STRELECOID · Stretchable mesh-electrodes interfacing human iPSC brain organoids

Stretchable mesh-electrodes interfacing human iPSC brain organoids

Human induced pluripotent stem-cells are a technology which allows to take a piece of human skin or a bit of blood, and turn that tissue into stem cells. Stem cells have the particularity of being able to become any cell in the human body given the correct environment, e.g tissues like lung, heart, liver, brain etc. It is therefore possible to take a bit of the patient's skin or blood and create a piece of brain tissue in the petri dish, by making the stem cells generated from the patient's skin or blood, turn into neurons, the cells which make up the brain. This is very advantageous because it is unfeasible to perform experiments on human's brain as it would involve opening up the skull and perform experiments which may not fail due to ethical and safety concerns. Using human induced pluripotent stem cells allows one to duplicate real, human neural tissue outside of the patient's body. In the case that this patient carries a genetic neuropsychiatric disorder like certain kinds of epilepsies, one can create a multiple copies of the afflicted brain tissue and study therapeutic approaches on it without risking to harm the patient. This constitutes a paradigm shift in studying human neuropsychiatric disorders and opens the door not only for therapeutics but also personalized medicine. Many neuropsychiatric disorders are characterized by abnormal electrical activity of the neurons making up the brain tissue. One therefore needs means of measuring such electrical activity. These neural tissues which we call organoids do not possess an immune system or a blood vessel network. Therefore, one cannot insert instruments and create tissue damage without inducing the death of the entire organoid, as it is incapable of shuffling out cell debris from itself. A possibility to circumvent the insertion of an electrical measuring device is to have the organoid proliferate and grow on top of a device and create a sort of symbiote: organoid and electrode-array. To minimize mechanical mismatch, which could lead to inflammation of the tissue, and to make the measuring device as imperceptible as possible to the neurons making up the organoid, it is important to reduce the footprint of the measuring device as much as possible while making it able to deform and reshape itself under the strain impacted by growing cells. To fulfill these characteristics, I develop mesh-electrode-arrays akin to fishnets which have a very low footprint and are able to deform and reconfigure their shapes when exposed to external stresses imposed by the cells. Cells can then grow freely around this mesh-electrode-array and incorporate it into themselves on the long term. In this way, the measurement device is constantly inside the organoid and no insertion needs to ever happen. Because this paradigm allows for continuous monitoring of cellular activity, we envision to couple the mesh-electrode-array with learning algorithms that over time figure out how to, for example, send in small electrical stimuli through various electrodes in order to disrupt epileptic seizures in such organoids. Hopefully, such therapeutic approaches can then be translated to humans in the form of implantable devices.

Data: CORDIS, © European Union