Primary Determination of Particle Number Concentration with Light Obscuration and Dynamic Imaging Particle Counters

Author:

Ripple Dean C.1,DeRose Paul C.1

Affiliation:

1. National Institute of Standards and Technology, Material Measurement Laboratory, Gaithersburg, MD 20899, USA

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 %.

Funder

Material Measurement Laboratory

Publisher

National Institute of Standards and Technology (NIST)

Subject

General Engineering

Reference23 articles.

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3. Anonymous (2014) USP/NF Monograph <787>. Subvisible particulate matterin in therapeutic protein injections. US Pharmacopeia, National Formulary (USP36-NF31) (United States Pharmacopeial Convention, Rockville, MD). http://www.uspnf.com

4. Anonymous (2016) JP 6.07 Insoluble Particulate Matter Test for Injections. 17th Japanese Pharmacopoeia. http://jpdb.nihs.go.jp/jp17e/000217651.pdf

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