An optical scientist considers the question: what do biologists want from a microscope?

Optics and biology have been intertwined for hundreds of years. Robert Hooke and Antonie van Leeuwenhoek both contributed greatly to the fields of microscopy and microbiology in their infancy, advancing each field by establishing a greater understanding in the other. As optics evolved and technologies derived from it became more refined, the number of discoveries in the realm of microbiology witnessed a concomitant increase. This fact was perhaps recognized in part with the award of the Nobel Prize in Physics in 1953 to Fritz Zernike for the phase contrast microscope, a tool which rendered otherwise invisible cells visible with relatively modest modifications to an existing microscope. Much work in microbiology followed as a result of this along with other developments in optics.

The relationship seemed to change, though, starting in the mid-twentieth century with the advent of molecular biology. During this time, molecular biological technologies evolved and matured to the point where discoveries were facilitated primarily by non-optical means, with microscopes serving as more of a tool for routine lab work than as significant drivers for learning something new. After all, a traditional light microscope is limited to observing structures no smaller than about one wavelength of light across, or about half a micron (one millionth of a meter). DNA, proteins, and all the other biomolecules are just too small to see, even for the most powerful microscope objectives.

Of course one could argue that the development of the targeted fluorescent proteins that reveal the location of a molecule's existence within a cell helped to advance the field of optics, but in this case the role of enabler switched sides; molecular biology led to an increase in the number of optical technologies for imaging fluorescent markers, such as fluorescence correlation spectroscopy. From the viewpoint of a scientist, this reversal is a bit distasteful. We would like for technology to enable new discoveries about the fundamentals of life, not for new discoveries to lead to technology that tells us what we already know.

Now we are well into the twenty first century and are rooted firmly within the scientific age of molecular biology and biotechnology. (The age of physics is now past and now concerns itself primarily with the ultimate limits of space: the infinitesimal quark and the awesomely large cosmos.) Given the history between optics and biology and the recent change in their relationship, I think it's necessary to make an assessment, so to speak, of this relationship.

In the near future I will write posts that explore this topic. I hope to answer questions like

1. What do biologists want out of a measurement technique?
2. Will the current trends in improving microscopies lead to answers of the fundamental questions of molecular and microbiology, or are we moving in the wrong direction?
3. Are optical scientists misguided in the search for improved images? Are there other forms of information carried by light that are more useful than images?
4. Will it be possible to better control biological processes using light?

Coming to conclusions

In the introduction of E. T. Jaynes's Probability Theory: The Logic of Science, Jaynes states

...the emphasis was therefore on the quantitative formulation of Polya’s viewpoint, so it could be used for general problems of scientific inference, almost all of which arise out of incomplete information rather than ‘randomness’.

As I learn more about the field of sensing, I find that this is the mentality, whether acknowledged by a practitioner or not, that is adopted when coming to a conclusion about the interpretation of data. The uncertainty involved in coming to a conclusion is not because the measurement process is inherently random but rather that one has not collected enough data to say whether this conclusion is true or false.

And in the light of Bayesian analysis, one will never be able to claim with 100% certainty that the conclusion is true (or false, for that matter).

A purpose for every project

A popular term in the field of optical sensing right now is "task-specific sensing." It is a system design paradigm in which the relationships between a system's components are optimized towards the purpose of the system. This is opposed to the idea of making the components perform as efficiently as possible on their own. For example, a system that only needs to detect an object in its field of view does not need to have a lens design that reduces aberrations and increases spatial resolution. Instead, a scene simply has to be imaged onto the sensor in a way that facilitates efficient image processing by the software. In other words, the relationships between the optics, electronics, and software should be optimized towards the goal of detecting an object, not seeing it clearly.

Nature has been performing task-specific design for a long time. The compound eye of a fly has very poor resolution since each bump on the eye acts as a single lens that couples to a sensing structure. Fortunately for the fly, it does not need to see well to find food. It does however need to avoid predators if it wishes to remain alive. The fly's eye has an extremely large field of view so that it can see things such as flyswatters coming at it from many different angles.

The task-specific paradigm has also led me to think about how to value research projects in academia. There is a very common notion that any research is good research. However, if a project creates some device or accomplishes some goal with no particular application in mind, then the idea of task-specific sensing might suggest that the simplest and least costly approach was not to have done the research at all since no need for it existed. I'll pose the question like this: which should come first, the need for a researched solution, or the solution itself?

Of course, the argument exists that research performed without a particular need may eventually find its uses, but I think that my question is still a valid one to ask before placing value upon research.