CADMAD : Microfluidic Integration for DNA Library Construction by Reuse

CADMAD is an EU funded Future Emerging Technologies project (2011-2014) that aims to extend the existing automation of DNA Library production based on DNA reuse using liquid handling robots to make it more robust and programmable on the one hand, and compatible with future microfluidics integration on the other. DNA reuse imparts a word-processing like capability to DNA text design, and potentially can deal with the error threshold restricting lengths in direct base-by-base (e.g. solid support) DNA synthesis. DNA library synthesis differs from single DNA synthesis tasks in posing a set of DNA sequences correlated in potentially complex combinatorial ways as the synthesis task, further motivating reuse of synthesised intermediates.

The BioMIP research group’s role was to investigate the future scalability of DNA library production with reuse down to nanoliter and picoliter scales using microfluidic integration. The proposal was to use isothermal ligation and amplification chemistry in connection with droplet processing and on chip electrophoretic length separation to allow iterative ligation-amplification-selection rounds implementing the published Y operation, which forms a basis for generic DNA word processing. Because of initial project partner difficulties with the robustness of isothermal reactions for longer sequences, the project switched attention to the well known Gibson Assembly reaction during year two.

The on-chip procedures investigated initially focussed on BioMIP’s area of expertise in integrating on chip microelectrode separation, extending it to establish processing from and to flow-by droplets into a microfluidic chip operation at the nanoliter scale. A complete chain of compatible microfluidic processing steps at the nanoliter scale, including input and output (e.g. to capillaries or multiwell plates) was established, firstly for a single round of processing.

In the final year of the project, the requirements shifted from ensuring future scalability to the short term production of a test library. Consequently BioMIP developed and employed a novel droplet-on-demand microfluidic device to produce a nanoliter scale DNA library, exported to MWPs. 

Here are links to lists of publication output in the CADMAD project, which are not yet correctly rendered in EU or coordinator lists:

This is the coordinator's CADMAD project web page

Computer Aided Design and Manufacturing of DNA libraries (CADMAD)


Here is the EU page for CADMAD.

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