Novel microchip system mEM speeds up antibody analysis
A new microchip can help researchers map antibody interactions in minutes, not days.
Scripps Research (CA, USA) scientists have developed an innovative microchip technology that analyzes how antibodies interact with viruses using minimal blood samples. This technological breakthrough, called microfluidic EM-based polyclonal epitope mapping (mEM), represents a significant advancement in immunological research capabilities and could help accelerate vaccine development and antibody discovery.
During viral infection or vaccination, the immune system produces antibodies with varying affinities, specificities and effector functions against the pathogen. First author of the paper Leigh Sewall explains: “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.”
Back in 2018, the researchers developed a technique called EMPEM (electron microscopy-based polyclonal epitope mapping) that allowed direct observation of antibody-virus binding interactions using patient blood samples. Though this technique represented a major scientific advancement, it suffered from practical constraints, specifically the need for large blood quantities and a time-consuming analytical process that stretched across an entire week.
To overcome these challenges, the team developed a new system: mEM. This innovative approach dramatically reduces sample requirements, needing just 4 microliters of blood, which is about 1% of what the previous method demanded.
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The technique employs a small, reusable chip containing viral proteins attached to a specialized surface. When blood flows through this microfluidic system, antibodies naturally seek out and attach to their viral targets. After binding occurs, researchers gently remove these antibody-virus complexes from the chip and prepare them for detailed examination under an electron microscope. This streamlined process takes only 90 minutes to complete.
The research team evaluated mEM’s capabilities by analyzing antibody responses in both human and mouse subjects who had developed immunity through either vaccination or natural infection. Their experiments included several major pathogens, including influenza, SARS-CoV-2 and HIV.
The results demonstrated that mEM not only processed samples significantly faster than the previous method but also showed enhanced sensitivity. This improved detection capability revealed previously undiscovered antibody binding locations on both influenza and coronavirus protein structures that had escaped detection using the older EMPEM technique.
To understand how immune responses develop over time, the researchers conducted longitudinal studies in mice following vaccination. The minimal blood requirements of mEM allowed them to collect small samples from the same mouse at multiple intervals, enabling them to track the evolution of antibody responses within individual subjects throughout the immune development process.
“That was something that wouldn’t have been possible in the past, because of the amount of blood needed for EMPEM,” says Sewall. “So to be able to look at an individual over time was really exciting.”
The scientific team is currently working to enhance their mEM system through automation and multiplexing capabilities. These improvements aim to enable simultaneous processing of numerous samples, significantly increasing throughput. Their long-term vision positions mEM as a standard research tool that could transform vaccine development across a wide spectrum of diseases.
The technology offers particular advantages in scenarios with limited biological material or when rapid preliminary results are essential and the team hopes to make the system more accessible to the broader scientific community by simplifying its operation and streamlining its processes, potentially democratizing access to this powerful analytical approach.
