Using FIDA for sepsis and lipid-signalling research: a conversation with Prof. Markus Gräler

Prof. Markus Gräler is a professor in the Department of Anesthesiology and Intensive Care Medicine at Jena University Hospital, Germany, where his group studies lipid signalling in sepsis. In a conversation with Fidabio, Prof. Gräler described how Flow Induced Dispersion Analysis (FIDA) fits that work. This is a summary of what he said.

Why Prof. Gräler chose FIDA for sepsis research

The lipid at the centre of this research, sphingosine-1-phosphate (S1P), circulates in blood bound to carrier molecules, chiefly serum albumin and high-density lipoprotein (HDL), and the choice of carrier appears to change how it signals. Measuring that binding, and how it shifts in disease, called for a method that works on real patient samples rather than idealised mixtures. FIDA fit because it reads binding in solution from a change in molecular size: with a fluorescently labelled S1P as the indicator, the dispersion profile broadens as the lipid binds a carrier, and two complementary methods separate albumin binding from HDL binding.

What FIDA makes possible in patient plasma

For time-critical sepsis work, the capability that matters most is that FIDA measures directly in unpurified plasma. The sample is simply diluted about tenfold to reduce its natural background fluorescence, with no separation of lipoproteins from albumin beforehand, which is exactly the step that used to make this analysis slow. Where the group previously needed liquid chromatography coupled to triple-quadrupole mass spectrometry (LC-MS/MS), with several biochemical separations first, a FIDA run takes about seven minutes per method, roughly fourteen minutes in total. It also consumes very little: under 30 microlitres of plasma, against at least half a millilitre, and more than a millilitre for repeated analysis, on the mass-spectrometry route. Together, working straight from crude plasma at that speed and volume is what makes it realistic to process cohorts of several hundred patients, and the instrument is straightforward enough for junior staff to run.

The finding that mattered

Across surgical trauma, sepsis and septic shock patients, S1P binding shifted away from albumin and toward HDL. In the septic shock group, the amount of HDL-S1P complex separated survivors from non-survivors, from samples taken on the day of admission, before a patient's course could be known. The work was published in the journal iScience.

Where the work is heading

The Gräler group plans to extend the same approach to other lipids, beginning with cholesterol binding and transport, which also changes in sepsis. On the translational side, the team is exploring whether restoring normal carrier binding, for instance through supplementation, could shift signalling back toward a healthier state. Prof. Gräler was explicit that this remains basic research, while seeing real potential for FIDA to contribute to diagnosis and treatment monitoring in future.

What we learned from this conversation

• Works in unpurified plasma (about a tenfold dilution, no lipoprotein separation), decisive for the speed sepsis research needs.
• Fast and sample-sparing: roughly fourteen minutes on under 30 microlitres, replacing a multi-step LC-MS/MS workflow, so cohorts of hundreds become feasible.
• Resolves the carrier switch: two methods separate S1P binding to albumin from binding to HDL.
• Research stage, with promising translational and possible diagnostic value.

Curious how FIDA measures binding and size directly in complex samples? Explore the FIDA technology and the Fida instrument, or browse the peer-reviewed literature. Read more scientists’ experiences with FIDA.