The early fluidic and optical physics of cytometry.

All forms of cytometry, depend on the basic laws of physics, including those of fluidics, optics, and electronics, most of which were established centuries ago. Flow cytometry depends critically on the fluidics presenting each individual cell with precision to the sensing volume. This is intersected by a high-intensity light source, and light scattering and fluorescence from suitably stained constituents in each cell are captured by the light-collecting optics and measured. The works and observations of Bernoulli and Euler in the 18th century, Reynolds in the 19th century, and Crosland-Taylor in the 20th century in the field of fluid dynamics laid the foundations for hydrodynamic focussing, which is the primary prerequisite for presenting individual cells to the sensing volume. In addition, electrostatic cell sorters must have the ability to generate stable droplet formation in the jet-stream issuing from the flow chamber nozzle. The origins here can be traced to work carried out in the early to mid-19th century by Savart, Magnus, and Thomson. Flow, image, and confocal cytometry are all dependent on the laws of optics, including those of reflection and refraction as well as numerous other optical principles. The observations and works of Socrates, Ptolemy, Snel, and Descartes between about BC 370 and 1637 were of seminal importance in developing the laws of reflection and refraction. In the mid-17th century Hooke illustrated the power of magnifying glasses and microscopy in his Micrographia and Newton was responsible for explaining colours in the spectrum. Huygens, toward the end of the 17th century, put forward the concept of point source light propagation contributing to a wave front. Finally, Thomas Young, early in the 19th century, established the wave form of light from interference patterns. Most people will be familiar with some of these discoveries and the investigators who carried out the work; some people will be familiar with all of these. However, very few people are likely to have had the opportunity and privilege to access the very early works and the original data and manuscripts, or translations thereof, which laid the foundations of physics that enabled our discipline to be established. It is always important for any discipline to remember its roots and to appreciate the seed from which those roots grew, for it is much easier to learn and fully understand when we have a knowledge of the source and the logical progressions that lead from one discovery to the next. This knowledge lends perspective to our current endeavours as the past, after all, created the present, which in turn contributes to the future. In this article, which was presented as an invited lecture at the 9th Canadian Consensus meeting on AIDS, I have attempted to trace the origins of the early work on the physics of fluidics and optics, which laid the foundations.