Can detergents in my sample interfere with a mass photometry measurement?
As a general advice, it is best to reduce the detergent concentration as much as possible for optimal results. Detergents increase the noise background in mass photometry measurements, even at concentrations below the critical micelle concentration. How much noise a detergent generates is detergent- and protein-dependent and conditions need to be optimised on a case by case basis.
The noise signature of detergent buffer oftentimes leads to false-positive detections by DiscoverMP. These false detections usually form two mirroring population at positive and negative peak contrast in the histogram. The mass value that can be assigned to these populations has no biological relevance and should be disregarded. Events that are detected outside this contrast range are usually real and can be trusted.
The presence of a detergent commonly leads to histogram peak broadening, compromising the accuracy and resolution of the system.
Recommended procedure to measure a sample in the presence of detergent: in-drop dilution
Load buffer (e.g. 18 ul) without detergent in the mass photometer and set the focus position.
Add the detergent-containing sample (e.g. 2ul) to the same drop, mix and start recording.
For negative control repeat the procedure but add instead of sample a detergent-containing buffer.
Use the negative control to identify the detergent noise peak that should be disregarded. If the apparent mass of this peak overlaps with that of the particles of interest, a further detergent dilution should be considered.
This procedure results in a rapid dilution of the detergent (1 in 10 in this example), reducing the apparent mass of the noise peak. Unless the off-rate of the detergent-sample interaction is fast, the detergent will still be bound to the sample to a sufficient extent during the 60 seconds of a standard mass photometry measurement.