The Potentiostat and the Voltage Clamp by Jackson E. Harrar n the history of science and technology, and biophysics. In electrochemistry, and this signal is transmitted to the negative there have been many instances when potentiostats are used for fundamental studies input of the differential amplifier, where it is Itwo or more persons have independently of electrode processes, analytical chemistry, compared to the desired control voltage (E) created an invention or concept at almost battery research, the synthesis of chemicals, at the positive input. The amplifier is a DC- the same time, but for various reasons, and corrosion research. Variations of the coupled, differential input amplifier. It has a one inventor takes precedence or credit. voltage clamp are employed in research high open-loop gain (>105), fast response, Examples are the telephone, the integrated on the properties of living biological cells. and its inputs have high input impedances circuit, calculus in mathematics, and the Adaptations of these instruments have also so very little current (nanoamperes) flows in theory of evolution. Once the invention or been made to control the electric current this part of the circuit. The amplifier, by the concept is introduced, further development rather than voltage. During most of this time, action of negative feedback, continuously soon proceeds along a single path. A rare however, research in these disparate fields of adjusts its output voltage and current to instance is an innovation that was developed electrochemistry and electrophysiology, and keep the potential measured by the reference by two different scientists in two different their investigators, has remained virtually electrode equal to the control voltage. fields at almost the same time, and then independent. The electrolysis current flowing between widely used for many years in these two electrodes CE and WE is measured by fields without the investigators being aware The Potentiostat additional instrumentation (M) in either of the other application. This happened the counter electrode part (as shown) or the in the case of the potentiostat and the Figure 1 shows a simplified version of a working electrode part of the circuit. voltage clamp, which are basically similar potentiostat connected to a three-electrode In electrochemistry, potentiostats are instruments, but whose actual applications electrolytic cell. The electrolysis current used with working electrodes of inert are quite dissimilar. in the electrolytic cell is provided by the elements (e.g., platinum, gold, mercury, and Both the potentiostat and the voltage output of the amplifier (Amp) to the cell via carbon), semiconductors, and for corrosion clamp operate on the principle of negative the counter electrode (CE). The desired or studies, the metal of interest. Sizes range in feedback control. Both instruments employ studied reaction takes place at the working area from >100 cm2 for controlled-potential an amplifier in a feedback arrangement to electrode (WE). The reference electrode (RE) coulometry and electrosynthesis, to very control the voltage (or electrode potential) senses the potential at the working electrode small (radius <103 cm) microelectrodes for in, respectively, an electrolytic cell or a biological specimen. In their simplest forms, they are essentially the same circuit. In the early 1940s, Archie Hickling at the University of Leicester, England, who was working in the field of electrochemistry, invented the potentiostat and coined the apt name for the device.1 He used the potentiostat to control the voltage (i.e., the potential) of an electrode to perform electrolysis in an M electrolytic cell. - In the late 1940s, at the University of Amp Chicago, Kenneth Cole, with the help of George Marmont, invented an electronic + circuit called a voltage clamp,2 which was used to investigate ionic conduction in CE nerves. Concurrently, these voltage clamp Cell RE techniques were adopted by Alan Hodgkin, Andrew Huxley, and Bernard Katz at E WE Cambridge University in England for their research in this field. In 1963, Hodgkin and Huxley were awarded the Nobel Prize in Physiology or Medicine for this work. Further development and elaboration of these circuits has been carried on for many years, including the marketing of many commercial instruments—some for electrochemistry and some for biochemistry FIG. 1. Simplified potentiostat and three-electrode electrolytic cell. 42 The Electrochemical Society Interface • Winter 2013 chemical analysis and fundamental studies.3 ions are transported through ion channels clamp arrangements that can influence the Counter electrodes are usually made of in the membrane.2,4 Later studies have dealt measurements of high-speed signals.6 platinum, while reference electrodes are with calcium and chloride ion flow. The stability of the cell/feedback loop most often made of silver, coated with silver Advances in technique and instrumenta- in controlling the potential may also be chloride, or mercury-mercurous chloride tion in the field of electrophysiology have an issue. In the case of potentiostatic (saturated calomel). led to an apparatus for clamping with a sin- measurements, this was examined in gle intracellular electrode, and patch clamp- terms of classical control-system theory in The Voltage Clamp ing, which enables measuring the properties the 1960s and 1970s,7 and has also been of single ion channels in a membrane.5,6 For addressed for voltage clamp systems.6,8 Figure 2 shows a simplified version of the invention of the patch clamp technique, Data interpretation in electrophysiology a “two-electrode” voltage clamp connected Bert Sakmann and Erwin Neher received the may also be complicated because the to an apparatus in which the properties of 1991 Nobel Prize in Physiology or Medi- microelectrode contacts a point while the the membrane of a biological specimen are cine. cell is obviously three dimensional. The examined. The specimen in this arrangement patch clamp technique is advantageous in is contained in a bathing medium such as Common Problems this respect because the microelectrode saline solution. The electrodes (CE and RE) in the Experiments in this configuration is attached directly penetrate the membrane of the specimen. to an ion channel or small group of ion Electrode CE is the current-carrying Although the electronic circuits of channels. In both electrochemistry and electrode within the specimen, while the potentiostatic and voltage clamps are similar, electrophysiology, quite sophisticated second electrode (RE) senses the potential the laboratory apparatus and experiments instrumentation has been designed and (with reference to ground) across the using them are quite different. Nevertheless, techniques of data interpretation have membrane. The current flows from electrode been developed to deal with all of these some problems that complicate the 5-9 CE through the membrane of the specimen experiments are present in both fields. problems. to ground. Measurements of the current, in Electrophysiologists are always dealing either the amplifier output circuit (M) or the with extremely small microelectrodes History ground circuit, yields information on the which have high resistances that may properties of the membrane. The electrodes introduce errors in potential control.6 Further development of potentiostatic typically are constructed of fine-tipped glass Certain investigations using potentiostats and voltage clamp instrumentation from the pipets containing a chlorided silver wire also employ very small working electrodes, simple circuits described here has proceeded or platinum, and the experiments are often and when more exact potential control is in parallel. The first circuits used amplifiers performed on a microscope stage. required, solution resistances exist that may that were assembled from the individual The similarity of the voltage-clamp have to be compensated, particularly at the electronic components (resisters, capacitors, configuration to that of the potentiostat is working electrode.7 and vacuum tubes). Some early potentiostats readily apparent. The amplifier/feedback There are also many electrical also used mechanical servomechanisms. The voltage clamp circuit functions the same capacitance effects that complicate the advent during the 1950s of commercially way it does as a potentiostat to impose a measurements. First of all, a cell membrane available, plug-in, modular amplifiers, potential equal to the command voltage at itself constitutes an electrical capacitance called operational amplifiers,10 or “op amps,” the membrane. As in potentiostatic circuits, that must be charged before the desired made possible many extensions of the basic the current passing through the membrane in potential is established. This is analogous potentiostat and voltage clamp and more measured with auxiliary circuitry not shown to potentiostatic work in which the working elaborate circuits.6,9 At first, using these in the figure. In the study of nerve cells, electrode/solution double-layer capacitance modular op amps, experimenters who were early work in voltage clamping revealed must first be charged. There are also “stray” not trained engineers, but who were versed information on how sodium and potassium capacitances in both electrolytic and voltage in electronics, could assemble their own functioning instruments. Quite advanced instruments incorporating integrated-circuit operational amplifiers are now commercially available for many specialized