz Institute for Natural Product Research and Infection Biology -Hans Knöll Institute-, Bio Pilot PlantJenaGermany
  3. 3.Faculty of Biological SciencesFriedrich Schiller UniversityJenaGermany

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