Synthetic molecular machines for active self-assembly : prototype algorithms, designs, and experimental study

<p>Computer science and electrical engineering have been the great success story of the twentieth century. The neat modularity and mapping of a language onto circuits has led to robots on Mars, desktop computers and smartphones. But these devices are not yet able to do some of the things that life takes for granted: repair a scratch, reproduce, regenerate, or grow exponentially fast���all while remaining functional.</p> <p>This thesis explores and develops algorithms, molecular implementations, and theoretical proofs in the context of ���active self-assembly��� of molecular systems. The long-term vision of active self-assembly is the theoretical and physical implementation of materials that are composed of reconfigurable units with the programmability and adaptability of biology���s numerous molecular machines. En route to this goal, we must first find a way to overcome the memory limitations of molecular systems, and to discover the limits of complexity that can be achieved with individual molecules.</p> <p>One of the main thrusts in molecular programming is to use computer science as a tool for figuring out what can be achieved. While molecular systems that are Turing-complete have been demonstrated [Winfree, 1996], these systems still cannot achieve some of the feats biology has achieved.</p> <p>One might think that because a system is Turing-complete, capable of computing ���anything,��� that it can do any arbitrary task. But while it can simulate any digital computational problem, there are many behaviors that are not ���computations��� in a classical sense, and cannot be directly implemented. Examples include exponential growth and molecular motion relative to a surface.</p> <p>Passive self-assembly systems cannot implement these behaviors because (a) molecular motion relative to a surface requires a source of fuel that is external to the system, and (b) passive systems are too slow to assemble exponentially-fast-growing structures. We call these behaviors ���energetically incomplete��� programmable behaviors. This class of behaviors includes any behavior where a passive physical system simply does not have enough physical energy to perform the specified tasks in the requisite amount of time.</p> <p>As we will demonstrate and prove, a sufficiently expressive implementation of an ���active��� molecular self-assembly approach can achieve these behaviors. Using an external source of fuel solves part of the the problem, so the system is not ���energetically incomplete.��� But the programmable system also needs to have sufficient expressive power to achieve the specified behaviors. Perhaps surprisingly, some of these systems do not even require Turing completeness to be sufficiently expressive. </p> <p>Building on a large variety of work by other scientists in the fields of DNA nanotechnology, chemistry and reconfigurable robotics, this thesis introduces several research contributions in the context of active self-assembly.</p> <p>We show that simple primitives such as insertion and deletion are able to generate complex and interesting results such as the growth of a linear polymer in logarithmic time and the ability of a linear polymer to treadmill. To this end we developed a formal model for active-self assembly that is directly implementable with DNA molecules. We show that this model is computationally equivalent to a machine capable of producing strings that are stronger than regular languages and, at most, as strong as context-free grammars. This is a great advance in the theory of active self- assembly as prior models were either entirely theoretical or only implementable in the context of macro-scale robotics.</p> <p>We developed a chain reaction method for the autonomous exponential growth of a linear DNA polymer. Our method is based on the insertion of molecules into the assembly, which generates two new insertion sites for every initial one employed. The building of a line in logarithmic time is a first step toward building a shape in logarithmic time. We demonstrate the first construction of a synthetic linear polymer that grows exponentially fast via insertion. We show that monomer molecules are converted into the polymer in logarithmic time via spectrofluorimetry and gel electrophoresis experiments. We also demonstrate the division of these polymers via the addition of a single DNA complex that competes with the insertion mechanism. This shows the growth of a population of polymers in logarithmic time. We characterize the DNA insertion mechanism that we utilize in Chapter 4. We experimentally demonstrate that we can control the kinetics of this re- action over at least seven orders of magnitude, by programming the sequences of DNA that initiate the reaction.</p> <p>In addition, we review co-authored work on programming molecular robots using prescriptive landscapes of DNA origami; this was the first microscopic demonstration of programming a molec- ular robot to walk on a 2-dimensional surface. We developed a snapshot method for imaging these random walking molecular robots and a CAPTCHA-like analysis method for difficult-to-interpret imaging data.</p>

Design, specification, and synthesis of aircraft electric power systems control logic

<p>Cyber-physical systems integrate computation, networking, and physical processes. Substantial research challenges exist in the design and verification of such large-scale, distributed sensing, ac- tuation, and control systems. Rapidly improving technology and recent advances in control theory, networked systems, and computer science give us the opportunity to drastically improve our approach to integrated flow of information and cooperative behavior. Current systems rely on text-based spec- ifications and manual design. Using new technology advances, we can create easier, more efficient, and cheaper ways of developing these control systems. This thesis will focus on design considera- tions for system topologies, ways to formally and automatically specify requirements, and methods to synthesize reactive control protocols, all within the context of an aircraft electric power system as a representative application area.</p> <p>This thesis consists of three complementary parts: synthesis, specification, and design. The first section focuses on the synthesis of central and distributed reactive controllers for an aircraft elec- tric power system. This approach incorporates methodologies from computer science and control. The resulting controllers are correct by construction with respect to system requirements, which are formulated using the specification language of linear temporal logic (LTL). The second section addresses how to formally specify requirements and introduces a domain-specific language for electric power systems. A software tool automatically converts high-level requirements into LTL and synthesizes a controller.</p> <p>The final sections focus on design space exploration. A design methodology is proposed that uses mixed-integer linear programming to obtain candidate topologies, which are then used to synthesize controllers. The discrete-time control logic is then verified in real-time by two methods: hardware and simulation. Finally, the problem of partial observability and dynamic state estimation is ex- plored. Given a set placement of sensors on an electric power system, measurements from these sensors can be used in conjunction with control logic to infer the state of the system.</p>