Application of Empirical Phase Diagrams for Multidimensional Data Visualization of High-Throughput Microbatch Crystallization Experiments

Marieke E. Klijn, Jürgen Hubbuch

Research output: Contribution to journalArticleScientificpeer-review

6 Citations (Scopus)

Abstract

Protein phase diagrams are a tool to investigate the cause and consequence of solution conditions on protein phase behavior. The effects are scored according to aggregation morphologies such as crystals or amorphous precipitates. Solution conditions affect morphologic features, such as crystal size, as well as kinetic features, such as crystal growth time. Commonly used data visualization techniques include individual line graphs or phase diagrams based on symbols. These techniques have limitations in terms of handling large data sets, comprehensiveness or completeness. To eliminate these limitations, morphologic and kinetic features obtained from crystallization images generated with high throughput microbatch experiments have been visualized with radar charts in combination with the empirical phase diagram method. Morphologic features (crystal size, shape, and number, as well as precipitate size) and kinetic features (crystal and precipitate onset and growth time) are extracted for 768 solutions with varying chicken egg white lysozyme concentration, salt type, ionic strength, and pH. Image-based aggregation morphology and kinetic features were compiled into a single and easily interpretable figure, thereby showing that the empirical phase diagram method can support high-throughput crystallization experiments in its data amount as well as its data complexity.

Original languageEnglish
Pages (from-to)2063-2069
Number of pages7
JournalJournal of Pharmaceutical Sciences
Volume107
Issue number8
DOIs
Publication statusPublished - 2018
Externally publishedYes

Keywords

  • crystals
  • morphology
  • multivariate analysis
  • precipitation
  • protein aggregation
  • protein formulation
  • proteins
  • solubility
  • supersaturation

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