Browsing by Subject "molecular computing"

Synthetic biology is an emerging technology field whose goal is to use biology as a substrate for engineering. Self-assembly is one of the many methods for fabricating such synthetic biosystems.

Self-assembly is a process where components spontaneously arrange themselves into organized aggregates by the selective affinity of substructures. DNA is an excellent candidate for making synthetic biological systems using self-assembly because of its modular structure and simple chemistry. This thesis describes several

techniques which use DNA as a nano-construction material and

explores the computational capabilities of DNA self-assembly.

For this dissertation, I set out to build a biomolecular computing device with several

useful properties, including compactness, robustness, high degrees of complexity, flexibility, scalability and easily characterized yields

and convergence rates. However, a unified device that satisfies all these properties is still many years away. Instead, this thesis presents designs, simulations,

and experimental results for several distinct DNA nano-systems, as

well as experimental protocols, each of which satisfies a subset of the above-mentioned properties. The hope is that the lessons learned from building all these biomolecular computational devices would bring us closer to our ultimate goal and would eventually pave the path for a computing device that satisfies all the properties. We experimentally demonstrate how we can reduce errors in tiling assembly using an optimized set of physical parameters. We propose a novel DNA tile design

which enforces directionality of growth, reducing assembly errors. We build simulation models to characterize damage in fragile nanostructures under the impact of various external forces. Furthermore, we investigate reversible computation as a means to provide self-repairability to such damaged structures.

We suggest two modifications of an existing DNA computing device,

called Whiplash PCR machine, which allow it to operate robustly outside of controlled laboratory conditions and allow it to implement a simple form of inter-device communication. We present analysis techniques which characterize the yields and time convergence of self-assembled DNA nanostructures. We also present an experimental demonstration of a novel DNA nanostructure which is capable of tiling the plane and could prove to be a way of building 3D DNA assemblies.

The manufacturing of molecular-scale computing systems requires a scalable, reliable, and economic approach to create highly interconnected, dense arrays of devices. As a candidate substrate for nanoscale logic circuits, DNA self-assembled nanostructures have the potential to fulfill these requirements. However, a number of open challenges remain, including the scalability of DNA self-assembly, long-range signal propagation, and precise patterning of functionalized components. These challenges motivate the development of theory and experimental techniques to illuminate the connections among the physical, optical, and thermodynamic properties of DNA self-assembled nanostructures.

In this thesis, three tools are developed, validated, and applied to study the thermo-mechanical properties of DNA nanostructures: 1) a method to quantitatively measure the quality of DNA grid self-assembly, 2) a spectrofluorometer capable of capturing fluorescence and absorbance data under simultaneous multi-wavelength excitation, and 3) a Monte Carlo simulator that models the ensemble response of DNA nanostructures as simple harmonic oscillators.

The broad contributions of this dissertation are as follows: 1) insight into the thermo-mechanical properties of DNA grid nanostructures, and 2) a categorization of self-assembly defects and their impact on proposed logic circuits.

The results of the work presented in this dissertation show that: 1) the quality of self-assembly of DNA grid nanostructures can be quantitatively calculated to demonstrate the impact of changes in temperature or structure, 2) the optical absorbance of complex DNA nanostructures can be modeled to capture their thermo-mechanical properties (i.e., worst case within 10% of experimental melting temperatures and 70% of experimental thermodynamic parameters), 3) the structural resilience of DNA nanostructures can be quantifiably improved by chemical cross-linking with up to 60% retaining their original structure, and 4) DNA self-assembly introduces structural defects which create new fault models with respect to conventional technologies for logic circuits.