Innovative photoacoustic sensing could replace needle-based glucose testing

Blood glucose is usually measured using invasive methods involving pricking small needles into the skin. But people suffering from diabetes have to test their glucose levels many times in a day. This repeated use of needles is inconvenient and can increase the risk of potential infections. 

A new study by researchers at the Department of Instrumentation and Applied Physics (IAP), Indian Institute of Science (IISc) offers an alternative solution via a technique called photoacoustic sensing. 

In this technique, when a laser beam is shined on biological tissue, the tissue components absorb the light and the tissue heats up slightly (less than 1°C). This causes the tissue to expand and contract, creating vibrations which can be picked up as ultrasonic sound waves by sensitive detectors. Different materials and molecules inside the tissue absorb different amounts of the incident light at different wavelengths, creating individual "fingerprints" in the emitted sound waves. Importantly, this procedure does not damage the tissue sample being studied.

In the current study, the team exploited this approach to measure the concentration of a single molecule, namely glucose. They used polarized light – a light wave that oscillates only in a specific direction. Sunglasses, for example, reduce glare by blocking out light waves that oscillate in certain directions. 

Glucose is a chiral molecule, which means that it has an inherent structural asymmetry that causes polarized light to rotate its orientation of oscillation when it interacts with the molecule. Surprisingly, the team found that the intensity of the emitted sound waves changed when the orientation of the polarized light interacting with glucose in the solution was changed.

"We don't actually know why the acoustic signal changes when we change the polarization state. But we can establish a relationship between the glucose concentration and the intensity of the acoustic signal at a particular wavelength," explains Jaya Prakash, Assistant Professor in IAP and corresponding author of the study published in Science Advances.

Glucose rotates the polarized light and the rotation increases with concentration, which is reflected in the acoustic signal intensity. Therefore, measuring the strength of the acoustic signal allowed the researchers to work backwards and estimate the concentration of glucose. 

The researchers were able to estimate glucose concentration in water and serum solutions as well as slices of animal tissue with near clinical accuracy. They were also able to measure glucose concentration at various depths within the tissue accurately. 

If we know the speed of sound in this tissue, we can use the time series data to map our acoustic signals to the depth at which they are coming from."

Swathi Padmanabhan, PhD student and first author of the paper

Since sound waves don't scatter much inside tissue, the researchers were able to get accurate measurements at various tissue depths.

The team has also conducted a pilot study in which they used the sensor setup to track the blood glucose concentrations of a healthy participant before and after meals over three days. 

"Finding the right setup to do this experiment was very challenging. Currently, the laser source we use has to generate very small nanosecond pulses, so it is expensive and bulky. We need to make it more compact to put it to clinical use. My lab mates have already started work on this," says Padmanabhan.

The authors believe that theoretically, this technique can work for any chiral molecule by changing the light wavelength. In the study, they were also able to estimate the concentration of naproxen – a commonly used drug for mild pain and inflammation – in an ethanol solution. As many commonly used drugs are chiral in nature, such a technique can have wide-ranging applications in healthcare and diagnostics.