DEVELOPMENT OF AN AUTOMATED METHOD TO PERFORM A QUANTITATIVE STUDY OF PARTICLE SIZE DISTRIBUTION AND THE EFFECT OF A CONDUCTIVE LAYER IN SCANNING ELECTRON MICROSCOPY

The determination of particle size distribution is an important parameter for controlling industrial processes, particularly in the field of pharmaceuticals. It is also an important parameter for characterizing nanoparticles. The best technique for determining particle size distribution is scanning electron microscopy. The process of counting particles is typically performed manually, which requires both more time and a higher standard deviation than automatic methods. This study shows the results of a particle counting procedure that relies on a fully automated method that was found to improve the reproducibility of the measurement. The effect on the diameter of near-spherical polymer nanospheres between 20 and 100 nm (mean of 60 nm) when samples were coated by a conducting layer (such as gold or carbon) was also evaluated. The images were collected using a field emission scanning electron microscope and then processed using the ImageJ program. Results showed that the method proposed in this work produces mean diameter values in accordance with NIST-traceable near-spherical polymer nanospheres for the sample without coating. The study also revealed two main effects of the conductive coating: changes to topography and an increase in mean particle diameter.

粒径分布的测定是工业过程调控的重要参数，在制药领域尤为关键，同时也是表征纳米颗粒（nanoparticles）的核心参数之一。扫描电子显微镜（scanning electron microscopy）是测定粒径分布的最优技术。传统颗粒计数流程多采用人工操作，相较于自动化方法，其耗时更长且标准差更高。本研究展示了基于全自动化颗粒计数流程的实验结果，该方法可有效提升测量的重现性。本研究同时评估了样品经导电层（如金或碳）镀膜后，对20~100 nm（平均粒径60 nm）的近球形聚合物纳米球直径的影响。图像采集采用场发射扫描电子显微镜（field emission scanning electron microscope），后续处理通过ImageJ软件完成。结果表明，针对未镀膜的样品，本研究提出的方法所测得的平均粒径值，与可溯源至美国国家标准与技术研究院（National Institute of Standards and Technology，NIST）的近球形聚合物纳米球标准值相符。本研究同时揭示了导电镀膜的两项主要影响：形貌改变与平均粒径增大。