Multi-pass transmission electron microscopy

Feynman once asked physicists to build better electron microscopes to be able to watch biology at work. While electron microscopes can now provide atomic resolution, electron beam induced specimen damage precludes high resolution imaging of sensitive materials, such as single proteins or polymers. Here, we use simulations to show that an electron microscope based on a simplemulti-pass measurement protocol enables imaging of single proteins at reduced damage and at nanometer resolution, without averaging structures overmultiple images. Whilewe demonstrate the method for particular imaging targets, the approach is broadly applicable and is expected to improve resolution and sensitivity for a range of electron microscopy imaging modalities, including, for example, scanning and spectroscopic techniques. The approach implements a quantum mechanically optimal strategy which under idealized conditions can be considered interaction-free. In practice, an order-of-magnitude reduction in damage at equivalent resolution appears feasible.