Cryocorrelative

Cryocorrelative microscopy is a technique used in biological research to study the structure and function of cells and tissues at the nanoscale. It combines cryo-electron microscopy (cryo-EM) with correlative light microscopy (CLM) to provide high-resolution structural information alongside functional data. This approach is particularly valuable in the study of complex biological systems, such as synapses, mitochondria, and other organelles, where both structural and functional details are crucial.

The process begins with the preparation of biological samples, which are rapidly frozen to preserve their native state. The frozen samples are then imaged using cryo-EM, which provides high-resolution, three-dimensional images of the sample's ultrastructure. Simultaneously, the same sample is imaged using CLM, which provides lower-resolution, but functional information about the sample's morphology and distribution of specific markers.

The data from both techniques are then correlated using image processing algorithms, allowing researchers to overlay the structural information from cryo-EM with the functional information from CLM. This correlation helps to identify specific structures or regions within the sample that are functionally active or inactive, providing a more comprehensive understanding of the sample's biology.

Cryocorrelative microscopy has been successfully applied in various fields, including neuroscience, where it has been used to study the structure and function of synapses, and in cell biology, where it has been used to study the organization and function of mitochondria. The technique is continually evolving, with ongoing developments in image processing algorithms and sample preparation methods, further enhancing its capabilities and applications.