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Most cells are transparent—in other words, they are not very good at reflecting or absorbing light. To look at them under a microscope thus requires trickery. Many of these tricks kill the cells, and even those that keep them alive look only at slices through each cell, rather than seeing the whole thing in three dimensions.

Michael Feld, of the Massachusetts Institute of Technology, and his colleagues, think they can change that. They have invented a way to look at cells that are still alive. Moreover, they can do so in three dimensions. Their method is called tomographic phase microscopy, and it is reported in this week's Nature Methods. Instead of relying on absorbed or reflected light, Dr Feld's technique celebrates transparency by looking at light that gets through unaltered. It does so by measuring a property called the refractive index.

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This index measures the speed of light in a material. (Light zips along at the actual “speed of light”, faster than which nothing can go, only when it is travelling through a vacuum.) The different components of a cell, though transparent, have different refractive indices. Dr Feld and his team therefore set out to map what these differences are, with a view to using them to distinguish between cellular components.

To measure the refractive indices of different parts of a cell they use a technique called interferometry, which involves splitting a beam of light in two. One half, known as the object beam, passes through the cell; the other is directed along a different path and acts as a reference. The length of the reference path is such that if no sample is present, the two daughter beams will be as perfectly in phase when they meet as they were when they were separated. The crests and the troughs of their waves will reinforce each other, and the result will be brightness. The more that the light passing through the sample is slowed down, however, the more the two beams will be out of phase. Crest will fall on trough, and the result will be darkness. It is this phase shift that gives Dr Feld's new form of microscopy its name.

A single pair of beams does not, however, produce a useful image. To do that requires scanning the object beam through the target about a hundred different ways. From the refractive index of each path it is possible—with the application of some suitably crunchy computing power—to produce a three-dimensional image.

To test his idea, Dr Feld looked at cervical-cancer cells. If you identify this cancer early, the patient will probably survive. Miss it, and she will die. Dr Feld wondered if the changes that occur during cancer would show up using his new method. They did, in a part of the cell called the nucleolus. This is the place where the components of protein factories are made. Since cancer cells grow rapidly, and thus have a high demand for proteins, it was a likely place to expect changes.

Dr Feld also has plans to use beams of different colours, since each colour has a slightly different refractive index in a given material. That would provide extra data for the computer to chew on, and probably result in better pictures. With enough pictures, Dr Feld's technique may make biology as transparent as the cells it studies.

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