Terahertz and sound waves enable needle-free blood sodium detection

In a new study, researchers demonstrated long-term, non-invasive monitoring of blood sodium levels using a system that combines optoacoustic detection with terahertz spectroscopy. Accurate measurement of blood sodium is essential for diagnosing and managing conditions such as dehydration, kidney disease and certain neurological and endocrine disorders.

Terahertz radiation, which falls between microwaves and the mid-infrared region of the electromagnetic spectrum, is ideal for biological applications because it is low-energy and non-harmful to tissues, scatters less than near-infrared and visible light and is sensitive to structural and functional biological changes.

For biomedical applications, terahertz spectroscopy still faces two key challenges: detecting molecules other than water in complex biological samples and penetrating thick tissue layers to enable detection inside the body. By adding optoacoustic detection, we were able to overcome these challenges and demonstrate the first in vivo detection of ions using terahertz waves. This is an important step toward making terahertz-based techniques practical for clinical use."

Zhen Tian, research team leader, Tianjin University, China

In Optica, Optica Publishing Group's flagship journal for high-impact research, the researchers describe their new multispectral terahertz optoacoustic system and show that it can be used for noninvasive, long-term monitoring of sodium concentration in live mice without the need for any labels. Preliminary tests performed with human volunteers were also promising.

"With further development, this technology could be used to monitor sodium levels in patients without the need for blood draws," said Tian. "The real-time sodium measurements could be used to safely correct imbalances in critical patients while avoiding dangerous neurological complications that can occur when sodium levels rapidly change."

Using sound to cut the noise

The new work is part of a larger project aimed at advancing and implementing terahertz technology in the biomedical field using terahertz optoacoustic techniques. One key aim of the project is to reduce signal interference caused by water, which strongly absorbs terahertz radiation.

To overcome this interference, the researchers developed a modular system that irradiates the sample with terahertz waves. As the sample absorbs these waves, it vibrates the sodium ions connected to water molecules in the blood, creating ultrasound waves that are detected with an ultrasonic transducer. This technique, known as optoacoustic detection, converts the absorbed terahertz energy into sound waves for measurement.

"Terahertz optoacoustic technology represents a groundbreaking advancement for biomedical applications by effectively overcoming the water absorption barrier that has historically limited these applications," said Tian. "The broader significance of this work extends far beyond blood sodium detection. This technology has the capability to identify various biomolecules-including sugars, proteins, and enzymes-by recognizing their unique terahertz absorption signatures."

Tracking sodium without needles

To test their new system, the researchers showed that it could measure increases in blood sodium levels in blood vessels under the skin of living mice on the millisecond timescale for over 30 minutes. These measurements were taken from the ear, with the skin surface cooled to 8 °C to dampen the background optoacoustic signal from water.

The researchers also demonstrated that the terahertz optoacoustic system could quickly distinguish between high and low sodium levels in human blood samples. Finally, they noninvasively measured sodium ion levels in the blood vessels of the hands of healthy volunteers. They found that the detected optoacoustic signal from sodium was proportional to the amount of blood flow under the skin surface, even though measurements were collected without any skin cooling. While more work is needed, these results suggest that the system could be useful for non-invasive real-time monitoring.

The researchers say that adapting the system for human use will require identifying suitable detection sites on the human body - such as inside of the mouth - that can tolerate rapid cooling and allow strong signal detection with minimal water background noise. They are also exploring alternative signal processing methods that might make it possible to suppress water interference without the need for cooling, making the approach more practical for clinical diagnostics.