Cryomicroscopy is a technique in which a

microscope A microscope () is a laboratory instrument used to examine objects that are too small to be seen by the naked eye. Microscopy is the science of investigating small objects and structures using a microscope. Microscopic means being invisibl ...

is equipped in such a fashion that the object intended to be inspected can be cooled to below room temperature. Technically, cryomicroscopy implies compatibility between a

cryostat A cryostat (from ''cryo'' meaning cold and ''stat'' meaning stable) is a device used to maintain low cryogenic temperatures of samples or devices mounted within the cryostat. Low temperatures may be maintained within a cryostat by using various r ...

and a microscope. Most cryostats make use of a cryogenic fluid such as liquid

helium Helium (from el, ἥλιος, helios, lit=sun) is a chemical element with the symbol He and atomic number 2. It is a colorless, odorless, tasteless, non-toxic, inert, monatomic gas and the first in the noble gas group in the periodic table. ...

or liquid

nitrogen Nitrogen is the chemical element with the symbol N and atomic number 7. Nitrogen is a nonmetal and the lightest member of group 15 of the periodic table, often called the pnictogens. It is a common element in the universe, estimated at seve ...

. There exists two common motivations for performing a cryomicroscopy. One is to improve upon the process of performing a standard microscopy. Cryogenic electron microscopy, for example, enables the studying of proteins with limited radiation damage. In this case, the

protein structure Protein structure is the molecular geometry, three-dimensional arrangement of atoms in an amino acid-chain molecule. Proteins are polymers specifically polypeptides formed from sequences of amino acids, the monomers of the polymer. A single ami ...

may not change with temperature, but the cryogenic environment enables the improvement of the electron microscopy process. Another motivation for performing a cryomicroscopy is to apply the microscopy to a low-temperature phenomenon. A

scanning tunnelling microscopy A scanning tunneling microscope (STM) is a type of microscope used for imaging surfaces at the atomic level. Its development in 1981 earned its inventors, Gerd Binnig and Heinrich Rohrer, then at IBM Zürich, the Nobel Prize in Physics in 1986. ...

under a cryogenic environment, for example, allows for the studying of

superconductivity Superconductivity is a set of physical properties observed in certain materials where electrical resistance vanishes and magnetic flux fields are expelled from the material. Any material exhibiting these properties is a superconductor. Unlik ...

, which does not exist at room temperature.

History

Although optical microscopes have existed for centuries, cryomicroscopy is a modern methodology. In the 1950s,

ice crystals Ice crystals are solid ice exhibiting atomic ordering on various length scales and include hexagonal columns, hexagonal plates, dendritic crystals, and diamond dust. Formation The hugely symmetric shapes are due to depositional growth ...

were studied by installing an electron microscope inside of an

igloo An igloo (Inuit languages: , Inuktitut syllabics (plural: )), also known as a snow house or snow hut, is a type of shelter built of suitable snow. Although igloos are often associated with all Inuit, they were traditionally used only ...

. Circa 1980, the adaption of the electron microscope, the vacuum, and the cryostat led to the conception of the modern cryomicroscopy. This development of the cryoelectron microscopy led to the awarding of the 2017 Nobel Prize in Chemistry to

Jacques Dubochet Jacques Dubochet (born 8 June 1942) is a retired Swiss biophysicist. He is a former researcher at the European Molecular Biology Laboratory in Heidelberg, Germany, and an honorary professor of biophysics at the University of Lausanne in Switze ...

Joachim Frank Joachim Frank () (born September 12, 1940) is a German-American biophysicist at Columbia University and a Nobel laureate. He is regarded as the founder of single-particle cryo-electron microscopy (cryo-EM), for which he shared the Nobel Prize i ...

, and Richard Henderson.

Cryogenic electron microscopy

The processes of scanning and

transmission electron microscopy Transmission electron microscopy (TEM) is a microscopy technique in which a beam of electrons is transmitted through a specimen to form an image. The specimen is most often an ultrathin section less than 100 nm thick or a suspension on a gr ...

carried out under cryogenic conditions are known as cryoSEM and cryoTEM, respectively.

Cryogenic optical microscopy

Cryogenic environments are used in combination with different types of

optical microscopy Optics is the branch of physics that studies the behaviour and properties of light, including its interactions with matter and the construction of instruments that use or detect it. Optics usually describes the behaviour of visible, ultraviol ...

techniques. Cryogenic environments also minimize bleaching, which, in turn, improves the contrast of the microscopy technique. The growth of artificial ice crystals is, for example, studied by optical microscopy. With

polarized light microscopy Polarized light microscopy can mean any of a number of optical microscopy techniques involving polarized light Polarization ( also polarisation) is a property applying to transverse waves that specifies the geometrical orientation of the osci ...

, the

birefringence Birefringence is the optical property of a material having a refractive index that depends on the polarization and propagation direction of light. These optically anisotropic materials are said to be birefringent (or birefractive). The birefrin ...

effect from, for example, orthorhombic domain structures, can be observed at cryogenic temperatures. In the field of biology,

fluorescence microscopy A fluorescence microscope is an optical microscope that uses fluorescence instead of, or in addition to, scattering, reflection, and attenuation or absorption, to study the properties of organic or inorganic substances. "Fluorescence micr ...

has enabled resolution beyond the

diffraction limit The resolution of an optical imaging system a microscope, telescope, or camera can be limited by factors such as imperfections in the lenses or misalignment. However, there is a principal limit to the resolution of any optical system, due to t ...

. The 2014 Nobel Prize in Chemistry was jointly awarded to

Eric Betzig Robert Eric Betzig (born January 13, 1960) is an American physicist who works as a professor of physics and professor of molecular and cell biology at the University of California, Berkeley. He is also a senior fellow at the Janelia Farm Resear ...

Stefan Hell Stefan Walter Hell HonFRMS (: born 23 December 1962) is a Romanian-German physicist and one of the directors of the Max Planck Institute for Biophysical Chemistry in Göttingen, Germany. He received the Nobel Prize in Chemistry in 2014 "for the ...

, and

William E. Moerner William Esco Moerner (born June 24, 1953) is an American physical chemist and chemical physicist with current work in the biophysics and imaging of single molecules. He is credited with achieving the first optical detection and spectroscopy of ...

for the development of super-resolved fluorescence microscopy.{{Cite journal, last=Möckl, first=Leonhard, last2=Lamb, first2=Don C., last3=Bräuchle, first3=Christoph, date=2014-12-15, title=Super-resolved Fluorescence Microscopy: Nobel Prize in Chemistry 2014 for Eric Betzig, Stefan Hell, and William E. Moerner, url=https://onlinelibrary.wiley.com/doi/10.1002/anie.201410265, journal=Angewandte Chemie International Edition, language=en, volume=53, issue=51, pages=13972–13977, doi=10.1002/anie.201410265

References

Microscopes