ProteinMentor is a high-throughput platform for biologic developability and comparability analysis. It is a real-time hyperspectral imaging tool that provides multivariate analysis of critical quality attributes (CQA) necessary for candidate selection and development.
PDS developed the ProteinMentor platform technology using Quality by Design and focused on providing State of the Art technology to provide a comprehensive, reproducible, and statistically robust solution to our customers.
ProteinMentor utilizes a first-in-class quantum cascade laser microscope, 200 x faster than the existing FT-IR microscopes, to deliver high-throughput and label-free analysis of liquid samples over an array of formulations and drug concentrations. The microscope-based platform is unique in its ability to visualize any particles or aggregates present. Sub-visible particles can be detected and characterized using their unique infrared spectra.
The highly automated platform supports any sample format including 96-well plates, tubes and vials. Samples of 1 microliter or less are transferred to a 24-plex array for interrogation. Analysis is executed at room temperature or all 24 samples may be ramped with exquisite thermal control to investigate relative protein stability under thermal stress.
Enhanced productivity is assured through a purpose-built user interface with fully automated data acquisition and analysis.
Traditional FT-IR methods produce spectra one-at-a-time so experimental design is limited by time-consuming data acquisition and analysis. Attempts at automation only allow comparison of one or two samples at a time, create unacceptably high background noise and employ microfluidics that are prone to clogging.
ProteinMentor is the first platform that interrogates each sample in situ and compares hundreds of thousands of spectra to track protein changes. For each sample, comparative analysis is performed and unique 3-D plots or fingerprints are generated. These synchronous and asynchronous plots provide high resolution data that is used by onboard CorrelationDynamics™ algorithms to inform the stability and structural changes between analyses.
Direct comparison of 24 samples at a time, under the exact same conditions, provides statistically robust results with minimal background noise. Experiments can be executed that were never before possible, varying the concentration of drug candidate, excipients and stabilizers, pH etc.
An entire 24-well array can be interrogated and analysed in just a few minutes. The same samples can be subjected to heat-stress and melting analysis in just a few hours.
Sub-visible particles have been demonstrated to be of significant risk in eliciting anti-drug antibody (ADA) or adverse immune responses in patients. The exquisite resolution and sensitivity of ProteinMentor hyperspectral imaging means protein aggregates and other contaminants can be seen by eye for the first time. Indeed, aggregates, adsorbed protein and crystals can be tracked and measured as they form in a sample when it is placed under stress. The unique spectral maps allow investigators to discern between protein states (solution, crystal, aggregate etc.) and to determine conditions that have a stabilizing effect on the protein.
ProteinMentor ramps sample temperature quickly and precisely to induce drug candidate melting and aggregation. At each temperature the quantum cascade laser excites the sample, causing vibration of the protein backbone and of amino acid side chains. Unique side chain vibrations and their relationship to structural motifs such as helices, sheets and turns are monitored and hyperspectral correlation tells the stepwise order of motifs and amino acids involved in structural changes.
In this way, specific amino acids can be identified as contributors to "weak spots" within the protein. These can be addressed through improved candidate selection or by directed re-engineering of the protein sequence. Similarly, drug formulations can be optimized by investigating specific conditions or excipients for use as stabilizers.
The ProteinMentor 24-sample array format allows simultaneous comparison of multiple samples for pre-clinical candidate selection, re-engineering or optimization of formulations. This leads to enhanced speed to market and lowering of drug development cost, while ensuring safety and efficacy for patients.
We routinely test samples for comparison to other modes of Critical Quality Attribute analysis and can deliver multiplexed results on Target Binding, Concentration, Higher Order Structure, Aggregates and Variants, Subvisible Particles, Truncations and Deamidation - all from a microliter or less of sample.
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Protein Dynamic Solutions is offering early-access customers an opportunity to implement ProteinMentor on site to support their candidate pipeline. We work closely with our clients to ensure their success in implementing this transformative technology for improved biologic development and generation of data for enhanced IP protection.