Fourteen years ago in Birwadi, India, just over one hundred miles southeast of Mumbai and about fifty miles from the Arabian Sea, Ambalika Tanak’s grandmother suffered a heart attack. Only her doctors didn’t know it. The 72-year-old woman’s symptoms were ambiguous, and the local hospital didn’t have the equipment to properly diagnose her. They mistakenly thought she was having an asthma attack. So she didn’t get the treatment she needed.
Even in Maharashtra, the most industrialized state in India, small towns like Birwadi, with a population of just over seven thousand, have fewer resources for treating complex medical conditions than those in Mumbai, nearly a five-hour drive away. When her grandmother’s condition worsened, Tanak’s parents decided to transfer her to Mumbai.
“By then her body was too weak, and she needed the assistance of a ventilator to breathe,” Tanak said. “If the countryside hospital had done an ECG, they would have known of her heart attack and started treatment right away.”
As she held her grandmother’s hand in the Mumbai hospital’s ICU, Tanak took note of the various medical tools to which she was hooked up. “The nurses kept coming in to test her blood pressure and vital signs,” she says. “I realized how much the doctors rely on these devices.”
At age sixteen, Tanak had just graduated high school. She already planned to study engineering, but she didn’t know exactly what kind of engineer she wanted to be. It was during her grandmother’s hospitalization that she realized engineering might be a way to save lives by building better medical tools. “Nurses, doctors, the entire health-care industry depend on those devices,” she says. “That was when I decided that biomedical engineering would be the best fit. As an engineer you’re able to contribute towards those real-life problems.”
Today, Tanak is a graduate student in biomedical engineering at the University of Texas at Dallas doing exactly that—and winning scientific honors in the process. She recently developed a biosensor that requires only a single drop of blood to give doctors a clinical snapshot of a patient with sepsis, the leading cause of death in U.S. hospitals and often overlooked as a potential diagnosis. Though much work remains to be done before it can be put to use in hospitals and clinics, Tanak’s device might help doctors recognize the condition much earlier, before the most severe symptoms begin to occur. That could someday save countless lives.
“There’s been a lot of research on sepsis, but the major thing missing was an active point-of-care testing device that can give feedback when the patient is at your bedside,” Tanak says. That’s the gap she hopes the DETecT Sepsis (Direct Electrochemical Technique Targeting Sepsis) biosensor will fill.
During sepsis, the immune system goes haywire in response to an infection. Some functions of the body’s defenses go into overdrive, others shut down, and chemicals get released into the bloodstream that cause inflammation throughout the body. If untreated, sepsis begins shutting down one organ after another, causing severe tissue damage and eventually death. “It’s not the pathogen causing you to die,” says Dr. Subbu Krishnan, one of the coauthors of Tanak’s study. “It’s the dysregulation of the immune response.”
Sepsis accounts for one in three hospital deaths in the United States, killing roughly 270,000 of the 1.7 million Americans who develop it every year, according to the Centers for Disease Control and Prevention. That’s only a fraction of sepsis deaths across the world. A study in The Lancet last month estimated that nearly 50 million people developed sepsis in 2017, which killed 11 million of them, accounting for one in five of all global deaths that year.
The death toll is so high because infections are common, and the condition is complex, according to Krishnan, who’s also the chief science strategist for Austere Environment Consortium for Enhanced Sepsis Outcomes. ACESO is a group of government, nonprofit, academic, and industry partners whose goal is to improve survival in sepsis patients by developing tools and treatment recommendations that can save lives even in remote areas with few resources.
Treating sepsis is challenging because so much is happening in the body at once, explains Dr. Charles Lerner, a retired infectious disease physician who consults for the Texas Medical Association’s Committee on Infectious Diseases. “Sepsis is the combination of changes in blood pressure and pulse, the immune system, the coagulation system, the ability to get oxygen through the lungs into the tissues, and occasionally diminished kidney blood flow,” Lerner says. “All kinds of things go on in sepsis.”
Sepsis can also sneak up on doctors who don’t suspect it, especially in its early stages, says Dr. Chandra Mohan, a professor of biomedical engineering at the University of Houston and an adjunct professor of medicine at the University of Texas Health Science Center in Houston. “It’s commonly called the ‘silent killer,’ meaning that we don’t even think of sepsis because the patient presents with just confusion, or maybe a heart rate increase or breathlessness,” he says.
Tanak’s biosensor detects levels of five inflammatory biomarkers that past research has suggested are measurable indicators of the immune system’s response to sepsis. In Tanak’s proof-of-concept study, published last month, the biosensor identified those biomarker levels in twenty dried blood samples with at least 85 percent accuracy in just five minutes. Further testing will seek to demonstrate that it’s capable of the same with fresh drops of blood.
The UTD team hopes to expand the biosensor’s capabilities to measure seven biomarkers and potentially even more. Though it’s not yet been demonstrated in clinical studies, Krishnan says the sensor’s measurement of the five biomarkers alone could help doctors determine whether an underlying infection is bacterial or viral. This would help doctors to know whether antibiotics should be used or avoided. Krishnan also believes the sensor can provide insight into the severity of a patient’s sepsis. All of this potential remains uncertain, however, until much more research has been done.
Tanak developed the sepsis biosensor by customizing technology developed by her adviser, Shalini Prasad, head of UTD’s department of bioengineering, and Sriram Muthukumar, a UTD adjunct bioengineering professor. Prasad and Muthukumar cofounded the company EnLiSense specifically for developing point-of-need electrical biosensors and then partnered with ACESO to determine what the greatest need was in sepsis care.
Muthukumar realized the potential for this kind of product after speaking with military doctors. A colonel described the challenge of being at an Army camp in Afghanistan and needing to know whether a patient has sepsis—and can still be saved—before deciding to airlift him or her to Germany at a cost of $30,000. “That defined the value of detecting sepsis in the field,” Muthukumar says.
Tanak initially developed a sensor to measure parathyroid hormone levels, which could help surgeons decide more precisely what tissue should be removed during surgeries. Then she applied that experience toward developing the sepsis biosensor after spending months learning which inflammatory biomarkers were most helpful in treating sepsis.
Doctors can already test these biomarkers with standard lab work, but that usually takes at least a few hours (compared with five minutes for Tanak’s sensor). Such lab work also may not be an option for smaller hospitals with fewer available resources. There are also devices to measure the type and severity of the underlying infection, as well as look at cellular changes, during sepsis. But Prasad says none of the available tools do what they hope DETecT Sepsis might someday do—assist doctors in tailoring their treatments of sepsis patients with information the sensor provides.
Tanak’s work earned her the first-tier Baxter Young Investigator Award, an honor granted by the health-care manufacturing company Baxter to just six graduate students and postdoctoral fellows each year for innovative, potentially life-saving research.
“As a PhD student, you try to delve into the challenges that have not been solved, those complicated problems especially within the health-care industry, and if you are given an opportunity to work hands-on with one which can directly affect or change a patient’s life, that is something always to look forward to,” Tanak says.
Her grandmother survived another month before a second cardiac arrest ultimately caused her death, but Tanak still wonders if she might have lived longer had she gotten the care she needed faster. She could then only offer her grandmother comfort by holding her hand. Today, Tanak is putting her hands to work, hoping to one day prevent others from losing their loved ones too soon.