Thehistory of electrophoresis for molecular separation andchemical analysis began with the work ofArne Tiselius in 1931, while newseparation processes and chemical speciation analysis techniques based onelectrophoresis continue to be developed in the 21st century.[1] Tiselius, with support from theRockefeller Foundation, developed theTiselius Apparatus formoving-boundary electrophoresis, which was described in 1937 in the well-known paper"A New Apparatus for Electrophoretic Analysis of Colloidal Mixtures".[2]
The method spread slowly until the advent of effectivezone electrophoresis methods in the1940s and1950s, which usedfilter paper orgels as supporting media. By the1960s, increasingly sophisticatedgel electrophoresis methods made it possible to separate biological molecules based on minute physical and chemical differences, helping to drive therise of molecular biology andbiochemistry. Gel electrophoresis and related techniques became the basis for a wide range ofbiochemical methods, such asprotein fingerprinting,Southern blot, other blotting procedures,DNA sequencing, and many more.[3]
Early work with the basic principle of electrophoresis dates to the early 19th century, based onFaraday's laws of electrolysis proposed in the late 18th century and otherearly electrochemistry. Theelectrokinetic phenomenon was observed for the first time in 1807 by Russian professors Peter Ivanovich Strakhov and Ferdinand Frederic Reuß atMoscow University,[4] who noticed that the application of a constant electric field causedclay particles dispersed inwater to migrate.
Experiments byJohann Wilhelm Hittorf,Walther Nernst, andFriedrich Kohlrausch to measure the properties and behavior of smallions moving throughaqueous solutions under the influence of anelectric field led to general mathematical descriptions of the electrochemistry of aqueous solutions. Kohlrausch created equations for varying concentrations of charged particles moving through solution, including sharp moving boundaries of migrating particles. By the beginning of the 20th century, electrochemists had found that such moving boundaries of charged particles could be created with U-shaped glass tubes.[5]
Methods of optical detection of moving boundaries in liquids had been developed byAugust Toepler in the1860s; Toepler measured theschlieren (shadows) or slight variations in optical properties in inhomogeneous solutions. This method combined with the theoretical and experimental methods for creating and analysing charged moving boundaries would form the basis of Tiselius'smoving-boundary electrophoresis method.[6]
The apparatus designed byArne Tiselius in 1931 enabled a range of new applications of electrophoresis in analyzing chemical mixtures. Its development, significantly funded by theRockefeller Foundation, was an extension of Tiselius's earlier PhD studies. With more assistance from the Rockefeller Foundation, the expensive Tiselius Apparatus was built at a number of major centers of chemical research.
By the late 1940s, new electrophoresis methods were beginning to address some of the shortcomings of themoving-boundary electrophoresis of the Tiselius Apparatus, which was not capable of completely separating electrophoretically similar compounds. Rather than charged molecules moving freely through solutions, the new methods used solid or gel matrices in new electrophoresis apparatuses to separate compounds into discrete and stable bands or zones. In 1950, Tiselius dubbed these methods "zone electrophoresis".
Zone electrophoresis found widespread application in biochemistry afterOliver Smithies introducedstarch gel as an electrophoretic substrate in 1955. Starch gel (and laterpolyacrylamide and other gels) enabled the efficient separation of proteins, making it possible with relatively simple technology to analyze complex protein mixtures and identify minute differences in related proteins.[7]
Despite the development of high-resolution zone electrophoresis methods, the accurate control of parameters such as pore size and stability of polyacrylamide gels was still a major challenge in the20th century. These technical problems were finally solved in the early2000s with the introduction of a standardizedpolymerization time for optimized polyacrylamide gels, making it possible for the first time to fractionate physiological concentrations of highly purified metal ion cofactors and associated proteins inquantitative amounts forstructure analysis.[8]
Since the 1950s, electrophoresis methods have diversified considerably, and new methods and applications are still being developed asaffinity electrophoresis,capillary electrophoresis,electroblotting,electrophoretic mobility shift assay,free-flow electrophoresis,isotachophoresis,preparative native PAGE, andpulsed-field gel electrophoresis.[8]
| By branch |
| ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Ancient history | |||||||||
| Periodic table (timeline) |
| ||||||||
| On specific discoveries | |||||||||
| Scientific disputes | |||||||||
| Other | |||||||||
