Single-Step Electrochemical Aptasensor for Melatonin Detection in Unprocessed Plasma

Source: Advanced Science, written by Hamed Shieh; Arash Khorrami Jahromi; Fernando Gonzales‐Aste; Sajad Shiekh; Roozbeh Siavash Moakhar; Sahar Sadat Mahshid; Sara Mahshid (November 4, 2026). AI-generated summary by biochip.com, published November 10, 2026. Not independently reviewed.

A McGill University team has built an electrochemical aptasensor that detects melatonin directly in unprocessed human plasma, without a sample-extraction step or added reagents. The device detected the hormone at concentrations as low as 0.75 picomolar, within the low range found in the body. The result points toward a simpler way to measure melatonin, a marker used to assess the body’s internal clock, though the team has not yet tested the sensor in time-based clinical monitoring.

A sensor designed for low concentrations

Melatonin levels rise and fall over the day, and the timing of that rise can help identify circadian rhythm sleep disorders. Measuring it accurately is challenging: concentrations are low, and other substances in blood can interfere with some tests. Standard methods may also require multiple steps, specialized equipment, or sample preparation.

The new device uses an aptamer, a short strand of DNA selected to bind a particular target, in this case melatonin. The team attached these melatonin-binding strands to a custom-made gold working electrode and adjusted how many aptamers covered its surface. That tuning allowed the sensor to measure across different concentration ranges, including the picomolar range relevant to human physiology.

How the electrochemical readout works

Think of the sensor’s molecular components as a tiny spring that changes shape when it catches its target. Each aptamer carries a methylene blue tag, which acts as an electrochemical reporter. When melatonin binds, the aptamer changes shape, altering the reporter’s electron transfer to the electrode. The resulting change in electrical current indicates how much melatonin is present.

The team measured that current using square wave voltammetry, an electrochemical technique that applies a series of voltage pulses. The assay detected melatonin down to 0.75 picomolar and showed specificity against a panel of potential interferents. Fitting the measurements to a binding model produced an apparent dissociation constant of 37 picomolar, a measure of how tightly the sensor responds to melatonin.

Testing in plasma

The researchers also tested the sensor in human plasma that had been characterized using radioimmunoassay. The device produced a response in plasma without the extraction step often used to remove substances that could interfere with antibody-based measurements. In this study, “single-step” means exposing the already prepared electrode directly to the sample and then taking an electrochemical reading.

The team supported the proposed aptamer shape change with fluorescence resonance energy transfer measurements in solution and computer-based molecular docking. These checks provide evidence for the binding-related change, but the simulations offer only preliminary structural insight and do not fully represent aptamers attached to an electrode.

Why This Matters

The gold electrodes were made using stencil lithography and additive manufacturing, and the format can work with commercial or homemade potentiostats. Those design choices could support development of a portable melatonin test, but the study reports analytical testing rather than a finished point-of-care product.

The next step is to test whether the sensor can track melatonin over time in protocols used to assess circadian phase, including dim-light melatonin onset. The researchers identify that time-resolved application as future work, so the current results do not establish clinical performance for diagnosing sleep disorders.

Topics: Biosensors · Diagnostics & precision medicine

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