About 20 years ago, researchers excitedly announced the coming of so-called lab-on-chip devices that could revolutionize medicine. At the time, people marveled at the possibilities: The devices would take the capabilities of a large biochemistry lab and shrink them to a platform the size of a cell phone or smaller. With help from a portable scanner or reader, the chips could instantly tell whether you had a chronic disease, all from a tiny droplet of blood or other body fluid. It may have taken a while, but the tiny chips are finally starting to emerge from the lab and are poised to make an impact.
Researchers supported by the NHLBI are playing a key role in the development of this technology — and for good reason. The chips not only are capable of quickly diagnosing diseases, but they can also do so at a lower cost, faster speed, and with higher accuracy than their bulkier counterparts, researchers say. Some may be coming to a hospital or medicine cabinet near you.
“Watching discoveries move from the lab to the clinic is incredibly exciting,” said Stephanie M. Davis, Ph.D., NHLBI’s Small Business Program Coordinator. “The NHLBI Small Business Program is thrilled to see lab-on-a-chip technologies finally move toward the marketplace.”
These devices are usually made of plastic engineered with tiny channels, valves, and pumps that can transport, mix, and analyze proteins, DNA, and other chemicals in body fluids for a desired testing outcome. The fluid droplets form tiny hair-thin liquid streams that are moved around by air pressure, electricity, or even sound to precisely maneuver them to their destination, react with other chemicals, and ultimately yield clues about the presence of chronic disease or invisible pathogens.
The chips often require insertion into a portable reader or scanner. In some cases, results are captured by cell phone images and sent for off-site interpretation, which is especially helpful in remote areas that lack trained technicians and expensive equipment, researchers say. One notable example of lab-on-a-chip technology currently in use is an FDA-authorized device to screen newborn blood for the presence of lysosomal storage disorders, a group of rare, inherited metabolic diseases that are caused by enzyme deficiencies within the lysosome, an organelle that functions as the digestive system of the cell. These diseases can be fatal if untreated. Yet worldwide, most newborns—100 million of 137 million born annually—get no screening at all.
The new lab-on-a-chip blood tests could change that by allowing early detection and treatment. The testing platform combines a disposable plastic cartridge with micro-sized electronics and contains all the chemical reagents needed for onsite diagnostic testing of a blood droplet. Results can be read within minutes. The tests were developed by a company called Baebies, which was launched on the heels of funding support from the NHLBI SBIR program.
“The great thing about this test is that it’s all self-contained,” said Ronald Warren, Ph.D., an NHLBI program officer for the former SBIR project and a member of the Molecular, Cellular and Systems Blood Science Branch in NHLBI’s Division of Blood Diseases and Resources. “All you have to do is collect the blood, put it in the cartridge, and hit ‘go’.”
Here’s a look at some of the other NHLBI-supported lab-on-a-chip technologies that researchers are developing:
A way to diagnose sickle cell disease
Perhaps one of the most anticipated lab-on-a-chip devices is one that can detect the presence of sickle cell disease in newborns with a simple droplet of blood. The device includes a miniature version of the electrophoresis test currently used to evaluate newborns for the disease. And it can travel anywhere – including to remote, underserved areas, such as parts of Africa and India, that lack access to modern diagnostic testing equipment. In those areas, more than 300,000 babies are born each year with sickle cell disease, yet many go undiagnosed and die before the age of five. But tests performed using this device can save many lives, says Umut Gurkan, Ph.D., a biomedical engineering professor at Case Western Reserve University, who is an NHLBI grantee and inventor of the technology.
“This device is a gamechanger,” Gurkan said. “It brings the power of a clinical laboratory to where it’s needed the most while making diagnostic testing affordable and easy to use.”
The battery-operated device is now available in nine countries, including India and Ghana. Called the Gazelle platform, developed and manufactured by a company called Hemex Health, it can also diagnose other types of anemia, as well as malaria.
Targeted treatments for asthma, COPD
This chip device, which is in the last phases of development, shows promise for improving the treatment of asthma, COPD, and other lung diseases. The chip collects tiny sputum samples taken from the lung, breaks them down into smaller cell components using sound waves, and then labels them with chemical tracers for easier detection. The chip can then be analyzed by flow cytometry, a technique that uses high-powered lasers to identify cell types and amounts. Those cells provide crucial clues into the type of inflammation present in the lungs.
“To miniaturize this complex testing process and have it all on a small mobile device is really quite remarkable,” said Stewart J. Levine, M.D., senior investigator in the NHLBI Laboratory of Asthma and Lung Inflammation and a collaborator in the initial development of the chip. “My guess is that devices like this will be achievable in the future and help promote medicine in a more personalized way, including applications in asthma and COPD.”
The device was initially developed by engineers at Penn State University in collaboration with the NHLBI and Washington University School of Medicine. It is now being refined by a biotech company, Ascent Bio-Nano Technologies, in preparation for eventual use.
Help for identifying drugs that fight COVID-19
Recently, researchers supported by the NHLBI have also developed a human-airway-on-a-chip for the rapid screening of drugs that might treat the virus that causes COVID-19. Don Ingber, M.D., Ph.D., founding director of the Wyss Institute at Harvard University, and his colleagues developed the chip to closely mimic the cellular environment of the lung, including cells that line the lung airway, blood vessels, and immune system.
In lab studies, they showed that their "airway chip” was effective in screening drugs that treat both influenza and SARS-CoV-2. The chip identified amodiaquine, an antimalarial compound, as a promising drug for fighting COVID. It is now in clinical trials at multiple sites in Africa, the researchers say.
A test for screening drugs for potential heart toxicity
In recent years, lab-on-chip devices have evolved into so-called organ-on-a-chip devices, which are essentially miniature models of human organs. An example of this technology is the so-called heart-on-a-chip.
Kevin Healy, Ph.D., a bioengineering professor at the University of California, led a research team that created a network of pulsating cardiac muscle cells housed in an inch-long chip that models human heart tissue. The heart cells were derived from adult stem cells. In lab studies, the researchers demonstrated that their device provides a viable way to screen a variety of cardiovascular drugs for their potential effects on the heart. “Ultimately, these chips could replace the use of animals to screen drugs for safety and efficacy,” said Healy, whose work is funded in part by the NHLBI. Animal models used to predict human reactions to new drugs are associated with a high failure rate, he noted. The heart-on-a-chip could significantly cut the cost and time typically needed to bring a new drug to market, he said.
In preliminary testing, the heart-on-a-chip platform showed promise in screening COVD-19 drugs for their potential toxicity.
A look at how to treat sleep disorders
Many view sleep as the “next frontier” of lab-on-a-chip technology. Researchers supported by the NHLBI are actively searching for biomarkers to improve the study of sleep and circadian rhythm disorders, including sleep apnea, insomnia, and even jet lag.
“Employing technological advancements such as lab-on-a-chip could lead to better diagnostic tests for sleep disorders and improved treatments for them,” said Marishka Brown, Ph.D., director of the National Center on Sleep Disorders Research at the NHLBI. “While the identification of viable sleep biomarkers remains a top priority and an ongoing challenge, success in this area will have an impact far beyond sleep health, with implications for heart, lung, and blood diseases. It is an exciting area the NHLBI and others are continuing to explore.” That next frontier is already moving closer. For example, researchers at Northwestern University were recently awarded a multimillion-dollar grant to develop an implantable chip that could control the body’s circadian clock, allowing people to quickly recover from jet lag. Described as a “living pharmacy,” the lab-on-a-chip device will produce the same peptides that the body uses to control sleep cycles. It holds promise for soldiers, who travel across multiple time zones, and shift workers, including first responders, who rotate between day and night shifts.
The experimental device is funded primarily by the Defense Advanced Research Project Agency (DARPA). NHLBI grantee Phyllis Zee, M.D., Ph.D., director of the Center for Sleep and Circadian Medicine at Northwestern University’s Feinberg School of Medicine, is part of a large, multi-institutional research team that is helping to develop the futuristic device. And Jonathan Rivnay, Ph.D., a biomedical engineer at Northwestern, is the principal investigator.
“This control system allows us to deliver a peptide of interest on demand, directly into the bloodstream,” Rivnay said. “No need to carry drugs, no need to inject therapeutics and — depending on how long we can make the device last — no need to refill the device. It’s like an implantable pharmacy on a chip that never runs out.”
If that sounds like something you’d like to try, you’ll have to wait: The device won’t be ready for several more years, the researchers say.