Ankit Kumar hesitated at the door of his professor’s office at Texas A&M University in College Station, Texas, wondering if the idea he was about to share was a breakthrough — or a bust. 

Kumar reported that he may have just discovered an unlikely clue to a biomechanical engineering problem that had frustrated his professor for years. With cautious optimism, Kumar described seeing an accordionist performing on the street outside.

His professor, Abhishek Jain, PhD, was initially puzzled, but he quickly got it. The inner workings of the relatively rare instrument could help them finally reproduce the waveforms of blood flow from the human heart. They went to work and developed a device they believe can assist research ranging from clinical trials to space medicine.

“It was brilliant,” Jain said of Kumar’s idea. “We knew we had stumbled upon something that has immense value.”

The heart’s blood flow waveforms are incredibly complex, with multiple frequencies and magnitudes per second. Changes in the wave patterns can affect endothelial cells, posing infectious, kidney, and cardiovascular disease risks. Researchers attempting to study the waveforms outside the body have struggled to replicate them using microphysiological systems (MPS). MPS have been around since the early 2000s, leading to the first organ-on-a-chip in 2010. Scientists use syringe or compressed air pumps to move fluid through MPS chips, but existing pumps have limitations.

“None of these technologies can truly mimic the complexity, the temporal speed, or the temporal resolution of blood flow,” said Jain, an associate professor of biomedical engineering at Texas A&M.

Why the Accordion?

Jain and Kumar both grew up in India, where accordion-like instruments called harmoniums are popular. Musicians use one hand to compress and relax air pockets called bellows and the other hand to stretch or compress the strings, resulting in musical harmonies.

The researchers hypothesized that applying those physical principles to a pump could produce fluid motion instead of music — with enough precision to replicate the heart’s blood flow waveforms.

From there they developed a device called the Hemadyne, which was described in a recent Nature Communications study. The device is the culmination of Kumar’s moment of inspiration and several years of experimenting.

The Hemadyne can replicate any blood flow waveform recorded from patients in clinical settings, allowing researchers to observe patterns over time. When connected to a living human vessel chip containing normal endothelial cells, the Hemadyne kept the chip alive and functional for 60 days.

The device can also produce transient diastolic backflow (also called diastolic blood flow reversal), brief reductions in fluid velocity to a negative value. The flow reversals are more common in blood vessels that have stiffened with age, and may lead to stroke. To replicate the reversals, the researchers programmed a proportional-integral-derivative (PID) controller to monitor flow inside the vessel chip and make adjustments as needed.

“When they get this negative flow, they did see real biological implications. It changed how the cell junction proteins behaved,” said David Eddington, PhD, a professor of bioengineering at the University of Illinois at Chicago who was not involved in the research. “This is the first paper, but if they show over and over again, ‘yes, you need this funky waveform to get a more in vivo-like readout,’ then people will start to believe it.”

The study shows Hemadyne-generated flow alongside the in vivo waveforms it reproduced during a 3-second period. Eddington, who has created devices that replicate blood pressure waveforms, is curious to see what the flow looked like after 10 or 20 hours. In response, Jain said, the PID controller that monitored flow throughout the experiment recorded no deviations from the prescribed value, suggesting “the flow characteristics were consistent with the short-term analysis.”

Accordion Meets Biomechanical Engineering

After Kumar’s lightbulb moment that day in 2020, the researchers dived into the idea. They revisited the street performer and watched online videos of accordion and harmonium players. In the university library, they discovered 1800-year-old papers on the original design of the accordion, which today is commonly played in polka, folk, zydeco, and other genres.

“Some of that literature was written in Latin or European language that we translated to really understand the physics of how the accordion works,” Jain said.

They purchased a one-ounce accordion-style glue dispenser, which is “essentially a bellow,” or plunger, Jain said. “When we got the bellow, we still needed to connect it to many different parts.”

For instance, the device needed a mechanism to turn air pressure into fluid flow, and software to control fluid movement per unit time, so that the bellow would compress and relax. Kumar used a custom algorithm to convert a patient’s blood flow waveform measurements into geometric code (G-code), a language used by three-dimensional (3D) printers, essentially creating instructions for the device to replicate specific waveforms.

The researchers then wrote code that would send the instructions to the Hemadyne motor, automating control of fluid flow through an attached vessel chip.

“They use geometric code, as if you were 3D-printing something, to drive the plunger. That is very cool. I’ve never seen anything like that,” said Anne Staples, PhD, an associate professor of mechanical engineering at Virginia Tech in Blacksburg who was not involved in the research.

In a comparison, the stability of the Hemadyne-generated flow was better than syringe and peristaltic pumps, but close to that of the Elveflow system, a piezoelectric-enabled pneumatic pump requiring an external air supply. The Hemadyne reproduced complex fluid perfusion for MPS chips faster than the three existing pumps.

The Hemadyne plunger needs to refill with air once or twice per day, Jain said. A built-in valve automatically disconnects the vessel chip, while simultaneously reconnecting the accordion bottle to filtered air from a small pressurized reservoir.

Next Steps and Space Flights

Eddington said the Hemadyne’s compact size may be an improvement over vacuum pumps fueled by separate compressed gas cylinders, which most labs have.

“Nothing needs to be connected to their pump. It’s more like a syringe pump, where you can just kind of put it wherever,” Eddington said.

That mobility could make the Hemadyne useful for remote on-site analysis. NASA is interested in using durable MPS systems instead of sending animals into space to study the effects of microgravity and space radiation on astronauts’ vascular health, Jain said.

The researchers have filed a patent and hope to commercialize the equipment, which Jain said could also aid in clinical trials. The Hemadyne could support “vascular avatars” — patient-specific vessel chips— enabling clinicians to see how different drugs affect blood flow.

Thinking back to that day in his office, when he and Kumar had their first inklings that an accordion-like pump could work, Jain is still a little awed. But he believes their lifelong connection to the instrument — Jain still has a harmonium at home — probably had something to do with it.

“I think it was somewhere in our subconscious,” Jain said. “You sometimes do not realize how simple things can become part of your inspiration.”

Jain and Eddington reported having no disclosures. Staples reported being a co-inventor on a pending US patent application related to pulse-driven microfluidic pump technology.

Sarah Amandolare is a freelance science and health journalist based in New York City who covers medicine, health technology, aging, and clinical trends.