pH stability screening
without the buffer series.
The Labbot instrument takes one sample across a pH range, unattended, and reads unfolding, aggregation and concentration at every step.
See where your candidate is stable,
where it isn’t, and what drives instability.
The pH stability window is hard to estimate
pH affects unfolding and aggregation at every stage of development, and what a coarse screen misses tends to surface later. The value of a high-resolution screen is clear. Running one is the hard part.
- 01
Every point is
a sample prep.
- 02
So screens are often limited
to a handful of points.
- 03
Where it is stable, and what
drives instability, remain
open questions.
One sample prep to map the pH stability window
One run to find the edges of stability. Labbot automatically screens a pH range with high resolution and returns a thorough stability profile. In about an hour.
- 01
Every point,
from one sample prep.Load the sample, set the range, start the run: about five minutes of preparation. No buffers to prepare, nothing to start over.
- 02
So a handful of points
becomes a curve.Step down to 0.05 pH for near-continuous data. A finer step needs no extra sample and no extra hands-on work.
- 03
Where it is stable, and what
drives instability, get answered.Unfolding and aggregation are read together, so you see which starts first, and at what pH.
THE RUN
From sample to insights. Try it on a virtual Labbot.
Easier to try than to explain. One sample goes into the cuvette, and the run does the rest. This one is sped up; the clock shows how long a real run takes, unattended.
One approach, several questions.
Same sample, same four signals, one variable changed in steps. No dilution series, no buffer matrix, no new sample per point.
Where is the molecule stable, and what drives instability as pH changes?
Take one sample across a pH range, in steps as fine as 0.05 pH. Scattering and intrinsic fluorescence are read at every step, so the stability window, where aggregation starts and where unfolding starts all come out of the same run.
Used for: choosing a formulation pH, comparing candidates on pH tolerance, and checking the margin around a buffer pH you already use.
Try it on the virtual run ↑- Scattering
- Fluorescence
- Absorbance
- Scattering
- Fluorescence
- Aggregation starts
- Unfolding starts
- Colloidal aggregation
- Stability window
- Concentration
Does an additive hold back aggregation once it has started, and how much does it take?
Run the sample under conditions where it aggregates and add the additive in doses, for example a polysorbate. The first dose goes in as soon as scattering rises above the noise, and the slope after each dose shows how much it helped, until the curve levels off. Buffer injections at the same times, and a run with nothing added, show the effect isn't dilution.
Used for: choosing a stabiliser, finding the dose that is enough, and comparing additives on the same molecule.
- Scattering
- With additive
- Buffer only
- No additive
- Onset
- Detection limit
Where does the protein come out of solution, and where does it go back in?
Add a salt or another additive in steps and follow light scattering. Scattering rises where the protein comes out of solution and falls again where more of it brings the protein back. One sample maps both edges, with no new preparation for each point.
Used for: finding the conditions a protein stays soluble in, and mapping phase boundaries such as re-entrant condensation with multivalent salts.
- Scattering
- Scattering
- Out of solution
How much does a formulation change shift the melt?
Ramp from 6 to 87 °C or hold at a set temperature. Intrinsic fluorescence (label-free) and scattering are read together, so unfolding and aggregation onset come out of the same run. The effect of an excipient or a ligand on thermal stability is read on the same instrument as the pH run.
Used for: ranking candidates and formulations by thermal stability, and seeing what a stabiliser adds.
- Fluorescence
- Scattering
- Absorbance
- Without stabiliser
- With stabiliser
Labbot changes conditions and measures at every step.
Labbot changes conditions around the sample, such as pH, excipients, concentration, temperature or shear, and measures light scattering, fluorescence, absorbance and pH at every step.
- 01One sample, standard cuvette
- 02Temperature held and ramped
- 02Titrant added mid-run
- 03Three beams through the cuvette
A small sample goes into a standard cuvette, and the conditions are programmed up front.
The instrument drives the sample through the conditions of interest, with no manual handling.
Every channel is recorded together, in real time, from that same sample. All in one dataset.
Your material. Your question. Our eyes on the data.
Fifteen years of measuring how proteins behave under changing conditions comes with the instrument. Experiment design, the first runs together, the data read with you.
A demo on your sample.
One sample of yours, run on the platform, the data reviewed together.
Every molecule behaves differently, and the first run on a new one is rarely the one that answers the question. We expect to be there for it.
No drug should fail late for a stability problem that could have been seen early.
Some drugs fail for physical reasons, not biological ones. Development often checks potency early and physical behaviour late, often after years of work. We built Labbot to close that gap.
More about Labbot