John S. McCaskill

Open problems in artificial life

This article lists fourteen open problems in artificial life, each of which is a grand challenge requiring a major advance on a fundamental issue for its solution. Each problem is briefly explained, and, where deemed helpful, some promising paths to its solution are indicated.

Optically programming DNA computing in microflow reactors

The programmability and the integration of biochemical processing protocols are addressed for DNA computing using photochemical and microsystem techniques. A magnetically switchable selective transfer module (STM) is presented which implements the basic sequence-specific DNA filtering operation under constant flow. Secondly, a single steady flow system of STMs is presented which solves an arbitrary instance of the maximal clique problem of given maximum size N. Values of N up to about 100 should be achievable with current lithographic techniques. The specific problem is encoded in an initial labeling pattern of each module with one of 2N DNA oligonucleotides, identical for all instances of maximal clique. Thirdly, a method for optically programming the DNA labeling process via photochemical lithography is proposed, allowing different problem instances to be specified. No hydrodynamic switching of flows is required during operation -- the STMs are synchronously clocked by an external magnet. An experimental implementation of this architecture is under construction and will be reported elsewhere.

Graph Replacement Chemistry for DNA Processing

The processing of nucleic acids is abstracted using operators on directed and labeled graphs. This provides a computational framework for predicting complex libraries of DNA/RNA arising from sequences of reactions involving hybridisation intermediates with significant combinatorial complexity. It also provides a detailed functional classification scheme for the reactions and side-reactions of DNA processing enzymes. It is complementary to the conventional string-based DNA Computing grammars such as splicing systems, in that the graph-based structure of enzyme-nucleic acid complexes is the fundamental object of combinatorial manipulation and in that the allowed reactions are specified by local graph replacement operators (i.e. catalysts for structural transitions) associated with enzymes. The focus of the work is to present a calculus for the compact specification and evaluation of the combined action of multiple DNA-processing reactions. Each enzyme and its side-reactions may be classified by a small set of small graph replacement operators. Complex replication and computation schemes may be computed with the formalism.

From Reconfigurability to Evolution in Construction Systems: Spanning the Electronic, Microfluidic and Biomolecular Domains

This paper investigates configurability, reconfigurability and evolution of information processing hardware in conventional and unconventional media. Whereas current electronic systems have an advantage in terms of processing speed, they are at a definite disadvantage in terms of plasticity, true hardware reconfiguration and especially reconfiguration and evolution of the hardware construction system itself. Here molecular computers, including the control of chemical reaction synthesis, hold the promise of being able to achieve these properties. In particular, combinatorially complex families of molecules (such as DNA) can direct their own synthesis. The intermediate level of microfluidic systems is also open to reconfiguration and evolution and may play a vital role in linking up the electronic and molecular processing worlds. This paper discusses opportunities for and advantages of reconfiguration across these various levels and the possibility of integrating these technologies. Finally, the threshold level of construction control required for iterative bootstrapping of nanoscale construction is discussed.

Flows in micro fluidic networks: from theory to simulation

When complex flow structures are designed, such as in DNA computing [McCaskill, J.S., (2001)], it is essential to be able to predict the flow pattern of the solutions in the fluidic network. A model based on the resistance of the channels and flow velocities of the inlets can eliminated reiterative design steps. We have constructed a symbolic model (using Mathematica/spl reg/) to determine the desired flow pattern based on the equations of Ohm and Kirchoff. The values from this simulation were used in a flow simulation program.

Steady Flow Micro-Reactor Module for Pipelined DNA Computations

Microflow reactors provide a means of implementing DNA Computing as a whole, not just individual steps. Contrary to surface based DNA Chips[1], microflow reactors with active components in closed flow systems can be used to integrate complete DNA computations[2]. Microreactors allow complicated flow topologies to be realized which can implement a dataflowlike architecture for the processing of DNA. A technologically feasible scalable approach with many reaction chambers however requires constant hydrodynamic flows. In this work, the experimental construction of a basic constant flow module for DNA processing in such a context is addressed. Limited diffusional exchange in parallel flows is used to establish spatio-temporal segregation of reaction conditions which can be crossed by magnetic beads without barriers. As previously outlined[2], linked up with an optical programming technology, this will enable DNA selection to be programmed and complex population selection to be performed. The basic first experimental step in the realization of this program is described here: the establishment of a stable hydrodynamic flow pattern which is scalable to many reactors in parallel and the demonstration of a scalable and synchronous clocking of magnetic beadbased processing. First results with fluorescently-labeled DNA transfer will also be presented at the conference. The way in which this module may be integrated to solve the maximal clique problem has been proposed elsewhere[2].