Microelectrodes allow human in vivo sensing without IR drop uncertainties. The small currents passed permit reliable use of a two-electrode voltage clamp system. The circuit bath is connected directly to a classical true reference electrode. The reference electrode is immersed in a beaker containing electrolyte and is connected to the circuit bath. The circuit can be completed by the human subject immersing a finger in the beaker with the reference electrode. The reliability of this approach is characterized by two control experiments. One involves the insertion of a salt bridge filled needle subcutaneously where a connected tube is immersed in the reference electrode beaker. The other control experiment uses a second identical reference electrode placed in the beaker. Electrical contact between this reference electrode and the human subject is made by physical contact at the second reference electrode lead. These two control experiments suggest no difference in the applied potential at the working microelectrode compared to experiments conducted with the human subject’s finger inserted in the beaker. However, completing the circuit by placing a copper wire in the reference electrode beaker, where the human subject physically contacts the dry air-end of the wire, does show evidence of an altered applied potential at the working microelectrode.
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