Mobious Biosystems’ single molecule sequencing [REPOST]

The following is a historical post from The Future of Biomolecules

Mobious Biosystems was founded in 1999. It is developing instruments to detect single polymerase conformation or mass changes during the sequencing-by-synthesis process, using physical methods not dependent on the use of fluorophores.

The start-up does not appear to have developed anything at this time that will significantly impact the third generation sequencing market. It does appear to have made progress on PCR and hybridization array technologies[1]. It is important, however, to note the impressive range of sequencing ideas and corresponding patents generated by founder Daniel Densham and the small company (see below). Conversely, it’s important to recognize that nearly all of Mobious’ technologies either currently are (or initially were) very early-stage and ambitious from a technical standpoint. Its set of proposed technologies span too many areas to be compatible with a start-up’s capabilities and resources. In fact, Mobious’ patent portfolio has the breadth one would expect from the likes of Roche Diagnostics or Life Technologies.

Schematic of SPR technology from US 2008/0014592
Schematic of SPR technology from US 2008/0014592

The following is a sampling of the core components of Mobious’ proposed sequencing methods and patents: 1) detect conformational changes in a single processing enzyme or a change in the polymerase’s mass (e.g. association with a nucleotide) using SPR, TIRM, or other light-based interrogation methods. In one embodiment, nucleotides are added sequentially, and in another, advanced blocking group chemistry is proposed to allow all nucleotide types to be present in the same reaction[2]; 2) measure polymerase dissociation rate from a target strand, leveraging differences in polymerase dissociation rate which are dependent on the presence or absence of a complementary base[3]; 3) detect conformational changes of an enzyme based on FRET[4]; 4) measure a single polymerase’s dielectric constant in order to detect conformational and/or energy level changes indicative of association with a specific nucleotide type[5]; 5) a variation on US2008/0014592 where a helicase is used to accomplish sequencing[6]; and 6) use of other advanced optical methods to detect enzyme conformational states (recent filing)[7].

At this time, Mobious should narrow its focus to only the most promising of its approaches and applications and open its business model to a variety of commercial partnership structures (if it has not done so already). Although fourth generation sequencing should not be ruled out, proteomics and other life sciences tools are likely a better bet. To access fourth generation sequencing, Mobious needs to be able to demonstrate the essential working components of a sequencing prototype at this time – and there should be clear competitive advantage versus other emerging sequencing technologies. Although many of Mobious’ proposed sequencing methods would be too expensive, time-consuming, or error-prone, there are a few strong approaches in the mix. Finally, it’s worth pointing out the degree of secrecy surrounding the company’s activities:  there is a lack of information available on its current sequencing capabilities; and, although it lists University of Exeter Innovation Centre as its headquarters[1], the Centre’s tenant list does not appear to include Mobious for whatever reason[8].

Copyright © Bruce A. Schiamberg 2010. All rights reserved.