PACE REPORT

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Microfluidic computers

The state-of-the-art of lab-on-a-chip technology developed at PACE is programmable microfluidics which adds the functionalities of computer-controlled flows (via programmable electrodes and actuators), and real-time monitoring (via processed read-outs from within the system), [3]. Microflows and bio-chemical reactions can now be not only controlled and programmed, e.g., in/out of a chemical microreactor, but also feed-back adjusted, based on e.g. fluorescent intensity of chosen reactants. The platform enables a completely new paradigm of chemical processing, and is appropriately termed microfluidic computers [4], or chemical Turing machines, likely to become the future lab-robot technicians in biochemical sciences [5].

The highly spatially resolved microfluidic networks integrated with feed-back program­mable flow-control units present then a remarkable experimental platform in stark contrast to the ordinary epruvette/beaker/tube systems. In particular, evolution of bio-molecular interactions involving various nucleic-acid molecules, lipids, etc. can be monitored and/or programmed in sequential and parallel ways not previously possible. This in turn opens avenues for realizing both natural and artificial metabolic-information pathways within microfluidic-based structures. Moreover, it enables the life-support of entirely new living systems - protocells - that present a transition from nonliving to living matter [6].

Evolution on a chip [4,7]

In-vitro enzyme independent molecular evolution has two main problems not fully resolved: (1) a robust and evolvable replication with a high yield, and (2) a build-up of more complex molecular interactions, both of which seem to be crucial traits of living entities. The strength of microfluidic computers is their ability to optimize individual processes (e.g. only self-replication) via loop operations, but also the possibility of optimizing evolution of more complex couplings between different chemical systems (e.g. genetic and metabolic). For example, two initially decoupled processes, self-replication and metabolism, can be integrated within a microfluidic computer into a synergistic gene-metabolism cycle characteristic for minimal protocells. The idea is to evolve and select the protocells both for their replication as well as their metabolic abilities, or in other words, to increase the complexity of replicators by assisting them to do more than just replicate - in this case catalyze a metabolism, Fig.3.

Figure. 3: Schematic of a microfluidic computer operating on “evolvable hardware”; the idea is to co-evolve metabolic (lower channel) and genetic (upper channel) functionalities of protocells. Such systems could provide initial life-support for protocells and a controlled evolution. In the long term we believe that such systems can be utilized to “program” protocells for useful tasks such as to grow in particular chemical environments.