Neurons on a chip to test neurotoxicity
The biochip developed by scientists from the Universities of Dortmund and Constanta, working under the leadership of Jonathan West, ensures the arrangement of nerve cells in a strictly defined order, which greatly facilitates the testing of neurotoxicity of drugs and other chemical compounds.
Despite the fact that the US Food and Drug Administration (FDA) still requires animal testing when developing medicines, the introduction of a new chip will reduce the amount of toxic substances reaching the animal testing stage.
At the same time, many European countries have already introduced a ban on testing cosmetic products on animals, while the European Union directive called REACH requires more chemical tests. According to experts, currently people are faced with about 30,000 chemical compounds whose toxic properties have not been fully tested.
Laboratory tests for neurotoxicity involve the cultivation of nerve cells, followed by counting the number of processes formed by them – axons and dendrites. The possibility of forming interneuronal contacts is at the heart of the brain and ensures the implementation of functions such as memorization and learning. Therefore, a violation of this mechanism is a reliable indicator of neurotoxicity. For example, the well-known neurotoxin acrylamide suppresses the formation of interneuronal contacts.
However, such tests are very time–consuming, and their results are not always reliable, since it is very difficult to objectively estimate the length of the processes formed between randomly located nerve cells when microscoping a sample (an example of chaotic growth of neurons with a generally accepted technique is in the picture above).
The developers of the new biochip proposed to standardize the test for the formation of a neural network by fixing neurons at a fixed distance from each other. This is provided by the chip coating, which is a layer of a nutrient substrate, on which a thin film of the hydrophobic polymer polydimethylsiloxane (PDMS) is applied, perforated in such a way that a pattern consisting of hexagons appears on its surface. Polydimethylsiloxane repels extracellular matrix proteins that ensure the attachment of cells to the surface, so neurons are automatically fixed at the perforation sites where they have access to the substrate. This allows researchers to quickly estimate the number of formed intercellular contacts and their length.
(In the middle of the figure is an electronic micrograph of the biochip site, at the bottom is a graphic reconstruction. On the website of the Leibniz Research Centre, you can watch an accelerated video recording of the process of growth of nerve processes).
Conducting one test using a standard technique usually takes about 10 hours, testing 10 dosages of one substance, respectively, requires ten times more time. The new chip allows you to complete this task in just a few hours.
The work on creating a new chip is described in the article "The network formation assay: a spatially standardized neurite outgrowth analytical display for neurotoxicity screening", published in the latest issue of the journal Lab on a Chip. Currently, developers are considering options for creating similar chips for testing other types of cells, including stem cells.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of TechnologyReview: Chip Makes Neurotoxicity Tests Faster and Easier01.02.2010