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  • Review Article
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Microtechnologies for single-cell and spatial multi-omics

Nature Reviews Bioengineering volume 1, pages 769–784 (2023)Cite this article

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Abstract

Single-cell omics assays allow the identification of the type, subtype and functional state of a single cell. To put such single-cell data in the context of tissues, spatially resolved omics can be applied to quantify gene expression and regulation in intact tissues at the genome scale. However, to obtain a full picture of gene regulatory networks in a cell, multi-omic assays are required that can assess two or more modalities of omics information. In this Review, we discuss microfabricated systems that can be engineered to isolate, probe, manipulate and process single cells at the micrometre scale for single-cell and spatial multi-omics studies. We outline microchannel-, microarray- and droplet-based microfluidic platforms, examining their application in multimodal cellular profiling at the cellular and subcellular level. Finally, we discuss the key challenges that need to be addressed to advance the translation and commercialization of such microchip-based technologies for fundamental research and medical applications.

Key points

  • Single-cell and spatial multi-omics technologies allow the investigation of cell types, fate and functional states in intact tissues.

  • Microchannel-, microarray- and droplet-based microfluidics platforms can be designed for single-cell and spatial multi-omics studies.

  • Microchip platforms enable cellular and subcellular resolution for genome analysis, epigenetics assessment and multimodal cellular profiling.

  • The sensitivity of microchip platforms and their multiplexing capacity will need to be improved to unleash their full potential in interrogating single cells in a tissue context.

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Fig. 1: Microtechnologies for single-cell or spatial multi-omics profiling.
Fig. 2: Microchannel-based platforms for single cell multi-omics.
Fig. 3: Microchannel-based platforms for spatial multi-omics.
Fig. 4: Microarray-based technologies for spatial profiling of intact tissue sections.
Fig. 5: Guiding principles for selecting microchip technologies for single-cell and spatial multi-omics.

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Acknowledgements

We acknowledge support from a Packard Fellowship for Science and Engineering (to R.F.), a Yale Stem Cell Center Chen Innovation Award (to R.F.) and the US National Institutes of Health (grant numbers RF1MH128876, U54AG076043, U54AG079759, UG3CA257393, UH3CA257393, R01CA245313 and U54CA274509 to R.F.).

Author information

Author notes

  1. Yanxiang Deng

    Present address: Department of Pathology and Laboratory Medicine, Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

  2. These authors contributed equally: Yanxiang Deng, Zhiliang Bai.

Authors and Affiliations

  1. Department of Biomedical Engineering, Yale University, New Haven, CT, USA

    Yanxiang Deng, Zhiliang Bai & Rong Fan

  2. Yale Stem Cell Center and Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA

    Yanxiang Deng & Rong Fan

  3. Human and Translational Immunology, Yale School of Medicine, New Haven, CT, USA

    Rong Fan

  4. Department of Pathology, Yale School of Medicine, New Haven, CT, USA

    Rong Fan

Authors
  1. Yanxiang Deng
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  2. Zhiliang Bai
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  3. Rong Fan
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Contributions

All authors made substantial contributions to the preparation of the manuscript.

Corresponding authors

Correspondence to Yanxiang Deng, Zhiliang Bai or Rong Fan.

Ethics declarations

Competing interests

R.F. is scientific founder and adviser for IsoPlexis, Singleron Biotechnologies, and AtlasXomics. The interests of R.F. were reviewed and managed by Yale University Provost’s Office in accordance with the University’s conflict of interest policies. Y.D. and Z.B. declare no competing interests.

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Nature Reviews Bioengineering thanks Katalin Susztak, Kun Zhang and Qin Ma for their contribution to the peer review of this work.

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CG000338: https://www.10xgenomics.com/support/single-cell-multiome-atac-plus-gene-expression/documentation/steps/library-prep/chromium-next-gem-single-cell-multiome-atac-plus-gene-expression-reagent-kits-user-guide

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Deng, Y., Bai, Z. & Fan, R. Microtechnologies for single-cell and spatial multi-omics. Nat Rev Bioeng 1, 769–784 (2023). https://doi.org/10.1038/s44222-023-00084-y

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