Organ-on-a-chip technology holds promise in applications including drug testing, but the inability to track oxygen levels in these devices in real time has hindered their progress.
The organ-on-a-chip concept creates small-scale, biological structures that mimic a specific organ function, such as transferring oxygen from the air into the bloodstream via the lungs. The goal is to use these organs-on-a-chip to accelerate high-throughput testing to assess toxicity – or to evaluate the effectiveness – of new drugs.
One obstacle to the use of these structures is the lack of tools designed to retrieve data from the system, but a new biosensor could change that.
“For the most part, the only existing ways of collecting data on what’s happening in an organ-on-a-chip are to conduct a bioassay, histology, or use some other technique that involves destroying the tissue,” said Michael Daniele, an assistant professor of electrical engineering at North Carolina State University and in the Joint Department of Biomedical Engineering at NC State and the University of North Carolina, Chapel Hill.
“What we really need are tools that provide a means to collect data in real time without affecting the system’s operation,” said Daniele, corresponding author of a paper on the new biosensor. “That would enable us to collect and analyse data continuously, and offer richer insights into what’s going on. Our new biosensor does exactly that, at least for oxygen levels.”
Oxygen directly affects tissue function, and levels of the gas vary across the body. According to NC State, “normal” oxygen levels need to be maintained in an organ-on-a-chip when conducting experiments.
“What this means in practical terms is that we need a way to monitor oxygen levels not only in the organ-on-a-chip’s immediate environment, but in the organ-on-a-chip’s tissue itself,” Daniele said. “And we need to be able to do it in real time. Now we have a way to do that.”
A phosphorescent gel is key to the new biosensor. It emits infrared light after being exposed to infrared light and the time lag between when the gel is exposed to light and when it emits an echoing flash varies, depending on the amount of oxygen in its environment.
The more oxygen there is, the shorter the lag time. These lag times last for microseconds but by monitoring those times researchers can accurately measure oxygen concentration.
In order for the biosensor to work, researchers must incorporate a thin layer of the gel into an organ-on-a-chip during its fabrication. Because infrared light can pass through tissue, researchers can use a ‘reader’ – which emits infrared light and measures the echoing flash from the phosphorescent gel – to monitor oxygen levels in the tissue repeatedly.
The biosensor has been tested successfully in three-dimensional scaffolds using human breast epithelial cells to model healthy and cancerous tissue.
“One of our next steps is to incorporate the biosensor into a system that automatically makes adjustments to maintain the desired oxygen concentration in the organ-on-a-chip,” Daniele said. “We’re also hoping to work with other tissue engineering researchers and industry. We think our biosensor could be a valuable instrument for helping to advance the development of organs-on-a-chip as viable research tools.”
The paper, “Integrated phosphorescence-based photonic biosensor (iPOB) for monitoring oxygen levels in 3D cell culture systems,” is published in Biosensors and Bioelectronics.