Systems and Methods for Uncertainty-Aware-Single-Particle Cryo-EM Data Collection Using Online Feedback

A computer implemented method for automated data collection in cryogenic electron microscopy (cryo-EM), the method comprising:

• identifying, by one or more processors and based on patch-level images taken by a cryo-EM instrument, a plurality of holes within a patch of a cryo-EM grid, wherein each identified hole is a candidate data collection point;
• estimating, by the one or more processors, an expected reward for each identified hole based on the patch-level images;
• determining, by the one or more processors and using stochastic approximation, a dynamically adjusted threshold quality score representing an estimated optimal time-average reward;
• and
• selecting, by the one or more processors, holes from the identified plurality of holes based on the expected reward by minimizing an objective function that depends on the dynamically adjusted threshold quality score, wherein the dynamically adjusted threshold quality score is based at least in part on observed rewards from the selected holes and microscope operation times.

A non-transitory computer-readable medium having stored thereon computer-executable instructions that, when executed by a processor, cause a computing system to perform operations for automated data collection in cryogenic electron microscopy (cryo-EM), the operations comprising:

• identifying, based on patch-level images taken by a cryo-EM instrument, a plurality of holes within a patch of a cryo-EM grid, wherein each identified hole is a candidate data collection point;
• estimating an expected reward for each identified hole based on the patch-level images;
• determining, using stochastic approximation, a dynamically adjusted threshold quality score representing an estimated optimal time-average reward;
• and
• selecting holes from the identified plurality of holes based on the expected reward by minimizing an objective function that depends on the dynamically adjusted threshold quality score, wherein the dynamically adjusted threshold quality score is based at least in part on observed rewards from the selected holes and microscope operation times.