It can be argued that the earliest example of an optical technology being used for biological applications, in a manner relevant to today's usage, is that of the optical microscope. The word microscope comes from the Greek, wherein micron means small and skopein means to look at or to see. Beyond the simple magnifying glass, compound optical microscopes were first used to observe biological structures invisible to the naked eye in the seventeenth century. The English scientist Robert Hooke [1635–1703] described what he observed with a low-power (∼40×) microscope in a popular book called Micrographia, which provided the first illustrations of a variety of biological objects, including detail of a fly's eye, and (barely resolved) plant cells. It was the Dutch scientist Anton van Leeuwenhoek [1632–1723], however, who made the first compound lenses that were of high enough quality and short enough focal length to lead to a magnification of 270×, powerful enough to be considered a true microscope, rather than a strong magnifying glass. He reported the first observations of bacteria, yeast, blood cells, and various microscopic life forms commonly found in a water droplet. Perhaps surprisingly, it took nearly another 200 years before the French chemist and microbiologist Louis Pasteur [1822–1895] was able to explain the workings of bacteria. It is also interesting to note that the microscopes commonly used today by histopathologists, to examine the cellular structure of tissues for diagnosing disease, do not exhibit dramatically better optical performance than van Leeuwenhoek's early creation.

The general field of optical microscopy is too large to be covered in one chapter, and numerous excellent resources are available to provide ample detail about the optical design and common configurations of “traditional” optical microscopes, including many general textbooks on optics. Some of these are listed under further reading at the end of this chapter. In Section 17.1 we provide an abbreviated review of the basics of traditional microscopy, because these core elements are also found as parts of modern developments in the field, especially those applied to biomedical imaging. Beyond the classical configuration, a variety of more recent inventions in types of microscopy and microscopes offer images with a range of information content and/or resolution beyond the traditional limits. Not all of these are optical microscopes, but many are, and in the subsequent sections of the chapter we introduce some of the important advances in non-traditional optical microscopy.