Exotic Microscopes

Really, optical systems used in microscopes. Some real, some cranky.

Richardson contrast

This one's as real as it gets - you can buy it from Improvision (under the name Real Time Microscope, RTM), and they came and demonstrated it at our institute. How does it work? According to Improvision:

Using the RTM, samples are illuminated in extreme dark-field. The RTM image is built from only those photons that contain sample information and have had their trajectories altered by interaction with the sample. This means that the images produced have a very high signal to noise ratio and therefore enhanced contrast.

So your guess is as good as mine.

The key thing is that it's clever, but entirely within the framework of classical optics, just like darkfield, phase contrast, Nomarski interference, Hoffman modulation contrast, Leica modulation contrast, etc. The upshot is that it's a really fancy brightfield system - you get lots of signal, lots of contrast, amazing resolution, and the real colours of the object, right in your eye. Which makes it completely bloody useless for research work, for which you need fluorescence images. A Richardson microscope can be used for fluorescence work, but i believe this involves bypassing the clever optics, much like doing fluorescence on a phase-equipped system, so no real benefit.

The resolution is better than conventional microscopes; somewhere in the region of 100 nm or something. This seems to be due to a modest increase in some constant in Abbé's formula, rather than a way of avoiding it.

Extended depth of field (EDF)

Specifically, extended depth of field acheived by wavecoding using a cubic phase plate (CPP). This sounds very much like pseudo-science, but appears to be absolutely real. There's a bunch of work being done at the Imaging Systems Laboratory of the University of Colorado at Boulder, which is hell-bent on "bringing you the future of imaging... today!". Ringleader seems to be W. Thomas Cathey.

The physics is way beyond me, but the idea is to use some sort of diffraction grating - this cubic phase plate and relatives - to do something to the incoming light, so that you can focus light from all sorts of focal lengths at once. You sacrifice some sharpness, but that seems to be recoverable via a dose of image processing (presumably, making the system more sensitive to noise, but i'm guessing here). You can also correct for aberrations in the optics

The key paper is online; they use LaTeX, so they're definitely legit.

The ISL guys mention that this idea was pioneered by Dr. Joseph van der Gracht of the Army Research Laboratory (ARL).

You can use wavecoding for other neat stuff: principally, passive ranging.

Apparently, they were even on Tomorrow's World in 1997.

Rife 'universal microscope'

Quackery of an exceptional level. Royal R. Rife, working in the 1930s, claimed to have hit on a radical new way of making microscopes which allowed him to transcend the Abbé limit; with this, he saw all sorts of crazy stuff. Sadly, none of his papers, and no complete, working microscopes survive, so we can't verify this. He also invented a cure for cancer (and, according to some sources, all forms of infectious disease) based on some kind of special ray. He died in 1971, but has left a huge cult of pseudo-science fans behind him.

Solid information on Rife's work is hard to find - there are a hundred crank pages for every sane one. However, Robert Cathey has kindly made available two useful sources. Firstly, a summary of the history of Rife's number 5 microscope, written by C. N. Brown, then senior curator of classical physics at the Science Museum, who've got it in their collection. Secondly, a transcription of a paper describing Rife's microscopes, namely: The new microscopes - R. E. Seidel, M. E. Winter (1944); J Franklin Inst 237(2):103 (also available in ScienceDirect!). Hmm. Wonder if Mr Cathey's any relation of Thomas Cathey, the EDF guy mentioned above?

Olbrich 'grayfield'

Kurt Olbrich, a German engineer, has come up with a type of microscope, which goes by the name 'Ergonom', which, he claims, provides sub-100 nm resolution, great depth of field, low aberration and enormous working distance. Using an air lens. Olbrich won't say how it works - there are no papers or patents - except that it uses a different illumination system, and perhaps extra optics in the light path. There are mentions of it being a 'light source like' system, which is reminiscent of Rife's work; there are other links to Rife, such as one assertion that Olbrich talked with Rife a few years before he died, that some of Olbrich's business partners also market Rife-based gizmos.

However, there's no reason to think that Olbrich's system is related to Rife's, and indeed, evidence that it's not is that you can buy working microscopes using it - from from Grayfield Optical Inc in the UK and US, and Orthikon in Germany.

Apparently, an Olbrich microscope (an Olbrich 4000 or an Ergonom 400, which may be the same thing) came to UCL's anatomy department in the late '80s; it was associated with a Dr Gary L. Greenberg, who may in fact have been at the University of Southern California instead, or at some other time. There even seems to have been a film, "Some Biological Preparations Viewed in the Olbrich 4000 Microscope", made.

Olbrich, in collaboration with Bernard Muschlein, has come up with a universal theory of disease or something based on some tiny symbiotic microorganisms called endobionts. This, and other uses of his microscope, are all shown in a film (yes, from a site called rife.de ...). There are a bunch more movies on various topics on the Grayfield site.

4Pi

4Pi is an improvement to the standard laser-scanning confocal approach. The name comes from the fact that the microscope collects light from both sides of the sample, rather than just one, thus coming close to covering 4π steradians of solid angle. It was invented by Prof Stefan Hell at the MPI Biophysical Chemistry (what is it with Germans and optics?), and commercialised by Leica.

The point of the whole 4π coverage thing is that the Abbé limit depends on the aperture of the lens; covering more of the angle around the sample effectively means a bigger aperture, and so higher resolution. Very clever! For some reason, though, this seems to give a much better improvement in z-resolution than xy-resolution, to the point where resolution is several times better in z than xy; makes a change from the normal situation, but not actually that practically useful. Still, xy resolution is better too.

Hell also has a technique called stimulated emission depletion (STED, rather than SED, for some reason), where you use a second beam of light to suppress fluorescent emission from the outer part of the confocal spot, thus effectively reducing its size and increasing resolution. On its own, this is not a great technique, for tedious physics reasons, but together with 4Pi, it works really rather well. Hell reckons 4Pi+STED has no theoretical resolution limit.

There aren't many 4Pi systems in the field yet, but everything i've seen makes me think that they really are very good indeed.

Review on 4Pi and I5.