Proceedings of the 2004 IEEE Conference on Cybernetics and Intelligent Systems Singapore, 1-3 December, 2004 Automation of microfluidics for molecular computers Danny van Noort School of Computer Science and Engineering, Seoul National University, San 56- I. Sinlim-dong, Gwanak-gu. Seoul 15 1-742, Korea. Email: danny0bi.snu.x. Abstract-Boolean problems can be solved by using DNA in microfluidic systems. It will be shown that computational problems can be solved with a programmable microfluidic system. Furthermore, microfluidics lend themselves to easy integration in automated set-ups. This paper will show that the optimal configuration of computing in microfluidics is a system containing components analogue with electronic elementary building blocks components, such as switches, logic gates and memory, making it programmable for any type of Boolean problem. I. INTRODUCTION Microfluidic systems prove to be an important tool to implement biomolccular computing (MC), using DNA, RNA or proteins. It gives the possibiIity to fully control the flow of the solution, comparable to electronic computing. Scaling down lab equipment to corresponding elemcnls on a microfluidic chip reduces not only the space requirements, but also ultimately the price and the amount of consumables used. Furthermore, microfluidic chips lend themselves to simplifications in automation, we just have think of devices made by Affymetrix [l], Nanogen [2] or Fluidigm [3]. Biomolecular computers are very promising because they are closely related to the biological world and therefore may have applications in fields such as medical diagnostics and drug lead- compound optimisation [4, 5, 61. They process information and present the solution in molecular form. The research on operations with biomolecules may give a better insight into biological systems, while the information processing and construction capabilities at a molecular levef may give rise to new computing paradigms. However, silicon computers still have their advantages, especially as controllers. With the latter in view, an optimal computing solution would be the integration of both silicon and molecular computers, to construct a completely automated molecular processing system. 0-7803-86434/04/$20.00 0 2004 IEEE Microfluidic networks can be incorporated as information carriers. The channels act like the interconnection wires in an electronic circuit, transporling molecular informalion from one operator to another, to fluidic flip-flops, i.e. logical operators. With fluidic valves and micro pumps the flow can bc (re-)directed [7, 8, 9, 101. By controlling the sequence of switch settings with an electronic controller, a specilic program can be executed. Several SD-systems have been proposed for largc scalc fluidic systems. Ikuia er d. [Ill already proposed a biochemical IC, consisting of a stack of basic elements containing micro reactor calculation circuits, pump, electrical and chemical busses, while Gehani and Reif [12] proposed a very general re-configurable microflow system. The disadvantage of such 3D-microsystems is that the internal reactions are invisible. 11. THE MICROFLUiDIC SYSTEM A. Logic operations Selections of single stranded DNA can be made by using capture probes (CP). such as short single stranded DNA, to select longer complementary single DNA strands containing coded information in the sequence of its base-pairs from a molecular library {Si}. Hybridisation between these two is equivalent to a selection step, a YES or NO, i.e. a logic operation. It is also possibIe to use this scheme of selections with proteins and their ligands, such as antibody- antigen interactions. However, in this case the specificity between the molecular components is not as well defined as DNA-DNA hybridisation, making the selection more analogue. B. Selections iii microreactors Logic operators can be implemented by using the selection procedures described above. Below, we schematically treat the selection procedure as a black box, since it is not important for the concept to know how the selection is precisely performed. 274