Cryo-EM

Cryogenic Electron Microscope (Cryo-EM)

Introduction

Cryogenic electron microscope (Cryo-EM) is an electronic instrument used to examine the three-dimensional (3D) structures of biological macromolecules at cryogenic temperatures. The Cryo-EM is primarily being researched for the structural analysis of small proteins, enhancement of protein resolution, and the integration between Cryo-EM and drug research.

The earlier forms of electron microscopes made it impossible to study the biomolecules in 3D form as the powerful beams often destroyed the biological matter. Cryo-Electron Microscopy has overcome several barriers, resulting in a new age in biochemistry.

Pic: Cryo-EM

ComponentsofCryo-EM

The electron gun is the component of the Cryo-EM that generates the electron beam. Here, the electron beam is focused on the frozen specimen sample.

Electron Gun

Image Producing System

Image Recording System

This is component consists of the objective, intermediate & projector lenses. The lenses are involved in the focusing of electrons on the frozen specimen sample, & leads to the formation of a magnified image.

This is component consists of a fluorescent screen that helps in producing an image. It also consist of specially designed high-tech camera that captures electrons to form an image.

WorkingPrinciple

The biomolecules in the specimen sample are free, and researchers need to freeze the biomolecules in mid-motion at -150°C, maintaining their natural structure. By this, the structure of molecules is revealed in an intricate detail.

The first step is to prepare the specimen sample such that its structure (tissue, cells, etc.) remains as closest to its natural form as possible.

These 3D images facilitates the study of fine viruses & protein complexes at a molecular resolution. It gives the scientists an opportunity to have a look at the biomolecules in a 3D form & develop better drugs.

A very thin slide of specimen sample is rapidly plunged into cold medium (ethane, liquid nitrogen, etc.) thus cryogenically preserving and protecting the specimen. It is essential that the specimen sample be plunged in to the cooling liquid rapidly so that only the water freezes around the specimen for clear images. 4

The thin slide of specimen sample is loaded into a Cryo-EM. The specimen sample is bombarded with an electron beam travelling at the speed of light through the sample. The electrons are then captured by an advanced camera in the Cryo-EM, generating an image.

The integrated advanced camera not only provides sharp image but can also record video instead of steady picture. A computer algorithm sorts the images and finds pictures of the sample in the same orientation. Then a software builds a composite – an accurate & high-resolution 3D image of the sample.

TopCompanies

LatestTech-Products

Company

Product Detail

ZEISS has released the next generation of ZEISS Lattice Light sheet 7. The microscope system opened up a new way for researchers to explore the dynamics of life at subcellular resolution.

Product

Gatan launched the Metro™ as a cutting-edge counting camera for ground-breaking imaging, diffraction, and in-situ transmission electron microscopy (TEM) below 200 kV. The aim was to build a high-quality camera for everyday scientists with lower budget.

Pic: ZEISS Lattice Light sheet 7

Pic: Gatan Metro™

Company

Product Detail

HITACHI's newest high-end SEM is the SU9000. The SU9000 is a tremendously powerful low-kV device. SU9000 a desirable instrument when integrated with a cryogenic sample holder.

Product

Bruker's QUANTAX EBSDEBSD is a very powerful device for analyzing microstructures. It has a fully autonomous, built-in ARGUS imaging system with the best spatial resolution down to 1.5 nm.

Pic: Scanning Electron Microscope SU9000

Pic: Electron microscope analyzer

Company

Product Detail

Agilent's Lionheart FX automated microscope is a compact & portable microscope. It provides oil immersion magnification up to 60x and 100x. Lionheart employs a camera with a wide field of view (WFOV) that allows for rapid automated imaging in microplates and slides.

Product

TESCAN CLARA Cryo is an excellent cryogenic imaging equipment. It can perform great imaging under cryogenic temperatures. With its broad field optics design, it provides an enlarged field of vision & easy navigation throughout the sample.

Pic: BioTek Lionheart FX Automated Microscope

Pic: TESCAN CLARA Cryo

Company

Product Detail

The Cryostream Compact is designed to be used with powder samples in capillaries and has a shorter nozzle that enables the Cryostream nozzle to be positioned coaxially with the capillary, reducing the possibility of ice formation.

Product

JEOL's JSM-IT510 InTouchScope™ Scanning

Electron Microscope is a simple yet excellent electron microscope that offers a specimen exchange navigation to set the specimen. It also offers automatic filament adjustment, gun alignment adjustment & beam alignment focus.

Pic: Cryostream Compact

Pic: Scanning Electron Microscope

LatestTech-Research

Research Institute

Research Details

Corresponding Image

Researchers from China have developed a method to use ultra-flat graphene (UFG) as the support for Cryo-EM specimen preparation to achieve better control of vitreous ice thickness. The homogeneity of ice thickness is a key factor to ensure high image quality.

Physicists from TU Delft have developed a 3-in-1 microscope where a light beam, electron beam and ion beam work together to precisely cut out specific slices from biological samples.

Scientists at Martin Luther University Halle-Wittenberg (MLU) & the European Molecular Biology Laboratory in Hamburg have developed a novel AI-based method to analyze Cryo-electron microscopy data.

Pic: Ultraflat Suspended Graphene

Pic: The 3-in-1 Microscope

Pic: Complex Protein Structure

PatentFiling

Filing Trend - Year Wise

Filing Trend - Global

Note: Charts of Filing Trend- Year Wise & Assignee Wise are prepared based on unique patent families. However, the chart of Filing Trend- Global is prepared based on the expanded data set.

*Number of patents/published applications filed in the years 2020 and 2021 may increase, as the patent applications filed in these years might not be published yet.

NotablePatents

Title: Cryo station system

JP6312811B2

Assignee: Hitachi Tech

The invention relates to handling of a sample for observation with an electron microscope. A technique for storing & moving a cooled sample without causing condensation or frost.

Title: Electronic imaging detector with thermal conduction layer

US20210193848A1

The invention relates to solid state active pixel image silicon sensor for direct back-illuminated exposure to an electron beam. The use of silicon as the sensor substrate minimizes the scatter of electrons.

Assignee: Gatan Inc

Title: Ablating material for an object in a particle beam device

US20220130639A1

Assignee: Carl Zeiss AG

The invention relates to a method for ablating a material from a material unit and for arranging the material on an object (sample) arranged in an electron microscope.

Title: Method for reducing or removing organic & inorganic contamination from a vacuum system of imaging & analytical devices & a device for carrying it out

US9782805B2

Assignee: Tescan Orsay

Holding AS

The present invention utilizes an incredibly low temperature to undercool a surface covered in a photocatalytic layer so that it can be used for decontamination.

Title: A mems device for transmission microscopy, & a method

WO2022075841A2

Assignee: Bruker

Nederland B.V.

The invention relates to a MEMS device that allows for holding a sample under vacuum in particular for cryoelectron microscopy, wherein a liquid sample is frozen into a vitreous state.

Title: Charged Particle Beam

Apparatus

US20220189731A1

Assignee: JEOL LTD

The present invention relates to a charged particle beam instrument. A specimen is inserted into a specimen chamber of the instrument such as transmission electron microscope where it is viewed and examined.