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Overview of Electron Microscopy

Overview of Electron Microscopy

The wavelengths of visible light ultimately limit the maximum theoretical resolution of images created by light microscopes. Most light microscopes can only magnify 1000X, and a few can magnify up to 1500X. Electrons, like electromagnetic radiation, can behave like waves, but with wavelengths of 0.005 nm, they produce significantly greater resolution up to 0.05 nm as compared to 500 nm for visible light. An electron microscope (EM) can create a sharp image that is magnified up to 2,000,000X.

Scanning Electron Microscopy

Scanning Electron Microscopy

A scanning electron microscope (SEM) is used to study the surface features of a sample by using an electron beam that scans the sample surface in a two-dimensional manner. Typically, areas between ~1 centimeter to 5 micrometers in width can be imaged. SEM can be used to image bacteria, viruses, tissues as well as larger samples like insects. Conventional SEM gives a magnification ranging from 20X to 30,000X and spatial resolution of 50 to 100 nanometers.
Fundamental Principles
Accelerated...

Cryo-electron Microscopy

Cryo-electron Microscopy

Conventional electron microscopy (EM) involves dehydration, fixation, and staining of biological samples, which distorts the native state of biological molecules and results in several artifacts. Also, the high-energy electron beam damages the sample and makes it difficult to obtain high-resolution images. These issues can be addressed using cryo-EM, which uses frozen samples and gentler electron beams. The technique was developed by Jacques Dubochet, Joachim Frank, and Richard Henderson, for...

$X-ray Diffraction of Biological Samples$ 01:10

X-ray Diffraction of Biological Samples

X-ray diffraction or XRD is an analytical tool that utilizes X-rays to study ordered structures such as crystalline organic and inorganic samples, polycrystalline materials, proteins, carbohydrates, and drugs.
According to Bragg's law, when X-rays strike the sample positioned on a stage, the rays are scattered by the electron clouds around the sample atoms. The X-ray diffraction or scattering is caused by constructive interference of the X-ray waves that reflect off the internal...

X-ray Crystallography

X-ray Crystallography

The size of the unit cell and the arrangement of atoms in a crystal may be determined from measurements of the diffraction of X-rays by the crystal, termed X-ray crystallography.
Diffraction
Diffraction is the change in the direction of travel experienced by an electromagnetic wave when it encounters a physical barrier whose dimensions are comparable to those of the wavelength of the light. X-rays are electromagnetic radiation with wavelengths about as long as the distance between neighboring...

Overview of Microscopy Techniques

Overview of Microscopy Techniques

The early pioneers of microscopy opened a window into the invisible world of microorganisms. In 1830, Joseph Jackson Lister created an essentially modern light microscope. The 20th century saw the development of microscopes that leveraged nonvisible light, such as fluorescence microscopy that uses an ultraviolet light source and electron microscopy that uses short-wavelength electron beams. These advances significantly improved magnification, image resolution, and contrast. By comparison, the...

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Related Experiment Video

Updated: Nov 1, 2025

$Microcrystal Electron Diffraction of Small Molecules$

Microcrystal Electron Diffraction of Small Molecules

Published on: March 15, 2021

An Overview of Microcrystal Electron Diffraction (MicroED).

Xuelang Mu^1,2,3, Cody Gillman^1,2,3, Chi Nguyen¹

¹Howard Hughes Medical Institute, Department of Biological Chemistry, University of California, Los Angeles, California 90095, USA;

Annual Review of Biochemistry

|June 21, 2021

Summary

This summary is machine-generated.

Microcrystal electron diffraction (MicroED) is a powerful new tool for determining the structure of molecules. This technique uses tiny crystals and advances cryo-electron microscopy for drug discovery and structural biology.

Keywords:

MicroED cryo-EM cryo–electron microscopy crystallography microcrystal electron diffraction proteins structures

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Last Updated: Nov 1, 2025

$Microcrystal Electron Diffraction of Small Molecules$

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Published on: March 15, 2021

$Synchrotron X-ray Microdiffraction and Fluorescence Imaging of Mineral and Rock Samples$

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Published on: June 19, 2018

Quantitative Atomic-Site Analysis of Functional Dopants/Point Defects in Crystalline Materials by Electron-Channeling-Enhanced Microanalysis

Quantitative Atomic-Site Analysis of Functional Dopants/Point Defects in Crystalline Materials by Electron-Channeling-Enhanced Microanalysis

Published on: May 10, 2021

Area of Science:

Structural biology
Biophysics
Drug discovery

Background:

Structure determination is crucial for understanding cellular functions and drug mechanisms.
Existing methods for structure determination have limitations.
New tools are needed to fill gaps in current techniques.

Purpose of the Study:

To review the development and applications of microcrystal electron diffraction (MicroED).
To highlight MicroED's potential to advance structural biology and drug discovery.
To discuss future directions for MicroED technology.

Main Methods:

Microcrystal electron diffraction (MicroED) is a technique utilizing cryo-electron microscopy.
MicroED can analyze samples previously challenging for X-ray crystallography.
It works with crystals significantly smaller than those required for X-ray methods.

Main Results:

MicroED has been successfully applied to small molecules, membrane proteins, and large protein complexes.
It expands the capabilities of electron microscopy for high-resolution structure determination.
MicroED offers a valuable addition to the biophysical toolkit.

Conclusions:

MicroED represents a significant advancement in structure determination.
This technique broadens the scope of samples amenable to high-resolution analysis.
MicroED holds great promise for future research in structural biology and drug discovery.