ArticleProceedings of the National Academy of Sciences of the United States of America2012
Functional single-cell hybridoma screening using droplet-based microfluidics.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.
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Who cites it
115 citing papers in PubMed.
- Microfluidics for protein interaction studies: current methods, challenges, and future perspectives.European biophysics journal : EBJ · 2026Review
- Droplet-based single-cell pairing for high-throughput interaction mapping of antigen-receptor combinations.Science advances · 2025Article
- Deterministic cell pairing with simultaneous microfluidic merging and sorting of droplets.Lab on a chip · 2025Article
- High-Throughput Activity Reprogramming of Proteases (HARP).ACS chemical biology · 2025Article
- Deterministic Cell Pairing with Simultaneous Microfluidic Merging and Sorting of Droplets.bioRxiv : the preprint server for biology · 2025Article
- Recent Advances in Antibody Discovery Using Ultrahigh-Throughput Droplet Microfluidics: Challenges and Future Perspectives.Biosensors · 2025Review
- Droplet Microfluidics for Advanced Single-Cell Analysis.Smart medicine · 2025Review
- From specialization to broad adoption: Key trends in droplet microfluidic innovations enhancing accessibility to non-experts.Biomicrofluidics · 2025Article
- Ultra-sensitive fluorescence-activated droplet single-cell sorting based on Tetramer-HCR-EvaGreen amplification.Microsystems & nanoengineering · 2025Article
- Challenges and future perspectives for high-throughput chimeric antigen receptor T cell discovery.Current opinion in biotechnology · 2024Review
- Review
- Fluorescence-activated droplet sequencing (FAD-seq) directly provides sequences of screening hits in antibody discovery.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A mini review on recent progress of microfluidic systems for antibody development.Journal of diabetes and metabolic disorders · 2024Review
- Unveiling the Potential of Single-Cell Encapsulation in Biomedical Applications: Current Advances and Future Perspectives.Small science · 2024Article
- Topological wetting states of microdroplets on closed-loop structured surfaces: Breakdown of the Gibbs equation at the microscale.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Screening for drivers of SARS-CoV-2 uptake.Nature biomedical engineering · 2024Article
- Cellular immunity analysis by a modular acoustofluidic platform: CIAMAP.Science advances · 2023Article
- Flow Cytometry: The Next Revolution.Cells · 2023Review
- Multiplexed volumetric CLEM enabled by antibody derivatives provides new insights into the cytology of the mouse cerebellar cortex.Research square · 2023Article
- Isolation of full-length IgG antibodies from combinatorial libraries expressed in the cytoplasm of Escherichia coli.Nature communications · 2023Article
55 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Monoclonal antibodies can specifically bind or even inhibit drug targets and have hence become the fastest growing class of human therapeutics. Although they can be screened for binding affinities at very high throughput using systems such as phage display, screening for functional properties (e.g., the inhibition of a drug target) is much more challenging. Typically these screens require the generation of immortalized hybridoma cells, as well as clonal expansion in microtiter plates over several weeks, and the number of clones that can be assayed is typically no more than a few thousand. We present here a microfluidic platform allowing the functional screening of up to 300,000 individual hybridoma cell clones within less than a day. This approach should also be applicable to nonimmortalized primary B-cells, as no cell proliferation is required: Individual cells are encapsulated into aqueous microdroplets and assayed directly for the release of antibodies inhibiting a drug target based on fluorescence. We used this system to perform a model screen for antibodies that inhibit angiotensin converting enzyme 1, a target for hypertension and congestive heart failure drugs. When cells expressing these antibodies were spiked into an unrelated hybridoma cell population in a ratio of 1:10,000 we observed a 9,400-fold enrichment after fluorescence activated droplet sorting. A wide variance in antibody expression levels at the single-cell level within a single hybridoma line was observed and high expressors could be successfully sorted and recultivated.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.