For those of you who haven't visited the websites of Carl Zeiss or Nikon lately, fluorescent microscopes are expensive. Typically, microscopes of the sort required by pathologists to make diagnosis are around $2,000, weigh something on the order of a small child, and require mains power. So lugging the microscope to a remote Indonesian clinic to carry out timely diagnosis of tuberculosis, for instance, is a bit problematic.

Naturally, the microscope manufacturers have no problem with this situation, because their microscopes still get purchased. Patients in many areas, however, may have issues, since they're required to travel to clinics, which is a journey that may be impossible to undertake immediately and may require several days of travel in each direction. In the meantime, the deadly bacillus is multiplying, making treatment more expensive and longer.

There are, therefore, excellent reasons for developing a cheap, portable, battery-powered fluorescent microscope. This is exactly what researchers at Rice University describe in recent PloS One and SPIE proceedings.

A fluorescent microscope uses fluorescent dyes to increase the contrast of the sample, allowing pathologists to identify particular objects, such as the TB bacillus, with less ambiguity. The idea is relatively simple: a dye is added to the sample, and it adheres preferentially to certain molecular structures. The dye absorbs light at a short wavelength—blue light, for instance—and re-emits the energy at a longer wavelength, a process called fluorescence. So, the microscope filters out the illuminating light, leaving only the fluorescence that comes from the parts of the sample that the dye stuck to.

The requirements are then: a bright light source, a set of filters, and some good optics. In the past, the light source has been the expensive part, since this was usually a laser. But the advent of bright white LEDs has changed all that—the Rice researchers used a standard, battery-powered LED flashlight. Not only does this provide a cheap and portable light source, but it also allows for easy replacement using readily available parts.

There were some compromises. The optics do not correct for aberration, and the flashlight uses a reflector rather than a condenser lens, so the lateral resolution is three times worse than it could ideally be. Nevertheless, it has sufficient resolving power for the job at hand, as proven by the diagnostic tests.

To test the performance of the microscope, the researchers prepared sputum samples from patients suspected of having TB and from people thought to be free of TB, and had them analyzed by a blinded pathologist using their microscope and a commercial microscope. Statistically speaking, the microscopes performed identically. The two microscopes produced slightly different TB burdens for identical samples, so larger sample numbers might show that the cheap microscope was marginally less sensitive. But that's still a hell of a lot more sensitive than no microscope at all.

So, how much would you pay for such a microscope? $500? $750? To build your own using optics out of catalogs will cost you $490. However, given the mark-up on equipment out of optical catalogs, the researchers estimate that a manufacturer could get this out the door for under $300.

Even at $500, this is all right. You can buy three of these for the cost of something from Nikon, and you can put them in traveling clinics to provide point-of-care diagnostics to a much larger number of people compared to a single microscope at a fixed facility. So, even if the researchers are a bit optimistic on the price, it is still a net win for overburdened healthcare systems in developing world countries.

PLoS One, 2010, DOI: 10.1371/journal.pone.0011890

Proceedings of SPIE, 2010, DOI: 10.1117/12.848605

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