The measurement principle of transcutaneous glucose sensors

The transcutaneous sensor has a very thin, flexible filament, much thinner than a needle, which is inserted just under the skin, into the fatty tissue there. This filament does not sit in a blood vessel but in the fluid between the cells, called interstitial fluid. The sensor does not measure directly from the blood but assesses the glucose concentration in this fluid, which closely follows the blood glucose [1].

The measurement is done electrochemically. The sensor converts the glucose concentration into a very small electric current, with the help of an enzyme and an electrode (that thin filament) [2]. The more glucose there is in the interstitial fluid, the larger the current generated locally. The result may lag slightly behind what is in the blood when glucose changes rapidly, because the glucose in this fluid synchronizes with the blood values with a small delay [3].

The tip of the filament under the skin is covered with an enzyme fixed to its surface, most often glucose oxidase. This enzyme is a biological catalyst, meaning it speeds up the chemical reaction of glucose with oxygen without being consumed in the process [4]. It is the part that actually recognizes the glucose and turns the sensor into an instrument dedicated specifically to glucose, not just a plain general electrode.

The enzyme's main role is to give the sensor specificity, that is, to respond to glucose and largely ignore other substances [5]. Without this enzyme, the sensor could not tell glucose apart from the other molecules in the interstitial fluid. Some older sensors use a related enzyme, glucose dehydrogenase, but the measurement principle remains the same [5] [6].

The enzyme (glucose oxidase) makes the glucose react with the oxygen in the interstitial fluid. This reaction produces an acid (gluconic acid) and hydrogen peroxide (H₂O₂). The amount of hydrogen peroxide produced is directly proportional to the glucose concentration, that is, more glucose means more hydrogen peroxide [4].

The hydrogen peroxide reaches the sensor's electrode, where it breaks down and releases electrons, which form a very weak electric current. This current is essentially the signal picked up by the sensor, and its magnitude reflects the glucose concentration in the interstitial fluid [5].

Yes, the reaction consumes a very small amount of glucose. Each glucose molecule that reacts with the local oxygen turns into gluconic acid, so it is used up on the spot. The enzyme attached to the filament is covered by a special membrane that lets only a small, controlled amount of glucose through, so that the reaction always stays limited and safe [7].

This consumed amount is small enough not to lower the blood glucose or alter the values measured later on. The body continuously replenishes the glucose in the interstitial fluid from the glucose in the blood. The enzyme is a catalyst and is not consumed, but over time both it and the membrane can wear out, which is why the sensor has a limited lifespan [8].

What you see as a simple filament under the skin actually contains several electrodes, arranged in very thin layers and insulated from one another on the same flexible support. The working electrode is coated with enzyme and produces the signal, the reference electrode provides a stable potential, and the counter (auxiliary) electrode closes the electrical circuit [6]. The electronic component attached to the sensor keeps a constant voltage between the working electrode and the reference electrode, and the chemical reaction does not change this voltage but rather the strength of the current. The higher the glucose concentration in the interstitial fluid, the greater the strength of the current passing through the working electrode. Some systems add a fourth electrode, without enzyme (it measures the background noise), whose signal is subtracted from the useful signal in order to remove the influence of other substances.

The measured current is read continuously by the electronic component (transmitter). A calibration factor converts this current into an estimated glucose value [2]. Many modern sensors are factory-calibrated, while others occasionally need a check and possibly a recalibration with the glucometer [9]. The system's internal software smooths the small electrical variations and partly corrects the delay between the interstitial fluid and the blood [3]. The result is expressed in mg/dl or mmol/L and sent wirelessly to a phone or another receiver.

Yes, the sensor needs a small source of power, usually a battery housed in the transmitter. This power maintains a constant electric potential on the electrode, and the chemical reaction catalyzed by glucose oxidase generates a current proportional to the glucose concentration [6]. It also powers the signal processing, the internal memory and the wireless sending of the data to the phone or receiver [10].

Power consumption is very low, so a miniature battery is enough for the whole time you wear the sensor. Most continuous monitoring systems work for between 7 and 15 days (recently even 21 days), after which the sensor is replaced with a new one, together with its power source [11] [12]. On older models the transmitter is reused across several sensors [10].