100% Plasma binding measurements
Change big pharma workflows
(anonymised business case).
.avif)
How did a large pharmaceutical company measure binding affinityand kinetics in-solution & in 100% plasma?
A big, German, pharma company had the ambition to measure Kd and binding kinetics in100% plasma to correlate it with values from surface based technologies in buffer solutions -& they succeeded by using the right technology to do so.
The challenge
The company knew that binding kinetics in buffer might not accurately represent how interactions behave in plasma. Without this insight, they risked advancing drug candidates based on misleading buffer-based kinetics, potentially leading to costly late-stage failures. Identifying these discrepancies early would allow them to prioritize the most promising compounds, reduce unnecessary follow-up experiments, ultimately improving efficiency and lowering development costs.
The solution:
While traditional methods provided valuable insights, they did not reflect the
complexity of physiological conditions. No available technology could provide direct, insolution kinetic measurements in a plasma environment-until they turned to FIDA. It was the only technology that allowed them to measure in-solution binding kinetics directly in 100% plasma, giving them the data needed to make better-informed decisions. The process is presented on the graph below.
1. Measuring Kd and
kinetic parameters
Directly in 100% plasma, ensuring physiological relevance.
2. Cross-validation with BLI
Assessing the correlation between in-solution Kdand on-/off-ratesmeasured with FIDA andvalues obtained from BLIin buffer.
3. Comparing with buffer conditions
Measuring the same interaction in buffer to identify key differences in affinity and kinetics.
4. Analyzing the impact of plasma
Quantifying how plasma components influence kinetic parameters and refining the decision-making.
.jpg)
What they discovered?
These differences highlighted why early validation of in-solution kinetics in plasma is critical to avoid investing in misleading buffer-based data. The in-solution Kd in plasma was 8×weaker than in buffer, revealing how plasma components affect affinity. On-rates were 5× slower, and off-rates were 2× faster in plasma than in buffer. The difference between buffer and plasma is clearly distinguishable with FIDA technology.
.jpg)
The benefits:
- The gain of physiologically relevant kinetic data early in the drug development process.
- By integrating early-stage FIDA measurements in 100% plasma, they streamlined their workflow, improved candidate selection,and minimized late-stage failures.
- The insights allowed them to confidently prioritize viabledrug candidates, avoid costly setbacks, and makemore reliable, physiologically relevant decisions.
- Accelerated the drug development process with reduced cost.
Screening denovo designedprotein binders inunpurified lysate
.avif)
Problems
Computational design produces binders at scale, but screening themefficiently is the bottleneck. Traditional validation does not provide structural data, requirespurified material and multiple assays to determine whether a design binds with sufficientaffinity and stability, slowing down the transition from design to decision.
Solutions
By providing functional and structural data in a single measurement and directly from crude expression material, FIDA allows evaluation of binding, stability, and solution behaviour at an early stage. This shifts validation from a sequential, resource-intensive process to an early, decision-driven step.
How to screen de novo design protein binders in unpurified lysate using flow induced dispersion analysis?
Lear about streamline binder
Screening de novo designed protein bindersin unpurified lysate using flow induceddispersion analysis
.png)
If we sparked your curiosity, go ahead, book a discovery call to explore if FIDA could be something just right for you.