Large-scale combinatorial optical barcoding of cells with laser particles

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 un...

Full description

Saved in:
Bibliographic Details
Main Authors: Nicola Martino, Hao Yan, Geoffrey Abbott, Marissa Fahlberg, Sarah Forward, Kwon-Hyeon Kim, Yue Wu, Han Zhu, Sheldon J. J. Kwok, Seok-Hyun Yun
Format: Article
Language:English
Published: Nature Publishing Group 2025-04-01
Series:Light: Science & Applications
Online Access:https://doi.org/10.1038/s41377-025-01809-x
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850265700909711360
author Nicola Martino
Hao Yan
Geoffrey Abbott
Marissa Fahlberg
Sarah Forward
Kwon-Hyeon Kim
Yue Wu
Han Zhu
Sheldon J. J. Kwok
Seok-Hyun Yun
author_facet Nicola Martino
Hao Yan
Geoffrey Abbott
Marissa Fahlberg
Sarah Forward
Kwon-Hyeon Kim
Yue Wu
Han Zhu
Sheldon J. J. Kwok
Seok-Hyun Yun
author_sort Nicola Martino
collection DOAJ
description 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.
format Article
id doaj-art-0939f7221fcb416981d665f31f6a2cd5
institution OA Journals
issn 2047-7538
language English
publishDate 2025-04-01
publisher Nature Publishing Group
record_format Article
series Light: Science & Applications
spelling doaj-art-0939f7221fcb416981d665f31f6a2cd52025-08-20T01:54:20ZengNature Publishing GroupLight: Science & Applications2047-75382025-04-0114111710.1038/s41377-025-01809-xLarge-scale combinatorial optical barcoding of cells with laser particlesNicola Martino0Hao Yan1Geoffrey Abbott2Marissa Fahlberg3Sarah Forward4Kwon-Hyeon Kim5Yue Wu6Han Zhu7Sheldon J. J. Kwok8Seok-Hyun Yun9Harvard Medical School and Wellman Center for Photomedicine, Massachusetts General HospitalHarvard Medical School and Wellman Center for Photomedicine, Massachusetts General HospitalLASE Innovation Inc.LASE Innovation Inc.LASE Innovation Inc.Harvard Medical School and Wellman Center for Photomedicine, Massachusetts General HospitalHarvard Medical School and Wellman Center for Photomedicine, Massachusetts General HospitalLASE Innovation Inc.LASE Innovation Inc.Harvard Medical School and Wellman Center for Photomedicine, Massachusetts General HospitalAbstract 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.https://doi.org/10.1038/s41377-025-01809-x
spellingShingle Nicola Martino
Hao Yan
Geoffrey Abbott
Marissa Fahlberg
Sarah Forward
Kwon-Hyeon Kim
Yue Wu
Han Zhu
Sheldon J. J. Kwok
Seok-Hyun Yun
Large-scale combinatorial optical barcoding of cells with laser particles
Light: Science & Applications
title Large-scale combinatorial optical barcoding of cells with laser particles
title_full Large-scale combinatorial optical barcoding of cells with laser particles
title_fullStr Large-scale combinatorial optical barcoding of cells with laser particles
title_full_unstemmed Large-scale combinatorial optical barcoding of cells with laser particles
title_short Large-scale combinatorial optical barcoding of cells with laser particles
title_sort large scale combinatorial optical barcoding of cells with laser particles
url https://doi.org/10.1038/s41377-025-01809-x
work_keys_str_mv AT nicolamartino largescalecombinatorialopticalbarcodingofcellswithlaserparticles
AT haoyan largescalecombinatorialopticalbarcodingofcellswithlaserparticles
AT geoffreyabbott largescalecombinatorialopticalbarcodingofcellswithlaserparticles
AT marissafahlberg largescalecombinatorialopticalbarcodingofcellswithlaserparticles
AT sarahforward largescalecombinatorialopticalbarcodingofcellswithlaserparticles
AT kwonhyeonkim largescalecombinatorialopticalbarcodingofcellswithlaserparticles
AT yuewu largescalecombinatorialopticalbarcodingofcellswithlaserparticles
AT hanzhu largescalecombinatorialopticalbarcodingofcellswithlaserparticles
AT sheldonjjkwok largescalecombinatorialopticalbarcodingofcellswithlaserparticles
AT seokhyunyun largescalecombinatorialopticalbarcodingofcellswithlaserparticles