A nanoliter-scale nucleic acid processor with parallel architecture

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Abstract

The purification of nucleic acids from microbial and mammalian cells is a crucial step in many biological and medical applications1. We have developed microfluidic chips for automated nucleic acid purification from small numbers of bacterial or mammalian cells. All processes, such as cell isolation, cell lysis, DNA or mRNA purification, and recovery, were carried out on a single microfluidic chip in nanoliter volumes without any pre- or postsample treatment. Measurable amounts of mRNA were extracted in an automated fashion from as little as a single mammalian cell and recovered from the chip. These microfluidic chips are capable of processing different samples in parallel, thereby illustrating how highly parallel microfluidic architectures can be constructed to perform integrated batch-processing functionalities for biological and medical applications.

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Figure 1: mRNA purification chip.
Figure 2: RT-PCR analysis of isolated mRNA.
Figure 3: DNA purification chip and schematic diagram of one instance of the DNA isolation process.
Figure 4: Verification of successful recovery of E. coli genomic DNA.

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Acknowledgements

The authors would like to thank Kathy Burke for assistance with the RT-PCR and Carl Hansen and James P. Landers for helpful discussions. This work was supported in part by the National Science Foundation (NSF), the Department of Defense Advanced Research Projects Agency (DARPA) and a gift from Farmal Biomedicine, LLC.

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Correspondence to Stephen R Quake.

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The intellectual property derived from this work has been licensed to Fluidigm, in which S.R.Q. and W.F.A. hold shares.

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Hong, J., Studer, V., Hang, G. et al. A nanoliter-scale nucleic acid processor with parallel architecture. Nat Biotechnol 22, 435–439 (2004) doi:10.1038/nbt951

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