Electrochemistry

While methods like spectrophotometry rely on light and color, electrochemistry takes a completely different approach. I want you to think of our electrochemical instruments as incredibly sensitive, specialized “tongues.” They don’t taste for sweet or sour; they are designed to “taste” for a specific ion like sodium or a gas like oxygen and report back with an electrical signal. It is the science of turning a chemical reaction or the presence of an ion into a measurable electrical property—either a voltage or a current. This is the fundamental technology that powers our blood gas analyzers and our electrolyte panels, making it one of the most critical and frequently used principles in the entire hospital

Core Principle: The Electrochemical Cell

Every electrochemical measurement, no matter how complex the instrument, is based on a simple device called an electrochemical cell. A cell always has two essential parts:

• The Measuring (or Indicator) Electrode: This is the “taster.” It’s the electrode that is specifically designed to interact with the analyte we want to measure (e.g., potassium ions) and change its electrical properties in response
• The Reference Electrode: This is the “unwavering baseline.” It is designed to be completely stable and maintain a constant, known electrical potential, no matter what’s in the sample. It’s the zero point on our ruler, giving us a stable signal to measure against

The instrument never measures the measuring electrode alone. It always measures the difference in potential (voltage) between the measuring electrode and the stable reference electrode. This difference is what tells us the concentration of our analyte

Potentiometry: Measuring Voltage

This is, without a doubt, the most common electrochemical technique in the clinical lab. The name says it all: “potentio” refers to electrical potential, or voltage. In potentiometry, we measure the voltage difference between our two electrodes under conditions of essentially zero current flow. We are not consuming the analyte; we are simply sensing its presence

The superstars of potentiometry are Ion-Selective Electrodes (ISEs). An ISE is a measuring electrode with a special, magical membrane. This membrane is designed to be selectively permeable to only one specific ion. A potassium ISE has a membrane (often containing the antibiotic valinomycin) that only allows K⁺ ions to pass through or interact with it. A sodium ISE has a glass membrane that specifically binds Na⁺ ions

• How it Works: When a sodium ISE is placed in a patient’s serum, Na⁺ ions from the sample accumulate at the surface of the specialized membrane. This buildup of positive charge creates a small electrical potential (voltage) across the membrane. The magnitude of this voltage is directly proportional to the concentration (or more accurately, the activity) of the sodium ions in the sample, a relationship described by the Nernst Equation. The instrument measures this voltage against the stable reference electrode and converts it into a concentration value
• Key Applications: This is the technology behind all of our electrolyte measurements on chemistry and blood gas analyzers: Na⁺, K⁺, Cl⁻, and Ionized Calcium (Ca²⁺). The single most common ISE is the pH electrode, which specifically measures the activity of hydrogen ions (H⁺)

Amperometry: Measuring Current

If potentiometry is about measuring voltage, amperometry is about measuring electrical current. “Ampere” is the unit of current, which is the flow of electrons

In this technique, we apply a fixed, constant voltage to our measuring electrode. This applied voltage is specifically chosen to force a chemical reaction (either oxidation or reduction) to occur with our analyte. When the analyte reacts at the electrode surface, it either consumes or releases electrons, creating a small electrical current. The amount of current that flows is directly proportional to the concentration of the analyte being consumed in the reaction

• The Classic Example: The Clark Electrode for pO₂.: This is the definitive amperometric application. The electrode has a platinum cathode and a silver anode. A fixed voltage is applied between them. Oxygen from the blood sample diffuses across a membrane and is reduced at the platinum cathode. This reaction consumes electrons, and the flow of these electrons from the anode to the cathode creates the current we measure. More oxygen means a faster reaction, which means a higher current

Coulometry: Measuring Total Charge

This method is less common in modern automated analyzers but is historically important and beautifully clever. In coulometry, we are measuring the total quantity of electricity (in coulombs) required to completely consume an analyte in a chemical reaction. It’s an electrochemical titration

• Classic Example: The Cotlove Chloridometer.: This instrument was used for decades to measure chloride concentration. The instrument generates silver ions (Ag⁺) at a constant rate. These silver ions immediately react with the chloride ions (Cl⁻) in the sample to form an insoluble precipitate (AgCl). As long as there is chloride left in the sample, the Ag⁺ ions are consumed. The instant all the chloride is used up, free Ag⁺ ions suddenly appear in the solution. A sensor detects these free Ag⁺ ions and shuts off a timer. The total time the reaction ran is directly proportional to the initial amount of chloride in the sample

Blood Gas Analyzer: An Electrochemical Symphony

A modern blood gas analyzer is the perfect integration of these techniques, with multiple specialized electrodes working in harmony:

• pH: Measured directly by a potentiometric glass ISE
• pCO₂ (Partial Pressure of CO₂): Measured by a clever potentiometric device called the Severinghaus electrode. This is actually a complete pH electrode system housed behind a special membrane that is permeable to CO₂ gas. As CO₂ diffuses in, it forms carbonic acid, which changes the pH of the internal buffer. The electrode measures this internal pH change, which is proportional to the pCO₂ of the sample
• pO₂ (Partial Pressure of O₂): Measured directly by the amperometric Clark electrode

Key Terms

• Potentiometry: An electrochemical technique that measures the difference in electrical potential (voltage) between a measuring electrode and a stable reference electrode to determine analyte concentration
• Amperometry: An electrochemical technique that measures the electrical current generated when a fixed voltage is applied to an electrode, causing the analyte to undergo oxidation or reduction
• Ion-Selective Electrode (ISE): The key component of potentiometry; a measuring electrode with a membrane that is specifically permeable to a single type of ion (e.g., Na⁺, K⁺, H⁺)
• Electrode: A conductor through which electricity enters or leaves an object, substance, or region. In a sensor, it is the interface where a chemical reaction is coupled to an electrical signal
• Reference Electrode: An electrode that has a stable and well-known electrode potential, providing a constant reference point against which the potential of the measuring electrode is measured
• Clark Electrode: The specific name for the amperometric electrode system used to measure the partial pressure of oxygen (pO₂)
• Nernst Equation: The fundamental mathematical formula in potentiometry that describes the relationship between the voltage generated across a membrane and the concentration (activity) of the specific ion being measured