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Biomedical subjects

R M Corn

Publications and source records attributed to R M Corn.

3 recordsLinked to original sources

A surface-based approach to DNA computation.

A scalable approach to DNA-based computations is described. Complex combinatorial mixtures of DNA molecules encoding all possible answers to a computational problem are synthesized and attached to the surface of a solid support. This set of molecules is queried in successive MARK (hybridization) and DESTROY (enzymatic digestion) operations. Determination of the sequence of the DNA molecules remaining on the surface after completion of these operations yields the answer to the computational problem. Experimental demonstrations of aspects of the strategy are presented.

Automation

DNA computing on surfaces: encoding information at the single base level.

The feasibility of encoding a bit (0 or 1) of information for DNA-based computations at the single nucleotide level is evaluated, particularly with regard to the efficiency and specificity of hybridization discrimination. Hybridization experiments are performed on addressed arrays of 32 (2(5)) distinct oligonucleotides immobilized on chemically modified glass and gold surfaces with information encoded in a binary (base 2) format. Similar results are obtained on both glass and gold surfaces and the results are generally consistent with thermodynamic calculations of matched and mismatched duplex stabilities. It is found that under the conditions required to obtain single nucleotide specificity in the hybridization process, hybridization efficiency is low, compromising the utility of single nucleotide encoding for DNA computing applications in the absence of some additional mechanism for increasing specificity. Several methods are suggested to provide such increased discrimination.

Base Composition

Demonstration of a word design strategy for DNA computing on surfaces.

A strategy for DNA computing on surfaces using linked sets of 'DNA words' that are short oligonucleotides (16mers) is proposed. The 16mer words have the format 5'-FFFFvvvvvvvvFFFF-3' in which 4-8 bits of data are stored in 8 variable ('v') base locations, and the remaining fixed ('F') base locations are used as a word label. Using a template and map strategy, a set of 108 8mers each of which possesses at least a 4 base mismatch with the complements to all the other members of the set (4bm complements) are identified for use as a variable base sequence set. In addition, sets of 4 and 12 word labels of the form ABCD....DCBA that are respectively 8bm and 6bm complements with each other are identified. The 16mers are chosen to have a G/C content of 50% in order to make the thermodynamic stability of the perfectly matched hybridized DNA duplexes similar; a simple pairwise additive method is used to estimate the perfect match and mismatch hybridization thermodynamics. A series of preliminary experiments are presented that use small arrays of 16mers attached to chemically modified gold surfaces and fluorescently labeled complements to study the hybridization adsorption and enzymatic manipulation of the oligonucleotides.

Base Sequence