Electron Mediator Technologies

An electron mediator is the go-between on an electrochemical test strip. The enzyme on the strip pulls electrons off glucose, and the mediator carries them to the electrode, where the meter reads them as a tiny electrical current that tracks the amount of glucose in the drop [1]. That sounds like a minor detail. It isn't: the mediator a company picks shapes how the strip copes with oxygen, which other blood chemicals it responds to, and even how close together its electrodes can sit.

Why strips needed a mediator

The earliest enzyme sensors used oxygen to carry the electrons. Glucose oxidase (GOx) handed its electrons to oxygen dissolved in the sample, and the sensor measured either the oxygen used up or the hydrogen peroxide made along the way [1]. Two problems followed. Oxygen dissolves poorly in blood, so its level swings from sample to sample, a weakness researchers called the "oxygen deficit." Reading hydrogen peroxide also needed a high electrode voltage [1].

Mediators solved both. Researchers swapped oxygen for synthetic electron carriers, called redox mediators, that move electrons from the enzyme to the working electrode. The electrode then strips the electrons back off the mediator, so each mediator molecule can make the trip again [1]. Many candidates were tried, from ferrocene and ferricyanide to methylene blue and methyl viologen [1].

Ferrocene and the first electrochemical home meter

Ferrocene met nearly every test for a good mediator. It doesn't react with oxygen. It stays stable whether it is carrying an electron or not, works across a range of pH, and trades electrons with the enzyme quickly [1].

Cass and colleagues reported the first ferrocene-mediated amperometric glucose sensor (one that measures current) in 1984 [1]. Here's what surprised us: it took only three years to reach a consumer product. In 1987 MediSense launched the ExacTech, a pen-sized meter and the first electrochemical blood glucose monitor for self-testing, which paired the enzyme GDH-PQQ (glucose dehydrogenase with a pyrroloquinoline quinone cofactor) with a ferrocene derivative [1]. Writing in 2010, Yoo and Lee said most commercial glucose biosensors still worked much like the ExacTech [1].

Ferricyanide in OneTouch strips

Yoo and Lee also wrote that many self-monitoring strips use ferrocene or ferricyanide mediators [1]. When we read FDA decision summaries, ferricyanide was the mediator named most explicitly. LifeScan's 2011 clearance for OneTouch Verio strips lists, per strip, 2 units of FAD-dependent glucose dehydrogenase (GDH-FAD) and 41 µg of potassium ferricyanide [2]. The strips for the OneTouch Ultra Plus Flex system, cleared in 2015, list the same enzyme and the same 41 µg of ferricyanide [3]. In both summaries, the redox reaction produces the current the meter measures [2][3].

Osmium in Abbott FreeStyle strips

Abbott's FreeStyle strips went another way. They came out of TheraSense, now part of Abbott Diabetes Care, and in a 2010 account Heller and Feldman described the chemistry: GDH plus an osmium (Os2+/3+) mediator, inside a strip whose carbon and silver/silver chloride electrodes face each other across a 50-micrometer gap [4]. The strip works as a coulometer, measuring the total charge over the reaction rather than the current at one instant [4][5].

That tight gap created a risk. A mediator could shuttle electrons back and forth between the two facing electrodes and inflate the count. The designers chose an osmium complex with a formal potential between 0.0 and -0.2 V relative to the facing electrode, which makes that shuttling current virtually impossible [4]. FreeStyle strips started with GDH-PQQ and later moved to GDH-FAD [4]. FDA's 2010 summary for FreeStyle Lite strips records that change, GDH-FAD in place of the predicate strip's GDH-PQQ, and says electrons are "transferred via a co-factor and mediator" to the meter [5].

Osmium also anchors Abbott's wired enzyme work. The FreeStyle Navigator CGM, which reached the US market in 2008, bound glucose oxidase into a hydrogel holding a polymer-bound osmium complex, so the mediator was fixed in place rather than free to diffuse [1][4]. Very little current flowed without glucose present, which helped the system get by with one-point calibration [4].

Ruthenium, and what changed when it left

Ruthenium shows up in FDA records too. In the version FDA cleared for Nipro Diagnostics in 2013, True Metrix strips used hexaammineruthenium(III) together with a second compound, Meldola's Blue. In 2014 FDA cleared a switch to potassium ferricyanide, with GDH-FAD as the enzyme [6].

The same summary shows why mediator choice matters to users. Before the switch, the labeling listed xylose as an interfering substance. Afterward it listed xylose, uric acid and ascorbic acid (vitamin C), and FDA's reviewer noted those two additions came "as the result of a mediator change" [6].

As of October 2026, True Metrix meters, now sold by Trividia Health, are under a Class I recall because one error code (E-5) covers both a very high glucose reading and a strip error. That's a software and labeling problem, not a mediator one. FDA's April 28, 2026 safety communication recommends that users move to another way of testing when possible [7]. Picking a replacement is a decision to make with your care team.

How mediators connect to interference

An interfering substance is anything that reacts at the electrode at the sensor's operating voltage [1]. Ascorbic acid is a common one: it gets oxidized at the electrode, adds electrons of its own and pushes the reading up [1]. Interference from ascorbic acid, uric acid and some drugs became a major research focus in the late 1980s, when sensors still read hydrogen peroxide at high voltage [1].

The enzyme matters as well as the mediator. In strips that use glucose oxidase, oxygen from red blood cells can compete with the mediator for electrons, while GDH enzymes don't use oxygen at all [1]. Our enzyme chemistry article covers those trade-offs.

Which enzyme and mediator pairs the FDA records list

Yoo and Lee describe strips as carrying GDH-PQQ, GDH-NAD, GDH-FAD or GOx along with a redox mediator [1]. FDA summaries don't always name the mediator, though. The 2016 Contour Next One summary lists GDH-FAD and "an electron mediator" without saying which [8]. The 2016 Accu-Chek Guide summary describes the GDH-FAD reaction and doesn't mention a mediator [9].

Strips without a mediator

Researchers have also built third-generation sensors that skip the mediator and pass electrons straight from the enzyme to the electrode, an approach Yoo and Lee credit with better selectivity [1]. None of the FDA strip summaries we read for this article describes a mediator-free strip, and five of the six name or mention a mediator [2][3][5][6][8].