Mimicking the brain on a microchip

Researchers hope to develop drugs more efficiently using electronic chip systems that mimic processes in the body’s organs. One part of Anna Herland’s work is to develop models for how cells in the blood-brain barrier interact with brain tissue.

Anna Herland

Associate professor in Applied Physics

Wallenberg Academy Fellow 2015

Institution:
KTH Royal Institute of Technology

Research field:
“Organ-on-a-chip” – creating a model in which the blood-brain barrier interacts with surrounding neurons.

Herland has an abiding interest in the brain. She is a bioengineer, and when she was a PhD student at Linköping University her work involved biomarkers for Alzheimer’s. Now she is combining her knowledge of biomaterials, stem cells and brain cells to build chip-based models of blood vessels and surrounding cells in the brain – a “brain-on-a-chip”, in other words.

“People sometimes ask me why I focus on the brain. It’s so complicated – how can I manage to make a model of it? ‘It’s impossible,’ they say, ‘try something easier’. But the brain is what I’m interested in.”

An “organ-on-a-chip” is actually a microfluidic system on a polymer chip. The body’s blood vessels and their interaction with surrounding tissue are simulated in the system’s microchannels. Electrodes in the chip enable researchers to monitor signals from the cells, and study processes.

“First we are trying to build the basic functions of the organ – the blood-brain barrier in this case. When we’re sure it works, we’ll be able to administer a drug and see whether the model behaves like a human does. I want to understand and measure this in real time.”

Few animal experiments

Organ-on-a-chip is hot research topic. There is an urgent need for models for human tissue and for various diseases. At present, experiments are often carried out on animals, but there are significant differences between animals and humans. Drugs tested and shown to be effective on animals then go to clinical trials, where they are often found not to work on humans. The current drug development process is thus inefficient and very costly.

It is expected that organ-on-a-chip technology will result in more efficient drug development. It may also reduce the need for animal experiments. Herland explains:

“Drug companies themselves are studying systems of this kind and how they can be used. We researchers are considering how we can take the next step, and improve the models. As a Wallenberg Academy Fellow, much of my work is devoted to ways of improving the monitoring in the systems we build.

“The marvelous thing about this grant is that it provides funding for such a long time. And it allows me great freedom. I have been given the opportunity to focus on the project and set long-term goals. This is essential when there are so many dimensions that must fit together.”

Collaboration with Karolinska Institutet and Harvard

Herland’s research team is based at the Department of Micro and Nanosystems at KTH Royal Institute of Technology in Stockholm. The chip and its electronic monitoring system are being developed in the lab opposite her office. The cells used in the models are cultured in a laboratory in the Department of Chemistry. Herland is also attached to the Department of Physiology and Pharmacology at Karolinska Institutet.

“I really like the dynamic between developing technology and medicine. We have a collaborative project with AstraZeneca, for example, in which we share an industry-sponsored PhD student.”

Herland spent three years as a guest researcher with Professor Donald Ingber at Harvard University in the U.S., during which time she learnt to build models of blood vessels from the foremost experts in the field.

­“It was a wonderfully creative working environment. Donald Ingber was one of the instigators of the ‘organ-on-a-chip’ research field. I have continued to collaborate on the blood-brain barrier and in other areas with the Wyss Institute at Harvard. I am one of the scientific parts of a major international project that aims to create a ‘body-on-a-chip’”.

Making the complex simple

The greatest challenge is to translate the complex human system of organs into the simplest possible models, while maintaining sufficient function.

“We have to be able to monitor the processes. There are also different kinds of complexity, depending on the questions we are addressing. The simplest example in the studies we are making now is that we create a layer of blood vessel containing active cells that resemble blood vessel cells as closely as possible. The question we want to resolve is whether a drug entering our mini-blood vessel will then pass into the brain, and if so, how?”

Herland explains that study of the brain poses challenges all of its own. It is very hard to get hold of neurons on which to experiment. The brain is one of the organs that deteriorate most rapidly after death, and tissue samples are not normally taken from a healthy brain.

“That’s why we make great use of stem cells, which we culture, and use to create neurons and brain blood cells. They are produced at Karolinska Institutet, and can take some time to mature. Neurons take the longest. It takes a few months to get them to form the networks of neurons found in the brain, with mature electrical activity between them, which we try to monitor in various ways using electrodes.”

To date, researchers in the field have mainly concentrated on the normal body. Herland thinks it is time to study various disease scenarios.

“We want to see whether we can make a model of Alzheimer’s, for instance. We’re also interested in stroke models. I think these advanced in vitro systems, in which living cells are studied outside the body, combined with stem cell science, will create radical new ways of developing drugs, and possibly also individually tailored therapies in the future.”

Text Susanne Rosén
Translation Maxwell Arding
Photo Magnus Bergström