IMAGE CAPTION: Cooper Thome, a PhD candidate in the Department of Chemical and Biological Engineering, uses a new "acoustic pipette," which could someday be used to deliver swift test results at the bedside with only a finger-prick of blood. (Credits: Patrick Campbell/CU Boulder.)
Go to the doctor to provide a blood sample and you're typically faced with a needle and syringe and hours or even days of waiting to get results back from a lab.
CU Boulder researchers hope to change that with a new handheld, sound-based diagnostic system able to deliver precise results in an hour with a mere finger prick of blood.
The team describes the system in a new paper published Oct. 16 in the journal Science Advances.
"We've developed a technology that is very user friendly, can be deployed in various settings and provides valuable diagnostic information in a short time frame," said senior author Wyatt Shields, assistant professor in the Department of Chemical and Biological Engineering at CU Boulder.
The findings come as scientists have been racing to democratize diagnostic testing, which can be hard for people in rural areas or developing countries to access and, in the case of blood tests, frightening for those averse to needles.
While existing rapid tests, known as lateral-flow assays, like COVID tests or pregnancy tests can provide a quick "yes" or "no" as to whether a specific biomarker or biomolecule in the blood or urine is present, they typically can't say how much, and they aren't sensitive enough to detect very small amounts.
Meanwhile, the gold standard for clinical blood tests, known as an enzyme-linked immunosorbent assay (ELISA), is highly sensitive and specialized enough to detect rare or scarce biomarkers but requires expensive equipment and complex techniques, and it can take hours or days for patients to receive results.
The authors acknowledge that skepticism exists in the biosensing field since the highly publicized downfall of Theranos Inc., which promised as far back as 2015 to detect hundreds of biomarkers with a drop of blood. Their invention works differently, they said, and unlike the now-defunct start-up, it is based on systematic experiments and peer-reviewed research.
Above, the acoustic pipette uses sound waves to test for biomarkers in blood. Below, Cooper Thome, left, and Wyatt Shields in the lab. (Credits: Patrick Campbell/CU Boulder.)
"While what they claimed to do isn't possible right now, a lot of researchers are hoping something similar will be possible one day," said first-author Cooper Thome, a PhD candidate in Shields lab. "This work could be a step toward that goal-but one that is backed by science that anybody can access."
Using sound waves in a new way
Shields and Thome set out to develop a tool that is simultaneously sensitive, highly portable and easy-to-use.
Their secret ingredients: tiny particles they call "functional negative acoustic contrast" particles (fNACPs) and a custom-built, hand-held instrument or "acoustic pipette" that delivers sound waves to the blood samples inside.
As part of his PhD work, Thome designed the fNACPs (essentially cell-sized rubber balls) to be customized with functional coatings so they recognize and capture a designated biomarker of interest, such as an infectious virus or a protein deemed a red flag for a brewing health problem. The particles also respond to the pressure from sound waves differently than blood cells. Thome designed the acoustic pipette to harness this unique response.
"We're basically using sound waves to manipulate particles to rapidly isolate them from a really small volume of fluid," said Thome, who specializes in the study of "acoustofluidics." "It's a whole new way of measuring blood biomarkers."
When a small amount of blood is mixed with the custom particles and placed inside the acoustic pipette, sound waves force the particles to the side of a chamber where they are trapped inside while the rest of the blood is flushed out.
The remaining biomarkers, attached to the particles, are then labeled with fluorescent tags and hit with lasers to determine the amount present.
All this happens in under 70 minutes inside a device that can fit in the palm of a hand.
Matching the gold standard clinical test
"In our paper, we demonstrate that this pipette and particle system can offer the same sensitivity and specificity as a gold-standard clinical test can but within an instrument which radically simplifies workflows," said Shields, noting that this time could likely be reduced more with future refinements. "It gives us the potential to perform blood diagnostics right at the patient's bedside."
This could be particularly useful for assessing not only whether a patient has an infectious disease but also what their viral load is and how fast it is growing, he said. The device could also potentially play a role in measuring antibodies to determine whether someone needed a booster shot or not, testing for allergies or detecting proteins associated with certain cancers.
The study is a proof of concept, and more research is necessary before the device could be commercialized. The authors have applied for patents and are now exploring ways to make the technology work for multiple patients at once (which would be useful in mobile clinics in rural areas, for instance) or test for multiple biomarkers simultaneously.
"We think this has a lot of potential to address some of the longstanding challenges that have come from having to take a blood sample from a patient, haul it off to a lab and wait to get results back," said Shields.
