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Multi-angle Dynamic Light Scattering (MADLS) Technology

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Multi-angle dynamic light scattering (MADLS) technology is a powerful tool for characterizing protein/peptide biopharmaceutical products and is widely used to determine the molecular weight and size of molecules during product development, downstream processing, product characterization, quality control, and biosimilarity studies. CD Formulation's cGMP laboratory is equipped with state-of-the-art MADLS instruments and breakthrough technologies, dedicated to providing the biopharmaceutical industry with unparalleled MADLS-based particle characterization services to accelerate drug development and production processes.

What is Multi-angle Dynamic Light Scattering (MADLS)?

MADLS is a technique that is relative to single-angle light scattering, i.e. dynamic light scattering (DLS).

DLS is an effective method for measuring submicrons and nanoparticles. It is based on the Brownian motion of particles in a suspended solution, which causes the scattered light to fluctuate over time, thereby obtaining the particle size and its distribution. This technology is an excellent tool for rapid, non-invasive measurement of particle size distribution (PDI) and polydispersity index (PdI). However, DLS is a low-resolution technology and has certain limitations in resolving nanoparticles with multiple components or size groups that differ by less than 3:1.

Fig. 1 Multi-angle dynamic light scattering.Fig. 1 Schematic of a system for measurement and analysis of dynamic light scattering. (Minton AP, et al., 2016)

MADLS technology combines the scattering angle information of Mie theory (the intensity of scattered light from the sample depends on the size and refractive index of the particles, as well as the angle at which the scattering is detected) with the particle size distribution analysis measured by DLS into a comprehensive method.

Compared with single-angle dynamic light scattering, multi-angle dynamic light scattering technology has lower noise and lower smoothness. Therefore, reliable and more accurate particle size information can be obtained, which can avoid the loss of information caused by improper selection of scattering angles, thereby obtaining a more accurate particle size distribution and improving the characterization of each component in a multi-component sample.

Multi-angle Dynamic Light Scattering (MADLS) Principle

In MADLS measurements, correlated data from multiple detection angles are combined with knowledge of Mie theory to generate a higher resolution particle size distribution. The working principle is that a particle dispersion is illuminated by a coherent light source. The particles in the sample scatter a portion of the light. The partially scattered light is detected at multiple angles. The fluctuations in the scattered intensity are then analyzed to derive information on the size, shape, and composition of the particles in the dispersion.

MADLS allows obtaining concentration information about particles with the help of robust particle size distribution information without relying on calibration curves.

Our Services Related to Multi-angle Dynamic Light Scattering (MADLS)

With decades of experience supporting protein/peptide biopharmaceutical development and manufacturing, our team of highly qualified experts can provide a range of MADLS-related services to accelerate the implementation and success of your project.

Our MADLS technology supports all stages of your protein/peptide drug development and production - from early research to late-release testing under GMP. It overcomes the limitation of dynamic light scattering (DLS) that it cannot accurately characterize polydisperse samples (i.e., when the particle size distribution is very close and the size difference is less than three times), and can determine the size of multimodal samples with higher resolution.

In our analytical laboratory, MADLS uses three different angles (back, side, and forward scatter detection) and combines the obtained information into a size distribution map to better resolve the size distribution.

Using advanced MADLS technology, we provide the following MADLS-related services, including but not limited to:

Protein/Peptide Aggregation Studies

In protein/peptide biopharmaceutical development, MADLS plays a vital role in studying protein aggregation. Our scientists help you evaluate the stability and quality of your biopharmaceutical products by analyzing the size and distribution of protein aggregates.

Polymer Drug Carrier Characterization

Our scientists use MADLS to analyze the size and molecular weight distribution of polymer-drug carriers. This information is essential for understanding the properties of polymers such as viscosity, molecular structure, and solution behavior, which helps develop advanced delivery carriers for various applications.

Protein/Peptide Nanoparticle Characterization

MADLS is widely used for nanoparticle characterization in the pharmaceutical field. It can accurately measure particle size distribution, including submicron and nanometer-sized particles, which is critical for quality control and formulation development. Our scientists use MADLS to gain a deeper understanding of the properties of protein/peptide nanoparticles, providing more reliable data support for their applications in areas such as drug delivery and therapy.

Our Equipment

  • Size Exclusion Chromatography With MADLS (SEC-MADLS)
  • Gel Permeation Chromatography With MADLS (GPC-MADLS)
  • Ion Exchange Chromatography With MADLS (IEX-MADLS)
  • Field Flow Fractionation With MADLS (FFF-MADLS)
  • Composition Gradient With MADLS (CG-MADLS)

Advantages of Our Multi-angle Dynamic Light Scattering (MADLS)

  • High resolution.
  • Simple operation, no calibration required.
  • Significantly shortened measurement time (compared to DLS technology).
  • No need for multiple sample filtration and long data collection.
  • Accurate, repeatable, and reliable particle size and concentration analysis.
  • Particle size measurement range: 0.5 nm to 10 μm.

Custom Multi-angle Dynamic Light Scattering (MADLS) Services

Proteins & Peptides Particle and Aggregation Characterization

Protein aggregation and particle characterization help assess the extent of protein degradation, stability, and aggregate formation in solution. We use MADLS analysis technology to characterize protein/peptide aggregation to in-depth understanding of the agglomeration of the product in the development and manufacturing process, thereby helping you optimize the manufacturing process.

Nanoparticle Characterization for Proteins & Peptides Formulation

Our nanoformulation scientists use MADLS technology to obtain key information about nano-drug delivery carriers and protein or peptide nanoparticles, which is very important for evaluating nanoparticle stability, biocompatibility, drug release performance, etc.

Why Choose Our Multi-angle Dynamic Light Scattering (MADLS) Technology?

  • We have a team of experts with rich experience in performing MADLS analytical method development and validation.
  • We have accumulated decades of expertise and successful project experience using MADLS technology to support protein/peptide biopharmaceutical development.
  • Our laboratories are equipped with state-of-the-art equipment and technologies to support any type of protein characterization.
  • We provide flexible experimental design and customized solutions.
  • Fast turnaround time: detailed technical reports are provided within 5-7 days.

Publication

Published Data

Technology: MADLS with UV-Vis Spectroscopy and SEC

Journal: AAPS PharmSciTech.

IF: 3.40

Published: 2023

Results:

The authors evaluated the application of MADLS in tandem with UV-Vis spectroscopy and SEC for the determination of protein size, concentration, and aggregation. Three different proteins, bovine serum albumin (BSA) and two biopharmaceuticals, including a monoclonal antibody (mAb) and an enzyme, were selected as model proteins. The results showed that MADLS coupled with UV-Vis spectroscopy and SEC can accurately measure protein nanoparticles of different sizes. This three-in-one approach can be used to assess protein size, concentration, and aggregation for product screening and development while reducing the number of samples and experiments required for analysis prior to other orthogonal tests.

Fig. 2 Particle concentration calibration curve.Fig. 2 Particle concentration calibration curve for a BSA, b mAb and c enzyme. (Sharma A, et al., 2023)

CD Formulation aims to provide a non-invasive and powerful analytical tool for the absolute characterization of proteins and their nanoformulations. Please feel free to contact us if you are interested in our services. Learn how our MADLS technology can support the smooth implementation of your protein/peptide biopharmaceutical program.

References

  1. Minton AP. Recent applications of light scattering measurement in the biological and biopharmaceutical sciences. Anal Biochem. 2016, 501:4-22.
  2. Austin J, Minelli C, Hamilton D. et al. Nanoparticle number concentration measurements by multi-angle dynamic light scattering. J Nanopart Res. 2020,108(22).
  3. Sharma A, Beirne J, Khamar D, et al. Evaluation and Screening of Biopharmaceuticals using Multi-Angle Dynamic Light Scattering. AAPS PharmSciTech. 2023, 24(4):84.
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