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 electrophoresis
and spectroscopic characterization of vesicles in solution (bulk measurements)
to the possibility of spectroscopic investigation of individual, size-separated/collected
liposomes after nES GEMMA. Surface-dried, size-selected vesicles were
collected intact on calcium fluoride (CaF2) substrates
and zinc selenide (ZnSe) prisms, respectively, for subsequent spectroscopic
investigation. Our proof-of-principle study demonstrates that the
off-line hyphenation of gas-phase electrophoresis and confocal Raman
spectroscopy 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-specific
information with nanoscale lateral resolution. The off-line hyphenation
of nES GEMMA and AFM-IR is introduced to enable chemical imaging of
single, i.e., individual, liposome particles.