Microfluidic synthesis of tail‐shaped alginate microparticles using slow sedimentation

This study reports the synthesis of tail‐shaped alginate particles using a microfluidic platform combined with a sedimentation strategy. By utilizing microfluidic emulsification in the cross‐junction channel, the formation of regular droplets was achieved. Following a facile and convenient sedimentation process and an ionic crosslinking process, sodium‐alginate droplets became tail‐shaped and then gradually developed into calcium‐alginate microparticles. The effects of the concentration of the CaCl2 crosslinker and the viscosity of the alginate solution on the shape and/or size of the particles were further investigated. The proposed synthesis methodology has the advantages of actively controlling the tail‐shape formation, having a narrow size distribution, as well as being a facile and convenient process with a high throughput. This approach can be applied to many applications in the pharmaceutical and biomedical arena.

[1]  M. Bousmina,et al.  Effect of interfacial modifier on single drop deformation and breakup in step increasing shear flow , 2012, Rheologica Acta.

[2]  Che-Hsin Lin,et al.  Microfluidic controlling monodisperse microdroplet for 5-fluorouracil loaded genipin-gelatin microcapsules. , 2009, Journal of controlled release : official journal of the Controlled Release Society.

[3]  Jing Liu,et al.  Shape-controlled production of biodegradable calcium alginate gel microparticles using a novel microfluidic device. , 2006, Langmuir : the ACS journal of surfaces and colloids.

[4]  Lorenzo Capretto,et al.  Effect of the gelation process on the production of alginate microbeads by microfluidic chip technology. , 2008, Lab on a chip.

[5]  Catarina P Reis,et al.  Review and current status of emulsion/dispersion technology using an internal gelation process for the design of alginate particles , 2006, Journal of microencapsulation.

[6]  S. Takeuchi,et al.  Monodisperse Alginate Hydrogel Microbeads for Cell Encapsulation , 2007 .

[7]  A. Khademhosseini,et al.  Microfluidic fabrication of microengineered hydrogels and their application in tissue engineering. , 2012, Lab on a chip.

[8]  Liang-Yin Chu,et al.  Monodisperse alginate microcapsules with oil core generated from a microfluidic device. , 2010, Journal of colloid and interface science.

[9]  Ethan Tumarkin,et al.  Microfluidic production of biopolymer microcapsules with controlled morphology. , 2006, Journal of the American Chemical Society.

[10]  Chih-Hui Yang,et al.  Synthesis of agar microparticles using temperature‐controlled microfluidic devices for Cordyceps militaris cultivation , 2011, Electrophoresis.

[11]  A. Boccaccini,et al.  Physicochemical, biological and drug-release properties of gallium crosslinked alginate/nanoparticulate bioactive glass composite films , 2011 .

[12]  Paula T Hammond,et al.  The effects of polymeric nanostructure shape on drug delivery. , 2011, Advanced drug delivery reviews.

[13]  D. Weitz,et al.  Microfluidic synthesis of monodisperse porous microspheres with size-tunable pores , 2012 .

[14]  Y. Rhee,et al.  Generation of monodisperse alginate microbeads and in situ encapsulation of cell in microfluidic device , 2007, Biomedical microdevices.

[15]  Kausik Sarkar,et al.  Viscoelastic drop falling through a viscous medium , 2011 .

[16]  G. Hadziioannou,et al.  A predictive approach of the influence of the operating parameters on the size of polymer particles synthesized in a simplified microfluidic system. , 2007, Langmuir : the ACS journal of surfaces and colloids.

[17]  A. Nir,et al.  Motion of viscous drops in tubes filled with yield stress fluid , 2009 .

[18]  A. Colin,et al.  Some recent advances in the design and the use of miniaturized droplet-based continuous process: applications in chemistry and high-pressure microflows. , 2011, Lab on a chip.

[19]  Xiangyang Shi,et al.  pH sensitive Laponite/alginate hybrid hydrogels: swelling behaviour and release mechanism , 2011 .

[20]  C. Tzeng,et al.  Microfluidic assisted synthesis of multi-functional polycaprolactone microcapsules: incorporation of CdTe quantum dots, Fe3O4 superparamagnetic nanoparticles and tamoxifen anticancer drugs. , 2009, Lab on a chip.

[21]  Ricardo Cortez,et al.  Shape oscillations of a droplet in an Oldroyd-B fluid , 2011 .

[22]  Ming-Ying Hsu,et al.  In situ synthesis of twin monodispersed alginate microparticles , 2011 .

[23]  S. Herminghaus,et al.  Droplet based microfluidics , 2012, Reports on progress in physics. Physical Society.

[24]  M. Joglekar,et al.  Effect of alginate encapsulation on the cellular transcriptome of human islets. , 2011, Biomaterials.

[25]  Yu-Cheng Lin,et al.  Using a T-junction microfluidic chip for monodisperse calcium alginate microparticles and encapsulation of nanoparticles , 2009 .

[26]  Yu-Che Huang,et al.  Microfluidic emulsification and sorting assisted preparation of monodisperse chitosan microparticles. , 2009, Lab on a chip.

[27]  T. Wong,et al.  Alginate graft copolymers and alginate–co‐excipient physical mixture in oral drug delivery , 2011, The Journal of pharmacy and pharmacology.

[28]  J. Baret.  Surfactants in droplet-based microfluidics. , 2012, Lab on a chip.

[29]  Andrew Belmonte,et al.  Motion and shape of a viscoelastic drop falling through a viscous fluid , 2003, Journal of Fluid Mechanics.

[30]  W. Liu,et al.  Generation of Janus alginate hydrogel particles with magnetic anisotropy for cell encapsulation. , 2009, Lab on a chip.

[31]  Kelly M. Schultz,et al.  High-throughput rheology in a microfluidic device. , 2011, Lab on a chip.

[32]  Yu-Cheng Lin,et al.  Using a microfluidic chip and internal gelation reaction for monodisperse calcium alginate microparticles generation. , 2007, Frontiers in bioscience : a journal and virtual library.

[33]  Anubhav Tripathi,et al.  Microfluidic reactors for diagnostics applications. , 2011, Annual review of biomedical engineering.

[34]  Feng Guo,et al.  On-demand preparation of quantum dot-encoded microparticles using a droplet microfluidic system. , 2011, Lab on a chip.

[35]  Abbas Fakhari,et al.  Investigation of deformation and breakup of a falling droplet using a multiple-relaxation-time lattice Boltzmann method , 2011 .

[36]  B. Paull,et al.  Centrifugally-driven sample extraction, preconcentration and purification in microfluidic compact discs , 2011 .

[37]  Dhananjay Dendukuri,et al.  Controlled synthesis of nonspherical microparticles using microfluidics. , 2005, Langmuir : the ACS journal of surfaces and colloids.

[38]  Motion and shape of an axisymmetric viscoplastic drop slowly falling through a viscous fluid , 2011 .

[39]  S. Leick,et al.  Alginate/poly-L-lysine capsules: mechanical properties and drug release characteristics , 2011 .

[40]  Keng-Shiang Huang,et al.  Anti-inflammatory effect with high intensity focused ultrasound-mediated pulsatile delivery of diclofenac. , 2012, Biomaterials.

[41]  Jingtao Wang,et al.  Fabrication of advanced particles and particle-based materials assisted by droplet-based microfluidics. , 2011, Small.

[42]  Min-Hsien Wu,et al.  Development of microfluidic alginate microbead generator tunable by pulsed airflow injection for the microencapsulation of cells , 2010 .

[43]  Kevin J Edgar,et al.  Alginate derivatization: a review of chemistry, properties and applications. , 2012, Biomaterials.

[44]  A. Reusken,et al.  Validated simulation of droplet sedimentation with finite-element and level-set methods. , 2010 .

[45]  Ning Fang,et al.  Recent advances in single‐molecule detection on micro‐ and nano‐fluidic devices , 2011, Electrophoresis.

[46]  D. Mooney,et al.  Alginate: properties and biomedical applications. , 2012, Progress in polymer science.

[47]  Chih-Yu Wang,et al.  Electrostatic droplets assisted synthesis of alginate microcapsules , 2011, Drug Delivery and Translational Research.

[48]  H. Hsu,et al.  Microfluidic Synthesis of Microfibers for Magnetic-Responsive Controlled Drug Release and Cell Culture , 2012, PloS one.

[49]  Yung-Sheng Lin,et al.  An Aluminum Microfluidic Chip Fabrication Using a Convenient Micromilling Process for Fluorescent Poly(dl-lactide-co-glycolide) Microparticle Generation , 2012, Sensors.

[50]  Dhananjay Dendukuri,et al.  The Synthesis and Assembly of Polymeric Microparticles Using Microfluidics , 2009 .