The origin of flow based analysis harks all the way to 1906 when M. Tswett, a botanist, proposed chromatography, which bears his encrypted name. It took, however, almost half a century until his method became widely accepted, following the works of J.P. Martin and R.M.L. Synge, who received in 1952 the Nobel price "for their invention of partition chromatography“
Reagent based assays were, for the first time, automated on continuous flow basis by L. Skeggs in 1952. His work revolutionized the way, in which clinical assays were performed, and his invention became both technical and a commercial success. As he recollects in his memoir “One day, it suddenly occurred to me that analyses could be done in a continuously flowing stream rather than batchwise” “At the outset I made every effort to prevent air from getting into the flowing stream. Occasionally an air bubble would get in between samples. Of course, I noticed that the separation of samples was much better with the air bubble than without. Thereafter I always introduced air between samples and soon was adding air during sampling and in the dialysate stream as well.”
Air segmentation, became the key feature of his system, since it besides preserving the identity of individual samples, it also allowed to fulfill the two principal requirements deemed, at that time, necessary for performing precise and reproducible assay:
- Homogenous mixing of sample with reagents
- Reaching chemical equilibrium
From Batch to Air Segmented Flow
AIR SEGMENTATION HOMOGENOUS MIXING CHEMICAL EQUILIBRIUM
In the Technicon AutoAnalyzer® air, sample and reagents are aspirated by a peristaltic pump
and propelled trough a mixing coil, with aim to provide sufficient reaction time to achieve
mixing and chemical equilibrium, within the individual segments of liquid, before the
debubled stream passed trough a colorimeter.
For almost quarter of century the AutoAnalyzer became a workhorse of clinical laboratories worldwide, as it became accepted that the only practical way to carry out flow analysis is to use air segmentation. Much has change since then, yet, updated version of Skeggs ingenious design are still marketed by Astoria Pacific, Seal Instruments, and OI Analytical, for the purpose of environmental and oceanographic research.
M . Tswett. Ber. Dtsch. Bod. Ges. 1906, 24, 314 LT Jr Skeggs. Am J Clin Pathol 1957;28:311..
L.T.Skeggs, Clinical Chemistry 46:9 1425–1436 (2000)