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Researchers Can Now Interrogate Body-on-Chip

The Interrogator system links ten organs-on-chips to predict how a human body metabolizes drugs

3 min read
Two researchers stand in front of The ‘Interrogator’, a platform that automates the culturing, linking, and maintenance of multiple human organ-on-chips.
Two researchers stand in front of the "Interrogator," a platform that automates the culturing, linking, and maintenance of multiple human organ-on-chips.
Photo: Wyss Institute at Harvard University

Scientists have just announced the completion of an eight-year-long project to integrate 10 human organs-on-chips in an automated system to study how drugs work in the body. The technology provides an alternative to testing drugs on humans or other animals.

Referred to as the “Interrogator” by its developers, the system links up to ten different human organ chips—miniaturized microfluidic devices containing living cells that mimic the function of the organs they represent, such as intestine, heart or lung—and maintains their function for up to three weeks. In two experiments, the system successfully predicted how a human body metabolizes specific drugs.

The technology, described in two papers published this week in the journal Nature Biomedical Engineering, was developed by Donald Ingber and colleagues at Harvard’s Wyss Institute for Biologically Inspired Engineering.

“This is a wonderful technology for the field of organ-on-a-chip,” says Yu Shrike Zhang, a bioengineer at Harvard University Medical School and Brigham and Women’s Hospital in Boston, who was not involved in the research. A platform that automates the culturing, linking, and maintenance of multiple human organ-on-chips, all while inside a sterile incubator, “represents a great technological advancement,” says Zhang, who last year wrote about the promises and challenges of organ-on-a-chip systems for IEEE Spectrum.

In 2010, Ingber and colleagues reported the first human organ-on-a-chip, a human lung. Each chip, roughly the size of a computer memory stick, is composed of a clear polymer containing hollow channels separated by a permeable membrane: one channel is lined with endothelial cellsthe same cells that line human blood vessels, and another hosts organ-specific cells, such as liver or kidney cells.

'Gut on a Chip'The “Gut on a Chip.”Photo: Wyss Institute at Harvard University

After creating numerous individual organ chips, Ingber received a 2012 DARPA grant worth $37 million to integrate 10 organs-on-chips and use them to study how drugs are absorbed and metabolized in the body.

Eight years and three prototypes later, the team succeeded. The most recent version of the platform took four years to develop, says Richard Novak, a senior staff engineer at the Wyss Institute who worked with a team to build the machine. Within that time, a whole year was needed to develop a user interface that biologists with no programming experience could easily operate.

“It enables a really complex experiment to be set up in two minutes,” says Novak.

The “Interrogator,” as Novak fondly calls it, consists of a robotic system that pipettes liquids—such as a blood substitute and/or a drug of choice—into the channels; a peristaltic pump to move those liquids through the microfluidic chips; custom software with an easy drag-n-drop interface; and a mobile microscope to monitor the chips and their connections without having to manually reach in and take out each chip for examination, as was done with older systems.

Best of all, says Novak, the whole machine fits into a standard laboratory incubator, which maintains living cells at constant temperature and light conditions.

Finally, the team was ready to interrogate the Interrogator. Could the system truly mimic the human body in a drug test? To find out, the scientists connected a human gut chip, liver chip, and kidney chip, then added nicotine to the gut chip to simulate a person orally swallowing the drug (such as if a person were chewing nicotine gum). The time it took the nicotine to reach each tissue, and the maximum nicotine concentrations in each tissue, closely matched levels previously measured in patients.

Linked chipsChips link up in the “Interrogator” to answer vital questions about substances in the body.Photo: Wyss Institute at Harvard University

In a second test, the researchers linked liver, kidney, and bone marrow chips and administered cisplatin, a common chemotherapy drug. Once again, the drug was metabolized and cleared by the kidney and liver at levels that closely matched those measured in patients. Cells in the kidney chip even expressed the same biological markers of injury as a living kidney does during chemotherapy treatment.

“Compared against clinical studies, they matched up really nicely,” says Novak. The team is now using their linked organ chips to study the gut microbiome and influenza transmission. The Interrogator technology IP has been licensed by a Wyss Institute spin-off company, Boston-based Emulate, which Ingber founded.

This post was updated on 31 January 2020. 

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Are You Ready for Workplace Brain Scanning?

Extracting and using brain data will make workers happier and more productive, backers say

11 min read
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A photo collage showing a man wearing a eeg headset while looking at a computer screen.
Nadia Radic
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Get ready: Neurotechnology is coming to the workplace. Neural sensors are now reliable and affordable enough to support commercial pilot projects that extract productivity-enhancing data from workers’ brains. These projects aren’t confined to specialized workplaces; they’re also happening in offices, factories, farms, and airports. The companies and people behind these neurotech devices are certain that they will improve our lives. But there are serious questions about whether work should be organized around certain functions of the brain, rather than the person as a whole.

To be clear, the kind of neurotech that’s currently available is nowhere close to reading minds. Sensors detect electrical activity across different areas of the brain, and the patterns in that activity can be broadly correlated with different feelings or physiological responses, such as stress, focus, or a reaction to external stimuli. These data can be exploited to make workers more efficient—and, proponents of the technology say, to make them happier. Two of the most interesting innovators in this field are the Israel-based startup InnerEye, which aims to give workers superhuman abilities, and Emotiv, a Silicon Valley neurotech company that’s bringing a brain-tracking wearable to office workers, including those working remotely.

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