Crystallization monitoring using simultaneous bright field and PlasDIC imaging

Toufic El Arnaout, Lauri Kurki, Tapio Vaarala, Kai Ojala, P.J. Cullen, Carl Sullivan

Research output: Contribution to journalArticleScientificpeer-review

3 Citations (Scopus)

Abstract

Crystal size, shape and form are critical factors governing the quality and safety of pharmaceutical products, with variation during crystal growth impacting downstream processes. Monitoring of crystallization is therefore paramount in ensuring end-product quality. In this work, a microscopy probe employing both bright field and PlasDIC techniques was developed as a process analytical technology to acquire and analyze crystal features under real-time conditions. The design benefits from not requiring electronics in the immersible component of the probe. Image analysis algorithms were developed and tested on glass sphere standards, illustrating the ability of these techniques to monitor size-shape features in situ. Lysozyme and taurine crystals as well as thin and transparent crystals of benzoic acid were monitored. Overall, the system in conjunction with image analysis techniques tracked the crystallization progress and identified complex shape features. Future incorporation of fast, automated edge detection and segmentation procedures would help with higher particle concentrations.
Original languageEnglish
Pages (from-to)64-74
JournalChemical Engineering Journal
Volume300
DOIs
Publication statusPublished - 2016
MoE publication typeA1 Journal article-refereed

Fingerprint

Crystallization
crystallization
crystal
Imaging techniques
Crystals
Monitoring
monitoring
Image analysis
image analysis
Benzoic Acid
probe
Benzoic acid
Taurine
Edge detection
Muramidase
Crystal growth
Drug products
Microscopic examination
Electronic equipment
Enzymes

Keywords

  • PlasDIC
  • Process analytical technology (PAT)
  • Image analysis
  • Crystallization
  • Particle size-shape
  • Image processing

Cite this

El Arnaout, Toufic ; Kurki, Lauri ; Vaarala, Tapio ; Ojala, Kai ; Cullen, P.J. ; Sullivan, Carl. / Crystallization monitoring using simultaneous bright field and PlasDIC imaging. In: Chemical Engineering Journal. 2016 ; Vol. 300. pp. 64-74.
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Crystallization monitoring using simultaneous bright field and PlasDIC imaging. / El Arnaout, Toufic; Kurki, Lauri; Vaarala, Tapio; Ojala, Kai; Cullen, P.J.; Sullivan, Carl.

In: Chemical Engineering Journal, Vol. 300, 2016, p. 64-74.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Crystallization monitoring using simultaneous bright field and PlasDIC imaging

AU - El Arnaout, Toufic

AU - Kurki, Lauri

AU - Vaarala, Tapio

AU - Ojala, Kai

AU - Cullen, P.J.

AU - Sullivan, Carl

PY - 2016

Y1 - 2016

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AB - Crystal size, shape and form are critical factors governing the quality and safety of pharmaceutical products, with variation during crystal growth impacting downstream processes. Monitoring of crystallization is therefore paramount in ensuring end-product quality. In this work, a microscopy probe employing both bright field and PlasDIC techniques was developed as a process analytical technology to acquire and analyze crystal features under real-time conditions. The design benefits from not requiring electronics in the immersible component of the probe. Image analysis algorithms were developed and tested on glass sphere standards, illustrating the ability of these techniques to monitor size-shape features in situ. Lysozyme and taurine crystals as well as thin and transparent crystals of benzoic acid were monitored. Overall, the system in conjunction with image analysis techniques tracked the crystallization progress and identified complex shape features. Future incorporation of fast, automated edge detection and segmentation procedures would help with higher particle concentrations.

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KW - Process analytical technology (PAT)

KW - Image analysis

KW - Crystallization

KW - Particle size-shape

KW - Image processing

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