Theory 28/Cryo-Electron Microscopy
Contrast Is a Defocus Ratio
The claim
Phase contrast in cryo-EM is set by the ratio of defocus to specimen thickness, so thick specimens lose contrast even at strong defocus.
01The mechanism
Defocus converts phase shifts into amplitude, but multiple scattering in a thick specimen scrambles the phase; the ratio sets how much survives.
02Predictions
- P1Contrast should track the ratio.
- P2Defocus alone should mispredict across thickness.
03Refutation
Contrast tracking defocus would remove the thickness term.