Even if you haven’t heard about lipid nanoparticles (LNPs) by this point, your body probably has.
LNPs are, as their name suggests, a class of lipid-based nano-sized particles. LNPs can trace their origins back to the discovery of the liposome in the 1960s.1 Since then, more complex LNPs have been designed. These include mRNA-containing LNPs which recently made headlines worldwide as the vectors of the Moderna and Pfizer-BioNTech SARS-CoV-2 vaccines. Their rapid, widespread use during the pandemic has spawned many a potential mRNA-containing LNP-based therapeutic, making this one of the largest growing areas of nanomedicine. With this comes an urgent need for high-resolution particle measurement techniques for LNPs.
The Exoid is Izon Science’s most advanced Tunable Resistive Pulse Sensing (TRPS) instrument. It uses the Coulter principle to simultaneously measure size and concentration or size and zeta potential in a particle-by-particle manner. In doing so, the Exoid has been shown to have superior resolution as compared to ensemble techniques such as Dynamic Light Scattering (DLS) and Nanoparticle Tracking Analysis (NTA).2 With its capabilities of measuring particles from 40 nm all the way up to 11 µm in diameter, the Exoid is well suited to a variety of particle measurement applications. One such application is the measurement of nanomedicine vectors such as LNPs.
Given the ability of mRNA-containing LNPs to revolutionise vaccines, and the Exoid having been successfully used to measure them in field, we decided it was time to put the Exoid through its paces.
Round 1 Preview: Size analysis of mRNA-loaded and empty lipid nanoparticles
The first trial for the Exoid was to detect tiny differences in size between two populations of LNPs. For this, we used empty LNPs and compared them to those loaded with mRNA, expecting to see a small size difference which would arise from the reorganisation of the lipid structure around the negatively charged mRNA molecules.
As shown in Figure 1, this was a success. Here you can see a representative size distribution chart comparing the empty and mRNA-loaded LNPs. In the sample shown in Figure 1, the size mode of the empty LNPs is 71 nm and the size of the mRNA-loaded LNPs is 66 nm. This small change in size was replicable between measurements, showing just how capable the Exoid is of consistently detecting small size differences between samples. Further information on LNP size over several repeats is shown in the application note.
Rounds 2-4: Analysing lipid nanoparticle concentration, aggregation, and zeta potential
We also put the Exoid through a number of other tests using the empty and mRNA-containing LNPs:
Round 2: Concentration. In those same samples, during those same measurements, the Exoid also calculated the sample concentrations.
Round 3: Aggregation analysis. Can the Exoid detect changes in mRNA-containing LNP size as a result of sub-standard storage?
Round 4: Zeta potential. Finally, we put the Exoid to the test of discerning any difference in the zeta potential – i.e., the surface charge – of the empty and mRNA-loaded LNPs.
- Round 2: Concentration. In those same samples, during those same measurements, the Exoid also calculated the sample concentrations.
- Round 3: Aggregation analysis. Can the Exoid detect changes in mRNA-containing LNP size as a result of sub-standard storage?
- Round 4: Zeta potential. Finally, we put the Exoid to the test of discerning any difference in the zeta potential – i.e., the surface charge – of the empty and mRNA-loaded LNPs.
Download the app note to see how the Exoid excels at lipid nanoparticle analysis
In our hands, the Exoid performed excellently when it came to LNP analysis for size, concentration and zeta potential. But don’t just take our word for it: download the app note to see the data for yourself!
Get the app note now: Analysing Lipid Nanoparticles Using Tunable Resistive Pulse Sensing With the Exoid
