Eur. Phys. J. H 38, 281–344 (2013)
https://doi.org/10.1140/epjh/e2012-20060-1

Review

Resolution enhancement techniques in microscopy

¹ Group Leader, Superresolution Microscopy, Institute of Molecular Biology (IMB), Ackermannweg 4, 55128 Mainz, Germany
² Kirchhoff Institute of Physics (KIP), University Heidelberg, Im Neuenheimer Feld 227, 69120 Heidelberg, Germany
³ Visiting Scholar, Department of the History of Science, Harvard University, Science Center, No. 1 Oxford Street, Cambridge, MA 02138, USA
⁴ Visiting Scientist, Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, NE47-220, Cambridge, MA 01239, USA

^a e-mail: cremer@kip.uni-heidelberg.de; c.cremer@imb-mainz.de

Received: 28 November 2011
Received in final form: 20 November 2012
Published online: 23 January 2013

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.