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Broad Team Begins Testing Low-Cost Microfluidic Sample Prep Tech in Clinical Trial


NEW YORK (GenomeWeb) – Following years of development and technical validation work, a group of Broad Institute researchers has begun testing a novel low-cost microfluidics-based sample preparation system for next-generation sequencing as part of a clinical study examining methods to combat recurrent methicillin-resistant Staphylococcus aureus (MRSA) infections.

The trial, called Project Changing Lives by Eradicating Antibiotic Resistance, or CLEAR, was launched in 2010 to compare two strategies for reducing the risk of MRSA infection in carriers of the bacteria — standard-of-care hygiene education and a MRSA decolonization regimen involving nasal and oral antibiotics and anti-infective body washes.

In collaboration with Harvard School of Public Health researcher and Project CLEAR investigator Yonatan Grad and with the support of a one-year, $221,250 grant from the National Institutes of Health, the Broad team — led by Massachusetts Institute of Technology's Paul Blainey — aim to use their sample prep technology to facilitate the sequencing of S. aureus samples in the study.

This work represents a field trial of sorts for the sample prep system, which will be used to help sequence an estimated 1,000 bacterial isolates — far more than it has been used for during its initial development and validation, Blainey told GenomeWeb.

Should things go according to plan in Project CLEAR, Blainey and his colleagues hope to begin deploying the system more broadly, beginning with the labs of other Broad researchers and institute collaborators, he said. Blainey said he may look to commercialize the system in the future, but he declined to comment further.

Blainey's development of the sample prep system stemmed from earlier research examining microbial evolution at the single-cell level. He aimed to obtain an unbiased, genome-wide mutational assay with single-cell and single-generation resolution, but found the work prohibitively expensive, not because of the sequencing process but because of the cost and labor requirements for sample prep.

"Sample prep has sort of been the poor stepchild of the sequencing" field, he said, with the majority of research and development efforts focusing on the latter steps of the NGS pipeline, rather than on the initial ones.

"What's needed … are [sample prep] systems that are fully integrated … [meaning] you put biomass in and you get libraries out," he explained.

Looking to address this need, he and collaborators began work on an approach that combined microfluidics with a transposase-based tagmentation library preparation protocol, yielding a reusable self-contained chip the size of a microscope slide that could prepare sequencing libraries for multiple samples at once. All the steps of library construction can be carried out on the chip, which includes microfabricator pumps for mixing reagents, and spent solids can be washed away.

In early 2014, Blainey presented data on the system at the Advances in Genome Biology and Technology meeting. Since that time, he and his team have performed additional refinements and generated technical validation data, which are currently being prepared for publication.

Now through the Project CLEAR trial, the system is being applied in a real-world setting to create a large number of libraries using samples obtained by other groups, he told GenomeWeb. "It's scale-up and field testing," he said.

Blainey added that his ultimate goal is to bring the cost of sample prep in line with that of sequencing. "It costs $1.50 or $2 to generate the data for a really high-quality draft microbial genome — it's literally a cup of coffee," he said. "That basically sets our cost target for sample prep."