Microchip Technology Revolutionizes Antibody Mapping for Vaccine Development

A groundbreaking advancement in vaccine development has emerged from Scripps Research, where scientists have developed an innovative microchip capable of mapping antibodies from just a drop of blood. This technology significantly accelerates the understanding of how antibodies interact with pathogens, offering researchers insights that could streamline vaccine design and improve global health preparedness.

The microchip, which was detailed in a study published in the *Nature Biomedical Engineering* on June 3, 2025, enables researchers to capture a rapid snapshot of antibody evolution post-vaccination or pathogen exposure. “This lets us take a quick snapshot of antibodies as they are evolving after a vaccine or pathogen exposure,” explained Dr. Andrew Ward, Professor in the Department of Integrative Structural and Computational Biology at Scripps Research and senior author of the study. Prior to this, traditional methods required larger blood samples and extended processing times, often up to a week.

Historically, researchers have relied on electron microscopy-based techniques for antibody mapping, such as the electron microscopy-based polyclonal epitope mapping (EMPEM) developed by Ward’s lab in 2018. However, EMPEM had limitations including lengthy processing times and sample size requirements. The advent of microfluidic EM-based polyclonal epitope mapping (mEM) represents a notable shift in methodology, allowing researchers to utilize only four microliters of blood—approximately one hundred times less than previously needed.

Alba Torrents de la Peña, a Scripps Research staff scientist involved in the project, emphasized the urgency for improved methods during the COVID-19 pandemic. “We began really wanting a way to do this faster,” she stated. The microchip operates by injecting a small blood sample into a chip where viral proteins are attached. The antibodies in the sample then bind to these proteins, allowing for detailed imaging and analysis using standard electron microscopy. Remarkably, the entire process now takes only about 90 minutes.

Initial tests showed that the mEM technique not only expedited antibody mapping but also improved sensitivity compared to EMPEM, revealing previously undetected antibody binding sites on viral proteins from pathogens such as influenza and SARS-CoV-2. The researchers successfully mapped antibodies from both human and mouse subjects, demonstrating the method’s versatility and potential applications in tracking antibody evolution over time.

Dr. Leigh Sewall, a graduate student and first author of the study, noted the significance of being able to monitor individual antibody responses over time. This capability could be transformative for vaccine development, allowing scientists to identify which antibodies yield the most effective protective 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,” Sewall added.

Looking ahead, the Scripps team aims to automate the mEM process, potentially enabling the simultaneous processing of multiple samples. This innovation is expected to make the technology accessible to a broader array of researchers, enhancing its utility in various contexts where limited sample volume is a constraint. “This technology is useful in any situation where you have really limited sample volume, or need initial results quickly,” Torrents de la Peña concluded.

The implications of this technological advancement extend beyond immediate vaccine development. As global health challenges evolve, the ability to rapidly map antibodies could play a vital role in responding to emerging infectious diseases, ultimately contributing to more efficient public health strategies and vaccine designs worldwide.

The study highlights an essential step in modern immunology and vaccine research, reflecting the critical need for innovation in response to global health crises. As the world continues to grapple with the repercussions of recent pandemics, tools like the mEM microchip will be crucial for accelerating our understanding of immune responses and improving vaccine efficacy against a variety of pathogens.

### References Sewall LM, de Paiva Froes Rocha R, Gibson G, et al. Microfluidics combined with electron microscopy for rapid and high-throughput mapping of antibody–viral glycoprotein complexes. *Nat Biomed Eng*. 2025. doi: 10.1038/s41551-025-01411-x.