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New: LNP Application Guide — quantifying mRNA payloads, targeting ligands, and co-encapsulation in a single run.

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What to Measure

Four critical quality attributes of LNP formulations

Particle size, concentration, targeting ligand density, and RNA payload each directly influence drug product safety and efficacy. Accurately characterizing all four requires a method that resolves individual particles — not population averages.

Quality Attribute 01 & 02

True LNP size distributions — and why DLS falls short

MRPS size distribution comparison for three LNP formulations — DLS fails to distinguish between them

Size distributions for three LNP formulations measured by MRPS. DLS failed to distinguish between the formulations and could not measure one sample.

The limitation

DLS averages scattered light from the entire sample. It cannot distinguish between LNP formulations with overlapping size ranges, and fails entirely on polydisperse or concentrated samples.

With MRPS

Each particle is measured individually as it passes through the microfluidic constriction. The result is a high-resolution size distribution with absolute concentration at every size — no assumptions, no population averaging.

Size accuracy validated against cryogenic transmission electron microscopy (CryoTEM). CryoTEM Validation App Note →

Quality Attribute 03 & 04

Per-particle payload and ligand quantification

The limitation of bulk assays

Bulk fluorescence assays such as RiboGreen and CuBit report a population-average encapsulation efficiency. They cannot reveal how RNA is distributed across individual particles, or distinguish empty from loaded LNPs.

With the ARC

The ARC measures RNA fluorescence, particle size, and concentration simultaneously for each individual particle. A one-step stain is all that is required — no wash steps, no calibration, no multiwell titration — with results in minutes.

Workflow and data from: ARC LNP Payload Quantification App Note (PDF) →

Single-particle fluorescence combo plot showing RNA loading distribution across three LNP formulations A, B, and C

Per-particle RNA loading for three LNP formulations. Formulation C carries significantly less RNA per particle than A and B; formulation A shows the highest median loading.

Method Comparison

How MRPS and F-MRPS compare to DLS and NTA for LNP work

No single technique answers every question. The table below summarizes where each method excels and where it falls short for lipid nanoparticle characterization.

Comparison of F-MRPS, MRPS, DLS, NTA, and NanoFCM for lipid nanoparticle characterization across key attributes

Resources

LNP application notes and technical guides

LNP Standard Operating Procedure Guide thumbnail

Standard Operating Procedure

LNP Measurement SOP Guide

Step-by-step measurement protocols for lipid nanoparticle analysis on Spectradyne instruments.

Download SOP Guide →

Ready to characterize your LNP formulations?

Submit a sample for a free measurement, or schedule a live demonstration with one of our applications scientists.