The difficulty in spotting minute amounts of disease circulating in the bloodstream has proven a stumbling block in the detection and treatment of cancers that advance stealthily with few symptoms. With a novel electrochemical biosensing device that identifies the tiniest signals these biomarkers emit, a pair of NJIT inventors are hoping to bridge this gap.
Their work in disease detection is an illustration of the power of electrical sensing β and the growing role of engineers β in medical research.
βIdeally, there would be a simple, inexpensive test β performed at a regular patient visit in the absence of specific symptoms β to screen for some of the more silent, deadly cancers,β says Bharath Babu Nunna, a recent Ph.D. graduate who worked with Eon Soo Lee, an assistant professor of mechanical engineering, to develop a nanotechnology-enhanced biochip to detect cancers,Β malariaΒ and viral diseases such as pneumonia early in their progression with a pin prick blood test.
Their device includes a microfluidic channel through which a tiny amount of drawn blood flowsΒ pastΒ a sensing platform coated with biological agents that bind withΒ targetedΒ biomarkers of diseaseΒ in body fluids such as blood, tears and urineΒ β thereby triggering an electrical nanocircuit that signals their presence.
One of the deviceβs core innovations is the ability to separate blood plasma from whole blood in its microfluidic channels. Blood plasma carries the disease biomarkers and it is thereforeΒ necessary to separate it toΒ enhance the βsignal to noise ratioβΒ in order to achieve a highly accurate test.Β The standalone deviceΒ analyzes aΒ bloodΒ sampleΒ within two minutesΒ with no need for external equipment.
βOur approach detects targeted disease biomolecules at the femto scaleΒ concentration,Β which is smaller than nano and even pico scale, and is akin to searching for a planet in a galaxy cluster. Current sensing technology is limited to concentrations a thousand times larger. Using a nanoscale platform allows us to identify these lower levels of disease,β Nunna says, adding, βAnd by separating the plasma from the blood, we are able to concentrate the disease biomarkers.β
Nunna is now a postdoctoral researchΒ fellow at Harvard Medical School, where he is expanding his expertise in microfluidic platforms, using them in organ-on-the-chip research conducted with Su Ryon Shin, a principal investigator and instructor in the medical schoolβs Department of Medicine who develops 3D-bioprintedΒ organoids β artificial organs composed of cultured cells within structured hydrogels β for medical experimentation.
βIβm primarily responsible for developing the microfluidic devicesΒ thatΒ will automate theΒ process of bioprinting 3D organs that willΒ be incorporated on a chip for a number of purposes. Iβm tasked, for example, with developing an automated platform for long-term drug efficacy and toxicity analysis to track liver cancer and cardiac biomarkers. Iβll be integrating the microfluidic biosensor with the liver cancer- and heart-on-a-chip model for continuous monitoring,β he says.
By measuring the biomarker concentrations secreted from drug-injected 3D-bioprinted organs, we can study drug effects on several organs without harming a live patient. Creating artificial organs allows us to experiment freely.β
Down the road, he adds, the work at Harvard could potentially be applied in regenerative medicine. βThe goal is to developΒ fully functional 3D-bioprintedΒ organoids and clinically relevant 3D tissues to address the issue of donor shortages in transplantation.β
Nunna says his research at Harvard Medical School will expand his knowledge of programmable microfluidics andΒ preciseΒ electrochemical sensing techniques, which will in turn help him advance his biochip technology.Β The goal is a simple, standard assay for cancer diagnosis that avoids conventional, complex diagnostic steps.
Lee and NunnaΒ have been workingΒ with oncologists at Weill Cornell Medicine and Hackensack Medical Center to identify clinical applications. As currently designed, the device would provide both qualitative and quantitative results of cancer antigens in blood samples, providing information on the presence and the severity of the cancer. Their next step, he says, will be to expand the platform to detect multiple diseases using a single blood sample obtained with a pin prick.
βAlthough healthcare technology is considered to be a fast-evolving technology, there are still many unmet needs that need to be addressed. Diagnosing potentially deadly diseases at the early stages is the key to saving lives and improving patient treatment outcomes,β he says, adding, βThere is a huge need for healthcare technology, including a universal diagnostic platform that can provide instant results at the physician’s office and other point-of-care settings.β
Nunna is the co-founder and chief research scientist for Abonics, Inc., a startup formed by Lee to commercialize their device. He is named as a co-inventor with Lee on three published biochip patents and six additional patents that are now under review by the U.S. Patent and Trademark Office. Their technology has won financial backing from the National Science Foundation I-Corps program and the New Jersey Health Foundation (NJHF), a not-for-profit corporation that supports topΒ biomedical research and health-related education programs in New Jersey.
βAs we know, early detection can improve treatment outcomes for patients significantly,β explained George F. Heinrich, M.D., vice chair and CEO of NJHF, in announcing the award.Β βCurrently, doctors rely on diagnostic devices requiring a minimum of four hours of sample preparation through centralized diagnostic centers rather than their local offices.β
In 2017, Nunna received the βBest Design in Healthcare Innovations and Point-of-Care Innovations Awardβ at the Healthcare Innovation and Point-of-Care Technologies conference from the Engineering in Medicine and Biology Society, held at the National Institute of Health headquarters in Bethesda, MD.Β That same year, the technology received the national innovation award at the TechConnect World Innovation Conference and Expo, an annual gathering of technology transfer offices, companies, and investment firms who meet to identify promising technologies from across the globe.
βI come from an engineering background with experience in developing large machinery for the company, Caterpillar. The connection to my present work is particle transportation in fluid dynamics β identifying the unique sensing signals that particular particles generate in a dynamic fluid environment,β he notes. βIt has been very exciting to work with Eon Soo Lee, who is one of the leaders in the field of microfluidic biosensing. He introduced me to a fascinating new career that took me from the production plant to the cleanroom environment at Brookhaven National Laboratory. Importantly, he gave me the freedom to test out novel ideas.β
Learn more: Minute levels of disease detected with nanotechnology-enhanced biochip
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