Accelerate Drug Discovery with Cryo-TEM
Cryo-TEM can unveil many aspects of a sample in just one study, including particle size distribution, drug encapsulation, shape, morphology, impurities, and integrity, all with only ~50μl of sample.
Cryo-TEM is a powerful orthogonal technique to complement your nanoparticle characterization toolkit. Where a sample contains multiple particle types (adjuvanted vaccine drug products, for example), cryo-TEM outperforms other methods. Cryo-TEM requires only microliters of sample and images the product as-formulated in its hydrated state, without staining or buffer exchange, making it well suited to dose-limited material and to formulations that would be altered by sample preparation.
| Multiple Particle Types | Low-Volume, As-Formulated Samples | |
| Use Case | Samples containing mixed particle populations (e.g., vaccine drug products) | Dose-limited samples, or formulations that would be altered by dilution, staining, or buffer exchange |
| Why Cryo-TEM Excels | Resolves individual particle types that bulk methods average together | Requires only microliters of sample and preserves the formulation in its native, hydrated state |
| Advantage Over Other Methods | Cryo-TEM resolves structural subpopulations that size-based methods cannot separate. Particles that are indistinguishable by size can differ substantially in structure and payload. | No dilution or concentration adjustment required, preserving native sample state |
CQAs Revealed by Cryo-TEM
Cryo-TEM evaluates multiple critical quality attributes on a per-particle basis in a single measurement, directly visualizing the product in its hydrated state, without labeling or separation. Several of these attributes are accessible only by direct imaging; others provide orthogonal confirmation of results from ensemble methods.
- Particle size distribution
- Drug and payload encapsulation & distribution
- Morphology; including shape, circularity, lamellarity, and blebbing
- Sample integrity and impurities
- Full/empty/partial capsid ratios (AAV)
- Antigen distribution on particle surfaces
Why Cryo-TEM for CQA Analysis
Therapeutic nanoparticles used in drug formulation and development, vaccine design and development, and gene therapy delivery are complex and vary in composition, shape, and size. As structure can change under stress, characterization of nanoparticles' physicochemical properties is required to understand how they interact with their environment, and this can provide insight into the potential safety and efficacy of the final formulation.
The study of drug cargo encapsulation when looking at gene or drug delivery systems is crucial, as the presence of many empty particles or impurities affects immunogenic response.
Method Validation for Regulatory Submissions
We offer method qualification and validation services to analyze critical quality attributes for regulatory submissions. A phase appropriate, qualified or validated method supports:
- Batch-to-batch reproducibility
- Scale Up
- Comparability
- Stability
