Skip to main content
SpringerLink
Log in

Pressure-driven generation of complex microfluidic droplet networks

  • Research Paper
  • Published:
Microfluidics and Nanofluidics Aims and scope Submit manuscript

Abstract

Droplet interface bilayers (DIBs) mimic the cell membrane and provide a model membrane platform for studying basic biophysical processes. This paper demonstrates a pressure-driven microfluidic system for the rapid and automated generation of alternating DIB networks, each comprised of four aqueous nanoliter droplets. The microfluidic device features five inlets, one for the continuous oil phase and four independent aqueous channels for T-junction droplet generation. Droplet production rates are controlled by adjusting the applied pressure of each inlet; therefore, controlling the pattern of droplets produced in the main channel and further stored in a downstream hydrodynamic trapping array. Each trap is designed to capture and hold in place one row of four droplets, forming three interfacial lipid bilayers per network. The potential for greater combinations of droplets in a network enables an increased complexity necessary for performing parallel multiplexed biological assays. We further examined flow behavior in response to changes in resistance of the microfluidic device when using a pressure driven source. This microfluidic system provides a high-throughput method for generating DIB networks of complex droplet patterning.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  • Allen-Benton M, Findlay HE, Booth PJ (2019) Probing membrane protein properties using droplet interface bilayers. Exp Biol Med 244(8):709–720

    Article  Google Scholar 

  • Bayley H, Cronin B, Heron A, Holden MA, Hwang WL, Syeda R, Thompson J, Wallace M (2008) Droplet interface bilayers. Mol Biosyst 4(12):1191

    Article  Google Scholar 

  • Booth MJ, Restrepo Schild V, Downs FG, Bayley H (2017) Functional aqueous droplet networks. Mol Biosyst 13(9):1658–1691

    Article  Google Scholar 

  • Carreras P, Elani Y, Law RV, Brooks NJ, Seddon JM, Ces O (2015) A microfluidic platform for size-dependent generation of droplet interface bilayer networks on rails. Biomicrofluidics 9(6):064121

    Article  Google Scholar 

  • Challita EJ, Najem JS, Freeman EC, Leo DJ (2017) A 3D printing method for droplet-based biomolecular materials. In: Nanosensors, Biosensors, info-tech sensors and 3d systems 2017, international society for optics and photonics

  • Chen X, Carolyn (2017) A microfluidic chip integrated with droplet generation, pairing, trapping, merging, mixing and releasing. RSC Adv 7(27):16738–16750

    Article  Google Scholar 

  • Chokkalingam V, Herminghaus S, Seemann R (2008) Self-synchronizing pairwise production of monodisperse droplets by microfluidic step emulsification. Appl Phys Lett 93(25):254101

    Article  Google Scholar 

  • Christopher GF, Anna SL (2007) Microfluidic methods for generating continuous droplet streams. J Phys D Appl Phys 40(19):R319

    Article  Google Scholar 

  • Elani Y, Solvas XCI, Edel JB, Law RV, Ces O (2016) Microfluidic generation of encapsulated droplet interface bilayer networks (multisomes) and their use as cell-like reactors. Chem Commun 52(35):5961–5964

    Article  Google Scholar 

  • Frenz L, Blouwolff J, Griffiths AD, Baret J-C (2008) Microfluidic production of droplet pairs. Langmuir 24(20):12073–12076

    Article  Google Scholar 

  • Friddin MS, Morgan H, De Planque MRR (2013) Cell-free protein expression systems in microdroplets: Stabilization of interdroplet bilayers. Biomicrofluidics 7(1):014108

    Article  Google Scholar 

  • Friddin MS, Bolognesi G, Elani Y, Brooks NJ, Law RV, Seddon JM, Neil MAA, Ces O (2016) Optically assembled droplet interface bilayer (OptiDIB) networks from cell-sized microdroplets. Soft Matter 12(37):7731–7734

    Article  Google Scholar 

  • Hong J, Choi M, Edel JB, Demello AJ (2010) Passive self-synchronized two-droplet generation. Lab Chip 10(20):2702–2709

    Article  Google Scholar 

  • Hori Y, Kantak C, Murray RM, Abate AR (2017) Cell-free extract based optimization of biomolecular circuits with droplet microfluidics. Lab Chip 17(18):3037–3042

    Article  Google Scholar 

  • Hung L-H, Choi KM, Tseng W-Y, Tan Y-C, Shea KJ, Lee AP (2006) Alternating droplet generation and controlled dynamic droplet fusion in microfluidic device for CdS nanoparticle synthesis. Lab Chip 6(2):174

    Article  Google Scholar 

  • Kehe J, Kulesa A, Ortiz A, Ackerman CM, Thakku SG, Sellers D, Kuehn S, Gore J, Friedman J, Blainey PC (2019) Massively parallel screening of synthetic microbial communities. Proc Natl Acad Sci 116(26):12804–12809

    Article  Google Scholar 

  • Lee Y, Lee H-R, Kim K, Choi SQ (2018) Static and dynamic permeability assay for hydrophilic small molecules using a planar droplet interface bilayer. Anal Chem 90(3):1660–1667

    Article  Google Scholar 

  • Lignel S, Salsac A-V, Drelich A, Leclerc E, Pezron I (2017) Water-in-oil droplet formation in a flow-focusing microsystem using pressure- and flow rate-driven pumps. Colloids Surf A Physicochem Eng Asp 531:164–172

    Article  Google Scholar 

  • Maglia G, Heron AJ, Hwang WL, Holden MA, Mikhailova E, Li Q, Cheley S, Bayley H (2009) Droplet networks with incorporated protein diodes show collective properties. Nat Nanotechnol 4(7):437–440

    Article  Google Scholar 

  • Mattern-Schain SI, Nguyen M-A, Schimel TM, Manuel J, Maraj J, Leo D, Freeman E, Lenaghan S, Sarles SA (2019) Totipotent cellularly-inspired materials. In: Smart materials, adaptive structures and intelligent systems 59131, American Society of Mechanical Engineers

  • Nguyen, M-A (2017) High-Throughput Functional System for Encapsulated Networks of Model Cell Membranes. PhD diss., University of Tennessee

  • Nguyen M-A, Srijanto B, Collier CP, Retterer ST, Sarles SA (2016) Hydrodynamic trapping for rapid assembly and in situ electrical characterization of droplet interface bilayer arrays. Lab Chip 16(18):3576–3588

    Article  Google Scholar 

  • Niu X, Gulati S, Edel JB, Demello AJ (2008) Pillar-induced droplet merging in microfluidic circuits. Lab Chip 8(11):1837

    Article  Google Scholar 

  • Saqib M, Şahinoğlu OB, Erdem EY (2018) Alternating droplet formation by using tapered channel geometry. Sci Rep 8(1):1606

    Article  Google Scholar 

  • Sarles SA, Leo DJ (2010) Physical encapsulation of droplet interface bilayers for durable, portable biomolecular networks. Lab Chip 10(6):710

    Article  Google Scholar 

  • Schlicht B, Zagnoni M (2015) Droplet-interface-bilayer assays in microfluidic passive networks. Sci Rep 5(1):9951

    Article  Google Scholar 

  • Schoeman R, Kemna E, Wolbers F, van den Berg A (2014) High-throughput deterministic single-cell encapsulation and droplet pairing fusion and shrinkage in a single microfluidic device. ELECTROPHORESIS 35(2-3):385–392. https://doi.org/10.1002/elps.201300179

  • Surya HPN, Parayil S, Banerjee U, Chander S, Sen AK (2015) Alternating and merged droplets in a double T-junction microchannel. Biochip J 9(1):16–26

    Article  Google Scholar 

  • Szabo M, Wallace MI (2016) Imaging potassium-flux through individual electropores in droplet interface bilayers. Biochimica et Biophysica Acta (BBA) - Biomembranes 1858(3):613-617

  • Taylor G, Nguyen M-A, Koner S, Freeman E, Collier CP, Sarles SA (2019) Electrophysiological interrogation of asymmetric droplet interface bilayers reveals surface-bound alamethicin induces lipid flip-flop. Biochim Biophys Acta BBA Biomembr 1861(1):335–343

    Article  Google Scholar 

  • Timm AC, Shankles PG, Foster CM, Doktycz MJ, Retterer ST (2016) Toward microfluidic reactors for cell-free protein synthesis at the point-of-care. Small 12(6):810–817

    Article  Google Scholar 

  • Ward T, Faivre M, Abkarian M, Stone HA (2005a) Microfluidic flow focusing: drop size and scaling in pressure versus flow-rate-driven pumping. Electrophoresis 26(19):3716–3724

    Article  Google Scholar 

  • Ward T, Faivre M, Abkarian M, Stone HA (2005b) Microfluidic flow focusing: drop size and scaling in pressureversus flow-rate-driven pumping. Electrophoresis 26(19):3716–3724

    Article  Google Scholar 

  • Wauer T, Gerlach H, Mantri S, Hill J, Bayley H, Sapra KT (2014) Construction and manipulation of functional three-dimensional droplet networks. ACS Nano 8(1):771–779

    Article  Google Scholar 

  • Zhang Y, Bracken H, Woolhead C, Zagnoni M (2020) Functionalisation of human chloride intracellular ion channels in microfluidic droplet-interface-bilayers. Biosens Bioelectron 150:111920

    Article  Google Scholar 

  • Zheng B, Tice JD, Ismagilov RF (2004) Formation of droplets of alternating composition in microfluidic channels and applications to indexing of concentrations in droplet-based assays. Anal Chem 76(17):4977–4982

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Mechanical, Aerospace, and Biomedical Engineering, University of Tennessee, Knoxville, TN, USA

    Tayler M. Schimel & Stephen A. Sarles

  2. Center for Agricultural Synthetic Biology, University of Tennessee, Knoxville, TN, USA

    Tayler M. Schimel, Mary-Anne Nguyen & Scott C. Lenaghan

  3. Department of Food Science, University of Tennessee, Knoxville, TN, USA

    Mary-Anne Nguyen & Scott C. Lenaghan

Authors
  1. Tayler M. Schimel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mary-Anne Nguyen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stephen A. Sarles
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Scott C. Lenaghan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tayler M. Schimel.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 2939 kb)

Supplementary file2 (AVI 50157 kb)

Supplementary file3 (AVI 95895 kb)

Supplementary file4 (AVI 56242 kb)

Supplementary file5 (AVI 92455 kb)

Supplementary file6 (AVI 35789 kb)

Supplementary file7 (AVI 272769 kb)

Supplementary file8 (AVI 261983 kb)

Supplementary file9 (AVI 79504 kb)

Supplementary file10 (AVI 263273 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Schimel, T.M., Nguyen, MA., Sarles, S.A. et al. Pressure-driven generation of complex microfluidic droplet networks. Microfluid Nanofluid 25, 78 (2021). https://doi.org/10.1007/s10404-021-02477-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10404-021-02477-0

Search

Navigation