[PDF][PDF] Artificial bacterial flagella for remote-controlled targeted single-cell drug delivery

R Mhanna, F Qiu, L Zhang, Y Ding, K Sugihara… - Small, 2014 - ethz.ch
Small, 2014ethz.ch
Rami Mhanna,* Famin Qiu, Li Zhang, Yun Ding, Kaori Sugihara, Marcy Zenobi-Wong, and
Bradley J. Nelson the swimming of helical microrobots was developed in our laboratory.[10]
These devices, which we call artificial bacterial flagella (ABFs), are capable of performing
precise 3D swimming in liquids similar to natural bacterial flagella (eg, E. coli) which makes
them suitable for several in vivo and in vitro applications.[11] ABFs can also be coated with a
biocompatible layer such as titanium to reduce cytotoxicity.[12] We hypothesized that ABFs …
Rami Mhanna,* Famin Qiu, Li Zhang, Yun Ding, Kaori Sugihara, Marcy Zenobi-Wong, and Bradley J. Nelson the swimming of helical microrobots was developed in our laboratory.[10] These devices, which we call artificial bacterial flagella (ABFs), are capable of performing precise 3D swimming in liquids similar to natural bacterial flagella (eg, E. coli) which makes them suitable for several in vivo and in vitro applications.[11] ABFs can also be coated with a biocompatible layer such as titanium to reduce cytotoxicity.[12] We hypothesized that ABFs can be functionalized with liposomes, thus allowing these micromachines to perform biological or biomedical tasks in a remotely controlled fashion. To test this hypothesis fluorescently labeled liposomes and calcein-loaded liposomes were adsorbed on the surface of ABFs. The adsorption of liposomes on the ABFs was confirmed by quartz crystal microbalance with dissipation monitoring (QCM-D) and fluorescence recovery after photobleaching (FRAP). The liposome-functionalized ABFs were then placed in contact with cells in vitro and the uptake of calcein (a model water soluble drug) by cells was monitored using fluorescence microscopy. The fabrication of ABFs was followed as described earlier by Tottori et al.[12] with the exception that the thickness of the Ni layer was 25 nm and the thickness of the Ti layer was 15 nm for the devices used in the current study. In our previous work, we showed the ability of Ni/Ti helical microswimmers to perform controlled swimming and cargo transport in 3D liquids.[12] The thickness of Ni used ranged from 50 to 100 nm while the Ti thickness ranged from 0 to 5 nm. In the current study, the Ni thickness was reduced to 25 nm to improve the transparency of the microswimmers and consequently the quality of acquired confocal laser scanning microscope (CLSM) images. The Ti thickness on the other hand was increased to 15 nm to ensure complete coating of the Ni layer resulting in better cytocompatibility and adsorption of intact liposomes. ABFs used in the current work had three turns and were fabricated with horizontal arrays (Figure 1a). An individual ABF had a length of 16 µm and a diameter of 5 µm (Figure 1 a). The filament cross section had an ellipsoidal shape with a thickness of approximately 1.19 µm along the short axis and 2.23 µm along the long axis (Supporting Information Figure S1). ABFs exhibit corkscrew swimming in liquids in response to a rotating magnetic field B at a frequency f. When a magnetic field of 3 mT was applied, ABFs wobbled about their longitudinal axis in response to a frequency below≈ 1 Hz. Smooth corkscrew motion was achieved at higher frequencies below the step-out frequency after
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