Abstract
We survey the history of resolution enhancement techniques in microscopy and their impact on current research in biomedicine. Often these techniques are labeled superresolution, or enhanced resolution microscopy, or light-optical nanoscopy. First, we introduce the development of diffraction theory in its relation to enhanced resolution; then we explore the foundations of resolution as expounded by the astronomers and the physicists and describe the conditions for which they apply. Then we elucidate Ernst Abbe’s theory of optical formation in the microscope, and its experimental verification and dissemination to the world wide microscope communities. Second, we describe and compare the early techniques that can enhance the resolution of the microscope. Third, we present the historical development of various techniques that substantially enhance the optical resolution of the light microscope. These enhanced resolution techniques in their modern form constitute an active area of research with seminal applications in biology and medicine. Our historical survey of the field of resolution enhancement uncovers many examples of reinvention, rediscovery, and independent invention and development of similar proposals, concepts, techniques, and instruments. Attribution of credit is therefore confounded by the fact that for understandable reasons authors stress the achievements from their own research groups and sometimes obfuscate their contributions and the prior art of others. In some cases, attribution of credit is also made more complex by the fact that long term developments are difficult to allocate to a specific individual because of the many mutual connections often existing between sometimes fiercely competing, sometimes strongly collaborating groups. Since applications in biology and medicine have been a major driving force in the development of resolution enhancing approaches, we focus on the contribution of enhanced resolution to these fields.
Highlights
Because of the importance of enhanced resolution for science, technology and medicine, microscopy is widely regarded an important discovery: advances in optical microscopy correlate well with advances in our understanding of biology, and medicine [Masters 2008; 2009a; 2009b]
Three main “nanoscopy” families for resolution enhancement in farfield fluorescence microscopy have been established: “nanoscopy” based on highly focused laser beams, such as 4Pi, Stimulated emission depletion (STED) (STimulated Emission Depletion), and GSD (Ground State Depletion; using focused excitation in the original publication) microscopy; nanoscopy based on Structured Illumination Excitation (SIE), such as Standing Wave (SW), Spatially Modulated Illumination (SMI), Structured Illumination (SI) and Patterned Excitation Microscopy (PEM); and nanoscopy allowing enhanced resolution even in the case of homogeneous excitation made possible by a variety of approaches which may be summarized under the names of localization microscopy and Superresolution Optical Fluctuation Imaging (SOFI)
A particular goal was to summarize the many lines of developments to overcome the hundred year old limitations in far-field light microscopy
Summary
Because of the importance of enhanced resolution for science, technology and medicine, microscopy is widely regarded an important discovery: advances in optical microscopy correlate well with advances in our understanding of biology, and medicine [Masters 2008; 2009a; 2009b]. The usable optical resolution of these microscopes was approximately 1 micron or 1/1000 millimeter This was not much better than what Leeuwenhoek had achieved 170 years earlier, there were large differences in the practical usefulness: instead of a single tiny lens that one had to keep very close to the eye for observation, Matthias Schleiden (1804–1881), the founder of the cellular theory of life, used a compound microscope of the French company Oberhauser (Paris/F), allowing precise focusing of the object. The preparations were at this microscope on glass slides that were clamped with steel springs on the stage, just as with conventional systems today These microscopes have a resolution down to the μm range already contained various elements (high quality optical components; appropriate illumination; high mechanical stability) essential for the modern development of enhanced resolution. Historical evidence demonstrates the utmost importance of improved resolution in science, technology, and in particular in biology and medicine
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have