It is a serious condition affecting 8 to 12 million people in the United States and millions more worldwide, yet peripheral artery disease (P.A.D.)—a problem in which clogged arteries reduce blood flow to the limbs—is rarely on the radar of many Americans. Health experts say it should be, especially for people age 50 and older with a history of smoking or diabetes.
P.A.D. can cause painful cramping or leg numbness and in its most severe form can result in gangrene, leg amputation, and sometimes death. It can often progress without symptoms, too, resulting in underdiagnosis. But with the right monitoring tools, the disease can be halted or even reversed. Only problem: clinicians lack a quick and reliable way to do the monitoring.
That could soon change, thanks to a device developed with funding support from the National Heart, Lung, and Blood Institute (NHLBI) through its Small Business Innovation Research (SBIR) program. The device is an injectable biosensor that can remotely measure tissue oxygen levels in people with P.A.D. The innovation—developed by Profusa, Inc., an Emeryville, Calif.-based company—gives patients a chance to get the necessary therapy before severe symptoms occur.
“Peripheral artery disease is a silent killer. We really have to shine the spotlight on it,” said Ben Hwang, Ph.D., chairman and chief executive officer of Profusa. “The Lumee™ Oxygen Platform provides a critical piece of knowledge that is missing from the clinic setting today: the ability to quickly and accurately detect the amount of oxygen in the tissues of patients with P.A.D.”
This oxygen sensing system has been available for almost two years in Europe, where it is helping doctors measure oxygen levels during and after surgery in a subpopulation of P.A.D. patients with critical limb ischemia, or severe blockage of the arteries of the lower limbs. So far, it has been used in a small number of patients, with promising results, Hwang noted. In the United States, the device is considered investigational and still undergoing clinical testing, with no serious side effects reported to date. The company plans to submit the device for FDA approval for the treatment of P.A.D. within the next year, he said.
P.A.D. is currently diagnosed using a method called the ankle-brachial index, which compares blood pressure in the ankle to blood pressure in the arm to give an idea of how well blood is flowing through the limbs. But it can’t show which blood vessels are narrowed or blocked, nor can it directly measure oxygen flow through the surrounding tissues, factors which limit its reliability. The Lumee system, whose name is a play on the word luminosity, offers a way to provide those measurements.
A key component of the system is its tiny biosensor, which is about the width and length of a few small eyelashes. The biosensor is made of a hydrogel material, like that in a soft contact lens. It is also composed of a phosphorescent chemical that, when activated, is specially engineered to emit light in proportion to the amount of oxygen present.
Doctors place a sensor under the skin of the leg or foot, using a special injection device. A surface “reader” then shines near-infrared light into the skin to activate the sensor. The reader detects the amount of fluorescence emitted from the sensor, and that information is sent through a cable to a special laptop computer that graphically translates and displays the amount of oxygen present.
The researchers are developing two types of easy-to-use readers: a disk-shaped device similar to a smart watch, as well as a thin, patch-like reader, which they call a smart bandage. Both types are designed to be applied to the skin and are equipped to wirelessly send signals to a cell phone, opening the door to at-home monitoring of P.A.D. in the future.
The biosensors have the added benefit of being biocompatible. The tiny sensors are porous, much like a honeycomb or sponge. Healthy tissue grows through the interior of the material, anchoring the sensor so that it becomes part of the body and is recognized by the immune system as a normal tissue. In tests so far, the device does not show any serious signs of being rejected by the body. It is designed to function in people for up to six months but could last two years or even longer, the researchers said. Nevertheless, the sensors can be removed if needed, using a simple hole punch in the skin.
The novel oxygen-sensing system doesn’t end at helping people with P.A.D. Researchers say the device can be used by soldiers in the field and even athletes to reveal signs of oxygen deprivation and to tell users when to rest or how to optimize training. Patients with sleep apnea or COPD might be able to benefit, too.
When researchers started Profusa around 2009, its founders originally set out to develop a continuous biosensor monitoring system to detect blood glucose levels. The oxygen sensor platform was developed in conjunction with the glucose sensor to be an internal reference point for glucose measurement. According to Hwang, the oxygen sensor was a spin-off from that original work.
“We soon realized that having a tissue oxygen sensing system could have tremendous clinical utility, especially for measuring tissue oxygen for patients suffering from P.A.D. The rest is history,” said Hwang, who has a background in biochemistry.
The development of the device comes at a time when peripheral artery disease is on the rise, in part because of lifestyle-related factors such as smoking, diabetes, obesity, and physical inactivity. While people can help keep P.A.D. at bay with better lifestyle management, the device offers hope for those who already have the condition.
“We’re looking forward to the day when tens of thousands of patients will benefit from this equipment,” Hwang said. “And that day is right around the corner.”
In addition to NHLBI funding, development of the oxygen-sensor technology was also supported in part by funding from other government entities, including the Defense Advanced Research Projects Agency (DARPA), the U.S. Army Research Office, and the National Institute of Biomedical Imaging and Bioengineering (NIBIB), part of the NIH.
The NHLBI Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs support the development of the next generation of commercially promising technologies and products to prevent, diagnose, and treat heart, lung, blood, and sleep-related diseases and disorders. For more information on NHLBI’s small business programs, visit the NHLBI Small Business Program Funding Area page.
Reference to any specific commercial products, process, service, manufacturer, and/or company does not constitute an endorsement or recommendation by the National Heart, Lung, and Blood Institute (NHLBI), the NHLBI's Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs, or any other portion of the U.S. Government.