Science Lab

Learn. Share. Contribute. The knowledge portal of Leica Microsystems. Find scientific research and teaching material on the subject of microscopy. The portal supports beginners, experienced practitioners and scientists alike in their everyday work and experiments. Explore interactive tutorials and application notes, discover the basics of microscopy as well as high-end technologies. Become part of the Science Lab community and share your expertise.

3D rendering of a mouse beta cell with mitochondria (blue), insulin SGs (orange), microtubules (red), nucleus (yellow), and plasma membrane (transparent).

High-Pressure Freezing Protocols for Ultrastructural 3D EM

High pressure freezing (HPF) can help preserve hydrated cells and tissues close to their biological state at the moment of immobilization, supporting more reliable ultrastructural interpretation than…

Foraminifera (Ammonia confertitesta) labeled with membrane-permeable calcein, high-pressure frozen in salt water using EM ICE. The sample was cryo-planed and targeted with the M205 on the Cryo-Fluo Enuity, then transferred under cryo conditions to the Cryo-Stellaris for widefield and confocal imaging, revealing details of the staining pattern. Image courtesy: David Evans, University of Southampton.

High-Pressure Freezing for Organoids: Cryo CLEM & FIB Lift Out

Master cryo EM workflow steps for challenging 3D samples: when to choose HPF vs. plunge freezing, reproducible blotting/ice control, contamination aware transfers, Cryo CLEM 3D targeting in organoids,…

Electron microscope (EM) image of a cross section of C. elegans (roundworm). Courtesy of T. Müller-Reichert, MPI-CBG, Dresden, Germany and K. McDonald, University of California, Berkeley, USA.

Brief Introduction to High-Pressure Freezing for Cryo-Fixation

Preparation of biological specimens for electron microscopy (EM) often requires cryo-fixation which does not introduce significant structural alterations of cellular constituents. A common method used…

Mouse brain slice which was immunostained with GFAP-A647 and imaged using a THUNDER Imager Tissue. Courtesy of H. Xu, University of Pennsylvania, Philadelphia, USA.

A Guide to Neuroscience Research

Neuroscience often requires investigating challenging specimens to better understand the nervous system and disorders. Leica microscopes helps neuroscientists obtain insights into neuronal functions.

Mouse hippocampus brain slice on a grid after HPF using the “Waffle Method”.

The “Waffle Method”: High-Pressure Freeze Complex Samples

This article describes the advantages of a special high pressure freezing method, the so-called “Waffle Method”. Learn how the “Waffle Method” uses EM grids as spacers for high-pressure freezing,…

Micrograph of dinoflagellate cells. Scale bar = 1 µm.

How Marine Microorganism Analysis can be Improved with High-pressure Freezing

In this application example we showcase the use of EM-Sample preparation with high pressure freezing, freeze substiturion and ultramicrotomy for marine biology focusing on ultrastructural analysis of…

How to Successfully Perform Live-Cell CLEM

The Leica Nano workflow provides a streamlined live-cell CLEM solution for getting insight bout structural changes of cellular components over time. Besides the technical handling described in the…

HeLa Kyoto cells (HKF1, H2B-mCherry, alpha Tubulin, mEGFP). Left image: Maximum projection of a z-stack prior to ICC and LVCC. Right image: Maximum projection of a mosaic z-stack after ICC and LVCC.

How to Improve Live Cell Imaging with Coral Life

For live-cell CLEM applications, light microscopy imaging is a critical step for identifying the right cell in the right state at the right time. In this article, Leica experts share their insights on…

How to Keep Your Samples Under Physiological Conditions

The Coral Life workflow combines dynamic data with the best possible sample fixation by high pressure freezing. However, good sample preservation won’t help if your cells are stressed by temperature…