Company Profile:

Reveo is focused on the development of new frontiers in science and technology. It was founded by Dr. Sadeg Faris, a prolific inventor with a successful track record of taking new technologies to the marketplace. He established Reveo with the mission to invent the frontiers of science and technology and turn them into products for the benefit of humanity. Since commencing operations in 1991, Reveo has successfully built R&D and management infrastructure composed of a team of talented scientists, engineers, and business leaders. Reveo has developed a strategy, called the Edison Technology Portfolio (ETP) Strategy, to spin out subsidiaries that focus exclusively on particular technology applications and bring products to the marketplace. To date five independent companies have been spun out of Reveo's ETP model: VRex (stereoscopic imaging) eVionyx (fuel cells and batteries), Chelix (cholesteric liquid crystals), PetaComm (optical communication components) and ReVase (ultra-fast DNA sequencing). The mission of ReVase is to develop the fundamental enabling technologies leading to an ultra-fast ultra-compact direct all-electronic DNA sequencing instrument. This instrument will have the potential to simultaneously sequence the genome, epigenome and protein genome directly using solid-state based components that are unique to ReVase.

Description of Proposed Sequencing Methodology:

All DNA sequencing methods to date are indirect-read approaches (based on wet chemistry) with the exception of nano-pores (direct-read) and our proposed method (direct-read). Our proprietary sequencing approach uses a solid-state system derived from a nano-edge probe arrays that are stepped with sub-Angstrom resolution over a stretched and immobilized ssDNA. The atomically sharp knife edge probes are the key to the simplification because it always locates the sample eliminating otherwise needed imaging components. As the nano-edge probes pass over every base, tunneling electrons with energy tuned to excite unique vibrations of each nucleotide are measured and recorded. This direct-read approach can theoretically achieve error-free sequencing to unambiguously recognize any molecule with sub-nm resolution. The key components that make our concept potentially realizable emanate from our experience in instrumentation, noise suppression, and extracting low signals from noise. Our proprietary concepts include Synchronous Gated Scanning (SGS), Scan and Hold (SnH), Detect and Vote (DnV), and Latched Translation (LT) that turns off all noisy power sources during detection.

The ultimate mission of this proposed program is to commercialize an instrument in 5-10 years that will cost less than a $1000 and sequence the whole genome and simultaneously the epigenome (methylation code) nearly error free in a minute for pennies per genome. Because our sequencing method does not rely on wet chemistry approaches to fragment and stitch DNA together, our Detect and Vote (DnV) concept can potentially enable error-free reading. Comparatively, existing methods including the Sanger methods, biochip arrays, pyrosequencers, and others that use syntheses are prone errors during laborious pre-sequencing and post-sequencing. The nano-pore direct method is promising. Great teams are working to overcome few limitations to ensure its viability. We call our method the Omni Molecular Recognizer Application (OmniMoRA) instrument because it is a solid state device that can sequence using the same principle any macro-molecule with sun-nm precision, at high speed and neatly error free. This includes the genome and epigenome, proteins sequencing, RNA, etc. The DnV principle is the key to error free operation. Imagine that each of 16 nano-edge probes measure recognized every base pair in the stretched molecule. At the end the processor tallies the votes to ensure unanimity. If a base pair receives less than 50% vote, then the ambiguity is resolved by retesting it 16 more times more carefully. Thus error free operation is achievable. It is imperative that we distinguish real errors from SNP's. While 1 ppm error may be okay for the short term to fulfill their promise in the future, the fields of genomics, epigenomics and proteomics must be error free.

The path to achieve sequencing tools requires reducing the cost, the error rate, and also the sequencing time. In order to be able to compare sequencing methods on an objective basis, we propose the Coverage, Time, Error, Cost (CTEC) Index methodology that will guide researchers and innovators to pursue the appropriate goal. For instance, reducing the cost significantly without paying attention to also reducing the error rate may not be relevant. This index hopefully will prevent balance of reduction of the pertinent parameters so that resources are directed optimally.

Team Quote:

Great many scientists, engineers and entrepreneurs are challenged and inspired by the high stakes and the gratification that results from pushing the envelope to achieve the ultimate sequencing machine. The beneficiary, of course, will be personalized medicine for all humans to achieve longer and healthier lives. The recently announced Archon XPRIZE for Genomics race is yet another catalyst that will lead so many different inventions and innovations of sequencing machines. The bold requirements of this competition certainly raise the bar to new heights enabling the quest for personalized medicine and opening new vistas for life science newer triumphs. Simply imagine how much we will advance our understanding of the beginnings of all fauna and flora nearly five billion years ago and how they evolved to their present state of development. Imagine the great strides to be made unraveling the mysteries of the field of developmental biology for all living species to ultimately reach maturity to usher in great applications. The benefits of all this will be manifested in longer, healthier, and happier lives for humans in symbiotic relationship with their environment and its other inhabitants. We understand and appreciate the arduous tasks set forth by the X-prize organizing committee, but in order to truly realize the path to predictive and personalize medicine in the near future, these requirements need to be raised even higher. A sequencing instrument having 1 error in 100,000 base pairs covering 98% of the genome will not be adequate to achieve personalized medicine solutions. Why can't we demand methods that guarantee completely error-free sequencing? Our intent to raise this bar even higher is not to undermine the efforts of the Archon XPRIZE for Genomics committee and the brilliant works of the sequencing pioneers who brought us here, but rather bring to this competition a disruptive technology that is capable of error-free sequencing covering 100% of the genome in an instrument that can make personalized sequencing a reality in the near future. Our unique method described herein has the potential to get us there.