Transforming AAV Capsid Analysis With Single Particle Analysis Using Mass Photometry

Accurately characterizing the empty-to-full (E/F) ratio of your AAV capsids is one of the most consequential quality decisions you make in gene therapy development. Get it wrong, and you risk compromised therapeutic efficacy, patient safety concerns, and costly batch failures. Yet the gold standard, analytical ultracentrifugation (AUC), is expensive, slow, and incapable of capturing the true heterogeneity of your AAV preparation, since it only reports population averages.

Mass photometry (MP) changes that calculus significantly. By measuring the mass of individual particles via light interference, MP resolves empty, partially full, and full AAV capsids in as little as three to five minutes per sample, using as little as 15 µL of material. Across multiple AAV serotypes and constructs, MP achieved accuracy within a 30% deviation threshold compared to AUC, with average precision CVs of just 3% to 10% for full and empty capsids. The lower limit of quantitation sits at 3.0 x 10¹⁰ cp/mL, comfortably within standard production titers.

Beyond speed and accuracy, MP supports real-time capsid composition monitoring during manufacturing, enabling tighter batch-to-batch consistency without adding resource burden. Its compatibility with 96-well automated liquid handlers also makes it a practical fit for existing PAT workflows.

Whether you are optimizing upstream processes or building out your analytics strategy for early development, MP offers a credible, data-backed alternative to AUC. Download the full application note to review the complete accuracy, precision, and representative composition data across multiple AAV serotypes.