A team of scientists and engineers at Lawrence Livermore National Laboratory is developing “human-on-a-chip,” a miniature external replication of the human body, integrating biology and engineering with a combination of microfluidics and multi-electrode arrays. Photos by Julie Russell/LLNL
By Jeremy Thomas
Development of new prescription drugs and antidotes to toxins currently relies extensively on animal testing in the early stages of development, which is not only expensive and time consuming, it can give scientists inaccurate data about how humans will respond to such agents.
But what if researchers could predict the impacts of potentially harmful chemicals, viruses or drugs on human beings without resorting to animal or even human test subjects?
To help achieve that, a team of scientists and engineers at Lawrence Livermore National Laboratory is developing a “human-on-a-chip,” a miniature external replication of the human body, integrating biology and engineering with a combination of microfluidics and multi-electrode arrays.
The project, known as iCHIP (in-vitro Chip-based Human Investigational Platform), reproduces four major biological systems vital to life: the central nervous system (brain), peripheral nervous system, the blood-brain barrier and the heart.
“It’s a testing platform for exposure to agents whose effects are unknown to humans,” said LLNL engineer Dave Soscia, who co-leads development of the “brain-on-a-chip” device used to simulate the central nervous system. “If you have a system that is engineered to more closely replicate the human environment, you can skip over the really lengthy process of animal testing, which doesn’t necessarily give us information relevant to humans.”
The iCHIP team is focusing its efforts on the brain, where they’re looking to understand how neurons interact with each other and react to chemical stimuli such as caffeine, atropine (a drug used to treat poisonings and cardiac arrest) and capsaicin, the compound that gives chili peppers their hotness, as well as real chemical agents in the Lab’s Forensic Science Center.
Unique to the iCHIP platform is combining multiple brain types on the same device without barriers between those regions. To study the brain, primary neurons are funneled or “seeded” onto a microelectrode array device, which can accommodate up to four brain regions (such as the hippocampus, thalamus, basal ganglia and cortices). After the cells grow, a chemical (atropine for example) is introduced and the electrical activity from the neurons is recorded.
“The idea is that we can look at network-wide effects across different brain regions,” Soscia said. “It adds a level of complexity that has never been done before.”
Preliminary results have shown that hippocampal and cortical cells can survive on the chip for several months while their responses are recorded and analyzed, Soscia said.
Filtering out chemicals and toxins before they reach the central nervous system in the body is accomplished by the blood-brain barrier, which is being reproduced by a team led by LLNL engineer Monica Moya. The device uses tubes and microfluidic chips to simulate blood flow through the brain. Moya and her team are testing the device with caffeine and other agents to ensure the system is performing and the cells are reacting as they would in a human body.