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 in the same way that a lung does. The goal is to use these organs-on-a-chip — also called microphysiological models — to expedite high-throughput testing to assess toxicity or to evaluate the effectiveness of new drugs.
But while organ-on-a-chip research has made significant advances in recent years, one obstacle to the use of these structures is the lack of tools designed to actually retrieve data from the system. Existing ways of collecting data are to conduct a bioassay, histology, or use some other technique that involves destroying the tissue. What is needed are tools that provide a means to collect data in real time without affecting the system’s operation.
Oxygen levels vary widely across the body; for example, in a healthy adult, lung tissue has an oxygen concentration of about 15 percent, while the inner lining of the intestine is around 0 percent. This is important because oxygen directly affects tissue function. To know how an organ is going to behave normally, “normal” oxygen levels must be maintained in the organ-on-a-chip when conducting experiments. This means monitoring oxygen levels not only in the organ-on-a-chip’s immediate environment but in its tissue as well.
To meet these challenges, a biosensor was developed that allows researchers to track oxygen levels in real time in organ-on-a-chip systems, making it possible to ensure that such systems more closely mimic the function of real organs. This is essential if organs-on-a-chip hope to achieve their potential in applications such as drug and toxicity testing.
The key to the biosensor is a phosphorescent gel that emits infrared light after being exposed to infrared light. But the lag time between when the gel is exposed to light and when it emits the 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 only for microseconds but by monitoring those times, researchers can measure the oxygen concentration down to tenths of a percent.
In order for the biosensor to work, a thin layer of the gel must be incorporated into an organ-on-a-chip during its fabrication. Because infrared light can pass through tissue, a “reader” — which emits infrared light and measures the echoing flash from the phosphorescent gel — is used to monitor oxygen levels in the tissue repeatedly, with lag times measured in the microseconds.
The biosensor has been tested successfully in three-dimensional scaffolds using human breast epithelial cells to model both healthy and cancerous tissue. The next step is to incorporate it into a system that automatically makes adjustments to maintain the desired oxygen concentration.