Ultra-high throughput synthesis of nanoparticles with homogeneous size distribution using a coaxial turbulent jet mixer.
High-throughput production of nanoparticles (NPs) with controlled quality is critical for their clinical translation into effective nanomedicines for diagnostics and therapeutics. Here we report a simple and versatile coaxial turbulent jet mixer that can synthesize a variety of NPs at high throughput up to 3 kg/d, while maintaining the advantages of homogeneity, reproducibility, and tunability that are normally accessible only in specialized microscale mixing devices. The device fabrication does not require specialized machining and is easy to operate. As one example, we show reproducible, high-throughput formulation of siRNA-polyelectrolyte polyplex NPs that exhibit effective gene knockdown but exhibit significant dependence on batch size when formulated using conventional methods. The coaxial turbulent jet mixer can accelerate the development of nanomedicines by providing a robust and versatile platform for preparation of NPs at throughputs suitable for in vivo studies, clinical trials, and industrial-scale production.
Department of Mechanical Engineering, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
Jong-Min
JM
Lim
Archana
A
Swami
Laura M
LM
Gilson
Sunandini
S
Chopra
Sungyoung
S
Choi
Jun
J
Wu
Robert
R
Langer
Rohit
R
Karnik
Omid C
OC
Farokhzad
D000465:Algorithms; D004573:Electrolytes / Q000737:chemistry; D004867:Equipment Design; D005290:Ferric Compounds / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D008422:Materials Testing; D046210:Microfluidic Analytical Techniques; D044085:Microfluidics; D050997:Nanomedicine / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011137:Polystyrenes / Q000737:chemistry; D034741:RNA, Small Interfering / Q000378:metabolism; D015203:Reproducibility of Results; D014162:Transfection
D004573:Electrolytes; D005290:Ferric Compounds; D008055:Lipids; D011137:Polystyrenes; D034741:RNA, Small Interfering; C000499:ferric oxide; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols