Abstract
Degradation of ionizable lipids in mRNA-based vaccines was recently found to deactivate the payload, demanding rigorous monitoring of impurities in lipid nanoparticle (LNP) formulations. However, parallel screening for lipid degradation in customized delivery systems for next-generation therapeutics maintains a challenging and unsolved problem. Here, we describe a nanopore electrochemical sensor to detect ppb-levels of aldehydes arising from lipid degradation in LNP formulations that can be deployed in massively parallel fashion. Specifically, we combine nanopore electrodes with a block copolymer (BCP) membrane capable of hydrophobic gating of analyte transport between the bulk solution and the nanopore volume. By incorporating aldehyde dehydrogenase (ALDH), enzymatic oxidation of aldehydes generates NADH to enable ultrasensitive voltammetric detection with limits-of-detection (LOD) down to 1.2 ppb. Sensor utility was demonstrated by detecting degradation of N-oxidized SM-102, the ionizable lipid in Moderna's SpikeVax™ vaccine, in mRNA-1273 LNP formulation. This work should be of significant use in the pharmaceutical industry, paving the way for automated on-line quality assessments of next-generation therapeutics.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
