Bead-based approaches for increased sensitivity and multiplexing of CRISPR diagnostics

CRISPR-based diagnostics have emerged as a promising tool for fast, accurate and portable pathogen detection. There has been rapid progress in pre-amplification processes and CRISPR-related enzymes used in these approaches, but the development of reporter systems and reaction platforms has lagged behind. In this paper, we develop bead-based techniques to address these gaps. First, we develop a novel bead-based split-luciferase reporter system with up to 20× sensitivity compared with standard fluorescence-based reporter design in CRISPR diagnostics. Second, we develop a highly deployable, bead-based platform capable of detecting nine distinct viral targets in parallelized, droplet-based reactions, with sensitivity reaching as low as 2.5 copies per µl of input RNA. We demonstrate the enhanced performance of both approaches on synthetic and clinical sample sensitivity, speed, multiplexing and deployability.

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Publication Details

Journal
Nature Biomedical Engineering
Published
2025-09-22
DOI
https://doi.org/10.1038/s41551-025-01498-2
Citations
2
Primary Topic
CRISPR and Genetic Engineering
Type
article
Field-Weighted Citation Impact
1.61

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article

Bead-based approaches for increased sensitivity and multiplexing of CRISPR diagnostics

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Nature Biomedical Engineering
CRISPR and Genetic Engineering
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article

Bead-based approaches for increased sensitivity and multiplexing of CRISPR diagnostics

David R. Stirling, Nicole L. Welch, Paul C. Blainey, Sameed M. Siddiqui, Beth A. Cimini, Rebecca A. Senft, Jon Arizti-Sanz, Pardis C. Sabeti, Marzieh Ezzaty Mirhashemi, Cameron Myhrvold, Tianyi Chang, Cheri M. Ackerman, Amaya Razmi, Tien G. Nguyen
article en
2 citations

Abstract

CRISPR-based diagnostics have emerged as a promising tool for fast, accurate and portable pathogen detection. There has been rapid progress in pre-amplification processes and CRISPR-related enzymes used in these approaches, but the development of reporter systems and reaction platforms has lagged behind. In this paper, we develop bead-based techniques to address these gaps. First, we develop a novel bead-based split-luciferase reporter system with up to 20× sensitivity compared with standard fluorescence-based reporter design in CRISPR diagnostics. Second, we develop a highly deployable, bead-based platform capable of detecting nine distinct viral targets in parallelized, droplet-based reactions, with sensitivity reaching as low as 2.5 copies per µl of input RNA. We demonstrate the enhanced performance of both approaches on synthetic and clinical sample sensitivity, speed, multiplexing and deployability.

Nature Biomedical Engineering
Broad Institute (US), Howard Hughes Medical Institute (US), Harvard University (US), Princeton University (US), Critical Path Institute (US), Concord Consortium (US), Massachusetts General Hospital (US), Harvard–MIT Division of Health Sciences and Technology (US), Evolutionary Genomics (United States) (US), Massachusetts Institute of Technology (US)
Broad Institute, Open Philanthropy Project, Skoll Foundation, ELMA Foundation, Centers for Disease Control and Prevention, Advanced Research Projects Agency
Openalex Percentile: Top 15%
CRISPR and Genetic Engineering
1.61
DOIOpen Access PDFOpenAlex
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