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A microdroplet dilutor for high-throughput screening

Nature Chemistry volume 3, pages 437–442 (2011)Cite this article

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Abstract

Pipetting and dilution are universal processes used in chemical and biological laboratories to assay and experiment. In microfluidics such operations are equally in demand, but difficult to implement. Recently, droplet-based microfluidics has emerged as an exciting new platform for high-throughput experimentation. However, it is challenging to vary the concentration of droplets rapidly and controllably. To this end, we developed a dilution module for high-throughput screening using droplet-based microfluidics. Briefly, a nanolitre-sized sample droplet of defined concentration is trapped within a microfluidic chamber. Through a process of droplet merging, mixing and re-splitting, this droplet is combined with a series of smaller buffer droplets to generate a sequence of output droplets that define a digital concentration gradient. Importantly, the formed droplets can be merged with other reagent droplets to enable rapid chemical and biological screens. As a proof of concept, we used the dilutor to perform a high-throughput homogeneous DNA-binding assay using only nanolitres of sample.

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Figure 1: Design and operation of the droplet dilutor.
Figure 2: Calibration of sequential dilution.
Figure 3: Application of the droplet dilution module in a homogeneous DNA-binding assay.

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Acknowledgements

This work was partially supported by the Research Councils UK Basic Technology Programme (Grant EP/D048664/1) and the National Research Foundation of Korea (Grant Number R11-2009-044-1002-0K20904000004-09A050000410).

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Author notes

  1. Andrew J. deMello

    Present address: Present address: Department of Chemistry and Applied Biosciences, Institute for Chemical and Bioengineering, ETH Zürich, HCI E125, Wolfgang Pauli Strasse 10, CH-8093 Zürich, Switzerland,

Authors and Affiliations

  1. Department of Chemistry, Imperial College London, Exhibition Road, South Kensington, SW7 2AZ, London, UK

    Xize Niu, Fabrice Gielen, Joshua B. Edel & Andrew J. deMello

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  1. Xize Niu
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  2. Fabrice Gielen
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  3. Joshua B. Edel
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  4. Andrew J. deMello
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Contributions

X.N. conceived the dilution module, X.N., F.G., J.B.E. and A.J.D. designed the experiments, X.N. and F.G. performed the experiments, X.N., J.B.E. and F.G. analysed the data, and X.N. and A.J.D. co-wrote the manuscript. All authors discussed the results and commented on the manuscript.

Corresponding authors

Correspondence to Joshua B. Edel or Andrew J. deMello.

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The authors declare no competing financial interests.

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Niu, X., Gielen, F., Edel, J. et al. A microdroplet dilutor for high-throughput screening. Nature Chem 3, 437–442 (2011). https://doi.org/10.1038/nchem.1046

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