Because achieving the first programmable electronic chemical cells will require a major fraction of the time-period available in the project, the in-depth application prototype proposed to be developed as a first application of the technology cannot yet rely on the completed integration of ECCells. Instead we plan to investigate one of two application scenarios involving partial ECCell functionality.
1. Integrated smart gel network for algorithmic DNA processing.
This relies on the core functionalities of electronically reversible sequence-specific gelation and electronically programmable microscopic transport and concentration (connected with the compartmentation core function) and optionally also on the molecular amplification functionality. To analyze complex DNA multisets (and other biomolecules), instead of using conventional gels, designed statically and homogeneously in advance, the reversibly programmable cross-linked matrix will allow the local programming both of matrix composition and local electric field pulse sequences for separation. Importantly, the microscopic feedback system involved in ECCell chemical microprocessing will allow the iterative local adaptation of separation to achieve target objectives. Furthermore, the ability to program the immobilization of specific DNA capture sequences into the local gel matrix allows traditional capillary electrophoretic gel separations to be complemented by programmable affinity chromatographic functionality and the construction of DNA specific filters. Local samples can be concentrated and individually exported from the system (export packaging of informational molecules in this initial application scenario will be via self-assembled ionic liquid droplet chains in the resource network). Since the separation and extraction processes will be data specific, information rich, and result from an automated dynamic interplay of electronic manipulations and self-measurements (via the imaging system) this system qualifies as fully-fledged molecular information processing. The algorithms associated with this processing can be stored, optimised and communicated to allow robust repeatability and quality control in applications of the technology. The local algorithmic programmability of a powerful separation medium, with iterative feedback during analysis, will reach a new level in the integration of core ICT microprocessing technology into this domain of molecular diagnostics and synthesis.
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2.Realization of closed loop integrated molecular evolution under programmable control.
The ECCell project, with its integration of amplification and programmable gel separation technology can greatly enhance the programmability of so-called directed evolution processes, allowing programmable selection and feedback of separated molecular information during the evolution process. This is a core application area for ICT, where algorithmic enhancements (cf evolutionary algorithms) and the quality of microscopic feedback control can make a major difference between a marginal application area and a mainstream ICT application domain. Compatible with the chemistry developed in ECCell, this application scenario will investigate the programmable evolution of scpDNA molecules, selecting for specific properties, using the short-DNA tagged library of starting copolymers as one of the sequence elements in the population and the programmable amplification modules developed in ECCell. Because of realistic project constraints, only one of these two application scenarios will be chosen during the project, to best illustrate the exciting new ICT processing potential along the ECCell trajectory.
