Researchers advance ‘placenta-on-a-chip’

…with sensing, imaging technology.

A research poster dated Dec. 9, 2015, hangs just outside Nicole Hashemi’s Iowa State University laboratory. It introduces a major project for Hashemi and her research group. And it’s evidence that scientific persistence sometimes equals scientific advancement.

Hashemi, an associate professor of mechanical engineering, and her students have been working all these years to develop a “placenta-on-a-chip.” In this case that’s a thin, rectangular, clear, polymer block with two tiny microchannels – just millionths of a meter wide and high – and a porous membrane in between.

One channel represents maternal blood flow. The other represents fetal blood flow. And the membrane between represents the placental barrier, especially when it’s lined with growing endothelial or barrier-forming cells.

By pumping fluids through the model, researchers can test how substances such as medicines and nutrients cross the placental barrier from mother to fetus and vice versa.

That’s the basic concept introduced on that hallway poster. Now, with Hashemi recently winning a National Science Foundation (NSF) Mid-Career Advancement grant for the project, the next poster could describe all kinds of technological additions.

The three-year, $350,000 grant is funded by the NSF’s Partnerships for Innovation program and its Established Program to Stimulate Competitive Research. The mid-career grants are designed to give scientists and engineers the opportunity “to substantively enhance and advance their research program and career trajectory,” according to the NSF.

Advancing their original idea

The new grant will help Hashemi’s group explore developments of the placenta model in three major areas: sensing, personalized medicine and commercialization.

“We’re still working on our ‘placenta-on-a-chip’ project,” Hashemi said. “With this grant we’re trying to design sensing platforms that can be integrated to the model.”

One sensing platform would use ions – atoms and molecules with different numbers of electrons, creating positive or negative charges – to sense how cells react to mechanical forces or chemical stressors.

The other would use “hyperspectral” imaging technology, which records a broad spectrum of light, to sense how cells respond to chemical stressors. Hashemi is incorporating the technology in a collaboration with Juan Santiago, the Charles Lee Powell Foundation Professor and vice chair of mechanical engineering at Stanford University in California. The collaboration grew out of Hashemi’s Faculty Professional Development Assignment to Stanford for the 2021-’22 academic year.

Hashemi is also hoping the model can eventually use a patient’s cells to advance personalized medicine. Such models could lead to “higher accuracy in testing for the transport rate of specific compounds and setting safe exposure levels,” according to a project summary.

In addition, the NSF’s mid-career grants ask researchers to explore commercializing their new technologies with a startup or industry partnerships. Hashemi – who has an early stage startup called NISTRON that manufacturers carbon microstructures for biotechnology uses – said her graduate students will explore commercialization by joining entrepreneurship programs around campus.

Hashemi’s research group has already demonstrated several applications of the technology. One published study tracked caffeine transport across the placental barrier. A research partnership with the University of Nebraska College of Medicine also plans to measure nanomedicines moving through the placental barrier.

“There are a lot of ideas about how to use this platform technology,” Hashemi said.

Building a better prototype

Back in 2015 when Hashemi and a former doctoral student, Rajeendra Pemathilaka, used their expertise in microfluidics to develop their initial placenta-on-a-chip, they weren’t sure about their model’s potential.

“It was a completely innovative project for our lab,” Hashemi said. “We didn’t know much about the function of the placenta when we started. We pushed this idea significantly when there weren’t a lot of resources. This award wouldn’t have been possible without the dedication and hard work of my graduate students.”

The project has earned Hashemi some recent scientific recognition, including as a cochair of the women’s health track at last month’s annual meeting of the Biomedical Engineering Society in Seattle and as an associate editor of “npj Women’s Health,” part of the Nature Portfolio of scientific journals. She’s also part of the leadership team for Iowa State’s Center for Multiphase Flow Research and Education.

Now, with the mid-career grant, Hashemi’s group has new resources to develop and test their latest ideas.

“The goal is to have a new prototype by the end of the grant’s third year,” Hashemi said. “But we’ll be spending a lot of time on the basic science to develop these two new sensing systems. We hope to ultimately contribute to solving the critical challenges related to human health, in this case for both women and their children.”