Stereo Vision Probe: A New PAT Instrument for Real-time Characterisation of Particulate Systems

颗粒形状的研究对制药、生物制药、人体保健产品和特种化学品等许多工业应用都非常重要。例如，对于药品，形态可以影响诸如干粉密度、凝聚力和流动性等重要特性，这可能对公司将药物颗粒配制成成品的能力产生重大影响。此外，晶体形态会影响药物的溶解，潜在地影响制剂的生物利用度，在极端情况下，导致公司失去生产药品的许可证。然而，尽管有各种过程分析技术（PAT）仪器可用于测量颗粒系统的其他特性，但在诸如结晶、沉淀、造粒和碾磨等单元操作过程中，还没有有效的在线仪器能够提供颗粒形状的实时信息。在过去的几年里，在线高速成像已经被证明是一种非常有前途的在线实时测量粒子形状的PAT仪器，这导致了一些新的仪器产品的开发，如Lasentec的PVM（过程视觉系统）（uk.mt.com）， MessTechnik Schwartz GmbH的PIA（过程图像分析仪）（www.mts-duesseldorf.de），荷兰Perdix的ISPV（原位粒子查看器）（www.perdix.nl），葛兰素史克（GlaxoSmithKline）的在线显微镜系统，其中一些包含探针设计，可以方便地访问处理反应器容器。然而，所有这些技术在本质上都是有限的，因为它们只能提供粒子形状的二维信息。因此，本研究旨在开发一种新的仪器立体视觉探针，它可以在实际处理反应器中直接成像颗粒的完整3D形状。这种基本的操作模式是基于一个数学原理，即如果从两个不同的角度获得一个物体的二维图像，就可以恢复完整的三维粒子形状。预计对研究能力和工业应用的潜在影响将是重大的，但拟议的研究将集中在立体视觉探头的开发和从两个不同角度获得的两个2D图像的3D构建方法上。该系统的测试将主要通过使用可变温度结晶电池。

Research on particle shape is extremely important to many industrial applications such as pharmaceuticals, biopharmaceuticals, human health products and speciality chemicals. For example, for pharmaceuticals, the morphology can affect important properties such as dry powder density, cohesion, and flowability, that can have major impact on a company's ability to formulate drug particles into finished products. Moreover, crystal morphology can affect drug dissolution, potentially affecting formulated product bioavailability and, in extreme, resulting in a companies loss of the license to making the drug product. However, despite the availability of various Process Analytical Technology (PAT) instruments for measuring other properties of particulate systems, there have been no effective on-line instruments capable of providing real-time information on particle shape during the processing of particles in unit operations such as crystallisation, precipitation, granulation and milling. In the past few years, on-line high speed imaging has shown to be a very promising PAT instrument for real-time measurement of particle shape on-line which has resulted in the development of some new instrumentation products just released to the market such as the PVM (Process Vision system) of Lasentec (uk.mt.com), the PIA (Process Image Analyser) of MessTechnik Schwartz GmbH (www.mts-duesseldorf.de), the ISPV (In-Situ Particle Viewer) of Perdix (www.perdix.nl) in Netherlands, and the On-line Microscopy systems of GlaxoSmithKline, some of which incorporate a probe design which allows easy access to a processing reactor vessel. However, all these techniques are essentially limited in that they can only provide 2D information of the particle shape. Hence, this proposed research aims to develop a new instrument Stereo Vision Probe which can directly image the full 3D shape of particles within a practical processing reactor. This basic mode of operation is based on the mathematical principle that if the 2D images of an object are obtained from two different angles, the full 3D particle shape can be recovered. The potential impact on research capability and industrial applications is predicted to be major but the proposed research will focus on the development of the Stereo Vision Probe and the 3D construction method from the two 2D images obtained from two different angles. The testing of the system will be mainly via the use of a variable temperature crystallisation cell.