Gas-Phase Electrophoresis (nES GEMMA Instrumentation) of SARS-CoV-2-Based Virus-like Particles

Gas-phase electrophoresis separates singly charged particles according to their size at ambient pressure in a high laminar sheath flow of particle-free air and a tunable electric field. Subsequent detection of analytes is particle-number-based. Such a setup is very robust and has been successfully applied for several (bio)-nanoparticle-containing materials, e.g., virus-like particles (VLPs). These resemble their parent viruses but due to lack of genomic material are noninfectious. Hence, VLPs find great interest, e.g., in the fields of vaccine development, shielded cargo transport, gene therapy, or parent virus characterization. In all those cases, information on particle size, size distribution, analyte stability, particle numbers, and particle-size derived molecular weight (MW) values yields valuable insights into the VLP in question. Focusing on SARS-CoV-2 VLPs, the source of the recent COVID-19 pandemic, we demonstrate for the first time that gas-phase electrophoresis on a nES GEMMA (nano-electrospray gas-phase electrophoretic mobility molecular analyzer) also known as nES DMA (differential mobility analyzer) or SMPS instrument is possible. VLPs can be detected as broad, size-heterogeneous peaks next to low MW material. Host-cell proteins as well as VLP building blocks can thus be analyzed with the same setup as native macromolecules. Therefore, nES GEMMA measurements are able to support characterization of SARS-CoV-2 VLP-containing samples in terms of VLP stability, particle size, number concentration, and MW values (based on a MW/nES GEMMA-derived particle size correlation).