Parallel Function Application on a DNA Substrate

In this paper I present a new model that employs a biological (specifically DNA -based) substrate for performing computation. Specifically, I describe strategies for performing parallel function application in the DNA-computing models described by Adelman, Cai et. al., and Liu et. al. Employing only DNA operations which can presently be performed, I discuss some direct algorithms for computing a variety of useful mathematical functions on DNA, culminating in an algorithm for minimizing an arbitrary continuous function. In addition, computing genetic algorithms on a DNA substrate is briefly discussed

General Purpose Parallel Computation on a DNA Substrate

In this paper I describe and extend a new DNA computing paradigm introduced in Blumberg for building massively parallel machines in the DNA-computing models described by Adelman, Cai et. al., and Liu et. al. Employing only DNA operations which have been reported as successfully performed, I present an implementation of a Connection Machine, a SIMD (single-instruction multiple-data) parallel computer as an illustration of how to apply this approach to building computers in this domain (and as an implicit demonstration of PRAM equivalence). This is followed with a description of how to implement a MIMD (multiple-instruction multiple-data) parallel machine. The implementations described herein differ most from existing models in that they employ explicit communication between processing elements (and hence strands of DNA)

Investigating the dynamics of surface-immobilized DNA nanomachines

Surface-immobilization of molecules can have a profound influence on their structure, function and dynamics. Toehold-mediated strand displacement is often used in solution to drive synthetic nanomachines made from DNA, but the effects of surface-immobilization on the mechanism and kinetics of this reaction have not yet been fully elucidated. Here we show that the kinetics of strand displacement in surface-immobilized nanomachines are significantly different to those of the solution phase reaction, and we attribute this to the effects of intermolecular interactions within the DNA layer. We demonstrate that the dynamics of strand displacement can be manipulated by changing strand length, concentration and G/C content. By inserting mismatched bases it is also possible to tune the rates of the constituent displacement processes (toehold-binding and branch migration) independently, and information can be encoded in the time-dependence of the overall reaction. Our findings will facilitate the rational design of surface-immobilized dynamic DNA nanomachines, including computing devices and track-based motors

Another expert system rule inference based on DNA molecule logic gates

With the help of silicon industry microfluidic processors were invented utilizing nano membrane valves, pumps and mi-croreactors. These so called lab-on-a-chips combined together with molecular computing create molecular-systems-on-a-chips. This work presents a new approach to implementation of molecular inference systems. It requires the unique representation of signals by DNA molecules. The main part of this work includes the concept of logic gates based on typical genetic engineering reactions. The presented method allows for constructing logic gates with many inputs and for executing them at the same quantity of elementary operations, regardless of a number of input signals. Every microreactor of the lab-on-a-chip performs one unique operation on input molecules and can be connected by dataflow output-input connections to other ones

DNA computation

This is the first ever doctoral thesis in the field of DNA computation. The field has its roots in the late 1950s, when the Nobel laureate Richard Feynman first introduced the concept of computing at a molecular level. Feynman's visionary idea was only realised in 1994, when Leonard Adleman performed the first ever truly molecular-level computation using DNA combined with the tools and techniques of molecular biology. Since Adleman reported the results of his seminal experiment, there has been a flurry of interest in the idea of using DNA to perform computations. The potential benefits of using this particular molecule are enormous: by harnessing the massive inherent parallelism of performing concurrent operations on trillions of strands, we may one day be able to compress the power of today's supercomputer into a single test tube. However, if we compare the development of DNA-based computers to that of their silicon counterparts, it is clear that molecular computers are still in their infancy. Current work in this area is concerned mainly with abstract models of computation and simple proof-of-principle experiments. The goal of this thesis is to present our contribution to the field, placing it in the context of the existing body of work. Our new results concern a general model of DNA computation, an error-resistant implementation of the model, experimental investigation of the implementation and an assessment of the complexity and viability of DNA computations. We begin by recounting the historical background to the search for the structure of DNA. By providing a detailed description of this molecule and the operations we may perform on it, we lay down the foundations for subsequent chapters. We then describe the basic models of DNA computation that have been proposed to date. In particular, we describe our parallel filtering model, which is the first to provide a general framework for the elegant expression of algorithms for NP-complete problems. The implementation of such abstract models is crucial to their success. Previous experiments that have been carried out suffer from their reliance on various error-prone laboratory techniques. We show for the first time how one particular operation, hybridisation extraction, may be replaced by an error-resistant enzymatic separation technique. We also describe a novel solution read-out procedure that utilizes cloning, and is sufficiently general to allow it to be used in any experimental implementation. The results of preliminary tests of these techniques are then reported. Several important conclusions are to be drawn from these investigations, and we report these in the hope that they will provide useful experimental guidance in the future. The final contribution of this thesis is a rigorous consideration of the complexity and viability of DNA computations. We argue that existing analyses of models of DNA computation are flawed and unrealistic. In order to obtain more realistic measures of the time and space complexity of DNA computations we describe a new strong model, and reassess previously described algorithms within it. We review the search for "killer applications": applications of DNA computing that will establish the superiority of this paradigm within a certain domain. We conclude the thesis with a description of several open problems in the field of DNA computation

Advance the DNA computing

It has been previously shown that DNA computing can solve those problems currently intractable on even the fastest electronic computers. The algorithm design for DNA computing, however, is not straightforward. A strong background in both the DNA molecule and computer engineering are required to develop efficient DNA computing algorithms. After Adleman solved the Hamilton Path Problem using a combinatorial molecular method, many other hard computational problems were investigated with the proposed DNA computer. The existing models from which a few DNA computing algorithms have been developed are not sufficiently powerful and robust, however, to attract potential users. This thesis has described research performed to build a new DNA computing model based on various new algorithms developed to solve the 3-Coloring problem. These new algorithms are presented as vehicles for demonstrating the advantages of the new model, and they can be expanded to solve other NP-complete problems. These new algorithms can significantly speed up computation and therefore achieve a consistently better time performance. With the given resource, these algorithms can also solve problems of a much greater size, especially as compared to existing DNA computation algorithms. The error rate can also be greatly reduced by applying these new algorithms. Furthermore, they have the advantage of dynamic updating, so an answer can be changed based on modifications made to the initial condition. This new model makes use of the huge possible memory by generating a ``lookup table'' during the implementation of the algorithms. If the initial condition changes, the answer changes accordingly. In addition, the new model has the advantage of decoding all the strands in the final pool both quickly and efficiently. The advantages provided by the new model make DNA computing an efficient and attractive means of solving computationally intense problems

A Surface-Based Approach to DNA Computation

A new model of DNA-based computation is presented. The main difference between this model and that of Adleman is in manipulation of DNA strands that are first immobilized on a surface. This approach greatly reduces losses of DNA molecules during purification steps. A simple, surface-based model of computation is described and it is shown how to implement an exhaustive search algorithm for the SAT problem on this model. Partial experimental progress in solving a 5-variable SAT instance is described, and possible extensions of our model that allow general computations are discussed. Liu, Guo, Corn and Smith are in the Chemistry Department, Condon is in the Computer Sciences Department and Lagally is in the Materials Sciences Department. Email address for further communication: [email protected]. 1 Introduction Adleman [1] and subsequently Lipton [5] described how genetic engineering tools can be used to solve instances of NP-complete combinatorial problems. Their work has led to ho..