Infectious diseases are a serious worldwide health problem. Although a range of diagnostic assays exist, many of these are invasive and are difficult to perform. For example, enteric fever, which is an acute febrile illness caused by Salmonella enterica bacteria and which affects more than 11 million people each year, usually needs to be detected in bacteria cultures of bone marrow samples.

Detecting secreted antibodies directly from antibody-secreting cells (ASCs) that activate when exposed to a pathogen is a promising alternative technique. This is because ASCs are detectable in blood as early as three days after infection. A team of researchers led by Hakho Lee at Massachusetts General Hospital and Harvard Medical School has now developed a new magnetic capture and detection assay for sensing ASCs.

Significantly shorter assay time

Lee and colleagues’ technique involves first labelling the ASCs using zinc ferrite magnetic particles, which have high magnetic moments. Next, the researchers briefly cultured the captured ASCs inside a microfluidic chip to increase the concentration of antibodies. They then detected the secreted antibodies using a miniaturized nuclear magnetic resonance (NMR) system.

“Since the approach is completely based on magnetism, it significantly shortens the assay time to just five hours as compared to 48 hours for conventional assays, and improves sensitivity,” says Ki Soo Park of Konkuk University in the Republic of Korea. Indeed, the technique can detect antibodies secreted from as few as five hybridoma cells.

Towards clinical study

The researchers detected enteric fever antibodies as a model system in their experiments but say that the platform could easily be used to detect various other acute infections, such as tuberculosis, Zika and Middle East respiratory syndrome coronavirus. “Being able to do this will be especially important in areas of the world with limited laboratory capacity for testing blood cultures or performing nucleic acid amplification tests, like PCR,” Park tells nanotechweb.org.

The team, reporting its work in ACS Nano DOI: 10.1021/acsnano.7b06074, says that it will now be working on combining the magnetic capture and NMR detection modules in its device into a single system. “We will also be looking to perform a clinical study on a large cohort of patients to fully evaluate how analytically accurate the assay is so that we can define operation parameters, like detection threshold, bacterial culture time and so forth,” says Park.