Clark electrode

The Clark electrode emerged because Leland Clark needed to measure oxygen in blood to prove his bubble oxygenator worked—and a journal rejection forced him to invent the solution. The device he created to satisfy skeptical reviewers became the foundation for all modern biosensors.

Clark, a professor at Antioch College and the Fels Research Institute in Yellow Springs, Ohio, had developed the first bubble oxygenator for cardiac surgery. The device worked by bubbling oxygen through blood, but when Clark submitted his paper to Science, the journal rejected it. The reviewers' complaint: he hadn't actually measured the oxygen tension in the oxygenated blood. He had no way to prove his oxygenator was doing what he claimed.

The problem was fundamental. Electrochemical oxygen reduction had been known since Danneel and Nernst discovered it in 1897. Polarography using dropping mercury, discovered by Jaroslav Heyrovsky in Prague in 1922, had produced the first measured oxygen values in plasma by the 1940s. But bare platinum electrodes became 'poisoned' when immersed in blood—proteins coated the metal surface and stopped the reaction.

In October 1954, Clark had a sudden insight: what if he separated the electrode from the blood with a membrane? He sealed a platinum cathode in glass and covered it first with cellophane, then tested silastic and polyethylene membranes. The polyethylene worked brilliantly—it was permeable to oxygen but blocked the proteins that poisoned the electrode. By mounting both the reference electrode and cathode behind the membrane in a sealed probe filled with electrolyte solution, Clark created a self-contained oxygen sensor.

Clark presented his invention at a FASEB meeting in April 1956. The device applied 0.6 volts across a platinum cathode and silver/silver chloride anode in potassium chloride electrolyte. Oxygen diffusing through the membrane was reduced at the cathode, generating a current proportional to oxygen concentration. For the first time, clinicians could continuously monitor blood oxygen during surgery.

Clark never called his invention 'the Clark electrode'—the name would have seemed immodest to his contemporaries. His paper described it as a 'polarographic' electrode for continuous recording of blood oxygen tensions. Others attached his name to it.

The true significance emerged in 1962, when Clark and colleague Champ Lyons used the oxygen electrode principle to create the first glucose biosensor. By trapping glucose oxidase enzyme between membranes, they could measure glucose concentration through the oxygen consumed in the enzymatic reaction. This was the first biosensor of any type—the ancestor of the glucose meters used by diabetics worldwide.

Clark became known as the 'Father of Biosensors.' A device born from journal rejection had launched an entire field of medical diagnostics. The pattern repeats: a scientist forced to measure what he claims discovers a measurement technique that transforms medicine.