Aggregates & Particles Analysis

The size of aggregates of biopharmaceuticals ranges from tens of nanometers to hundreds of micrometers. We analyze the concentration and size distribution of aggregates using a variety of analytical techniques.

Analytical Ultracentrifugation (AUC)

Analytical ultracentrifugation (AUC) is a method for analyzing the shape, molecular weight, and dispersion/aggregation state of solutes by applying a large centrifugal force to a solution and observing the sedimentation of the solute over time.

In the analysis of biopharmaceuticals, there are cases in which aggregates of size cannot be detected by SEC but can be detected by AUC. It is used by many pharmaceutical companies as one of the most appropriate methods for the quantification of aggregates in biopharmaceuticals. On the other hand, the measurement and analysis of AUC require specialized training and extensive experience.

U-Medico measures samples under the most suitable analytical conditions for each sample based on its accumulated know-how and provides the world’s highest level of analytical results.

In recent years, AUC has attracted attention in the field of gene therapy. U-Medico has extensive experience in the quantification of full and empty adeno-associated virus (AAV) vector particles by analytical ultracentrifugation (AUC).

XL-I

XL-A

Example of analysis of antibody drugs

We also conduct studies under our reliability assurance system to obtain the data necessary for drug applications. The setting up of the BSL2 facility is also in progress.

Fluorescence Detection System – Analytical Ultracentrifugation (FDS-AUC)

As the number of biopharmaceuticals on the market increases, there has been a growing demand for the evaluation of biopharmaceutical aggregates in serum. However, due to the interference of foreign substances in serum, the usual AUC cannot be used for accurate analysis.

The fluorescence detection system for analytical ultracentrifuges allows analysis of the solution properties of labeled molecules at pico-molar concentrations. The high selectivity of fluorescence detection allows the evaluation of aggregation and interaction in unpurified samples, serum, tissue extracts, and mixtures.

U-Medico provides dispersion analysis of biopharmaceuticals in serum and interaction analysis in solution using the FDS-AUC.

Flow Imaging Analysis

Micron-sized aggregates can be analyzed by flow imaging analysis. FlowCam provides information on the size, number, and shape of particles by continuously capturing high-resolution images of particles in a liquid as they pass through a glass flow cell.

U-Medico provides aggregate analysis for quality testing, characterization, and stability testing of biopharmaceuticals using the FlowCam 8100.

FlowCam 8100

Mass Photometry

The Mass Photometry (MP) method measures the molecular weight of biomolecules (nucleic acids, proteins, AAV vectors, aggregates, etc.) and nanoparticles in solution from the scattered light intensity of a single molecule on a glass substrate surface.

Mass photometry allows quantification using small sample volumes, as follows.

Sample Required Volume
Antibody drugs A few nM, Less than 10 µL
AAV vectors < 1012 vg/mL, 10 µL

Using the MP method, we analyze the association state of antibodies, antibody-receptor interaction analysis (determination of dissociation constant KD), and the relative ratio of empty capsids (EC) and full particles (FP) of AAV vectors.

Examples of analyses

Refeyn OneMP

Although this technique requires only a small amount of sample and a short time to obtain results, it is not easy to obtain reproducibility and to interpret the results. Based on our experience, we provide high-quality analytical results.