Electron microscopy of whole cells in liquid with nanometer resolution

TLDR

The authors used a liquid scanning transmission electron microscope with a microfluidic device to image gold‑tagged epidermal growth factor bound to receptors on fixed fibroblast cells in buffer solution. They achieved a 4‑nm spatial resolution with a 20‑µs pixel dwell, demonstrating that liquid STEM can image single molecules in whole cells with higher resolution and speed than existing methods, and the results agree with theoretical predictions.

Abstract

Single gold-tagged epidermal growth factor (EGF) molecules bound to cellular EGF receptors of fixed fibroblast cells were imaged in liquid with a scanning transmission electron microscope (STEM). The cells were placed in buffer solution in a microfluidic device with electron transparent windows inside the vacuum of the electron microscope. A spatial resolution of 4 nm and a pixel dwell time of 20 micros were obtained. The liquid layer was sufficiently thick to contain the cells with a thickness of 7 +/- 1 microm. The experimental findings are consistent with a theoretical calculation. Liquid STEM is a unique approach for imaging single molecules in whole cells with significantly improved resolution and imaging speed over existing methods.