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Theoretical and Experimental DNA Computation (Natural ...

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140 5 Physical Implementations<br />

process was repeated three more times for the remaining three clauses, leaving<br />

a surface containing only str<strong>and</strong>s encoding a legal solution to the SAT<br />

problem.<br />

The remaining molecules were amplified using PCR <strong>and</strong> then hybridized<br />

to an addressed array. The results of fluorescence imaging clearly showed four<br />

spots of relatively high intensity, corresponding to the four regions occupied<br />

by legal solutions to the problem (S3,S7,S8, <strong>and</strong>S9).<br />

Although these results are encouraging as a first move toward more errorresistant<br />

<strong>DNA</strong> computing, as the authors themselves acknowledge, there remain<br />

serious concerns about the scalability of this approach (1,536 individual<br />

oligos would be required for a 36-bit, as opposed to 4-bit, implementation).<br />

5.9.3 Gel-Based Computing<br />

A much larger (20 variable) instance of 3-SAT was successfully solved by Adleman’s<br />

group in an experiment described in [33]. This is, to date, the largest<br />

problem instance successfully solved by a <strong>DNA</strong>-based computer; indeed, as<br />

the authors state, “this computational problem may yet be the largest yet<br />

solved by nonelectronic means” [33].<br />

The architecture underlying the experiment is related to the Sticker Model<br />

(see Chap. 3) described by Roweis et al. [133]. The difference here is that only<br />

separation steps are used – the application of stickers is not used. Separations<br />

are achieved by using oligo probes immobilized in polyacrylamide gelfilled<br />

glass modules, <strong>and</strong> str<strong>and</strong>s are pulled through them by electrophoresis.<br />

Str<strong>and</strong>s are removed (i.e., retained in the module) by virtue of their hybridizing<br />

to the immobilized probes, with other str<strong>and</strong>s free to pass through the<br />

module <strong>and</strong> be subject to further processing. Captured str<strong>and</strong>s may be released<br />

<strong>and</strong> transported (again via electrophoresis) to other modules for further<br />

processing.<br />

The potential benefits of such an approach are clear; the use of electrophoresis<br />

minimizes the number of laboratory operations performed on<br />

str<strong>and</strong>s, which, in turn, increases the chance of success of an experiment.<br />

Since str<strong>and</strong>s are not deliberately damaged in any way, they, together with<br />

the glass modules, are potentially reusable for multiple computations. Finally,<br />

the whole process is potentially automatable, which may take us one step further<br />

towards a fully integrated <strong>DNA</strong>-based computer that requires minimal<br />

human intervention.<br />

The problem solves was a 20-variable, 24-clause 3-SAT formula Φ, witha<br />

unique satisfying truth assignment. These are

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