The history of electrophoresis for molecular separation and

chemical analysis Analytical chemistry studies and uses instruments and methods to separate, identify, and quantify matter. In practice, separation, identification or quantification may constitute the entire analysis or be combined with another method. Separati ...

began with the work of

Arne Tiselius Arne Wilhelm Kaurin Tiselius (10 August 1902 – 29 October 1971) was a Swedish biochemist who won the Nobel Prize in Chemistry in 1948 "for his research on electrophoresis and adsorption analysis, especially for his discoveries concerning t ...

in 1931, while new

separation process A separation process is a method that converts a mixture or a solution (chemistry), solution of chemical substances into two or more distinct product mixtures, a scientific process of separating two or more substance in order to obtain purity. At ...

es and chemical analysis techniques based on

electrophoresis Electrophoresis, from Ancient Greek ἤλεκτρον (ḗlektron, "amber") and φόρησις (phórēsis, "the act of bearing"), is the motion of dispersed particles relative to a fluid under the influence of a spatially uniform electric fie ...

continue to be developed in the 21st century. Tiselius, with support from the

Rockefeller Foundation The Rockefeller Foundation is an American private foundation and philanthropic medical research and arts funding organization based at 420 Fifth Avenue, New York City. The second-oldest major philanthropic institution in America, after the Carneg ...

, developed the " Tiselius apparatus" for

moving boundary electrophoresis Moving-boundary electrophoresis (MBE also free-boundary electrophoresis) is a technique for separation of chemical compounds by electrophoresis in a free solution. History Moving-boundary electrophoresis was developed by Arne Tiselius in 1930. Tis ...

, which was described in 1937 in the well-known paper " A New Apparatus for Electrophoretic Analysis of Colloidal Mixtures". The method spread slowly until the advent of effective zone electrophoresis methods in the 1940s and 1950s, which used

filter paper Filter paper is a semi-permeable paper barrier placed perpendicular to a liquid or air flow. It is used to separate fine solid particles from liquids or gases. The raw materials are different paper pulps. The pulp may be made from softwood, hardwo ...

gel A gel is a semi-solid that can have properties ranging from soft and weak to hard and tough. Gels are defined as a substantially dilute cross-linked system, which exhibits no flow when in the steady-state, although the liquid phase may still di ...

s as supporting media. By the 1960s, increasingly sophisticated

gel electrophoresis Gel electrophoresis is a method for separation and analysis of biomacromolecules ( DNA, RNA, proteins, etc.) and their fragments, based on their size and charge. It is used in clinical chemistry to separate proteins by charge or size (IEF ...

methods made it possible to separate biological molecules based on minute physical and chemical differences, helping to drive the rise of molecular biology. Gel electrophoresis and related techniques became the basis for a wide range of biochemical methods, such as protein fingerprinting,

Southern blot A Southern blot is a method used in molecular biology for detection of a specific DNA sequence in DNA samples. Southern blotting combines transfer of electrophoresis-separated DNA fragments to a filter membrane and subsequent fragment detecti ...

, other blotting procedures,

DNA sequencing DNA sequencing is the process of determining the nucleic acid sequence – the order of nucleotides in DNA. It includes any method or technology that is used to determine the order of the four bases: adenine, guanine, cytosine, and thymine. Th ...

, and many more.

Electrophoresis before Tiselius

Early work with the basic principle of electrophoresis dates to the early 19th century, based on

Faraday's laws of electrolysis Faraday's laws of electrolysis are quantitative relationships based on the electrochemical research published by Michael Faraday in 1833. First law Michael Faraday reported that the mass (m) of elements deposited at an electrode is directly prop ...

proposed in the late 18th century and other early electrochemistry. Experiments by

Johann Wilhelm Hittorf Johann Wilhelm Hittorf (27 March 1824 – 28 November 1914) was a German physicist who was born in Bonn and died in Münster, Germany. Hittorf was the first to compute the electricity-carrying capacity of charged atoms and molecules (ions), an ...

Walther Nernst Walther Hermann Nernst (; 25 June 1864 – 18 November 1941) was a German chemist known for his work in thermodynamics, physical chemistry, electrochemistry, and solid state physics. His formulation of the Nernst heat theorem helped pave the wa ...

, and Friedrich Kohlrausch to measure the properties and behavior of small

ions An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conven ...

moving through

aqueous solution An aqueous solution is a solution in which the solvent is water. It is mostly shown in chemical equations by appending (aq) to the relevant chemical formula. For example, a solution of table salt, or sodium chloride (NaCl), in water would be re ...

s under the influence of an

electric field An electric field (sometimes E-field) is the physical field that surrounds electrically charged particles and exerts force on all other charged particles in the field, either attracting or repelling them. It also refers to the physical field fo ...

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. Methods of optical detection of moving boundaries in liquids had been developed by

August Toepler August Joseph Ignaz Toepler (7 September 1836 – 6 March 1912) was a German chemist and physicist known for his experiments in electrostatics. Biography August Toepler was born on 7 September 1836. He studied chemistry at the Gewerbe-Insti ...

in the 1860s; Toepler measured the

schlieren Schlieren ( ; , ) are optical inhomogeneities in transparent media that are not necessarily visible to the human eye. Schlieren physics developed out of the need to produce high-quality lenses devoid of such inhomogeneities. These inhomogeneitie ...

(''shadows'') or slight variations in optical properties that 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's

method.Vesterberg, p. 5

Development and spread of the Tiselius apparatus

The apparatus designed by

enabled a range of new applications of electrophoresis in analyzing chemical mixtures. Its development, significantly funded by the Rockefeller 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.

Rise of zone electrophoresis

By the late 1940s, new electrophoresis methods were beginning to address some of the shortcomings of the

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 to separate compounds into discrete and stable bands (zones); in 1950 Tiselius dubbed these methods " zone electrophoresis". Zone electrophoresis found widespread application in biochemistry after

Oliver Smithies Oliver Smithies (23 June 1925 – 10 January 2017) was a British-American geneticist and physical biochemist. He is known for introducing starch as a medium for gel electrophoresis in 1955, and for the discovery, simultaneously with Mario Capec ...

introduced

starch Starch or amylum is a polymeric carbohydrate consisting of numerous glucose units joined by glycosidic bonds. This polysaccharide is produced by most green plants for energy storage. Worldwide, it is the most common carbohydrate in human diets ...

gel as an electrophoretic substrate in 1955. Starch gel (and later

polyacrylamide Polyacrylamide (abbreviated as PAM) is a polymer with the formula (-CH2CHCONH2-). It has a linear-chain structure. PAM is highly water-absorbent, forming a soft gel when hydrated. In 2008, an estimated 750,000,000 kg were produced, mainly fo ...

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.

Widespread application

Since the 1950s, electrophoresis methods have diversified considerably, and new methods and applications are still being developed as

Affinity electrophoresis Affinity electrophoresis is a general name for many analytical methods used in biochemistry and biotechnology. Both qualitative and quantitative information may be obtained through affinity electrophoresis. The methods include the so-called electr ...

Capillary electrophoresis Capillary electrophoresis (CE) is a family of electrokinetic separation methods performed in submillimeter diameter capillaries and in micro- and nanofluidic channels. Very often, CE refers to capillary zone electrophoresis (CZE), but other electr ...

Electroblotting Electroblotting is a method in molecular biology/biochemistry/ immunogenetics to transfer proteins or nucleic acids onto a membrane by using PVDF or nitrocellulose, after gel electrophoresis. The protein or nucleic acid can then be further anal ...

Electrophoretic mobility shift assay An electrophoretic mobility shift assay (EMSA) or mobility shift electrophoresis, also referred as a gel shift assay, gel mobility shift assay, band shift assay, or gel retardation assay, is a common affinity electrophoresis technique used to stud ...

Isotachophoresis Isotachophoresis (ITP) is a technique in analytical chemistry used for selective separation and concentration of ionic analytes. It is a form of electrophoresis; charged analytes are separated based on ionic mobility, a quantity which tells h ...

Pulsed-field gel electrophoresis Pulsed field gel electrophoresis is a technique used for the separation of large DNA molecules by applying to a gel matrix an electric field that periodically changes direction. Historical background Standard gel electrophoresis techniques for ...

, and Preparative electrophoresis.

Notes

References

* Vesterberg, Olof (1989). "History of Electrophoretic Methods", ''Journal of Chromatography'', volume 480, pp. 3–19. {{DEFAULTSORT:History Of Electrophoresis