Microfluidic Bead Suspension Hopper

Overview

Journal Anal Chem

Specialty Chemistry

Date 2014 Apr 26

PMID 24761972

Citations 14

Authors

Alexander K Price

Andrew B MacConnell

Brian M Paegel

Affiliations

Soon will be listed here.

Abstract

Many high-throughput analytical platforms, from next-generation DNA sequencing to drug discovery, rely on beads as carriers of molecular diversity. Microfluidic systems are ideally suited to handle and analyze such bead libraries with high precision and at minute volume scales; however, the challenge of introducing bead suspensions into devices before they sediment usually confounds microfluidic handling and analysis. We developed a bead suspension hopper that exploits sedimentation to load beads into a microfluidic droplet generator. A suspension hopper continuously delivered synthesis resin beads (17 μm diameter, 112,000 over 2.67 h) functionalized with a photolabile linker and pepstatin A into picoliter-scale droplets of an HIV-1 protease activity assay to model ultraminiaturized compound screening. Likewise, trypsinogen template DNA-coated magnetic beads (2.8 μm diameter, 176,000 over 5.5 h) were loaded into droplets of an in vitro transcription/translation system to model a protein evolution experiment. The suspension hopper should effectively remove any barriers to using suspensions as sample inputs, paving the way for microfluidic automation to replace robotic library distribution.

Citing Articles

Offsetting Dense Particle Sedimentation in Microfluidic Systems.

Anyaduba T, Rodriguez-Manzano J Micromachines (Basel). 2024; 15(9).

PMID: 39337723 PMC: 11434299. DOI: 10.3390/mi15091063.

Hydrogel-Encapsulated Beads Enable Proximity-Driven Encoded Library Synthesis and Screening.

Cavett V, Chan A, Cunningham C, Paegel B ACS Cent Sci. 2023; 9(8):1603-1610.

PMID: 37637732 PMC: 10451030. DOI: 10.1021/acscentsci.3c00316.

Shaking Device for Homogeneous Dispersion of Magnetic Beads in Droplet Microfluidics.

Poles M, Meggiolaro A, Cremaschini S, Marinello F, Filippi D, Pierno M Sensors (Basel). 2023; 23(12).

PMID: 37420565 PMC: 10304097. DOI: 10.3390/s23125399.

Translating the Genome into Drugs.

Dixit A, Barhoosh H, Paegel B Acc Chem Res. 2023; 56(4):489-499.

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Picoliter Droplet Generation and Dense Bead-in-Droplet Encapsulation via Microfluidic Devices Fabricated via 3D Printed Molds.

Anyaduba T, Otoo J, Schlappi T Micromachines (Basel). 2022; 13(11).

PMID: 36363966 PMC: 9695966. DOI: 10.3390/mi13111946.

References

Zhang , Chung , OLDENBURG . A Simple Statistical Parameter for Use in Evaluation and Validation of High Throughput Screening Assays. J Biomol Screen. 2000; 4(2):67-73. DOI: 10.1177/108705719900400206. View

Upert G, Merten C, Wennemers H . Nanoliter plates--versatile tools for the screening of split-and-mix libraries on-bead and off-bead. Chem Commun (Camb). 2010; 46(13):2209-11. DOI: 10.1039/b927017e. View

Hertzberg R, Pope A . High-throughput screening: new technology for the 21st century. Curr Opin Chem Biol. 2000; 4(4):445-51. DOI: 10.1016/s1367-5931(00)00110-1. View

Mazutis L, Araghi A, Miller O, Baret J, Frenz L, Janoshazi A . Droplet-based microfluidic systems for high-throughput single DNA molecule isothermal amplification and analysis. Anal Chem. 2009; 81(12):4813-21. DOI: 10.1021/ac900403z. View

Eastburn D, Sciambi A, Abate A . Ultrahigh-throughput Mammalian single-cell reverse-transcriptase polymerase chain reaction in microfluidic drops. Anal Chem. 2013; 85(16):8016-21. DOI: 10.1021/ac402057q. View

Furka A, Sebestyen F, Asgedom M, Dibo G . General method for rapid synthesis of multicomponent peptide mixtures. Int J Pept Protein Res. 1991; 37(6):487-93. DOI: 10.1111/j.1399-3011.1991.tb00765.x. View

Granieri L, Baret J, Griffiths A, Merten C . High-throughput screening of enzymes by retroviral display using droplet-based microfluidics. Chem Biol. 2010; 17(3):229-35. DOI: 10.1016/j.chembiol.2010.02.011. View

Liang R, Yan L, Loebach J, Ge M, Uozumi Y, Sekanina K . Parallel synthesis and screening of a solid phase carbohydrate library. Science. 1996; 274(5292):1520-2. DOI: 10.1126/science.274.5292.1520. View

Dishinger J, Reid K, Kennedy R . Quantitative monitoring of insulin secretion from single islets of Langerhans in parallel on a microfluidic chip. Anal Chem. 2009; 81(8):3119-27. PMC: 2679996. DOI: 10.1021/ac900109t. View

10.

Chen X, Tan P, Zhang Y, Pei D . On-bead screening of combinatorial libraries: reduction of nonspecific binding by decreasing surface ligand density. J Comb Chem. 2009; 11(4):604-11. PMC: 2765537. DOI: 10.1021/cc9000168. View

11.

Theberge A, Mayot E, El Harrak A, Kleinschmidt F, Huck W, Griffiths A . Microfluidic platform for combinatorial synthesis in picolitre droplets. Lab Chip. 2012; 12(7):1320-6. DOI: 10.1039/c2lc21019c. View

12.

Stapleton J, Swartz J . Development of an in vitro compartmentalization screen for high-throughput directed evolution of [FeFe] hydrogenases. PLoS One. 2010; 5(12):e15275. PMC: 2997796. DOI: 10.1371/journal.pone.0015275. View

13.

Austin C, Brady L, Insel T, Collins F . NIH Molecular Libraries Initiative. Science. 2004; 306(5699):1138-9. DOI: 10.1126/science.1105511. View

14.

Dressman D, Yan H, Traverso G, Kinzler K, Vogelstein B . Transforming single DNA molecules into fluorescent magnetic particles for detection and enumeration of genetic variations. Proc Natl Acad Sci U S A. 2003; 100(15):8817-22. PMC: 166396. DOI: 10.1073/pnas.1133470100. View

15.

Chueh B, Zheng Y, Torisawa Y, Hsiao A, Ge C, Hsiong S . Patterning alginate hydrogels using light-directed release of caged calcium in a microfluidic device. Biomed Microdevices. 2009; 12(1):145-51. PMC: 2825700. DOI: 10.1007/s10544-009-9369-6. View

16.

Baret J, Miller O, Taly V, Ryckelynck M, El-Harrak A, Frenz L . Fluorescence-activated droplet sorting (FADS): efficient microfluidic cell sorting based on enzymatic activity. Lab Chip. 2009; 9(13):1850-8. DOI: 10.1039/b902504a. View

17.

Kemna E, Schoeman R, Wolbers F, Vermes I, Weitz D, van den Berg A . High-yield cell ordering and deterministic cell-in-droplet encapsulation using Dean flow in a curved microchannel. Lab Chip. 2012; 12(16):2881-7. DOI: 10.1039/c2lc00013j. View

18.

Paegel B, Joyce G . Microfluidic compartmentalized directed evolution. Chem Biol. 2010; 17(7):717-24. PMC: 2912841. DOI: 10.1016/j.chembiol.2010.05.021. View

19.

Kiss M, Ortoleva-Donnelly L, Beer N, Warner J, Bailey C, Colston B . High-throughput quantitative polymerase chain reaction in picoliter droplets. Anal Chem. 2009; 80(23):8975-81. PMC: 2771884. DOI: 10.1021/ac801276c. View

20.

Huebner A, Olguin L, Bratton D, Whyte G, Huck W, de Mello A . Development of quantitative cell-based enzyme assays in microdroplets. Anal Chem. 2008; 80(10):3890-6. DOI: 10.1021/ac800338z. View