Natural-product discovery

Microfluidic fractionation for compound-resolved bioactivity

Pair rapid chromatographic fraction collection with LC-MS/MS and luminescent bioreporters to connect chemical signals with antibacterial responses.

Analytical Chemistry · 2025 · 10.1021/acs.analchem.5c04612

LC-MSNatural-product discovery

What does this strategy enable?

Pair rapid chromatographic fraction collection with LC-MS/MS and luminescent bioreporters to connect chemical signals with antibacterial responses.

Transferable workflow

Workflow

  1. 1

    Collect fractions during LC-MS/MS

    Spot eluent onto a paper microfluidic device at approximately one fraction per second while acquiring spectra.

  2. 2

    Measure reporter responses

    Expose fractions to luminescent bioreporters and image the response.

  3. 3

    Align activity with chemistry

    Match reporter signals to chromatographic profiles to prioritize active compounds.

Strategy profile

Related objectives

Phenotype association

Components

Chromatography, Data acquisition, Biological validation

Scope and considerations

Designed for

  • Antibacterial activity screening of extracts or compound mixtures.

Important requirements

  • Custom rapid fractionation hardware and compatible paper devices.
  • LC-MS/MS, luminescent bioreporters and response imaging.
  • Reliable correspondence between fraction positions and retention times.

Considerations

  • Reporter responses are assay-specific; confirm prioritized activity with follow-up experiments.
  • Coelution can complicate assigning activity to one compound.

Reusable resources

✓ Published method available

Publication

Geibel C, et al. Analytical Chemistry 97, 24093-24104 (2025).

doi:10.1021/acs.analchem.5c04612

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