DNA computing on surfaces

Abstract

DNA computing was proposed as a means of solving a class of intractable computational problems in which the computing time can grow exponentially with problem size (the 'NP-complete' or non-deterministic polynomial time complete problems). The principle of the technique has been demonstrated experimentally for a simple example of the hamiltonian path problem (in this case, finding an airline flight path between several cities, such that each city is visited only once). DNA computational approaches to the solution of other problems have also been investigated. One technique involves the immobilization and manipulation of combinatorial mixtures of DNA on a support. A set of DNA molecules encoding all candidate solutions to the computational problem of interest is synthesized and attached to the surface. Successive cycles of hybridization operations and exonuclease digestion are used to identify and eliminate those members of the set that are not solutions. Upon completion of all the multistep cycles, the solution to the computational problem is identified using a polymerase chain reaction to amplify the remaining molecules, which are then hybridized to an addressed array. The advantages of this approach are its scalability and potential to be automated (the use of solid-phase formats simplifies the complex repetitive chemical processes, as has been demonstrated in DNA and protein synthesis). Here we report the use of this method to solve a NP-complete problem. We consider a small example of the satisfiability problem (SAT), in which the values of a set of boolean variables satisfying certain logical constraints are determined.

DNA biomolecular-electronic encoder and decoder devices constructed by multiplex biosensors

“…1-11 A decade ago, for example, Adleman performed a now-classic experiment in which computations were conducted using DNA molecules, demonstrating that biology can provide new computing substrates. [12][13][14][15] In the decade since Adleman's invention, reports have been made of a wide and diverse range of DNA logic devices. [16][17][18][19][20][21][22] Winfree, Stojanovic, Willner, Katz and their co-workers have, for example, developed optically reported 'AND' , 'OR' and 'SET-RESET' logic gate operations.…”

Optically programming DNA computing in microflow reactors

“…This is in contrast to speculation about the integration of all manner of microfluidic components for the implementation of microflow biomolecular computing (Gehani and Reif, 1999). It also differs from the surface (DNA chip) based approach (Frutos et al, 1997) and (Liu et al, 2000), which entails large numbers of external processing steps and DNA synthesis. The use of microflow reactors as described here was first proposed in talks by the author at two international workshops on DNA computing (Leiden, USA 1998;Princeton, USA 1999) and is now under construction in St.…”

“…The above approach differs in the type of programming from previous experimental approaches to DNA computing in vitro (Adleman, 1994;Guarnieri et al, 1996;Sakamoto et al, 1999;Ouyang et al, 1997;Liu et al, 2000;Faulhammer et al, 2000) and in vivo (Khodor and Gifford, 1999). Instead of programming by a manual series of biochemical pipetting operations, the entire fluid flow is held constant and a single light pattern determines the program.…”

“…For problems of significant size (N= 20-100), both procedures are prohibitive. A more recent DNA chip based implementation of 3-SAT (Liu et al, 2000) also scales poorly with problem size in terms of the number of different DNA syntheses and manual biochemical processing steps.…”

Molecular Computing by PNA

“…DNA computer has been intensively used for solving a class of intractable computational problems, 13,17,18 such as 3-satisfiability (3-SAT) problems, in which the computing time can grow exponentially with the problem size.…”