Cross-faculty lab collaborative team to develop molecular oxygen-sensing technology for fetal health monitoring during labor
By Benjamin Boettner
(BOSTON) — Awarded a contract for up to $12M from the Advanced Research Projects Agency for Health (ARPA-H), researchers at the Wyss Institute at Harvard University, across several of its Technology Platforms and faculty labs, have joined forces to address a critical unmet need in maternal and women’s health: clinicians’ inadequate ability to monitor oxygen support of fetuses during labor (intrapartum). This is critical because insufficient oxygen support of unborn babies (fetal hypoxia) significantly increases the risks for infant and maternal health.
ARPA-H, whose mission it is “to solve the most significant health challenges facing Americans today – the ones that are deemed too big, too complex, and too high-risk for traditional funding or industry,” released a call for its newly formed Making Obstetrics Care Smart (MOCS) program in 2025 to solve the problem of inadequate intrapartum oxygen monitoring of fetuses. In fact, the United States has the highest rates of maternal and infant morbidity and mortality among wealthy nations, despite spending more per capita on maternal care. “A significant driver of this crisis is the continued reliance on a 50-year-old “fetal electronic monitoring” technology that lacks the precision to accurately assess fetal oxygenation during labor. As a result, clinicians are often forced to make critical decisions with unreliable information, leading to unnecessary cesarean deliveries, missed fetal distress, and preventable birth injuries with sometimes lifelong consequences,” said Wyss Senior Scientist Peter Nguyen, Ph.D., who together with Wyss Scientist Sandy Elmehrath, Ph.D. conceptualized the FEMOx project. FEMOx stands for Fetal Extracellular Vesicle Monitoring of Oxygenation. “Technologies developed across multiple Wyss faculty labs uniquely position the Institute to make rapid detection of fetal oxygen deprivation during labor a clinical reality.”
Clinicians are often forced to make critical decisions with unreliable information, leading to unnecessary cesarean deliveries, missed fetal distress, and preventable birth injuries with sometimes lifelong consequences[…] Technologies developed across multiple Wyss faculty labs uniquely position the Institute to make rapid detection of fetal oxygen deprivation during labor a clinical reality.
Leveraging and integrating multiple of the Wyss Institute’s technological innovations and advanced analytical capabilities, the Wyss Institute’s FEMOx project will develop a molecular diagnostic test that is able to quantify small stable RNA species, known as microRNAs (miRNAs), whose expression levels change with the degree of fetal oxygen deprivation. To non-invasively access and measure those miRNAs, as well as validate clinically practical diagnostic assays, four faculty labs, including those of Wyss Faculty members James Collins, Ph.D., the project’s Principal Investigator (PI), as well as David Walt, Ph.D., Donald Ingber, M.D., Ph.D., and David Mooney, Ph.D. (the project’s Co-PIs), join forces in FEMOx to each bring unique expertise and technological capabilities to the common cause.
In the FEMOx project, we will capitalize on several recently developed Wyss technologies that enable us to isolate and concentrate tiny so-called extracellular vesicles (EVs) from maternal blood samples[…] In fact, about 10 to 15% of EVs in maternal blood are derived from fetal tissues and the placenta, which provide a window into feto-maternal communication, including the flow of oxygen.
“In the FEMOx project, we will capitalize on several recently developed Wyss technologies that enable us to isolate and concentrate tiny so-called extracellular vesicles (EVs) from maternal blood samples and determine hypoxia-associated molecular signatures in them,” said Elmehrath, adding that “EVs are released by virtually all cells in the body and found in biofluids such as blood, and they carry cargo, including miRNA molecules, from their cells of origin. In fact, about 10 to 15% of EVs in maternal blood are derived from fetal tissues and the placenta, which provide a window into feto-maternal communication, including the flow of oxygen.”
In short, the team’s strategy starts with technology developed in Walt’s and Ingber’s labs, the FEMOx researchers can load a sample of maternal whole blood into a sophisticated multi-layer microfluidic chip to first isolate its cell-free plasma component from which placental EVs are isolated, using state-of-the-art high-affinity antibody arrays that are integrated into the chip environment. On-chip, they will then apply a process of “ambient nucleic acid molecular sensing” that has been advanced in the Collins lab and employs a cell-free sensor technology, called INSPECTR, to translate the presence of hypoxia-associated miRNAs into bioluminescent signals. “We envision that those signals can be easily and accurately read out in a point-of-care portable detector and the resulting pattern analyzed with the help of a cloud-based machine-learning algorithm developed by the Ingber group. This can provide clinically relevant values for stratifying the risk of babies during labor,” explained Elmehrath.
In moving their technology toward patients, the FEMOx team will benefit from the product commercialization experience of Mooney, who has successfully translated biomaterial-based therapies into clinical settings. FEMOx’s clinical team members Andrea Edlow, M.D., M. Sc., Vice Chair of obstetrics and gynecology (OBGYN) Research at Massachusetts General Hospital, and Thomas McElrath, M.D., Ph.D., Professor of Reproductive Biology at Boston’s Brigham and Women’s Hospital, will regularly provide vital end-user feedback to the rest of the team, which will be coordinated by Wyss Assistant Director, Transformational Awards, Shana Ashar as a liaison between the clinical and technology development teams. Ashar will work with Senior Business Development Manager Alex Li, M.B.A., a member of the Wyss Institute’s Business Development Team, and Lisa Smeester, Ph.D., an experienced Program Manager at the Wyss Institute, to keep the technology and commercial development of FEMOx aligned with the experience of doctors and nurses in maternity wards, while building and prototyping a diagnostic device. In addition, “to achieve our ambitious goal of bringing better care for infants and mothers on an accelerated timeline, we will also be working closely with other stakeholders like regulatory professionals, industry partners, and payers,” said Li.
Finally, the team will follow the broader success-driven guidelines the ARPA-H MOCS program has for its awardees. “Beyond vigorously pursuing our efforts in the Wyss’ FEMOx project, we also aim to work together with other teams supported by the MOCS program to address this unmet obstetric challenge in an even more concerted effort,” said Smeester.
As a team, we are all extremely grateful to be supported by the ARPA-H MOCS program and for being able to bring our combined capabilities to bear on a problem in Women’s and Child Health that ultimately concerns us all. The talent and technology brought together by Peter and Sandy under this award are poised to synergize in wonderful ways.
“As a team, we are all extremely grateful to be supported by the ARPA-H MOCS program and for being able to bring our combined capabilities to bear on a problem in Women’s and Child Health that ultimately concerns us all,” said Collins. “The talent and technology brought together by Peter and Sandy under this award are poised to synergize in wonderful ways in the FEMOx project.” In addition to being a Wyss Founding Core Faculty member, Collins is also the Termeer Professor of Medical Engineering & Science and a Professor in the Department of Biological Engineering at MIT.
“This contract by the ARPA-H MOCS program awarded to the Wyss team demonstrates how faculty and research teams across many of the Institute’s Technology Platforms unite and respond to medical problems that urgently need to be solved, taking advantage of the Institute’s world-leading expertise and cutting-edge technological portfolio, and working seamlessly with clinical collaborators and the Wyss’ unique business development infrastructure,” said Wyss Institute Founding Director Ingber.
Wyss Core Faculty member David Walt is also the Hansjörg Wyss Professor of Biologically Inspired Engineering at Harvard Medical School, Professor of Pathology at Brigham and Women’s Hospital, and Institute Professor at the Howard Hughes Medical Institute; Wyss Founding Director Donald Ingber is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children’s Hospital, and the Hansjörg Wyss Professor of Biologically Inspired Engineering at Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS); and Wyss Founding Core Faculty member David Mooney is also the Robert P. Pinkas Professor of Bioengineering at SEAS.