The body of a human being engaged in its vital actions consists of multiple systems interacting with one another. The precision of systems such as neurotransmitters and the immune system is nothing short of astounding. The workings of DNA and cells are gradually being revealed, due to the remarkable progress being made in medicine and science. However, many more unseen mysteries still remain. An in-depth understanding of the structures and functions of living cells is required for the elucidation of the mechanisms of vital actions and for efforts to further develop medical treatment, for example through the development of new drugs and the establishment of treatment methods.

Accordingly, live-cell imaging is now being widely used in cellular research and has shed light on many subjects. With the development of the biosciences in recent years, there is now a greater need than ever for more detailed observation of the minute structures of the cell, such as the membrane and the organelles.

One such feature is an organelle known as the mitochondrion, which plays an important role in support of the vital actions of the cell. Using conventional optical microscopes it has not been possible to visualize the internal structure of mitochondrion in living cells clearly. Electron microscopes, which have higher resolutions than optical microscopes, are used in the examination of the minute structures of cells. However, since this requires the specimen to be frozen and imaged in a vacuum, it is impossible to capture images of live cells using an electron microscope. Thus, although it has been possible to formulate hypotheses based on the results of imaging with an electron microscope, it has been difficult to prove them for living cells.

For reasons such as these, the need has arisen for an optical microscope that can overcome existing limitations and achieve a high degree of resolution.

Captured with a conventional microscope (left) and with the N-SIM (right)
The minute structure in the mitochondria can be clearly observed using the N-SIM.

In the context of optical technology such as cameras and microscopes, the term "resolution" signifies the ability to distinguish two close objects as being separate. This is also referred to as "resolving power."

For conventional optical microscopes this resolution has been limited to approximately 200 nm, meaning it is impossible to distinguish two objects that are less than 200 nm apart. To allow this, the objective lens would have to accept a larger angle of the cone of light than that which conventional microscopes can accept. In practice, however, there are theoretical limits to the light acceptance angle of an objective lens, which is restricted by the NA of the objective lens and the wavelength of the light.

Super Resolution Microscope N-SIM has overcome the limitations of the optical microscope, achieving a spectacularly improved resolution of nearly double that of conventional microscopes. The N-SIM is an optical microscope that achieves super resolution by combining proprietary Nikon optical technology with Structured Illumination Microscopy (SIM), a technique that uses the moiré phenomenon to increase resolution and which was announced by a team led by Dr. Mats G. L. Gustafsson of the University of California, San Francisco, in 2000.

• *Group leader (2008—2011), Janelia Farm Research Campus, Howard Hughes Medical Institute