§Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, 4056 Basel, Switzerland.
Anal Chem. 2015 Jun 16;87(12):6119-24. doi: 10.1021/acs.analchem.5b00688. Epub 2015 Jun 2.
Although light obscuration is the "gold standard" for subvisible particle measurements in biopharmaceutical products, the current technology has limitations with respect to the detection of translucent proteinaceous particles and particles of sizes smaller and around 2 μm. Here, we describe the evaluation of a modified light obscuration sensor utilizing a novel measuring mode. Whereas standard light obscuration methodology monitors the height (amplitude) of the signal, the new approach monitors its length (width). Experimental evaluation demonstrated that this new detection mode leads to improved detection of subvisible particles of sizes smaller than 2 μm, reduction of artifacts during measurements especially of low concentrations of translucent protein particles, and higher counting accuracy as compared to flow imaging microscopy and standard light obscuration measurements.
虽然光遮挡是生物制药产品中亚可见颗粒测量的“金标准”，但当前技术在检测半透明蛋白质颗粒和尺寸小于 2μm 的颗粒方面存在局限性。在这里，我们描述了一种改进的光遮挡传感器的评估，该传感器利用了一种新的测量模式。标准的光遮挡方法监测信号的高度（幅度），而新方法监测其长度（宽度）。实验评估表明，这种新的检测模式可以提高对小于 2μm 的亚可见颗粒的检测能力，减少测量过程中的伪影，特别是在低浓度的半透明蛋白质颗粒的测量中，并且与流动成像显微镜和标准光遮挡测量相比，具有更高的计数准确性。
