Polymerase Chain Reaction (PCR) has been the standard for detecting DNA mutations yet is limited in its ability to detect small amounts of mutated DNA present in human tissue samples. As a result, current cancer detection requires invasive procedures and biopsies, only possible late in the progression of the disease. The RainDance RainDropTM System, currently only used in research settings, promises to provide insights into cancer enabling improved diagnostics in the future. Digital PCR works by splitting a sample into thousands or millions of picodroplets and analyzing each partition individually.

Current PCR technologies require researchers to perform more experiments at greater costs in order to generate the data necessary to support their findings. Digital PCR offers new levels of sensitivity in DNA analysis to enhance understanding of cancer and advance diagnostics and therapy. RainDance needed help taking their revolutionary digital PCR technology to the next level and developing a system that was simple to use, reliable and economically viable. A DNA sample—a few drops of liquid solution extracted from a small tissue sample—had to be divided into 10 million droplets each measuring precisely 20 microns in diameter (1/4 the width of human hair) at a rate of 10,000 droplets/second. These droplets had to be read by very sensitive optics and real-time software was needed to determine whether each droplet is positive or negative. Finally, due to the extreme sensitivity demands, sample-to-sample contamination had to be eliminated.

RainDance Technologies came to us with a proof of principle experimental setup but needed help commercializing the technology. To make it a real, useful, functioning product, we leveraged a diverse team to apply deep knowledge of fluidics, software and hardware. With significant experience in the field of life science instrumentation, we identified attributes that would be critical to the success of the product: improved throughput, optimized automation or walk away time, streamlined engineering and overall usability. The team sought to think holistically by asking one question—“is there a better way to do this?” The end product is a simplified system with fewer moving parts, making it more reliable, lower cost and easy to use.

Our team has extensive experience designing benchtop instruments for use in life science research, including observation of researchers working in biochemistry labs. After mapping out the many intricate steps required by the system, our team set up an in-house lab to experiment and iterate. While the client had already validated the technology, our team had to determine ways of identifying and tracking samples through processing to ensure a true path to commercialization. The team considered various scenarios to determine the ideal architecture prior to developing system prototypes for testing. We worked closely with the client as well as Sony Corporation to develop the product from both the inside out and the outside in. Using a quality management system to define the role of each organization, we used online tools to achieve a truly global collaboration and develop an effective and promising diagnostics system.

When this project started, RainDance Technologies had a proven picodroplet platform that could be used for digital PCR applications but they required a method to transform the technology into a user-friendly device to be made commercially available to labs around the world. The team used novel technologies to integrate advanced fluidic controls to precisely drive flow within disposable plastic chips. In fact, Sony Corporation developed these chips using techniquesoriginally developed for molding CD’s. Additionally, precision laser-based optics, similar to those found in Blu-Ray players, were developed to read the droplets while a precision motion control mechanism positions the laser spot precisely within micron-scale channels on the chip. In order to create 10 million droplets, the user simply pipettes the initial sample into a chip then places the chip into the Raindrop “Source” instrument. After 20 minutes, the instrument delivers the “dropletized” sample in an inexpensive sample tube which the user then processes in a standard laboratory thermal cycler. Then, the user then places the tube and another chip into the “Sense” instrument and final results are delivered in another 20 minutes. This product was designed to: use low-cost pressure controls; ensure that the interfaces between the chip and machine are clean and reliable; require little to no user interaction; and decrease the amount of time it takes to get results. RainDrop's social impact is significant: it provides unparalleled sensitivity in analysis of DNA, providing new tools in the field of cancer research, potentially leading to improved cancer diagnostics and therapy.