The ISO 21501 standard outlines the instruments and calibration prerequisites for determination of particle size distribution by means of light interaction techniques. The standard is valuable to the life science industry where cleanrooms are monitored in real time for air particle contamination with the help of light scattering air particle counters.
Moreover, the impact of airborne particles on the quality of final products has been established in hard disk storage, flat panel display, and the semiconductor manufacturing industry.
Calibration of Liquid Particle Counters and Air Particle Counters
The ISO 21501 standard describes the calibration procedures for liquid particle counters to achieve accurate and reproducible performance in the determination of particle contamination in injections and infusions, thus providing an alternative to the IST calibration methods that were previously described in USP <788>.
The calibration of air particle counters is more difficult than that of liquid particle counters because of the necessity to produce air samples consisting of homogenously sized and distributed sub-microscopic particles. The calibration of any two air particle counters in order to generate the same results using the same air sample is a tedious task. The calibration method described by the ISO 21501 standard helps optimizing the reproducibility and repeatability of air particle counters.
There are many different techniques available to determine the particle count and size based on the size of the particles to be analyzed (Figure 1).
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Figure 1. Particle size range and counting techniques. Image credit: Beckman Coulter
Existing Standards to Which ISO 21501 Offers an Alternative
The ISO 14644 standard is commonly applied for the classification of cleanrooms by means of optical particle counters (OPCs). In spite of the availability of ISO 14644, before the approval and launch of ISO 21501 at the start of 2007, no ISO standards were available to describe the calibration and performance of OPCs employed in cleanroom classification as outlined by ISO 14644. However, several major particle counter manufacturers have used the following comprehensive non-ISO standards and calibration methods:
- ASTM F 328-98(2003) “Standard Practice for Calibration of an Airborne Particle Counter Using Monodisperse Spherical Particles” (withdrawn May 2007).
- IEST-RP-CC014.1 “Calibration and Characterization of Optical Airborne Particle Counters” (describing actual methods to perform the calibration).
- JIS B 9921:1997 “Light scattering automatic particle counter”, a Japanese standard describing the performance of OPC design, especially in the area of counting efficiency.
The counting efficiency parameter is the key factor pertaining to the actual count accuracy of OPCs, most notably air particle counters.
Counting Efficiency
The calibration of the size channels of OPCs is performed to count particles larger than a given particle size. The typical unit for particle size is micrometers (µm). The ability of an OPC instrument for counting particles of a specified size is defined as its counting efficiency.
The calibration procedure involves exposing the OPC’s sensor to a continuous stream of standard, mono-sized particles, yielding a stream of electrical pulses that vary in proportion to the size of each individual particle.
The median of a distribution of pulse heights generated by the mono-sized standard particles is considered as the appropriate channel calibration threshold for that particular size. Hence, the probability of counting a particle that has a size same as a given channel is 50% (Figure 2a). Therefore, the counting efficiency of OPCs that are calibrated in this fashion is 50%. However, it does not mean that only 50% of the particles will be practically counted by OPCs.
The ISO 21501 standard takes advantage of the specification for counting efficiency described in the JIS B 9921 standard, according to which the counting efficiency must be 50% ± 20% in the first channel (Figure 2a). In addition, particles of between 1.5X to 2.0 X the size of channel 1 particles must be counted with a counting efficiency o f 100% ± 10% in the first channel (Figure 2b).
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Figure 2. a) The 50% calibration point. b) Verifying 100% efficiency at a higher size. Image credit: Beckman Coulter
Significance of the ISO 21501 Standard
Before the ISO 21501 standard, the counting efficiency was not examined at each calibration interval. The counting efficiency of an OPC has been affected by a number of factors, including the slight optomechanical misalignment of the illumination source.
As a result, the OPC may miss counting some of the particles. The new ISO 21501 standard ensures the checking of all-critical counting efficiency element during calibration.
The counting efficiency of an OPC is checked by running the OPC following its calibration for sizing characteristics with the help of traceable size standards and comparing it with either a higher sensitivity OPC instrument or an Electrostatic Classifier.
This OPC is recognized as a “secondary standard” with 100% counting efficiency for the size of interest. Besides the basic size calibration, the ISO 21501 standard requires the following elements to be tested:
- Sampling volume
- Sampling flow rate
- Sampling time
- Concentration limit
- False count rate
- Sizing resolution
- Counting efficiency
The ability of OPC instruments to appropriately size and count particles will be ensured by the ISO 21501 standard with the help of a traceable reference instrument. As a result, there will be a close correlation between different OPC models from various manufacturers in terms of actual particle counts measured. This, in turn, yields traceable, accurate OPC instruments for cleanroom classification and validation according to ISO 14644.
Conclusion
Besides air particle counters, the ISO 21501 family of standards also covers extinction and scattering type liquid particle counters. Beckman Coulter Life Sciences offers a range of particle counters complying with the ISO 21501 standard, and is presently working on the deployment of an ISO 21501 field service capability to calibrate available products.
This information has been sourced, reviewed and adapted from materials provided by Beckman Coulter, Inc. - Particle Characterization.
For more information on this source, please visit Beckman Coulter, Inc. - Particle Characterization.