• Applications
  • Amyloids

    How it works
    The leading challenge in therapeutic approaches against neurodegenerative diseases is the accurate characterization of the interaction between drug candidates and pathogenic oligomeric or fibrillar forms of proteins. MDS overcomes the limitations of surface-based methods which induce conformational heterogeneity and alter disease-relevant epitopes and provides KD values and stoichiometry necessary to understand the mechanism of action of drug candidates.
    Overview

    Neurodegenerative diseases (ND) affect millions of people worldwide and are characterized by the accumulation of neurotoxic amyloid aggregates in the brain leading to loss of function and ultimately death of neuronal cells. Immunotherapeutic approaches against NDs focus on antibodies that target the pathogenic aggregated forms of proteins such as α-synuclein or Aß peptide related to Parkinson’s disease and Alzheimer’s disease, respectively. ELISA and other surface-based methods are commonly used to identify antibodies that specifically target these pathogenic aggregates but tethering these sensitive proteins to a surface is often not feasible or induces artificial structures that do not occur in patients. Microfluidic diffusional sizing (MDS) avoids surface immobilization and thus preserves the disease-relevant structures of the aggregates which enables identification of antibodies that bind with high specificity and have the most effective mode of action against disease progression.

    Key advantages of MDS
    Direct ELISA
    Each species immobilized
    • Loss of information through surface-induced conformational bias
    • No KD or stoichiometry
    • Assay development required
    Competition ELISA
    Monomer immobilized
    • No KD or stoichiometry
    • Challenging competition experiment
    • Assay development required
    MDS
    Immobilization-free
    • KD – specificity
    • Stoichiometry – mechanism of action
    • Biological samples (CSF, serum)
    • Quick and easy to perform
    Fig 1. Unlike ELISA, MDS uniquely measures the most crucial parameters (affinity and stoichiometry) to assess antibody specificity and mechanism of action.
    Case Study
    Kinetic fingerprints differentiate the mechanisms of action of anti-Aβ antibodies.
    Get started

    To study intrinsically-disordered or aggregated proteins in their native state in solution we recommend the following:

    Workflow specification and benefits:
    • 25 min run time
    • KD range from pM to uM
    • Amount of antibody 1-10 µg depending on affinity
    • Amount of oligomer or fibril 10-25 µg
    • Provides stoichiometry
    • 12 ul of sample per triplicate
    • Quick & easy to perform
    • Use of complex background e.g. serum, lysate, CSF

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