Large-scale combinatorial optical barcoding of cells with laser particles

Nicola Martino; Hao Yan; Geoffrey Abbott; Marissa Fahlberg; Sarah Forward; Kwon-Hyeon Kim; Yue Wu; Han Zhu; Sheldon J. J. Kwok; Seok-Hyun Yun

doi:10.1038/s41377-025-01809-x

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Large-scale combinatorial optical barcoding of cells with laser particles

Original Articles

- Large-scale combinatorial optical barcoding of cells with laser particles
- Large-scale combinatorial optical barcoding of cells with laser particles
- LSA 2025年14卷第6期页码：1541-1557
- Affiliations：
  
  1.Harvard Medical School and Wellman Center for Photomedicine, Massachusetts General Hospital, Cambridge, MA 02139, USA
  2.Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
  3.LASE Innovation Inc., Waltham, MA 02451, USA
  4.Harvard-MIT Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
  5.Present address: Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China
- Author bio：
  
  Seok-Hyun Yun (syun@mgh.harvard.edu)
- Funds：
- DOI：10.1038/s41377-025-01809-x
  中图分类号：
- 收稿日期：2024-07-19，
  
  修回日期：2025-03-02，
  
  录用日期：2025-03-04，
  
  网络出版日期：2025-04-01，
  
  纸质出版日期：2025-06-30
- Accepted：
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Large-scale combinatorial optical barcoding of cells with laser particles[J]. LSA, 2025,14(6):1541-1557.

Martino, N. et al. Large-scale combinatorial optical barcoding of cells with laser particles. Light: Science & Applications, 14, 1541-1557 (2025).
Large-scale combinatorial optical barcoding of cells with laser particles[J]. LSA, 2025,14(6):1541-1557. DOI： 10.1038/s41377-025-01809-x.

Martino, N. et al. Large-scale combinatorial optical barcoding of cells with laser particles. Light: Science & Applications, 14, 1541-1557 (2025). DOI： 10.1038/s41377-025-01809-x.

摘要

Abstract

The identification of individual cells is crucial for advancements in single-cell analysis. Optically readable barcodes provide a means to distinguish and track cells through repeated

non-destructive measurements. Traditional fluorophore-based methods are limited by the finite number of unique barcodes they can produce. Laser particles (LPs)

which emit narrowband peaks over a wide spectral range

have emerged as a promising technology for single-cell barcoding. Here

we demonstrate the use of multiple LPs to generate combinatorial barcodes

enabling the identification of a vast number of live cells. We introduce a theoretical framework for estimating the number of LPs required for unique barcodes and the expected identification error rate. Additionally

we present an improved LP-tagging method that is highly effective across a variety of cell types and evaluate its biocompatibility. Our experimental results show successful barcoding of several million cells

closely matching our theoretical predictions. This research marks a significant step forward in the scalability of LP technology for single-cell tracking and analysis.

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references

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