Finding alternatives to animal testing is an important endeavor. While the practice has been banned in the cosmetic products industry since 2013, it's still a central part of evaluating the effectiveness and dangers of new medication, with researchers usually using laboratory rodents to test out their latest drugs. Now, a team lead by scientists at Germany's Fraunhofer Institute for Cell Therapy and Immunology has created a microbioreactor that has the potential to provide medication testing using cultured liver cells rather than animals.

The liver is most important organ when it comes to removing dangerous toxins from the body, making cultured liver cells a good candidate for testing substance toxicity outside of the body. But there are difficulties in their use, most notably the fact that it's very difficult to keep them alive for long periods of time, making long-term effect tests practically impossible.

Researchers at the Fraunhofer Institute in Potsdam, working as part of the Hepatic Microfluidic Bioreactor project (HeMiBio), decided to use a microbioreactor to allow for longer-term observations, providing an environment in which the cells can survive for as long as four weeks. Furthermore, the device allows the researchers to observe how the liver reacts to toxic substances in real time – a big improvement over existing tests, which usually only observe changes at the end of the process.

The role of oxygen in the metabolic process is central to how the microreactor detects reactions to foreign substances. When a cell's metabolism is stimulated, oxygen consumption increases. Conversely, if it dies, then its oxygen consumption rate will drop to zero.

The bioreactor places liver cells with embedded microparticles into nine wells, each measuring 1.5 mm diameter(Credit: Fraunhofer)

When designing the reactor vessel, the researchers worked to come up with sensor technology that took advantage of this, while coping with a high concentration of cells without interference giving rise to false or misleading data. After some thought, they decided to use a series of tiny polymer particles housing a luminescent dye, embedding them in among the liver cells.

When the sensor particles are exposed to monochromatic LED light, the dye they contain emits a phosphorescent glow, exciting individual electrons, raising them to high levels of energy. The time required for the electrons to lower their energy is affected by the amount of oxygen present in the immediate environment, meaning that the researchers can use the time the phosphorescent glow takes to fade to analyze the rate of metabolic activity. Looking at the curve of oxygen consumption allows the researchers to pinpoint metabolic processes taking place in cells at specific times, detailing exactly how the cells are reacting to the foreign substance.

Early tests indicate that the microbioreactor could provide a liver-like environment in the lab, but there's still a lot of work to do. The researchers have tested the method extensively, confirming that it works as intended. Looking forward, they plan to populate it with different combinations of liver cells, fine-tuning the sensors as the work continues.

In the long run, the team believes that it might be possible to place tissue samples from different organs into the reactor, recording their reaction to foreign substances during the course of a single test.

Source: Fraunhofer

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