A human brain-on-a-chip sounds like something from a science fiction film, a gadget powering its cyborg villain. 

But chemical and biological engineer Dr Raquel Rodrigues at the International Iberian Nanotechnology Laboratory (INL) in Braga, Portugal, believes that such a device will be key to developing more effective treatments for serious neurological disorders, such as Alzheimer’s.

“The brain is a very complex and puzzling organ,” says Dr Rodrigues. “We need electronic monitoring of cells and experimental parts so we can learn how it works.”

Your brain on a chip

Thanks to research funding from the EU, Rodrigues and fellow researchers at the INL were able to build a unique brain-emulating microchip as part of a two-year research effort called BrainChip4MED that concluded in February 2024. 

The research included a 12-month secondment to Brigham and Women’s Hospital, part of Harvard Medical School and pioneers in the development of organs-on-a-chip (OoC) and biosensors. 

The ingenious, thumbnail-sized device developed by the researchers looks similar to chips in computers or smartphones, but is much more complex. 

 

'The brain is a very complex and puzzling organ.' Raquel Rodrigues, BrainChip4MED

The brain-on-a-chip simulates the way the human brain works, using a combination of chemistry, engineering and biology to create a complex micro-biosensor system for the real-time screening of new nanotherapeutics.

Using a technology called microfluidics, the chip features multiple micro-channels – with sizes of tens to hundreds of micrometres – through which fluids can run. This makes it possible to analyse very small quantities of a product and test many samples at the same time, reducing the overall cost of testing.

Protective brain barrier

A central goal of the researchers was to address the problem of how to develop medicines able to cross the so-called blood-brain barrier. This tightly locked layer of cells helps protect the brain from toxins, germs and other harmful substances that could be present in the blood. 

Only the very smallest molecules can get through the blood-brain barrier. Although this plays a very important protective role, it has also hindered efforts to develop drugs for the treatment of neurological disorders.

Any medicine meant to treat the brain needs to go through this membrane to reach its target. But short of testing on humans, there are few good ways to determine how well a drug will be able to penetrate into the brain itself.

“Today there are only four commercially available Alzheimer’s drugs, and none of those actually treat Alzheimer’s, they just work on the symptoms,” says Dr Rodrigues. 

“That’s because pharmaceutical companies need to invest large amounts of funds in drugs they are unsure will pass the blood-brain barrier. So they don’t,” she says.

A pharmaceutical company might spend millions developing a drug, only to find that it cannot get across the blood-brain barrier. The EU funding for the new brain-emulating chip developed at INL resolves this problem. 

Imitating life on a chip

The research team recreated the blood-brain barrier membrane on the chip using bioorganic material.

“That’s what sets our work apart,” says Dr Rodrigues. “We use a bio-membrane that more closely resembles the barrier in our brain. Other devices use physical barriers, made from polymeric components. We think a biological one is superior.”

With this new and improved brain-on-a-chip, researchers will be able to inject medicine under development into the chip to monitor its effects and see how well it is able to penetrate the brain.

The aim is to change the way these kinds of medicines are developed. Today, this type of testing is mostly carried out on animals, but that comes with a range of ethical and practical downsides. These organs-on-a chip microchips offer a potential alternative to traditional animal testing.

“The brain of an animal is different from the brain of a human,” says Dr Rodrigues. “That’s why a lot of medicines under development fail. Animal testing doesn’t necessarily reproduce for humans.”

 

'We need to combat Alzheimer's, it's one of the most problematic neurological diseases in the world. Our technology is a serious step forward in that direction.' Raquel Rodrigues, BrainChip4MED

The stakes are high. Brain disorders are one of the greatest health challenges faced today. It is estimated that about 165 million Europeans are living with a brain disorder. One in three people will suffer from a neurological and/or mental disorder at some point in their lives.

The global cost to European healthcare budgets is estimated to be €800bn per year, and this is expected to increase with an ageing population.

This includes well-known neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. It also covers other disorders like epilepsy, depression, stroke, migraines, sleep disorders, traumatic brain injury, pain syndromes and addiction.

Serious step forward

INL is a leading European research institute co-funded by the national governments of Portugal and Spain. It is also supported by the EU and by industry. Dr Manuel Bañobre-López, leader of the Nanomedicine Research Group at INL, supervised the work on the new chip.

“At INL we have extensive expertise in microfluidics, the field that studies the kind of chip we made in BrainChip4MED,” says Dr Bañobre-López. 

Still, we might need to wait a bit longer for the brain-on-a-chip to be ready for use, he cautions.

Even though the prototype is ready, further refinement is needed. It will also have to undergo rigorous testing to make sure it can be used for medicines that will eventually be administered to human patients. That process alone will take years.

Nevertheless, the researchers are optimistic. 

“We need to combat Alzheimer’s, it’s one of the most problematic neurological diseases in the world,” says Dr Rodrigues. “And to do that, we need to find new drugs. Our technology is a serious step forward in that direction.”

Author: Tom Cassauwers. This article first appeared in Horizon magazine.