The glass micropipette electrode: A history of its inventors and users to 1950

417 It is commonly, but erroneously, supposed that sharp glass micropipette electrodes were co-invented by Gilbert Ning Ling and Ralph Waldo Gerard (Ling and Gerard, 1949; much as the invention of the ubiquitous “Pasteur pipette” is incorrectly attributed to Louis Pasteur). Actually, fine, sharp-tipped examples of capillary glass microelectrodes had been developed and used successfully from the 1920s, mainly in plant cells (Bretag, 1983, 2003). Gerard was, however, involved in the successful transfer of their use to single skeletal muscle cells, although his participation in that, too, occurred long before his muchcited 1949 paper with Ling. These aspects of the history of the glass micropipette electrode seem to have been forgotten, accidentally or deliberately. Very narrow glass tubes aroused scientific interest when capillary action was first noticed in them as a curiosity in around 1660. Robert Boyle writes of “an odde kinde of siphon that I causd to be made a pretty while ago” (Boyle, 1660). He states that examples of slender and perforated “Pipes of Glass” had earlier been given to him by “An eminent Mathematician” who relayed the observations of “some inquisitive French Men (whose Names I know not)” that, when one end was dipped into water, it would “ascend to some height in the Pipe.” An explanation for this phenomenon was provided by Robert Hooke, who also reiterated Boyle’s version of the history of the small glass pipes (Hooke, 1661). It is pertinent that, soon afterward, Henry Power wrote a book chapter on the subject (Power, 1664) in which he says that he used glass tubes “almost as small as Hairs, or as Art could make them” and named them “Capillary Tubes.” Fine glass pipettes, filamentous glass loops and needles, and the first mechanical devices necessary for their manipulation were developed in the 19 century by Toldt in Germany (1869), Chabry in France (1887), and Schouten in the Netherlands (1899), among others (as reviewed by Chambers, 1918, 1922; Taylor, 1920; Péterfi, 1923). These refined glass instruments succeeded the earlier manufacture of glass tubes (as eyedroppers, medicine droppers, and ink fillers), glass needles, and decorative glass filaments that had, in many cases, dated back through the Renaissance to Roman times. Eventually, at the beginning of the 20 century, the method of preparing glass capillary micropipettes with tips that proved fine enough to capture a single bacterium was invented by the bacteriologist Marshall Albert Barber (Fig. 1) of the University of Kansas (Barber, 1904). Capillary tubing of hard or soft glass a few millimeters in diameter was held and heated over a microburner until the glass began to soften (as shown in Fig. 2). The hand holding the capillary with forceps was then pulled quickly away horizontally until the rapidly narrowing, and cooling, glass capillary thread, now outside the flame, separated with a slight tug (Barber, 1911). Barber also invented micromanipulators with the three-dimensional precision essential to handle these delicate instruments (Fig. 3), and so to allow them to be inserted through the plasma membranes of living cells without significantly damaging them. In this way, substances or even a single bacterium could be inoculated into the cytoplasm of a living cell, or fluids or structures could be extracted from the cell (Barber, 1914). Barber’s methods were soon noticed by German Nobel Laureate Heinrich Hermann Robert Koch, who subsequently visited the United States in 1908 and observed a demonstration by Barber at the Sixth International Congress on Tuberculosis in Washington, DC (KU History, 2016). Albert Prescott Mathews, Professor of Physiological Chemistry in the Department of Physiology at the Soon after the glass micropipette was invented as a micro-tool for manipulation of single bacteria and the microinjection and microsurgery of living cells, it was seen to hold promise as a microelectrode to stimulate individual cells electrically and to study electrical potentials in them. Initial successes and accurate mechanistic explanations of the results were achieved in giant plant cells in the 1920s. Long known surface electrical activity in nerves and muscles was only resolved at a similar cellular level in the 1930s and 1940s after the discovery of giant nerve fibers and the development of finer tipped microelectrodes for normal-sized cells. J G P 1 0 0 t h A n n i v e r s a r y