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Particle Measurement in Material Sciences Applications

 

Analyzing Chromatography Beads with MFI

Optimum and consistent performance of liquid chromatography columns requires close control of the size and circularity of chromatography beads. Contamination by debris or bead fragments must also be strictly controlled. Normally beads are counted using the coulter method and circularity is measured by SEM or standard microscopy.

Micro-Flow Imaging™ (MFI) is a new technique which employs digital imaging of a flowing sample stream to measure the size, circularity and fragment content of bead suspensions. A single sample run requiring 5 minutes provides size and circularity statistics on up to 30,000 10µm beads. The run also measures the concentration of debris/fragments with sizes down to 0.75µm. This rapid and comprehensive analysis can improve product quality and process yield both through more rigorous incoming and in-process inspection and, through the additional insight gained for process development and troubleshooting.

The MFI Advantage

  • Size Measurement: Unlike many indirect particle size measurement technologies, the direct, pixel based imaging technique employed in MFI makes no assumptions of particle size or shape.  Bead sizes from 0.75µm to 300µm are readily accommodated.
  • Circularity Measurement: Particle images are stored automatically and analyzed using the MFI morphological analysis module, providing measurement of ECD, Feret’s diameter, area, aspect ratio, perimeter, circularity and transparency.  Results are conveniently presented in the form of histograms or scatterplots.  Instances of agglomeration are easily detected and isolated in the analysis.
  • Debris and Fragment Measurement: MFI instruments provide sensitive detection, counting, and sizing of each individual particle present in each image frame.  Each frame represents an accurately known volume of sample, permitting direct measurement of particle concentration.  Debris or fragments present in the sample indicative of bead damage are quantified.
  • Selective Image Capture:  The selective image capture feature in MFI allows a user to store images of any particles detected during the run. These images serve to confirm numerical results and are valuable for process control, quality control and diagnosis and troubleshooting.
  • Speed and Convenience: MFI instruments are easy to operate and analyze multiple image frames per second providing a full population analysis in less than 5 minutes.
  •  Direct Observation: During analysis, image frames are displayed providing immediate visual feedback on the nature of a particle population.

The charts and images below provide an example of an MFI analysis of two liquid chromatography bead samples. In this analysis the second sample had a known problem with fragmentation.

The relative concentration of smaller particles to primary particle population can be used to quantify the degree of fragmentation.  In addition the circularity of the bead population can be measured while fragmented versus whole bead populations are easily distinguished.

 

 LC Bead Particle Size Distributions

LC Beads

LC Beads

 

 LC Bead Circularity

LC Bead Circularity

LC Bead Fragmentation