Summary: Staying sharp in space or during graveyard shifts is a matter of biological timing. Researchers have developed an inexpensive, 15-minute test that allows astronauts and shift workers to monitor their internal clocks using just a drop of blood and a smartphone.
The study describes a paper-based test strip that uses fluorescent nanoparticles to measure melatonin levels with “gold standard” accuracy, identifying exactly when a person’s “physiological night” begins.
Key Facts
Source: Washington State University
A simple test developed at Washington State University could eventually allow astronauts and others in round-the-clock occupations to monitor their biological rhythms in just minutes using a drop of blood, a paper test strip and a smartphone-based reader.
An interdisciplinary team of WSU researchers created an inexpensive, 15-minute test using fluorescent nanoparticles to measure melatonin levels, which rise and fall along with a person’s internal biological clock.
That clock orchestrates circadian rhythms, or 24-hour cycles, throughout the body, from digestion and metabolism to brain functioning and alertness levels. Monitoring circadian rhythms is vital in shift work settings – and especially in space operations, where the normal 24-hour rhythms of light and darkness are disrupted and the biological clock becomes dysregulated. This interferes with optimal brain functioning, which in space can make the difference between mission success and disaster.
The work, published in Nanoscale Horizons, describes a melatonin assay integrated with a 3D-printed fluorescence smartphone reader that can quantify melatonin at levels relevant to identifying the start of a person’s biological night.
“One motivation for this study is monitoring astronauts’ circadian cycles, that’s the target,” said Annie Du, a research professor in the College of Pharmacy and Pharmaceutical Sciences, and corresponding author of the new publication.
“We focused on developing the sensing method, connected with a smartphone reader that can quantify the result. That is very important because it allows measurements to be taken on the spot, without needing to send blood samples to a laboratory for analysis. The method involves a ‘lateral flow immunoassay’ based on a paper strip, similar to COVID or pregnancy test strips. The method provides exact melatonin levels, not just a yes or no answer.”
The new test can make melatonin testing in space easy and quick. It is the latest of a number of simple test-strip-and-smartphone systems Du has created for monitoring health conditions, including one that allows firefighters and others to quickly check their personal exposure to wildfire smoke. Her work has also focused on developing nanomaterials-based drug delivery techniques for treating cancer, arthritis, and other conditions.
Melatonin is a hormone produced by the pineal gland in the brain, with levels rising in the evening and dropping in the morning. Melatonin thus acts as an internal time cue signaling “physiological nighttime”, knowing when an individual’s physiological night begins is useful in scheduling jobs that require high performance at night or over long stretches. It is also important for diagnosing and treating so-called “circadian rhythm sleep disorders,” which are caused by problems with the biological clock.
Melatonin concentrations in blood samples are low, making it difficult to detect with conventional techniques. The researchers developed the test-strip method using nanoparticles made of europium, a rare-earth material known for strong fluorescent properties, to improve the sensitivity of the assay.
The fluorescent nanoparticles helped researchers achieve the “gold standard” level of sensitivity for measuring melatonin, an accuracy of up to 10 picograms per milliliter. That level indicates the beginning of an individual’s physiological night, the point at which the biological clock no longer promotes alert wakefulness and brain functioning may be compromised.
Researchers are now validating the device by testing plasma samples from individuals studied in WSU’s Sleep and Performance Research Center. Eventually, Du hopes the technology can be used to create a continuous melatonin monitoring system, akin to glucose monitoring systems used by people with diabetes.
The project brought together researchers in pharmaceutical science, engineering and sleep science across WSU. Authors on the paper include Zhansen Yang, Xinyi Li, Hans Van Dongen, Yuehe Lin, Yang Song and Dan Du.
Funding: This work was partially supported by the NASA-funded state of Washington, Biology in Space Consortium, BioS-ENDURES.
A: In space, you can see 16 sunrises and sunsets a day. Without a steady 24-hour day/night cycle, the brain’s internal clock gets “de-synced.” An astronaut might feel okay but have the reaction time of someone who is sleep-deprived. This test provides objective data on when their brain is actually entering “night mode.”
A: Potentially. Most “circadian rhythm sleep disorders” are treated by guessing when to take melatonin or use light therapy. This test would allow a doctor (or an app) to see exactly when your biological night starts, allowing you to time your treatments with surgical precision.
A: In this specific context, yes. The “magic” isn’t in the phone’s camera alone, but in the europium nanoparticles. Because they are so bright and the 3D-printed reader blocks out all interfering light, the phone can detect concentrations as small as a trillionth of a gram.
Author: Shawn Vestal
Source: Washington State University
Contact: Shawn Vestal – Washington State University
Image: The image is credited to Neuroscience News
Original Research: Closed access.
“Europium nanoparticle label/lateral flow test strip integrated with a 3D-printed fluorescence smartphone reader for detection of melatonin in human blood” by Zhansen Yang, Xinyi Li, Hans P. A. Van Dongen, Yuehe Lin, Yang Song, and Dan Du. Nanoscale Horizons
DOI:10.1039/D5NH00853K
Abstract
Europium nanoparticle label/lateral flow test strip integrated with a 3D-printed fluorescence smartphone reader for detection of melatonin in human blood
Melatonin secretion by the pineal gland occurs predominantly at night, although ocular exposure to bright light suppresses its secretion. When measured under dim light conditions, the melatonin concentration in plasma provides a reliable indicator of the state of an individual’s central circadian pacemaker in the hypothalamus.
Specifically, the onset of melatonin secretion in the evening, conventionally defined as the time when the plasma concentration surpasses a threshold of 10 pg mL−1, serves as a gold-standard measure of the start time of physiological night.
Current melatonin detection methods typically require expensive assays and instrumentation as well as trained personnel, or they lack sufficient sensitivity and anti-interference capabilities, which limit their use in point-of-need settings.
To address these challenges, we developed a europium nanoparticle-based lateral flow immunoassay (EuNP-LFIA) integrated with a 3D-printed smartphone-based fluorescence reader for on-site melatonin detection in plasma.
Six key parameters, namely readout time, EuNP size, antibody conjugation level, Tween-20 concentration, EuNP deposition volume, and the concentration of melatonin–bovine serum albumin on the nitrocellulose membrane, were systematically optimized.
Upon optimization, the sensing platform exhibited highly sensitive detection of melatonin in buffer solution and achieved a limit of detection (LOD) of 9.99 pg mL−1. For melatonin-spiked plasma samples, the recovery rates ranged from 82.58% to 114.70%, indicating excellent repeatability and reliability.
Overall, the proposed method possesses high sensitivity and accuracy, offering a portable, rapid (<15 min), cost-effective, and user-friendly solution for real-time monitoring of plasma melatonin.
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Astronaut Clock: Blood Test Tracks Biological Rhythms in Minutes – Neuroscience News
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