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Reimagining how we study biomolecules
9 Apr 2025
Our latest effort to push label-free microscopy is now published!
In this project, we set out to answer two key questions about interferometric imaging under rotating, (near-)TIR illumination:
1. Can we boost contrast and suppress background without cranking up illumination or integration time?
2. Which angles and polarizations actually maximize performance?
By combining iSCAT with rotating coherent scattering (ROCS), we show that scanning around total internal reflection makes the PSF tighter and reduces speckle—delivering ~4× higher contrast and ~2× lower background, and keeping SNR high even at low power. We show that we can detect 20 nm gold nanoparticles with better SNR for the same power and exposure than in typical iSCAT.
These results challenge the idea that TIR inevitably kills interferometric contrast and point to a practical route to more sensitive, quantitative label-free imaging and improved single-molecule mass measurements.
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