Reveo’s direct DNA sequencing using tunneling microscopy

Reveo is developing an ambitious technology to stretch out and deposit taut DNA on conductive surfaces for electronic base detection using one or more STM tips and tunneling current measurements. The linearization and deposition of nucleic acid sequences will likely be done using molecular combing. Reveo’s approach requires atomically flat and positively charged substrate surfaces (e.g. self-assembled monolayers on gold substrates or treated graphite substrates). In addition to molecular combing, Reveo has proposed other methods to linearize DNA, including electrophoretic and hydrodynamic stretching and transfer printing[1]. Furthermore, Reveo has proposed to develop STM tips that are knife-edge shaped, where the smallest dimension is nanoscale[2, 3].

Schematic of Reveo's DNA sequencing method from US 2009/0121133

Much like with IBM/Roche’s proposed DNA transistor, Reveo’s competitive advantage is largely based on the potential cost reduction associated with avoiding labels and the possibility of exceptionally long read lengths. In principle, there’s not much difference between Reveo’s technology and that of IBM’s DNA transistor: both stretch and confine DNA to allow for tunneling current measurement of individual bases (albeit in different geometrical arrangements). IBM’s approach will likely be more reproducible and offer a higher degree of control over local DNA segment position. It’s possible that Reveo’s immobilization approach will reduce smaller-scale configurational rearrangement and motion compared to IBM’s approach, but Reveo’s method will likely be undermined by irregularities in DNA deposition. Reveo’s knife-edge tip design is intriguing, as it would avoid cumbersome issues of probe tip and DNA backbone alignment. Interestingly, even with nanoscale knife-edge tips it appears that individual, isolated DNA molecules would be required as a starting point for analysis, as simultaneous analysis of multiple strands would only be feasible if local DNA contour were uniform along an entire chain length (thus permitting the deconvolution of signals from multiple DNA strands given each individual strand would generation a periodic signal).

Outside of its entry into the Archon X Prize for Genomics, little is known about Reveo’s efforts in DNA sequencing. The company was founded in 1991, has spun out a number of companies, and holds over 300 patents across multiple technology and product areas[4]. Furthermore, although Reveo announced a partnership with the University of Washington (Babak Parviz’s lab) in 2006[5], a 2008 Nature Methods article describing Reveo’s technology did not reference the University of Washington[3]. The University of Washington was awarded a $1.5 million grant in 2006 to develop this technology and Reveo has cited this as its own funding [6, 2]. US patent application 2009/121133 described above lists Parviz as the inventor and University of Washington as the assignee; it’s quite possible that Reveo has priority rights to this and related, future University of Washington patents.

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

References:

[1] US 2009/121133

[2] http://www.reveo.com/node/309

[3] Blow, Nature Methods, vol. 5, p. 267 (2008)

[4] http://www.reveo.com

[5] http://www.reveo.com/node/88

[6] http://www.moore.org/grants-awarded.aspx

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