Functional Surfactants for Molecular Fishing, Capsule Creation, and Single-Cell Gene Expression
Corresponding Author: Rainer Haag
Nano-Micro Letters,
Vol. 13 (2021), Article Number: 147
Abstract
Creating a single surfactant that is open to manipulation, while maintaining its surface activity, robustness, and compatibility, to expand the landscape of surfactant-dependent assays is extremely challenging. We report an oxidation-responsive precursor with thioethers and multiple 1,2-diols for creating a variety of functional surfactants from one parent surfactant. Using these multifunctional surfactants, we stabilize microfluidics-generated aqueous droplets. The droplets encapsulate different components and immerse in a bioinert oil with distinct interfaces where an azide-bearing surfactant allow fishing of biomolecules from the droplets, aldehyde-bearing surfactant allow fabrication of microcapsules, and hydroxyl-bearing surfactants, with/without oxidized thioethers, allow monitoring of single-cell gene expression. Creating multifunctional surfactants poses opportunities for broad applications, including adsorption, bioanalytics, catalysis, formulations, coatings, and programmable subset of emulsions.
Highlights:
1 We have demonstrated how to create a parent surfactant that is open to manipulation, while maintaining its surface activity, robustness, and compatibility, to expand the landscape of surfactant-dependent microfluidic-droplet-based assays.
2 To create a library of functional surfactants from the parent surfactant, an oxidation-responsive small building block with thioethers and multiple 1,2-diols was used as a head group, while a non-polar perfluoropolyether chain was used as a tail.
Keywords
Download Citation
Endnote/Zotero/Mendeley (RIS)BibTeX
- L.H. Urner, I. Liko, H.-S. Yen, K.-K. Hoi, J.R. Bolla et al., Modular detergents tailor the purification and structural analysis of membrane proteins including G-protein coupled receptors. Nat. Commun. 11, 564 (2020). https://doi.org/10.1038/s41467-020-14424-8
- Z. Tang, N. Kong, X. Zhang, Y. Liu, P. Hu et al., A materials-science perspective on tackling COVID-19. Nat. Rev. Mater. 5, 847–860 (2020). https://doi.org/10.1038/s41578-020-00247-y
- A.B. Theberge, F. Courtois, Y. Schaerli, M. Fischlechner, C. Abell et al., Microdroplets in microfluidics: an evolving platform for discoveries in chemistry and biology. Angew. Chem. Int. Ed. 49, 5846–5868 (2010). https://doi.org/10.1002/anie.200906653
- L. Liu, N. Xiang, Z. Ni, X. Huang, J. Zheng et al., Step emulsification: high-throughput production of monodisperse droplets. Biotechniques 68, 114–116 (2020). https://doi.org/10.2144/btn-2019-0134
- J.J. Agresti, E. Antipov, A.R. Abate, K. Ahn, A.C. Rowat et al., Ultrahigh-throughput screening in drop-based microfluidics for directed evolution. Proc. Natl. Acad. Sci. USA 107, 4004–4009 (2010). https://doi.org/10.1073/pnas.0910781107
- A.M. Klein, L. Mazutis, I. Akartuna, N. Tallapragada, A. Veres et al., Droplet barcoding for single-cell transcriptomics applied to embryonic stem cells. Cell 161, 1187–1201 (2015). https://doi.org/10.1016/j.cell.2015.04.044
- A. Gérard, A. Woolfe, G. Mottet, M. Reichen, C. Castrillon et al., High-throughput single-cell activity-based screening and sequencing of antibodies using droplet microfluidics. Nat. Biotechnol. 38, 715–721 (2020). https://doi.org/10.1038/s41587-020-0466-7
- J. Zhang, R.J. Coulston, S.T. Jones, J. Geng, O.A. Scherman et al., One-step fabrication of supramolecular microcapsules from microfluidic droplets. Science 335, 690–694 (2012). https://doi.org/10.1126/science.1215416
- T.E. Miller, T. Beneyton, T. Schwander, C. Diehl, M. Girault et al., Light-powered CO2 fixation in a chloroplast mimic with natural and synthetic parts. Science 368, 649–654 (2020). https://doi.org/10.1126/science.aaz6802
- M. Weiss, J.P. Frohnmayer, L.T. Benk, B. Haller, J.-W. Janiesch et al., Sequential bottom-up assembly of mechanically stabilized synthetic cells by microfluidics. Nat. Mater. 17, 89–96 (2018). https://doi.org/10.1038/nmat5005
- L. Cohen, N. Cui, Y. Cai, P.M. Garden, X. Li et al., Single molecule protein detection with attomolar sensitivity using droplet digital enzyme-linked immunosorbent assay. ACS Nano 14, 9491–9501 (2020). https://doi.org/10.1021/acsnano.0c02378
- C. Holtze, A.C. Rowat, J.J. Agresti, J.B. Hutchison, F.E. Angilè et al., Biocompatible surfactants for water-in-fluorocarbon emulsions. Lab Chip 8, 1632–1639 (2008). https://doi.org/10.1039/B806706F
- M.S. Chowdhury, W. Zheng, S. Kumari, J. Heyman, X. Zhang et al., Dendronized fluorosurfactant for highly stable water-in-fluorinated oil emulsions with minimal inter-droplet transfer of small molecules. Nat. Commun. 10, 4546 (2019). https://doi.org/10.1038/s41467-019-12462-5
- I. Platzman, J.-W. Janiesch, J.P. Spatz, Synthesis of nanostructured and biofunctionalized water-in-oil droplets as tools for homing T cells. J. Am. Chem. Soc. 135, 3339–3342 (2013). https://doi.org/10.1021/ja311588c
- M. Cui, T. Emrick, T.P. Russell, Stabilizing liquid drops in nonequilibrium shapes by the interfacial jamming of nanoparticles. Science 342, 460–463 (2013). https://doi.org/10.1126/science.1242852
- C. Huang, J. Forth, W. Wang, K. Hong, G.S. Smith et al., Bicontinuous structured liquids with sub-micrometre domains using nanoparticle surfactants. Nat. Nanotechnol. 12, 1060–1063 (2017). https://doi.org/10.1038/nnano.2017.182
- D. Kumar, J.D. Paulsen, T.P. Russell, N. Menon, Wrapping with a splash: high-speed encapsulation with ultrathin sheets. Science 359, 775–778 (2018). https://doi.org/10.1126/science.aao1290
- L.D. Zarzar, V. Sresht, E.M. Sletten, J.A. Kalow, D. Blankschtein et al., Dynamically reconfigurable complex emulsions via tunable interfacial tensions. Nature 518, 520–524 (2015). https://doi.org/10.1038/nature14168
- Z. Yang, J. Wei, Y.I. Sobolev, B.A. Grzybowski, Systems of mechanized and reactive droplets powered by multi-responsive surfactants. Nature 553, 313–318 (2018). https://doi.org/10.1038/nature25137
- A.S. Cheung, D.K.Y. Zhang, S.T. Koshy, D.J. Mooney, Scaffolds that mimic antigen-presenting cells enable ex vivo expansion of primary T cells. Nat. Biotechnol. 36, 160–169 (2018). https://doi.org/10.1038/nbt.4047
- D.M. Rissin, C.W. Kan, T.G. Campbell, S.C. Howes, D.R. Fournier et al., Single-molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations. Nat. Biotechnol. 28, 595–599 (2010). https://doi.org/10.1038/nbt.1641
- C. Wu, P.M. Garden, D.R. Walt, Ultrasensitive detection of attomolar protein concentrations by dropcast single molecule assays. J. Am. Chem. Soc. 142, 12314–12323 (2020). https://doi.org/10.1021/jacs.0c04331
- L. Cohen, D.R. Walt, Evaluation of antibody biotinylation approaches for enhanced sensitivity of single molecule array (Simoa) immunoassays. Bioconj. Chem. 29, 3452–3458 (2018). https://doi.org/10.1021/acs.bioconjchem.8b00601
- R.P. Lyon, T.D. Bovee, S.O. Doronina, P.J. Burke, J.H. Hunter et al., Reducing hydrophobicity of homogeneous antibody-drug conjugates improves pharmacokinetics and therapeutic index. Nat. Biotechnol. 33, 733–735 (2015). https://doi.org/10.1038/nbt.3212
- N. Boehnke, C. Cam, E. Bat, T. Segura, H.D. Maynard, Imine hydrogels with tunable degradability for tissue engineering. Biomacromolecules 16, 2101–2108 (2015). https://doi.org/10.1021/acs.biomac.5b00519
- E. Amstad, Capsules made from prefabricated thin films. Science 359, 743 (2018). https://doi.org/10.1126/science.aar4027
References
L.H. Urner, I. Liko, H.-S. Yen, K.-K. Hoi, J.R. Bolla et al., Modular detergents tailor the purification and structural analysis of membrane proteins including G-protein coupled receptors. Nat. Commun. 11, 564 (2020). https://doi.org/10.1038/s41467-020-14424-8
Z. Tang, N. Kong, X. Zhang, Y. Liu, P. Hu et al., A materials-science perspective on tackling COVID-19. Nat. Rev. Mater. 5, 847–860 (2020). https://doi.org/10.1038/s41578-020-00247-y
A.B. Theberge, F. Courtois, Y. Schaerli, M. Fischlechner, C. Abell et al., Microdroplets in microfluidics: an evolving platform for discoveries in chemistry and biology. Angew. Chem. Int. Ed. 49, 5846–5868 (2010). https://doi.org/10.1002/anie.200906653
L. Liu, N. Xiang, Z. Ni, X. Huang, J. Zheng et al., Step emulsification: high-throughput production of monodisperse droplets. Biotechniques 68, 114–116 (2020). https://doi.org/10.2144/btn-2019-0134
J.J. Agresti, E. Antipov, A.R. Abate, K. Ahn, A.C. Rowat et al., Ultrahigh-throughput screening in drop-based microfluidics for directed evolution. Proc. Natl. Acad. Sci. USA 107, 4004–4009 (2010). https://doi.org/10.1073/pnas.0910781107
A.M. Klein, L. Mazutis, I. Akartuna, N. Tallapragada, A. Veres et al., Droplet barcoding for single-cell transcriptomics applied to embryonic stem cells. Cell 161, 1187–1201 (2015). https://doi.org/10.1016/j.cell.2015.04.044
A. Gérard, A. Woolfe, G. Mottet, M. Reichen, C. Castrillon et al., High-throughput single-cell activity-based screening and sequencing of antibodies using droplet microfluidics. Nat. Biotechnol. 38, 715–721 (2020). https://doi.org/10.1038/s41587-020-0466-7
J. Zhang, R.J. Coulston, S.T. Jones, J. Geng, O.A. Scherman et al., One-step fabrication of supramolecular microcapsules from microfluidic droplets. Science 335, 690–694 (2012). https://doi.org/10.1126/science.1215416
T.E. Miller, T. Beneyton, T. Schwander, C. Diehl, M. Girault et al., Light-powered CO2 fixation in a chloroplast mimic with natural and synthetic parts. Science 368, 649–654 (2020). https://doi.org/10.1126/science.aaz6802
M. Weiss, J.P. Frohnmayer, L.T. Benk, B. Haller, J.-W. Janiesch et al., Sequential bottom-up assembly of mechanically stabilized synthetic cells by microfluidics. Nat. Mater. 17, 89–96 (2018). https://doi.org/10.1038/nmat5005
L. Cohen, N. Cui, Y. Cai, P.M. Garden, X. Li et al., Single molecule protein detection with attomolar sensitivity using droplet digital enzyme-linked immunosorbent assay. ACS Nano 14, 9491–9501 (2020). https://doi.org/10.1021/acsnano.0c02378
C. Holtze, A.C. Rowat, J.J. Agresti, J.B. Hutchison, F.E. Angilè et al., Biocompatible surfactants for water-in-fluorocarbon emulsions. Lab Chip 8, 1632–1639 (2008). https://doi.org/10.1039/B806706F
M.S. Chowdhury, W. Zheng, S. Kumari, J. Heyman, X. Zhang et al., Dendronized fluorosurfactant for highly stable water-in-fluorinated oil emulsions with minimal inter-droplet transfer of small molecules. Nat. Commun. 10, 4546 (2019). https://doi.org/10.1038/s41467-019-12462-5
I. Platzman, J.-W. Janiesch, J.P. Spatz, Synthesis of nanostructured and biofunctionalized water-in-oil droplets as tools for homing T cells. J. Am. Chem. Soc. 135, 3339–3342 (2013). https://doi.org/10.1021/ja311588c
M. Cui, T. Emrick, T.P. Russell, Stabilizing liquid drops in nonequilibrium shapes by the interfacial jamming of nanoparticles. Science 342, 460–463 (2013). https://doi.org/10.1126/science.1242852
C. Huang, J. Forth, W. Wang, K. Hong, G.S. Smith et al., Bicontinuous structured liquids with sub-micrometre domains using nanoparticle surfactants. Nat. Nanotechnol. 12, 1060–1063 (2017). https://doi.org/10.1038/nnano.2017.182
D. Kumar, J.D. Paulsen, T.P. Russell, N. Menon, Wrapping with a splash: high-speed encapsulation with ultrathin sheets. Science 359, 775–778 (2018). https://doi.org/10.1126/science.aao1290
L.D. Zarzar, V. Sresht, E.M. Sletten, J.A. Kalow, D. Blankschtein et al., Dynamically reconfigurable complex emulsions via tunable interfacial tensions. Nature 518, 520–524 (2015). https://doi.org/10.1038/nature14168
Z. Yang, J. Wei, Y.I. Sobolev, B.A. Grzybowski, Systems of mechanized and reactive droplets powered by multi-responsive surfactants. Nature 553, 313–318 (2018). https://doi.org/10.1038/nature25137
A.S. Cheung, D.K.Y. Zhang, S.T. Koshy, D.J. Mooney, Scaffolds that mimic antigen-presenting cells enable ex vivo expansion of primary T cells. Nat. Biotechnol. 36, 160–169 (2018). https://doi.org/10.1038/nbt.4047
D.M. Rissin, C.W. Kan, T.G. Campbell, S.C. Howes, D.R. Fournier et al., Single-molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations. Nat. Biotechnol. 28, 595–599 (2010). https://doi.org/10.1038/nbt.1641
C. Wu, P.M. Garden, D.R. Walt, Ultrasensitive detection of attomolar protein concentrations by dropcast single molecule assays. J. Am. Chem. Soc. 142, 12314–12323 (2020). https://doi.org/10.1021/jacs.0c04331
L. Cohen, D.R. Walt, Evaluation of antibody biotinylation approaches for enhanced sensitivity of single molecule array (Simoa) immunoassays. Bioconj. Chem. 29, 3452–3458 (2018). https://doi.org/10.1021/acs.bioconjchem.8b00601
R.P. Lyon, T.D. Bovee, S.O. Doronina, P.J. Burke, J.H. Hunter et al., Reducing hydrophobicity of homogeneous antibody-drug conjugates improves pharmacokinetics and therapeutic index. Nat. Biotechnol. 33, 733–735 (2015). https://doi.org/10.1038/nbt.3212
N. Boehnke, C. Cam, E. Bat, T. Segura, H.D. Maynard, Imine hydrogels with tunable degradability for tissue engineering. Biomacromolecules 16, 2101–2108 (2015). https://doi.org/10.1021/acs.biomac.5b00519
E. Amstad, Capsules made from prefabricated thin films. Science 359, 743 (2018). https://doi.org/10.1126/science.aar4027