Advances in Light Microscope Technology

Stochastic Optical Reconstruction Microscopy

A new type of microscopy invented by Xiaowei Zhuang and colleagues at Harvard University and the Howard Hughes Medical Institute that resolves 20 nanometer objects using high-accuracy localization of photoswitchable fluorophores.

Single-molecule and single-particle imaging
in vitro & in live cells

Zhuang Lab at Harvard University is developing real-time fluorescence imaging methods to track the behavior of single virus particles and of single viral genomes in live cells.

Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy

Michael J Rust, Mark Bates, Xiaowei Zhuang, Oct 2006 Nature Methods. The online version can be downloaded from the Natures Methods web site for a fee.

4Pi and STED

4Pi-Confocal Microscopy is coming of Age

J. Bewersdorf, A. Egner, S.W. Hell - GIT Imaging & Microscopy, Nov. 2004

Department of NanoBiophotonics, Max-Planck-Institute for Biophysical Chemistry

The website of includes the work of Prof. Stefan W. Hell, who developed the 4Pi system, and his team that built the STED. There are introductions to the principles of the 4Pi, Stimulated Emission Depletion (STED-) microscopy, 4Pi STED, and Multifocal Multiphoton Microscopy and pdf files of publications.

Fluorescence microscopy with super-resolved optical sections

Alexander Egner1 and Stefan W. Hell, TRENDS in Cell Biology Vol.15 No.4 April 2005

Shattering the diffraction limit of light: A revolution in fluorescence microscopy?

Weiss, S. (2000). Proc. Natl. Acad. Sci. USA 97: 8747-8749.

PALM

Imaging sparsely activated fluorescent molecules one at a time, the photoactivated localization microscope (PALM) light microscope provides resolution down to 20 nanometers.

The Palm Principle

Online movie illustrates the principle used in photoactivated localization microscopy (PALM). Harald Hess, HHMI.

Sharper Image

An overview of the development of the the Palm. HHMI Bulletin, November 2006

Imaging Intracellular Fluorescent Proteins at Nanometer Resolution

Eric Betzig, George H. Patterson, Rachid Sougrat, O. Wolf Lindwasser, Scott Olenych, Juan S. Bonifacino, Michael W. Davidson, Jennifer Lippincott-Schwartz, Harald F. Hess, Science 2006 Sep15; 313(5793):1642-5. Epub 2006 Aug 10. (Online Abstract)

Annular Condenser

High Resolution Light Microscopy of Live Cells

Microscopy Today, V. Vodyanoy, June 2005

Resolution of 90 nm (λ/5) in an optical transmission microscope with an annular condenser

Optics Letters, Vol. 31, Iss. 19, October 2006

Overviews

Squint Busters

October 2006 article on microscopes that are pushing resolution to single-molecule sharpness. Amato, Ivan, Chemical & Engineering News

Blinded by the Light

Published in 2004, the article reviews advances in light microscopy including 4Pi, STED, confocal imaging, and total internal reflection fluorescence. Bio-IT World Magazine , Rabiya S. Tuma

Optical Illusions

Overview of the efforts for developing new light and electron microscopy methods at At Janelia Farm, Howard Hughes Medical Institute by linking mathematics, physics, engineering and computing. HHMI Bulletin,

Light Sources

Devising Nano Vision for an Optical Microscope

Phase-sensitive, scatter-field optical imaging is under development at the National Institute of Standards and Technology (NIST). This hybrid version of the optical microscope might be able to image and measure features smaller than 10 nanometers.

Breakthrough Brings Laser Light to New Regions of the Spectrum

Researchers have created a "waveguide" that coaxes extreme-ultraviolet light waves into forming a tightly focused laser-like beam that will allow researchers to "see" tiny features and carve miniature patterns. From NSF.