ArticleProceedings of the National Academy of Sciences of the United States of America2012
High-resolution dose-response 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 90 papers.
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Who cites it
90 citing papers in PubMed.
- Gradient-driven microfluidic framework for the screening of ratiometric drug combinations towards precision oncology in paediatric leukaemia.Nature biomedical engineering · 2026Article
- Droplet-Interlaced Generator with On-Chip Metal-Liquid Micromirrors for Enhanced Microfluidic Absorbance Detection.Biosensors · 2026Article
- Droplet-Based Microfluidics Methods for Detecting Enzyme Inhibitors.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Targeted barcoding of variable antibody domains and individual transcriptomes of the human B-cell repertoire using Link-Seq.PNAS nexus · 2025Article
- Imaging-Based Efficacy Evaluation of Cancer Immunotherapy in Engineered Tumor Platforms and Tumor Organoids.Advanced healthcare materials · 2024Review
- The effects of droplet stabilization by surfactants and nanoparticles on leakage, cross-talk, droplet stability, and cell adhesion.RSC advances · 2024Article
- Microfluidic Organoid Cultures Derived from Pancreatic Cancer Biopsies for Personalized Testing of Chemotherapy and Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Deep learning-assisted concentration gradient generation for the study of 3D cell cultures in hydrogel beads of varying stiffness.Frontiers in bioengineering and biotechnology · 2024Article
- Ultrahigh-Throughput Enzyme Engineering and Discovery inChemical reviews · 2023Review
- Selectable encapsulated cell quantity in droplets via label-free electrical screening and impedance-activated sorting.Materials today. Bio · 2023Article
- Droplet Detection and Sorting System in Microfluidics: A Review.Micromachines · 2022Review
- High-Throughput Steady-State Enzyme Kinetics Measured in a Parallel Droplet Generation and Absorbance Detection Platform.Analytical chemistry · 2022Article
- A microfluidic Braille valve platform for on-demand production, combinatorial screening and sorting of chemically distinct droplets.Nature protocols · 2022Review
- Rapid parallel generation of a fluorescently barcoded drop library from a microtiter plate using the plate-interfacing parallel encapsulation (PIPE) chip.Lab on a chip · 2022Article
- Fungi-on-a-Chip: microfluidic platforms for single-cell studies on fungi.FEMS microbiology reviews · 2022Review
- Hydrodynamics of Droplet Sorting in Asymmetric Acute Junctions.Micromachines · 2022Article
- Facile and scalable tubing-free sample loading for droplet microfluidics.Scientific reports · 2022Article
- Combi-seq for multiplexed transcriptome-based profiling of drug combinations using deterministic barcoding in single-cell droplets.Nature communications · 2022Article
- From Microtiter Plates to Droplets-There and Back Again.Micromachines · 2022Article
- Signalling dynamics, cell decisions, and homeostatic control in health and disease.Current opinion in cell biology · 2022Review
30 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors.
Funding
Abstract
A critical early step in drug discovery is the screening of a chemical library. Typically, promising compounds are identified in a primary screen and then more fully characterized in a dose-response analysis with 7-10 data points per compound. Here, we describe a robust microfluidic approach that increases the number of data points to approximately 10,000 per compound. The system exploits Taylor-Aris dispersion to create concentration gradients, which are then segmented into picoliter microreactors by droplet-based microfluidics. The large number of data points results in IC(50) values that are highly precise (± 2.40% at 95% confidence) and highly reproducible (CV = 2.45%, n = 16). In addition, the high resolution of the data reveals complex dose-response relationships unambiguously. We used this system to screen a chemical library of 704 compounds against protein tyrosine phosphatase 1B, a diabetes, obesity, and cancer target. We identified a number of novel inhibitors, the most potent being sodium cefsulodine, which has an IC(50) of 27 ± 0.83 μM.
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Registered trials
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.