Topic
Flow Microscopy
About: Flow Microscopy is a research topic. Over the lifetime, 3 publications have been published within this topic receiving 23 citations.
Papers
TL;DR: Two methods, based on very simple modifications of commercial particle counter instruments, that can provide traceable number concentration measurements are described.
Abstract: Accurate number concentrations of particles in liquid media are needed to assess the quality of water, pharmaceuticals, and other liquids, yet there are limited reference materials or calibration services available with clear traceability to the International System of Units. We describe two methods, based on very simple modifications of commercial particle counter instruments, that can provide traceable number concentration measurements. One method used a light obscuration counter. Fitting a model to the data enabled correction for timing and coincidence errors, and gravimetric calibration of the syringe pump gave a traceable determination of measured volume. Other potential biases were diagnosed by analysis of the particle size distribution. The other method used a dynamic imaging particle counter (a flow imaging microscope). The instrument was intentionally configured so that each particle passing through the flow cell was imaged multiple times. Following the particle image acquisition runs, runs with a rinse solution released and counted microspheres adsorbed to tubing or flow-cell walls. Software assembled the redundant particle images into tracks, and the total number of tracks was assigned as the number of particles counted. Both light obscuration and dynamic imaging methods, when applied to polystyrene microspheres of approximately 4 μm diameter, achieved expanded uncertainties (k = 2) of approximately 2 % of number concentration and agreed to within a difference of 1.1 %.
18 citations
TL;DR: In this paper, Kullback-Leibler divergence and multidimensional scaling were used to compare the morphological properties of particles in sets of flow microscopy images and used these techniques with expectation maximization cluster analyses and used them to compare flow imaging microscopy data sets that had been collected by the U.S. Food and Drug Administration after severe adverse drug reactions (including 7 fatalities) were observed in patients who had been administered some lots of peginesatide formulations.
12 citations
1 Jan 2010
TL;DR: Because the light-obscuration h788i test procedures do not easily differentiate particle types, an alternative test procedure may be useful in differentiating foreign from intrinsic particulate matter to facilitate product improvement efforts and compliance with the limits specified by h7 88i.
Abstract: a ABSTRACT USP General Chapter Particulate Matter in Injections h788i sets limits and cites two enumeration procedures for subvisible particulate matter in parenteral products. Although h788i does not specifically target intrinsic sources of particulate matter such as protein aggregates, micelles, or precipitates, the h788i procedures can detect and enumerate these types of particles. The h788i procedure's performance (efficiency, reliability, and repeatability) for these particle types is unknown. Artifacts such as immiscible liquids, primarily silicone oil droplets, and air bubbles are counted by light obscuration but do not contribute to membrane microscopic counts. Protein-based pharmaceuticals may contain sizeable populations of aggregated or precipitated active ingredient in the size range of concern. The physical and optical properties of these particles can present challenges to light-obscuration procedures in achieving reliable detection and sizing. Because the light-obscuration h788i test procedures do not easily differentiate particle types, an alternative test procedure may be useful in differentiating foreign from intrinsic particulate matter to facilitate product improvement efforts and compliance with the limits specified by h788i. Flow microscopy is an imaging-based technology that uses automated classification algorithms to characterize suspended particle populations. The technology is currently used in an increasing number of applications in the formulation development phase of parenteral and biopharmaceutical development. The system operates by capturing an image of each particle in a flowing sample. Automated image analysis can differentiate subpopulations of foreign particles (e.g., metal, glass, rubber, and fibers) and intrinsic particles. This allows protein aggregates or other intrinsic particles to be considered separately from the total particle count to provide a more accurate representation of the foreign particle load. In addition, the particle images gathered by the system provide morphology information that can be used to determine the origin of contaminants and to monitor intrinsic particle populations.
6 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2018 | 2 |
| 2010 | 1 |