Design Of Dna Strand Displacement Based Circuits

DNA is the basic building block of any living organism. DNA is considered a popular candidate for future biological devices and circuits for solving genetic disorders and several other medical problems. With this objective in mind, this research aims at developing novel approaches for the design of DNA based circuits. There are many recent developments in the medical field such as the development of biological nanorobots, SMART drugs, and CRISPR-Cas9 technologies. There is a strong need for circuits that can work with these technologies and devices. DNA is considered a suitable candidate for designing such circuits because of the programmability of the DNA strands, small size, lightweight, known thermodynamics, higher parallelism, and exponentially reducing the cost of synthesizing techniques. The DNA strand displacement operation is useful in developing circuits with DNA strands. The circuit can be either a digital circuit, in which the logic high and logic low states of the DNA strand concentrations are considered as the signal, or it can be an analog circuit in which the concentration of the DNA strands itself will act as the signal. We developed novel approaches in this research for the design of digital, as well as analog circuits keeping in view of the number of DNA strands required for the circuit design. Towards this goal in the digital domain, we developed spatially localized DNA majority logic gates and an inverter logic gate that can be used with the existing seesaw based logic gates. The majority logic gates proposed in this research can considerably reduce the number of strands required in the design. The introduction of the logic inverter operation can translate the dual rail circuit architecture into a monorail architecture for the seesaw based logic circuits. It can also reduce the number of unique strands required for the design into approximately half. The reduction in the number of unique strands will consequently reduce the leakage reactions, circuit complexity, and cost associated with the DNA circuits. The real world biological inputs are analog in nature. If we can use those analog signals directly in the circuits, it can considerably reduce the resources required. Even though analog circuits are highly prone to noise, they are a perfect candidate for performing computations in the resource-limited environments, such as inside the cell. In the analog domain, we are developing a novel fuzzy inference engine using analog circuits such as the minimum gate, maximum gate, and fan-out gates. All the circuits discussed in this research were designed and tested in the Visual DSD software. The biological inputs are inherently fuzzy in nature, hence a fuzzy based system can play a vital role in future decision-making circuits. We hope that our research will be the first step towards realizing these larger goals. The ultimate aim of our research is to develop novel approaches for the design of circuits which can be used with the future biological devices to tackle many medical problems such as genetic disorders

Rate-Independent Constructs for Chemical Computation

This paper presents a collection of computational modules implemented with chemical reactions: an inverter, an incrementer, a decrementer, a copier, a comparator, a multiplier, an exponentiator, a raise-to-a-power operation, and a logarithm in base two. Unlike previous schemes for chemical computation, this method produces designs that are dependent only on coarse rate categories for the reactions (“fast” vs. “slow”). Given such categories, the computation is exact and independent of the specific reaction rates. The designs are validated through stochastic simulations of the chemical kinetics

Methodology for identifying alternative solutions in a population based data generation approach applied to synthetic biology

This thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University LondonDesign is an essential component of sustainable development. Computational modelling has become a useful technique that facilitates the design of complex systems. Variables that characterises a complex system are encoded into a computational model using mathematical concepts and through simulation each of these variables alone or in combination are modified to observe the changes in the outcome. This allows the researchers to make predictions on the behaviour of the real system that is being studied in response to the changes. The ultimate goal of any design process is to come up with the best design; as resources are limited, to minimize the cost and resource consumption, and to maximize the performance, profits and efficiency. To optimize means to find the best solution, the best compromise among several conflicting demands subject to predefined requirements. Therefore, computational optimization, modelling and simulation forms an integrated part of the modern design practice. This thesis defines a data analytics driven methodology which enables the identification of alternative solutions of computational design by analysing the generational history of the population based heuristic search used to generate the templates. While optimisation is focused on obtaining the optimal solution this methodology focuses on alternative solutions which are sub optimal by fitness or solutions with similar fitness but different structures. When the optimal design solution is less robust, alternative solutions can offer a sufficiently good accuracy and an achievable resource requirement. The main advantage of the methodology is that it exploits the exploration process of the solution space during a single run, by focusing also on suboptimal solutions, which usually get neglected in the search for an optimal one. The history of the heuristic search is analysed for the emergence of alternative solutions and evolving of a solution. By examining how an initial solution converts to an optimal solution core design patterns are identified, and these were used to improve the design process. Further, this method limits the number of runs of the heuristic search as more solution space is covered. The methodology is generic because it can be used to any instance where a population based heuristic search is applied to generate optimal designs. The applicability of the methodology is demonstrated using three case studies from mathematics (building of a mathematical function for a set target) and biology (obtaining alternative designs for genomic metabolic models [GEM] and DNA walker circuits). In each case a different heuristic search method was used: Gene expression programming (mathematical expressions), genetic algorithms (GEM models) and simulated annealing (DNA walker circuits). Descriptive analytics, visual analytics and clustering was mainly used to build the data analytics driven approach in identifying alternative solutions. This data analytics driven methodology is useful in optimising the computational design of complex systems

On The Design Of Low-Complexity High-Speed Arithmetic Circuits In Quantum-Dot Cellular Automata Nanotechnology

For the last four decades, the implementation of very large-scale integrated systems has largely based on complementary metal-oxide semiconductor (CMOS) technology. However, this technology has reached its physical limitations. Emerging nanoscale technologies such as quantum-dot cellular automata (QCA), single electron tunneling (SET), and tunneling phase logic (TPL) are major candidate for possible replacements of CMOS. These nanotechnologies use majority and/or minority logic and inverters as circuit primitives. In this dissertation, a comprehensive methodology for majority/minority logic networks synthesis is developed. This method is capable of processing any arbitrary multi-output Boolean function to nd its equivalent optimal majority logic network targeting to optimize either the number of gates or levels. The proposed method results in different primary equivalent majority expression networks. However, the most optimized network will be generated as a nal solution. The obtained results for 15 MCNC benchmark circuits show that when the number of majority gates is the rst optimization priority, there is an average reduction of 45.3% in the number of gates and 15.1% in the number of levels. They also show that when the rst priority is the number of levels, an average reduction of 23.5% in the number of levels and 43.1% in the number of gates is possible, compared to the majority AND/OR mapping method. These results are better compared to those obtained from the best existing methods. In this dissertation, our approach is to exploit QCA technology because of its capability to implement high-density, very high-speed switching and tremendously lowpower integrated systems and is more amenable to digital circuits design. In particular, we have developed algorithms for the QCA designs of various single- and multi-operation arithmetic arrays. Even though, majority/minority logic are the basic units in promising nanotechnologies, an XOR function can be constructed in QCA as a single device. The basic cells of the proposed arrays are developed based on the fundamental logic devices in QCA and a single-layer structure of the three-input XOR function. This process leads to QCA arithmetic circuits with better results in view of dierent aspects such as cell count, area, and latency, compared to their best counterparts. The proposed arrays can be formed in a pipeline manner to perform the arithmetic operations for any number of bits which could be quite valuable while considering the future design of large-scale QCA circuits

Molecular circuit for exponentiation based on the domain coding strategy

DNA strand displacement (DSD) is an efficient technology for constructing molecular circuits. However, system computing speed and the scale of logical gate circuits remain a huge challenge. In this paper, a new method of coding DNA domains is proposed to carry out logic computation. The structure of DNA strands is designed regularly, and the rules of domain coding are described. Based on this, multiple-input and one-output logic computing modules are built, which are the basic components forming digital circuits. If the module has n inputs, it can implement 2n logic functions, which reduces the difficulty of designing and simplifies the structure of molecular logic circuits. In order to verify the superiority of this method for developing large-scale complex circuits, the square root and exponentiation molecular circuits are built. Under the same experimental conditions, compared with the dual-track circuits, the simulation results show that the molecular circuits designed based on the domain coding strategy have faster response time, simpler circuit structure, and better parallelism and scalability. The method of forming digital circuits based on domain coding provides a more effective way to realize intricate molecular control systems and promotes the development of DNA computing

Computing, Modelling, and Scientific Practice: Foundational Analyses and Limitations

This dissertation examines aspects of the interplay between computing and scientific practice. The appropriate foundational framework for such an endeavour is rather real computability than the classical computability theory. This is so because physical sciences, engineering, and applied mathematics mostly employ functions defined in continuous domains. But, contrary to the case of computation over natural numbers, there is no universally accepted framework for real computation; rather, there are two incompatible approaches --computable analysis and BSS model--, both claiming to formalise algorithmic computation and to offer foundations for scientific computing. The dissertation consists of three parts. In the first part, we examine what notion of 'algorithmic computation' underlies each approach and how it is respectively formalised. It is argued that the very existence of the two rival frameworks indicates that 'algorithm' is not one unique concept in mathematics, but it is used in more than one way. We test this hypothesis for consistency with mathematical practice as well as with key foundational works that aim to define the term. As a result, new connections between certain subfields of mathematics and computer science are drawn, and a distinction between 'algorithms' and 'effective procedures' is proposed. In the second part, we focus on the second goal of the two rival approaches to real computation; namely, to provide foundations for scientific computing. We examine both frameworks in detail, what idealisations they employ, and how they relate to floating-point arithmetic systems used in real computers. We explore limitations and advantages of both frameworks, and answer questions about which one is preferable for computational modelling and which one for addressing general computability issues. In the third part, analog computing and its relation to analogue (physical) modelling in science are investigated. Based on some paradigmatic cases of the former, a certain view about the nature of computation is defended, and the indispensable role of representation in it is emphasized and accounted for. We also propose a novel account of the distinction between analog and digital computation and, based on it, we compare analog computational modelling to physical modelling. It is concluded that the two practices, despite their apparent similarities, are orthogonal

On the performance and programming of reversible molecular computers

If the 20th century was known for the computational revolution, what will the 21st be known for? Perhaps the recent strides in the nascent fields of molecular programming and biological computation will help bring about the ‘Coming Era of Nanotechnology’ promised in Drexler’s ‘Engines of Creation’. Though there is still far to go, there is much reason for optimism. This thesis examines the underlying principles needed to realise the computational aspects of such ‘engines’ in a performant way. Its main body focusses on the ways in which thermodynamics constrains the operation and design of such systems, and it ends with the proposal of a model of computation appropriate for exploiting these constraints. These thermodynamic constraints are approached from three different directions. The first considers the maximum possible aggregate performance of a system of computers of given volume, V, with a given supply of free energy. From this perspective, reversible computing is imperative in order to circumvent the Landauer limit. A result of Frank is refined and strengthened, showing that the adiabatic regime reversible computer performance is the best possible for any computer—quantum or classical. This therefore shows a universal scaling law governing the performance of compact computers of ~V^(5/6), compared to ~V^(2/3) for conventional computers. For the case of molecular computers, it is shown how to attain this bound. The second direction extends this performance analysis to the case where individual computational particles or sub-units can interact with one another. The third extends it to interactions with shared, non-computational parts of the system. It is found that accommodating these interactions in molecular computers imposes a performance penalty that undermines the earlier scaling result. Nonetheless, scaling superior to that of irreversible computers can be preserved, and appropriate mitigations and considerations are discussed. These analyses are framed in a context of molecular computation, but where possible more general computational systems are considered. The proposed model, the א-calculus, is appropriate for programming reversible molecular computers taking into account these constraints. A variety of examples and mathematical analyses accompany it. Moreover, abstract sketches of potential molecular implementations are provided. Developing these into viable schemes suitable for experimental validation will be a focus of future work