credit: N. Hanacek/NIST
Editor’s note (May 2, 2024): This news article has been updated to clarify that NIST’s heart-on-a-chip system is still in development and that the referenced Lab on a Chip article is a review of research on the technology across the scientific community.
Researchers at the National Institute of Standards and Technology (NIST) have developed a bioelectronic device that can measure cell behavior in real time. The researchers are integrating these components into a proprietary version of a system they call Heart-on-a-Chip (HoC). The technology aims to address the limitations of traditional cardiovascular drug development, which relies heavily on animal testing. By capturing key aspects of the human cardiovascular system in a laboratory environment, HoC has the potential to replace animal testing with a more accurate representation of the human body, shortening drug development timelines and reducing costs.
NIST researchers recently examined the current state of the technology, including efforts across the scientific community, in a review article published in the journal Nature. Lab on a chipNIST’s work on HoC is part of a larger organ-on-a-chip suite being developed at the agency, which also includes a “body cube” that mimics human organ functions in a 3D arrangement.
HoC is a device that records the complex interactions of cells in the heart on a tiny chip. The actual heart-on-chip designs vary, but they are typically tiny transparent or semi-transparent chips consisting of a network of microchannels printed on a polymer layer. These microchannels are elaborately engineered to mimic the blood vessels found in the human heart. Researchers place human cardiac cells within these microchannels to manipulate and observe their behavior. Researchers can stimulate cells individually or observe their behavior under different conditions, such as the introduction of drugs.
credit:
N. Hanacek/NIST
The heart-on-a-chip that NIST is designing aims to mimic conditions in a real heart, said Darwin Reyes, a NIST researcher who led the system’s development. The goal is to manipulate the environment to turn stem cells into heart cells that can contract and relax in the same way that heart cells produce a heartbeat in the body.
At the “heart” of the organ-on-a-chip system is something called microfluidics, which is essentially a miniature piping system that allows researchers to precisely control and manipulate tiny amounts of liquids. Researchers use microfluidics to create sophisticated models of organs and tissues on tiny chips in the lab.
Reyes said the bioelectronic device can be used with a variety of cell types: In the HoC project, the researchers are using cardiac cells, but customized versions of the system are also being used with other cells to visually and electronically monitor their behavior.
Researchers can create chips that mimic conditions in different organs, not just the heart, and these chips can also be interconnected to form multi-organ systems. For example, a heart-on-a-chip can be connected to a liver-on-a-chip to simulate how the heart and liver interact in response to a particular drug or disease state. This approach can provide a more comprehensive understanding of how different organs work together in the human body. NIST is working to understand sources of uncertainty in these devices and to develop design and manufacturing techniques to realistically replicate human physiology at the microscale.
Rethinking Animal Testing
In traditional drug development, animals are often used as test subjects. However, animal physiology does not perfectly match human physiology. A drug may pass animal testing but fail human testing. This not only delays the drug testing process but also exposes human subjects to the risk of side effects from the drug. Furthermore, there is an ongoing debate regarding the ethical considerations of animal testing.
“The ultimate goal is to be able to completely avoid animal testing, if possible,” Reyes says, “which would hopefully reduce the time it takes to test drugs and lower their costs.”
In 2022, President Joe Biden signed the FDA Modernization Act 2.0 into law. The bill essentially amends the Federal Food, Drug, and Cosmetic Act of 1938, which mandated animal testing for all new drug development protocols. Over the past century, this mandate was intended to ensure certain quality and safety standards for medicines and medical devices, but recent scientific advances are increasingly offering viable alternatives to animal testing, such as organ-on-a-chip systems.
International collaboration towards standardization of organ-chip technology
The development of this new technology is not happening in a vacuum. Researchers around the world are working to develop similar microfluidic devices to usher in a new era of drug development. But for this to happen, standardization is needed – establishing consistent guidelines and rules for these technologies. This will not only help with regulatory approval, but will also lead to wider acceptance across the scientific, industrial and medical communities. NIST is actively participating in the development of standards for this technology, along with scientific organizations around the world.
“The more collaborations we have outside of what’s currently being done and the direction we’re heading, the better this technology will be,” Reyes said.
Expanding horizons beyond cardiovascular
Although the HoC is focused on drug development for cardiovascular disease, the functionality of the OoC is not limited to specific organs: the system can be applied to a variety of cell types, including those relevant to cancer research.
“We are currently in the testing phase of figuring out how to track the movement and aggressiveness of cancer cells in real time,” Reyes said. “In the future, we hope that with further testing, this system will be able to measure the aggressiveness of cancer cells, which will aid in diagnosis.”
The development of this new technology, underpinned by rigorous standards, marks an important step towards a future in which drug development is characterized by increased precision, efficiency and ethical considerations.
Paper: Derrick Butler and Darwin R. Reyes. Heart-on-a-Chip Systems: Disease Modeling and Drug Screening Applications. A lab on a chip. Published online on February 6, 2024. DOI: 10.1039/D3LC00829K
