Conducting Polymeric Nanocomposites with a Three-Dimensional Co-flow Microfluidics Platform
<p>The building blocks for the microfluidics chip. (<b>1</b>) The inlet and outlet needle of flow; (<b>2</b>) Tapered inner capillary; (<b>3</b>) Outer capillary; (<b>4</b>) Assembly of individual parts on a glass slide.</p> "> Figure 2
<p>Workstation to fabricate polymer into nanoparticles (NPs). (<b>A</b>) Pump A; (<b>B</b>) Pump B; (<b>C</b>) Syringe A; (<b>D</b>) Syringe B; (<b>E</b>) Microfluidics chip; (<b>F</b>) Microscope; (<b>G</b>) Beaker; (<b>H</b>) Stirrer; (<b>I</b>) Monitor; (<b>J</b>) Computer.</p> "> Figure 3
<p>(<b>A</b>) A schematic representation of 3D co-flow microfluidics and (<b>B</b>) a digital view of the inner and outer capillary.</p> "> Figure 4
<p>Hydrodynamic diameters of the as-prepared NPs. (<b>A</b>) Hydrodynamic sizes at different acetalated dextran (Ac-DEX) concentrations with fixed I/O flow at 2:40 mL/h (8.5 × 10<sup>−</sup><sup>2</sup> mm) in the micro-channels; (<b>B</b>) Hydrodynamic sizes at a 1 mg/mL Ac-DEX concentration with different fixed I/O flows (8.5 × 10<sup>−2</sup> mm) in the micro-channels; (<b>C</b>) Hydrodynamic sizes at 1 mg/mL Ac-DEX concentration with fixed I/O flow at 1:40 mL/h in different micro-channels; (<b>D</b>) Hydrodynamic sizes at different spermine acetalated dextran (Sp-Ac-DEX) concentrations with fixed I/O flow at 2:40 mL/h (8.5 × 10<sup>−2</sup> mm) in the micro-channels; (<b>E</b>) Hydrodynamic sizes at 2 mg/mL Sp-Ac-DEX concentration with different I/O flows (8.5 × 10<sup>−2</sup> mm) in the micro-channels; (<b>F</b>) Hydrodynamic sizes at 2 mg/mL Sp-Ac-DEX concentration with fixed I/O flow at 2:40 mL/h in different micro-channels; (<b>G</b>) Hydrodynamic sizes at different poly(lactic-co-glycolic acid) (PLGA) concentrations with fixed I/O flow at 2:40 mL/h (8.5 × 10<sup>−2</sup> mm) in the micro-channels; (<b>H</b>) Hydrodynamic sizes at 1 mg/mL PLGA concentration with different I/O flows (8.5 × 10<sup>−2</sup> mm) in the micro-channels; (<b>I</b>) Hydrodynamic sizes at 1 mg/mL PLGA concentration with fixed I/O flow at 1:40 mL/h in different micro-channels; (<b>J</b>) Hydrodynamic sizes at different chitosan concentrations with fixed I/O flow at 2:40 mL/h (8.5 × 10<sup>−2</sup> mm) in the micro-channels; (<b>K</b>) Hydrodynamic sizes at 1 mg/mL chitosan concentration with different I/O flows (8.5 × 10<sup>−2</sup> mm) in the micro-channels; (<b>L</b>) Hydrodynamic sizes at 1 mg/mL chitosan concentration with fixed I/O flow at 2:40 mL/h in different micro-channels.</p> "> Figure 5
<p>TEM images of as-prepared NPs. (<b>A</b>–<b>C</b>): Ac-DEX; (<b>D</b>–<b>F</b>): Sp-Ac-DEX; (<b>G</b>–<b>I</b>): PLGA; (<b>J</b>–<b>L</b>): chitosan. Scale bars: (<b>D</b>,<b>E</b>,<b>J</b>): 100 nm; (<b>A</b>,<b>B</b>,<b>K</b>): 200 nm; (<b>C</b>,<b>G</b>,<b>H</b>): 500 nm; (<b>L</b>) 1 μm; (<b>I</b>) 2 μm; (<b>F</b>) 5 μm.</p> ">
Abstract
:1. Introduction
2. Materials and Methods
2.1. Building a Chip for Microfluidics
2.1.1. Syringe tip fabrication
2.1.2. Inner capillary tapering
2.1.3. Outer capillary Truncation
2.1.4. Put All Parts Together
2.1.5. Check the Chip
- -
- Did the tip of the inner capillary remain undamaged? View the tip under a microscope in the microfluidics lab.
- -
- It is damaged → start anew.
- -
- Does the system have a leakage/blockage? Run the system with ethanol to (A) and pure water to (B) with a flow rate of 2:40 mL/h (inner/outer), and collect the NPs from (C).
- -
- Blockage → start anew.
- -
- Leakage → dry the chip and apply some glue to the leaking areas; let the glue solidify and try again.
2.2. Materials for Nanofabrication
2.3. Fabrication of Polymeric Nanoparticles (NPs)
2.4. Characterization of Polymeric NPs
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Fessi, H.; Puisieux, F.; Devissaguet, J.P.; Ammoury, N.; Benita, S. Nanocapsule formation by interfacial polymer deposition following solvent displacement. Int. J. Pharm. 1989, 55, R1–R4. [Google Scholar] [CrossRef]
- Mahapatro, A.; Singh, D.K. Biodegradable nanoparticles are excellent vehicle for site directed in-vivo delivery of drugs and vaccines. J. Nanobiotechnol. 2011, 9, 55. [Google Scholar] [CrossRef] [PubMed]
- Yang, Y.; Hou, W.; Liu, S.; Sun, K.; Li, M.; Wu, C. Biodegradable Polymer Nanoparticles for Photodynamic Therapy by Bioluminescence Resonance Energy Transfer. Biomacromolecules 2017, 19, 201–208. [Google Scholar] [CrossRef] [PubMed]
- Masood, F. Polymeric nanoparticles for targeted drug delivery system for cancer therapy. Mater. Sci. Eng. C 2016, 60, 569–578. [Google Scholar] [CrossRef] [PubMed]
- Farias, P.V.S.; Aragão, D.C.; Farias, M.V.; Correia, L.M.; Carvalho, T.V.; Aguiar, J.E.; Vieira, R.S. Natural and Cross-Linked Chitosan Spheres as Adsorbents for Diesel Oil Removal. Adsorpt. Sci. Technol. 2015, 33, 783–792. [Google Scholar] [CrossRef]
- Kurlyandskaya, G.V.; Litvinova, L.S.; Safronov, A.P.; Schupletsova, V.V.; Tyukova, I.S.; Khaziakhmatova, O.G.; Slepchenko, G.B.; Yurova, K.A.; Cherempey, E.G.; Kulesh, N.A.; et al. Water-Based Suspensions of Iron Oxide Nanoparticles with Electrostatic or Steric Stabilization by Chitosan: Fabrication, Characterization and Biocompatibility. Sensers 2017, 17, 2605. [Google Scholar] [CrossRef] [PubMed]
- Ma, H.; Pu, S.; Ma, J.; Yan, C.; Zinchenko, A.; Pei, X.; Chu, W. Formation of multi-layered chitosan honeycomb spheres via breath-figure-like approach in combination with co-precipitation processing. Mater. Lett. 2018, 211, 91–95. [Google Scholar] [CrossRef]
- Karnik, R.; Gu, F.; Basto, P.; Cannizzaro, C.; Dean, L.; Kyei-Manu, W.; Langer, R.; Farokhzad, O.C. Microfluidic platform for controlled synthesis of polymeric nanoparticles. Nano Lett. 2008, 8, 2906–2912. [Google Scholar] [CrossRef]
- Campbell, F.; Bos, F.L.; Sieber, S.; Arias-Alpizar, G.; Koch, B.E.; Huwyler, J.; Kros, A.; Bussmann, J. Directing Nanoparticle Biodistribution through Evasion and Exploitation of Stab2-Dependent Nanoparticle Uptake. ACS Nano 2018, 12, 2138–2150. [Google Scholar] [CrossRef]
- Melzig, S.; Niedbalka, D.; Schilde, C.; Kwade, A. Spray drying of amorphous ibuprofen nanoparticles for the production of granules with enhanced drug release. Colloids Surf. A Physicochem. Eng. Asp. 2018, 536, 133–141. [Google Scholar] [CrossRef]
- Xue, X.; Huang, Y.; Wang, X.; Wang, Z.; Carney, R.P.; Li, X.; Yuan, Y.; He, Y.; Lin, T.Y.; Li, Y. Self-indicating, fully active pharmaceutical ingredients nanoparticles (FAPIN) for multimodal imaging guided trimodality cancer therapy. Biomaterials 2018, 161, 203–215. [Google Scholar] [CrossRef] [PubMed]
- Masuda, H.; Nakamura, T.; Noma, Y.; Harashima, H. Application of BCG-CWS as a systemic adjuvant by using nanoparticulation technology. Mol. Pharm. 2018, 15, 5762–5771. [Google Scholar] [CrossRef] [PubMed]
- Schubert, S.; Delaney, J.J.T.; Schubert, U.S. Nanoprecipitation and nanoformulation of polymers: From history to powerful possibilities beyond poly(lactic acid). Soft Matter 2011, 7, 1581–1588. [Google Scholar] [CrossRef]
- Mockus, L.; Peterson, J.J.; Lainez, J.M.; Reklaitis, G.V. Batch-to-Batch Variation: A Key Component for Modeling Chemical Manufacturing Processes. Org. Process Res. Dev. 2015, 19, 908–914. [Google Scholar] [CrossRef]
- Zhang, Y.; Liu, D.; Zhang, H.; Santos, H.A. Microfluidic mixing and devices for preparing nanoparticulate drug delivery systems. In Microfluidics for Pharmaceutical Applications; Elsevier: Amsterdam, The Netherlands, 2019; pp. 155–177. [Google Scholar]
- Liu, D.; Cito, S.; Zhang, Y.; Wang, C.F.; Sikanen, T.M.; Santos, H.A. A versatile and robust microfluidic platform toward high throughput synthesis of homogeneous nanoparticles with tunable properties. Adv. Mater. 2015, 27, 2298–2304. [Google Scholar] [CrossRef] [PubMed]
- Li, W.; Zhang, L.; Ge, X.; Xu, B.; Zhang, W.; Qu, L.; Choi, C.-H.; Xu, J.; Zhang, A.; Lee, H. Microfluidic fabrication of microparticles for biomedical applications. Chem. Soc. Rev. 2018, 47, 5646–5683. [Google Scholar] [CrossRef] [PubMed]
- Ghazal, A.; Gontsarik, M.; Kutter, J.P.; Lafleur, J.P.; Ahmadvand, D.; Labrador, A.; Salentinig, S.; Yaghmur, A. Microfluidic platform for the continuous production and characterization of multilamellar vesicles: A synchrotron small-angle X-ray scattering (SAXS) study. J. Phys. Chem. Lett. 2016, 8, 73–79. [Google Scholar] [CrossRef]
- Liu, E.Y.; Jung, S.; Weitz, D.A.; Yi, H.; Choi, C.-H. High-throughput double emulsion-based microfluidic production of hydrogel microspheres with tunable chemical functionalities toward biomolecular conjugation. Lab A Chip 2018, 18, 323–334. [Google Scholar] [CrossRef]
- Zhu, K.; Yu, Y.; Cheng, Y.; Tian, C.; Zhao, G.; Zhao, Y. All-Aqueous-Phase Microfluidics for Cell Encapsulation. ACS Appl. Mater. Interfaces 2019, 11, 4826–4832. [Google Scholar] [CrossRef]
- Choi, N.W.; Cabodi, M.; Held, B.; Gleghorn, J.P.; Bonassar, L.J.; Stroock, A.D. Microfluidic scaffolds for tissue engineering. Nat. Mater. 2007, 6, 908–915. [Google Scholar] [CrossRef]
- Miri, A.K.; Nieto, D.; Iglesias, L.; Goodarzi Hosseinabadi, H.; Maharjan, S.; Ruiz-Esparza, G.U.; Khoshakhlagh, P.; Manbachi, A.; Dokmeci, M.R.; Chen, S.; et al. Microfluidics-Enabled Multimaterial Maskless Stereolithographic Bioprinting. Adv. Mater. 2018, 30, 1800242. [Google Scholar] [CrossRef] [PubMed]
- Friend, J.; Yeo, L. Fabrication of microfluidic devices using polydimethylsiloxane. Biomicrofluidics 2010, 4, 026502. [Google Scholar] [CrossRef] [Green Version]
- Lee, J.N.; Park, C.; Whitesides, G.M. Solvent compatibility of poly (dimethylsiloxane)-based microfluidic devices. Anal. Chem. 2003, 75, 6544–6554. [Google Scholar] [CrossRef] [PubMed]
- Zhong, R.; Tang, Q.; Wang, S.; Zhang, H.; Zhang, F.; Xiao, M.; Man, T.; Qu, X.; Li, L.; Zhang, W. Self-assembly of enzyme-like nanofibrous G-molecular hydrogel for printed flexible electrochemical sensors. Adv. Mater. 2018, 30, 1706887. [Google Scholar] [CrossRef] [PubMed]
- Dirany, M.; Dies, L.; Restagno, F.; Léger, L.; Poulard, C.; Miquelard-Garnier, G. Chemical modification of PDMS surface without impacting the viscoelasticity: Model systems for a better understanding of elastomer/elastomer adhesion and friction. Colloids Surf. A Physicochem. Eng. Asp. 2015, 468, 174–183. [Google Scholar] [CrossRef]
- Paiè, P.; Bragheri, F.; Di Carlo, D.; Osellame, R. Particle focusing by 3D inertial microfluidics. Microsyst. Nanoeng. 2017, 3, 17027. [Google Scholar] [CrossRef] [PubMed]
- Vladisavljevic, G.T.; Shahmohamadi, H.; Das, D.B.; Ekanem, E.E.; Tauanov, Z.; Sharma, L. Glass capillary microfluidics for production of monodispersed poly (DL-lactic acid) and polycaprolactone microparticles: Experiments and numerical simulations. J. Colloid Interface Sci. 2014, 418, 163–170. [Google Scholar] [CrossRef] [PubMed]
- Bachelder, E.M.; Beaudette, T.T.; Broaders, K.E.; Dashe, J.; Fréchet, J.M. Acetal-derivatized dextran: An acid-responsive biodegradable material for therapeutic applications. J. Am. Chem. Soc. 2008, 130, 10494–10495. [Google Scholar] [CrossRef] [PubMed]
- Cohen, J.L.; Schubert, S.; Wich, P.R.; Cui, L.; Cohen, J.A.; Mynar, J.L.; Fréchet, J.M. Acid-degradable cationic dextran particles for the delivery of siRNA therapeutics. Bioconjugate Chem. 2011, 22, 1056–1065. [Google Scholar] [CrossRef] [PubMed]
- Ma, X.; Özliseli, E.; Zhang, Y.; Pan, G.; Wang, D.; Zhang, H. Fabrication of redox-responsive doxorubicin and paclitaxel prodrug nanoparticles with microfluidics for selective cancer therapy. Biomater. Sci. 2019, 7, 634–644. [Google Scholar] [CrossRef] [PubMed]
- Herranz-Blanco, B.; Ginestar, E.; Zhang, H.; Hirvonen, J.; Santos, H.A. Microfluidics platform for glass capillaries and its application in droplet and nanoparticle fabrication. Int. J. Pharm. 2017, 516, 100–105. [Google Scholar] [CrossRef] [PubMed]
- Makadia, H.K.; Siegel, S.J. Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier. Polymer 2011, 3, 1377–1397. [Google Scholar] [CrossRef] [PubMed]
- Danhier, F.; Ansorena, E.; Silva, J.M.; Coco, R.; Le Breton, A.; Préat, V. PLGA-based nanoparticles: An overview of biomedical applications. J. Control. Release 2012, 161, 505–522. [Google Scholar] [CrossRef] [PubMed]
- Sharma, S.; Parmar, A.; Kori, S.; Sandhir, R. PLGA-based nanoparticles: A new paradigm in biomedical applications. Trac Trends Anal. Chem. 2016, 80, 30–40. [Google Scholar] [CrossRef]
- Muxika, A.; Etxabide, A.; Uranga, J.; Guerrero, P.; de la Caba, K. Chitosan as a bioactive polymer: Processing, properties and applications. Int. J. Biol. Macromol. 2017, 105, 1358–1368. [Google Scholar] [CrossRef] [PubMed]
- Sahariah, P.; Másson, M. Antimicrobial Chitosan and Chitosan Derivatives: A Review of the Structure–Activity Relationship. Biomacromolecules 2017, 18, 3846–3868. [Google Scholar] [CrossRef] [PubMed]
- Liu, C.; Zhang, S.; McClements, D.J.; Wang, D.; Xu, Y. Design of astaxanthin-loaded core-shell nanoparticles consisting of chitosan oligosaccharides. J. Agric. Food Chem. 2019, 67, 18. [Google Scholar] [CrossRef] [PubMed]
- Mashaghi, S.; Abbaspourrad, A.; Weitz, D.A.; van Oijen, A.M. Droplet microfluidics: A tool for biology, chemistry and nanotechnology. Trac Trends Anal. Chem. 2016, 82, 118–125. [Google Scholar] [CrossRef] [Green Version]
- Xu, J.H.; Li, S.W.; Tan, J.; Wang, Y.J.; Luo, G.S. Controllable Preparation of Monodisperse O/W and W/O Emulsions in the Same Microfluidic Device. Langmuir 2006, 22, 7943–7946. [Google Scholar] [CrossRef]
- Zhao-Miao, L.I.U.; Yu, D.U.; Yan, P. Generation of Water-In-Oil-In-Water (W/O/W) Double Emulsions by Microfluidics. Chin. J. Anal. Chem. 2018, 46, 324–330. [Google Scholar] [CrossRef]
- Michelon, M.; Huang, Y.; de la Torre, L.G.; Weitz, D.A.; Cunha, R.L. Single-step microfluidic production of W/O/W double emulsions as templates for β-carotene-loaded giant liposomes formation. Chem. Eng. J. 2019, 366, 27–32. [Google Scholar] [CrossRef]
- Xu, Q.; Liu, Z.; Fu, J.; Zhao, W.; Guo, Y.; Sun, X.; Zhang, H. Ratiometric electrochemical aptasensor based on ferrocene and carbon nanofibers for highly specific detection of tetracycline residues. Sci. Rep. 2017, 7, 14729. [Google Scholar] [CrossRef] [PubMed]
- Wang, F.; Curry, D.E.; Liu, J. Driving Adsorbed Gold Nanoparticle Assembly by Merging Lipid Gel/Fluid Interfaces. Langmuir 2015, 31, 13271–13274. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Xuan, X.; Zhu, J.; Church, C. Particle focusing in microfluidic devices. Microfluid. Nanofluidics 2010, 9, 1–16. [Google Scholar] [CrossRef]
- Kheradvar, A.; Milano, M.; Gharib, M. Correlation between vortex ring formation and mitral annulus dynamics during ventricular rapid filling. Asaio J. 2007, 53, 8–16. [Google Scholar] [CrossRef] [PubMed]
- Akhmetov, D.G. Model of vortex ring formation. J. Appl. Mech. Tech. Phys. 2008, 49, 909–918. [Google Scholar] [CrossRef]
- Frohlich, E. The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles. Int. J. Nanomed. 2012, 7, 5577–5591. [Google Scholar] [CrossRef]
Material | Specification | Amount | Producer |
---|---|---|---|
Glass slide | 75 × 25 mm | 1 | BrandTech (Essex, CT, USA) |
Outer capillary | ODa = 1.5 mm; IDb = 1.12 mm | 1 | World Precision Instruments, Inc (Sarasota, FL, USA) |
Inner capillary | ODa = 1.0 mm; IDb = 0.58 mm | 1 | World Precision Instruments, Inc (Sarasota, FL, USA) |
Syringe tip | Blunt end needle | 3 | Warner Instruments (Hamden, CT, USA) |
Glue | 5 min Epoxy | --- | Devcon (Danvers, MA, USA) |
Puller | Model PN-31 | 1 | Narishige (Tokyo, Japan) |
Sandpaper | Grit = 1200 Only a small piece | 1 | Indasa–Rhynowet (Aveiro, Portugal) |
Diamond tip glass cutter | --- | 1 | Harden (Xi’an, China) |
Conditions | Ac-DEX | Sp-Ac-DEX | PLGA | Chitosan | ||||
---|---|---|---|---|---|---|---|---|
4 mg/mL | 0.308 | −8.8 | 0.214 | 16.2 | 0.160 | 1.2 | 0.179 | 14.3 |
3 mg/mL | 0.112 | −7.9 | 0.253 | 15.5 | 0.186 | 0.9 | 0.211 | 12.5 |
2 mg/mL | 0.178 | −7.1 | 0.100 | 15.1 | 0.198 | −1.3 | 0.249 | 11.9 |
1 mg/mL | 0.164 | −5.7 | 0.241 | 13.9 | 0.088 | 0.5 | 0.175 | 12.1 |
1:40 | 0.184 | −5.2 | 0.197 | 14.2 | 0.059 | −0.8 | 0.163 | 11.2 |
2:40 | 0.164 | −5.7 | 0.100 | 15.1 | 0.088 | 0.5 | 0.175 | 12.1 |
4:40 | 0.210 | −6.3 | 0.097 | 16.1 | 0.123 | 0.3 | 0.176 | 11.8 |
6:40 | 0.173 | −7.4 | 0.183 | 16.6 | 0.239 | 0.7 | 0.203 | 12.8 |
5.2 × 10−4 mm | 0.194 | −6.1 | 0.177 | 15.6 | 0.135 | 0.9 | 0.215 | 11.6 |
8.5 × 10−2 mm | 0.184 | −5.2 | 0.100 | 15.1 | 0.059 | −0.8 | 0.175 | 12.1 |
1.7 × 10−1 mm | 0.198 | −6.5 | 0.175 | 16.2 | 0.134 | −1.2 | 0.125 | 12.0 |
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Ma, X.; Zhang, Y.; Weisensee, K. Conducting Polymeric Nanocomposites with a Three-Dimensional Co-flow Microfluidics Platform. Micromachines 2019, 10, 383. https://doi.org/10.3390/mi10060383
Ma X, Zhang Y, Weisensee K. Conducting Polymeric Nanocomposites with a Three-Dimensional Co-flow Microfluidics Platform. Micromachines. 2019; 10(6):383. https://doi.org/10.3390/mi10060383
Chicago/Turabian StyleMa, Xiaodong, Yuezhou Zhang, and Korbinian Weisensee. 2019. "Conducting Polymeric Nanocomposites with a Three-Dimensional Co-flow Microfluidics Platform" Micromachines 10, no. 6: 383. https://doi.org/10.3390/mi10060383