Native Nano-electrospray Differential Mobility Analyzer(nES GEMMA) Enables Size Selection of Liposomal Nanocarriers Combinedwith Subsequent Direct Spectroscopic Analysis

摘要

Gas-phase electrophoresis employing a nano-electrospray differential mobility analyzer (nES DMA), aka gas-phase electrophoretic mobility molecular analyzer (nES GEMMA), enables nanoparticle separation in the gas-phase according to their surface-dry diameter with number-based concentration detection. Moreover, particles in the nanometer size range can be collected after size selection on supporting materials. It has been shown by subsequent analyses employing orthogonal methods, for instance, microscopic or antibody-based techniques, that the surface integrity of collected analytes remains intact. Additionally, native nES GEMMA demonstrated its applicability for liposome characterization. Liposomes are nanometer-sized, biodegradable, and rather labile carriers (nanoobjects) consisting of a lipid bilayer encapsulating an aqueous lumen. In nutritional and pharmaceutical applications, these vesicles allow shielded, targeted transport and sustained release of bioactive cargo material. To date, cargo quantification is based on bulk measurements after bilayer rupture. In this context, we now compare capillary electrophoresisand spectroscopic characterization of vesicles in solution (bulk measurements)to the possibility of spectroscopic investigation of individual, size-separated/collectedliposomes after nES GEMMA. Surface-dried, size-selected vesicles werecollected intact on calcium fluoride (CaF2) substratesand zinc selenide (ZnSe) prisms, respectively, for subsequent spectroscopicinvestigation. Our proof-of-principle study demonstrates that theoff-line hyphenation of gas-phase electrophoresis and confocal Ramanspectroscopy allows detection of isolated, nanometer-sized soft material/objects.Additionally, atomic force microscopy-infrared spectroscopy (AFM-IR)as an advanced spectroscopic system was employed to access molecule-specificinformation with nanoscale lateral resolution. The off-line hyphenationof nES GEMMA and AFM-IR is introduced to enable chemical imaging ofsingle, i.e., individual, liposome particles.