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Increasing the dynamic range of in situ PLA

Nature Methods volume 8, pages 892–893 (2011)Cite this article

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To the Editor:

Methods based on in situ rolling circle amplification (RCA), including those that we previously reported in Nature Methods such as in situ proximity ligation assays (PLA)1 and padlock probes2,3, have a limited dynamic range over which detected molecules may be quantified. To provide efficient detection, the RCA products are generally large with diameters of ∼0.8 μm. The formation of more than a hundred such RCA products per cell causes the signals to coalesce, limiting the dynamic range for digital quantification of target molecules. Here we present an approach to increase the dynamic range of in situ PLA.

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Figure 1: Extension of the dynamic range of in situ PLA.

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Acknowledgements

We thank F. Pontén (Uppsala University) for providing breast cancer tissue microarrays and R. Nong for help with data analysis. The research was funded by EU FP7 grant 259796 (DiaTools), the Knut and Alice Wallenberg Foundation and the Swedish Foundation for Strategic Research.

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Authors and Affiliations

  1. Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden

    Carl-Magnus Clausson, Irene Weibrecht, Ulf Landegren & Ola Söderberg

  2. Centre for Image Analysis, Science for Life Laboratory, Uppsala University, Uppsala, Sweden

    Amin Allalou & Carolina Wählby

  3. Department of Oncology-Pathology, Cancercentrum Karolinska, Karolinska Institutet, Stockholm, Sweden

    Salah Mahmoudi & Marianne Farnebo

  4. Imaging Platform, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

    Carolina Wählby

Authors
  1. Carl-Magnus Clausson
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  2. Amin Allalou
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  3. Irene Weibrecht
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  4. Salah Mahmoudi
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  5. Marianne Farnebo
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  6. Ulf Landegren
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  7. Carolina Wählby
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  8. Ola Söderberg
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Corresponding author

Correspondence to Ola Söderberg.

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Competing interests

U.L. is a founder of Olink Bioscience, which commercializes the in situ PLA technology.

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Supplementary Figures 1–3, Supplementary Table 1, Supplementary Methods (PDF 6411 kb)

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Clausson, CM., Allalou, A., Weibrecht, I. et al. Increasing the dynamic range of in situ PLA. Nat Methods 8, 892–893 (2011). https://doi.org/10.1038/nmeth.1743

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