No longer just science fiction, fully integrated molecular diagnostic devices are being developed to take raw sample loaded at the intake port, process it through the device, and deliver an answer at the other end. A number of companies have made significant progress toward this goal, and it seems, based on presentations at Knowledge Foundation’s recent sample-prep meeting, that hand-held devices will be a reality in the very near future, allowing scientists to take a real world sample, process it, and produce an accurate identification in real time.
A droplet-based digital microfluidics technology is at the heart of the solution from Advanced Liquid Logic. Michael Pollack, Ph.D., and Vamsee Pamula, Ph.D., are co-founders of the company that, to date, has commercialized two products based on this core technology, one for genomic sample preparation and a second for newborn screening.
The microfluidic device enables precise and programmable manipulation of droplets using an array of electrodes that obviate the need for traditional pumps, valves, and fixed channels, according to Dr. Pollack. The electrode array is fabricated on a printed circuit board with 1 mm2 electrodes. Droplets are processed within an oil-filled chamber formed by an injection-molded plastic top piece. Sample and reagents are loaded via dedicated ports.
Volumes ranging from less than a microliter to hundreds of microliters can be processed with individual droplets being joined together, split apart, moved to locations adjacent to a magnet, or to a thermal region for PCR, etc. All movements through the device are defined by SpotLogic software scripts.
“A couple of years ago we identified an opportunity to apply our technology to the problem of library preparation for next generation sequencing (NGS),” shared Dr. Pollack, CTO. “The flexibility of the technology was a key benefit because of the diversity of workflows that can be enabled and the ability to adapt as workflows evolve. We can essentially ‘reprogram’ the device to perform a wide range of protocols. Automation to improve reliability and consistency, and miniaturization to reduce reagent consumption are additional benefits.”
The microfluidic device is a disposable cartridge about the size of a standard microtiter plate. The system is sold into the research market under the brand name Mondrian™ SP by NuGEN Technologies to perform fully automated NGS sample prep.
Advanced Liquid Logic has also commercialized the LSD-100, a newborn screening system for lysosomal storage disorders (LSD). This automated system enables processing of up to 40 dried blood spot extracts, along with controls and calibrators, for multiplex testing of an LSD panel.