Tiny devices for screening antibodies could speed the search for new medicines
Separating droplets that contain a cell which produces the desired antibody from those that don’t – one of the steps in a new, miniaturised method developed by EMBL scientists. Credit: EMBL/B. el Debs
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EMBL scientists have developed a novel technique for screening antibodies for a specific function – such as the ability to inhibit a drug target – with speed and at the single cell level. The study, published in July in PNAS, could pave the way to the direct screening of antibodies from human donors, thereby accelerating the development of new treatments for diseases.
Antibodies are becoming increasingly prominent human therapeutics. But they exist in such enormous diversity that screening them for therapeutic properties on a large scale using current methods is not possible.
Existing screens use hybridoma cells that are immortalised and allowed to multiply over many generations so that they produce detectable concentrations of antibodies in conventional test tubes. Less than 1/10,000th of the antibody repertoire of a mouse – a few thousand cells – can be screened in this relatively inefficient process.
Researchers led by Christoph Merten at EMBL Heidelberg developed a solution; a technique for screening antibody-producing cells at the single cell level. The method could allow up to 300 000 cells to be screened per day.
The scientists used a microfluidics device, a plastic chip barely bigger than a coin and consisting of a miniature maze of tiny channels, into which droplets containing single cells were injected. Each droplet was one millionth of the size of a conventional test tube, allowing detectable antibody concentrations to be obtained from individual cells. As they flowed through the channels, droplets were sorted according to whether contained antibodies that inhibited the enzyme ACE-1 – a drug target for high blood pressure.
“Now that we’ve proved our functional assay works with hybridoma cells, we are trialling it with antibody-producing cells taken directly from a mouse – an impossible task for conventional screening methods.” says Merten. “Because the number of cells we need in the assay is very low and because it can be performed at a single cell level, eventually it may be possible to screen antibody-releasing cells from human donors.”
People infected with HIV are one class of donors to which such a screen could be applied. “Two per cent of all HIV infected individuals are estimated to develop neutralising antibodies. You could take antibody-producing cells from these individuals and use our technique to try to find cells that neutralise HIV.” says lead author Bachir El Debs.
The work was done in collaboration with Irina Balyasnikova from the University of Chicago and Andrew Griffiths from the University of Strasbourg.
The video accompanying this story is available on the EMBL YouTube Channel.