LA JOLLA, CA—A groundbreaking microchip developed by scientists at Scripps Research is set to transform the landscape of vaccine development by providing rapid insights into how antibodies interact with viruses, utilizing just a drop of blood. This innovative technology promises to expedite the process of vaccine creation and enhance antibody discovery.
“This lets us take a quick snapshot of antibodies as they are evolving after a vaccine or pathogen exposure,” stated Andrew Ward, professor in the Department of Integrative Structural and Computational Biology at Scripps Research and senior author of the new paper published in Nature Biomedical Engineering on June 3, 2025. “We’ve never been able to do that on this timescale or with such tiny amounts of blood before.”
Understanding Antibody-Virus Interactions
When an individual is exposed to a virus or receives a vaccine, their immune system generates antibodies to combat the foreign entity. Identifying which antibodies effectively neutralize the virus is crucial for scientists aiming to optimize vaccines, as they strive to design vaccines that trigger robust immune responses.
“If we know which particular antibodies are leading to the most protective response against a virus, then we can go and engineer new vaccines that elicit those antibodies,” explained Leigh Sewall, a graduate student at Scripps Research and first author of the study.
From EMPEM to mEM: A Technological Leap
In 2018, Ward’s lab introduced electron microscopy-based polyclonal epitope mapping (EMPEM), a technique that allowed visualization of antibody-virus interactions in blood samples. Although pioneering, EMPEM had limitations, including a week-long process and the need for substantial blood samples.
“During the COVID-19 pandemic, we began really wanting a way to do this faster,” noted Alba Torrents de la Peña, a staff scientist at Scripps Research who co-led the work. “We decided to design something from scratch.”
The new system, microfluidic EM-based polyclonal epitope mapping (mEM), requires only four microliters of blood—about one hundred times less than EMPEM. Blood is introduced into a tiny, reusable chip where viral proteins adhere to a specialized surface. As blood flows through the chip, antibodies bind to the proteins. The proteins and attached antibodies are then gently released and prepared for imaging using standard electron microscopy. The entire process is completed in approximately 90 minutes.
Proving the Power of mEM
To evaluate mEM’s efficacy, researchers mapped antibodies in humans and mice exposed to viruses such as influenza, SARS-CoV-2, and HIV. The technique not only accelerated the mapping of antibody-virus interactions but also demonstrated greater sensitivity than EMPEM, identifying new antibody binding sites on influenza and coronavirus proteins.
“That was something that wouldn’t have been possible in the past, because of the amount of blood needed for EMPEM,” said Sewall. “So to be able to look at an individual over time was really exciting.”
Future Prospects and Applications
The research team is now focused on automating and multiplexing the system, potentially allowing for the simultaneous processing of multiple samples. They envision mEM becoming a standard tool in vaccine development for a range of pathogens, from coronaviruses to malaria.
“This technology is useful in any situation where you have really limited sample volume, or need initial results quickly,” Torrents de la Peña remarked. “We hope this becomes accessible to more researchers as it is simplified and streamlined.”
In addition to Ward, Sewall, and Torrents de la Peña, the study’s authors include Rebeca de Paiva Froes Rocha, Grace Gibson, Michelle Louie, Sandhya Bangaru, Andy S. Tran, Gabriel Ozorowski, Blanca Chocarro Ruiz, Nathan Beutler, Thomas F. Rogers, Dennis R. Burton, and Andrew B. Ward of The Scripps Research Institute; Zhenfei Xie and Facundo D. Batista of the Ragon Institute of MGH, MIT and Harvard; and Subhasis Mohanty and Albert C. Shaw of Yale University School of Medicine.
This research was supported by funding from the National Institutes of Health (AI136621, AI089992, and AI144462) and the Bill and Melinda Gates Foundation (INV-002916).
About Scripps Research
Scripps Research is an independent, nonprofit biomedical institute recognized as one of the most influential in the world for its impact on innovation by Nature Index. The institute is committed to advancing human health through groundbreaking discoveries that address pressing medical challenges globally. Its drug discovery and development division, Calibr-Skaggs, collaborates with scientists across disciplines to expedite the delivery of new medicines to patients. Meanwhile, the Scripps Research Translational Institute leverages genomics, digital medicine, and cutting-edge informatics to enhance individual health and healthcare delivery. Scripps Research also educates the next generation of leading scientists at its Skaggs Graduate School, consistently ranked among the top 10 U.S. programs for chemistry and biological sciences. For more information, visit www.scripps.edu.
