NEW YORK (GenomeWeb) – For about two decades, widespread use of point-of-care molecular testing technologies has seemed to be just beyond the horizon, but microfluidics' manufacturing costs may have limited their uptake.
Researchers at the Fraunhofer Center for Manufacturing Innovation in Brookline, Massachusetts have now developed a low-cost method to construct continuous-flow real-time PCR devices, which could potentially push POC molecular testing further into the mainstream.
The method has the potential to use a high-volume manufacturing technique called roll-to-roll manufacturing, as well as hot embossing of thermoplastics using a rolling cylinder and a technique of layering and fusing chip elements in order to generate large sheets of microfluidics capable of 40-cycle, 20-minute PCR.
A proof-of-principle evaluation of the device, published this month in Biomedical Microdevices, demonstrated it was able to detect Chlamydia trachomatis and Escherichia coli 0157:H7 down to 10 copies per microliter with efficiencies between 90 and 100 percent.
Alexis Sauer-Budge, a senior research scientist at Fraunhofer, told GenomeWeb in an interview that a primary reason point-of-care molecular testing hasn't taken off is because it continues to be less expensive to test in clinical laboratories.
But relying on centralized labs also limits the services that can be provided to patients in some areas.
"Many of the locations for point-of-care testing are going to be in low-resource settings — whether that's low resources in still-developing countries or whether that's low resources in developed countries — where you don't have large centralized clinical laboratories," Sauer-Budge dais. "If you can do those tests at the doctor's office you can really improve healthcare."
Located on the campus of Boston University and with a staff of about 35, the Fraunhofer Center is part of a much larger non-profit network based in Munich. The US branch is a wholly-owned subsidiary of Fraunhofer Gesellschaft and was started about 20 years ago. Like all the various centers, it's mission is to work "in the space between academia and industry" to help bridge the gap between research and product development.
"The Fraunhofer society works across all areas of science and technology and each institute has its own individual focus," explained Sauer-Budge. There are over 60 different centers and institutes around the world, many of which are in Germany, and there are seven others in the US besides the Brookline location.
"We're very focused on implementation of technology, bringing it to the next level so that it can then be taken over by industry, [and] we work with industry in a number of different ways," Sauer-Budge said. These can take the form of licensing opportunities or spinout companies, for example, including potential spinouts that sell services such as custom microfluidic chip manufacturing.
Sauer-Budge said the recent publication describes a continuous-flow qPCR chip in a prototype form for potential roll-to-roll manufacture. The heat-embossing of the thermoplastic for the published version was done using flat surfaces, but the researchers are now moving toward a rolling drum method.
The chip is also demonstrated on a system that includes heaters and optics, but a future publication may describe a more complex chip with heaters and sensors printed into separate layers and laminated together with the qPCR element. These layers can be created in thin sheets which are stored in rolls, much like textiles or plastic wrap. These can be reeled out such that the layers are sandwiched one on top of the other. Once laminated, large numbers of chips can then be cut from the resulting sheets.
The current work is also part of a larger-scale microfluidics development project, called ML2, aimed at developing a cost-efficient production system for next-generation devices that combine microfluidics, microelectronics, and microoptics.
The chip itself uses continuous flow qPCR, with two heaters placed below and the sample flowing across temperature zones. "In general, the longest part of the PCR is heating up the thermal mass of the sample, so as a scientist trying to think about how can we do this better, I liked the concept of moving the fluid between different heat zones as opposed to having a static, stationary well," Sauer-Budge said.
And while the overall system was built with off-the-shelf components costing around $9,000, incorporating miniaturized pumps, heaters, and lower-cost optics is expected to bring the manufacturing cost down to below $2,000 for larger-scale production and also make the device truly portable.
Three firms have launched molecular point-of-care platforms recently, but the lowest price-tag device so far is in the $3,000 range.
Fraunhofer is pursuing IP options at the moment. The ML2 consortium partners have "first dibs" on the method, Sauer-Budge said, and "there are always ongoing business development discussions happening."