Fabrication of functionalized double-lamellar multifunctional envelope-type nanodevices using a microfluidic chip with a chaotic mixer array.
Multifunctional envelope-type nanodevices (MENDs) are very promising non-viral gene delivery vectors because they are biocompatible and enable programmed packaging of various functional elements into an individual nanostructured liposome. Conventionally MENDs have been fabricated by complicated, labor-intensive, time-consuming bulk batch methods. To avoid these problems in MEND fabrication, we adopted a microfluidic chip with a chaotic mixer array on the floor of its reaction channel. The array was composed of 69 cycles of the staggered chaotic mixer with bas-relief structures. Although the reaction channel had very large Péclet numbers (>10(5)) favorable for laminar flows, its chaotic mixer array led to very small mixing lengths (<1.5 cm) and that allowed homogeneous mixing of MEND precursors in a short time. Using the microfluidic chip, we fabricated a double-lamellar MEND (D-MEND) composed of a condensed plasmid DNA core and a lipid bilayer membrane envelope as well as the D-MEND modified with trans-membrane peptide octaarginine. Our lab-on-a-chip approach was much simpler, faster, and more convenient for fabricating the MENDs, as compared with the conventional bulk batch approaches. Further, the physical properties of the on-chip-fabricated MENDs were comparable to or better than those of the bulk batch-fabricated MENDs. Our fabrication strategy using microfluidic chips with short mixing length reaction channels may provide practical ways for constructing more elegant liposome-based non-viral vectors that can effectively penetrate all membranes in cells and lead to high gene transfection efficiency.
Department of Applied Chemistry, Graduate School of Engineering, Nagoya University, Nagoya, Japan.
Katsuma
K
Kitazoe
Yeon-Su
YS
Park
Noritada
N
Kaji
Yukihiro
Y
Okamoto
Manabu
M
Tokeshi
Kentaro
K
Kogure
Hideyoshi
H
Harashima
Yoshinobu
Y
Baba
D018014:Gene Transfer Techniques; D008051:Lipid Bilayers / Q000737:chemistry; D044085:Microfluidics / Q000295:instrumentation*; D049329:Nanostructures / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry; D010316:Particle Size; D010957:Plasmids / Q000737:chemistry; D011073:Polyamines / Q000737:chemistry; D000071228:Polyelectrolytes
D008051:Lipid Bilayers; D009842:Oligopeptides; D011073:Polyamines; D000071228:Polyelectrolytes