Talking about human brains on a chip sounds like a science fiction movie, as if it were a device that gives life to a cyborg villain. However, Dr. Raquel Rodrigues, a chemical and biological engineer at the International Iberian Nanotechnology Laboratory (INL) in Braga, believes that such a device would be key in the development of more effective treatments for serious neurological disorders, such as Alzheimer’s. “The brain is a very complex and enigmatic organ,” said Rodrigues. “Experimental components and electronic monitoring of cells are required to understand their functioning.”
Thanks to EU research funding, Rodrigues and his team of INL researchers were able to create a unique microchip that mimics the brain as part of BrainChip4MED, a two-year project that concluded in February 2024.
The research also included a 12-month secondment at Harvard Medical School’s Brigham and Women’s Hospital, a pioneer in the development of organs-on-chips (OoC) and biosensors. This ingenious and tiny device developed by the researchers looks like chips in computers or smartphones, but is much more complex.
The brain-on-a-chip simulates the functioning of the brain and combines chemistry, engineering and biology to create a complex system of microbiosensors for real-time screening of new nanotherapies.
The chip has numerous microchannels – whose size is between tens and hundreds of micrometers – through which liquids can pass and which work with a technology called microfluidics. This allows very small quantities of a product to be analyzed and many samples to be examined at once, reducing the overall cost of testing.
The brain’s protective barrier
One of the researchers’ main objectives was to develop drugs capable of crossing what is known as the blood-brain barrier. This layer of cells closely packed together protects the brain from toxins, germs and other harmful substances that could be present in the blood. Only the smallest molecules can cross this barrier that separates brain tissue from the bloodstream. Its protective function is very important, but it has also frustrated attempts to develop drugs to treat neurological disorders.
Any drug intended to treat the brain must cross this membrane to reach its target. But, in the absence of human trials, there are few adequate methods to determine whether a drug could penetrate the brain. “Currently, there are only four drugs available on the market for Alzheimer’s, and none of them actually treat the disease, only its symptoms,” explains Rodrigues.
“This is because the pharmaceutical industry would have to invest large amounts of money in drugs without knowing with certainty whether they would cross the blood-brain barrier. So they don’t do it,” he says. Pharmaceutical companies could invest millions in the development of a drug only to discover that it cannot cross this barrier. The funds that the EU has allocated to this new brain simulator chip developed at the INL solve this problem.
Imitate life on a chip
The research team has recreated the blood-brain barrier membrane on the chip with bio-organic material. “That’s what sets our work apart,” Rodrigues declares. “We use a biomembrane more similar to the barrier of our brain. Other devices use physical barriers, made of polymer components. We consider that a biological one is better.”
With this new and improved brain-on-a-chip, researchers will be able to inject experimental drugs into the chip to analyze their effects and test their ability to penetrate the brain. The goal is to modify the way these types of drugs are developed. Currently, these tests are carried out mainly on animals, which entails a series of ethical and practical problems. These types of organs on chips present a possible alternative to traditional animal experimentation.
“The animal brain is different from the human brain,” Rodrigues commented. “Therefore, there are a large number of drugs in development that fail. The results obtained in experiments with animals are not always reproduced in humans.” There is a lot at stake. Brain disorders are one of the biggest health problems that exist today. It is estimated that approximately 165 million Europeans suffer from a brain disorder. One in three people will suffer from a neurological or mental disorder at some point in their lives.
The total cost to the European health budget is estimated at €800 billion per year, and is expected to increase with the aging of the population. These are well-known neurodegenerative diseases, such as Alzheimer’s or Parkinson’s. It also covers disorders such as epilepsy, depression, stroke, migraines, sleep disorders, traumatic brain injuries, pain syndromes and addictions.
A big step forward
The INL is a leading European research institute co-financed by the Governments of Portugal and Spain. It is also financed by the EU and industry. Dr. Manuel Bañobre López, director of the nanomedicine research group at the INL, supervises the work developed for the new chip. “At INL we have a lot of experience in microfluidics, the field that studies the type of chips that we develop in the BrainChip4MED project,” explained Bañobre López.
However, Bañobre warns that we will still have to wait a little longer before being able to use the brain on a chip. Although the prototype is already ready, it must be perfected. It must also undergo rigorous testing to ensure that it can be used with drugs that will be administered to human patients. This process alone takes years.
However, researchers are optimistic. “We have to combat Alzheimer’s, it is one of the neurological diseases that causes the most problems throughout the world,” said Rodrigues. “And, for that, we must discover new drugs. “Our technology is a big step in that direction.”
The research referred to in this article has been funded through the Marie Skłodowska-Curie Actions (MSCA). The opinions of those interviewed do not necessarily reflect those of the European Commission.
Article originally published inhorizonthe European Union’s research and innovation magazine.
