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Improved packing of preparative biochromatography columns by mechanical vibration

机译:通过机械振动改善制备生物扫描柱的包装

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The bioprocessing industry relies on packed-bed column chromatography as its primary separation process to attain the required high product purities and fulfill the strict requirements from regulatory bodies. Conventional column packing methods rely on flow packing and/or mechanical compression. In this work, the application of ultrasound and mechanical vibration during packing was studied with respect to packing density and homogeneity. We investigated two widely used biochromatography media, incompressible ceramic hydroxyapatite, and compressible polymethacrylate-based particles, packed in a laboratory-scale column with an inner diameter of 50 mm. It was shown that ultrasonic irradiation led to reduced particle segregation during sedimentation of a homogenized slurry of polymethacrylate particles. However, the application of ultrasound did not lead to an improved microstructure of already packed columns due to the low volumetric energy input (~152 W/L) caused by high acoustic reflection losses. In contrast, the application of pneumatic mechanical vibration led to considerable improvements. Flow-decoupled axial linear vibration was most suitable at a volumetric force output of ~1,190 N/L. In the case of the ceramic hydroxyapatite particles, a 13% further decrease of the packing height was achieved and the reduced height equivalent to a theoretical plate (rHETP) was decreased by 44%. For the polymethacrylate particles, a 18% further packing consolidation was achieved and the rHETP was reduced by 25%. Hence, it was shown that applying mechanical vibration resulted in more efficiently packed columns. The application of vibration furthermore is potentially suitable for in situ elimination of flow channels near the column wall.
机译:生物处理工业依赖于填充床柱色谱作为其主要分离过程,以获得所需的高产品纯度,并满足监管机构的严格要求。常规柱包装方法依赖于流量填料和/或机械压缩。在这项工作中,研究了填充密度和均匀性的填充过程中的超声波和机械振动。我们研究了两种广泛使用的生物十字瘤介质,不可压缩的陶瓷羟基磷灰石和可压缩的聚甲基丙烯酸酯基颗粒,其在实验室级柱中填充,内径为50mm。结果表明,超声辐射导致在聚甲基丙烯酸酯颗粒的均质浆料沉降期间降低颗粒偏析。然而,由于高声学反射损耗引起的低容量能量输入(〜152W / L),超声波的应用没有导致已经包装的柱的改进的微观结构。相比之下,气动机械振动的应用导致了相当大的改进。流动解耦的轴向线性振动最适合于〜1,190n / l的体积力输出。在陶瓷羟基磷灰石颗粒的情况下,实现了填料高度的13%进一步降低,并且减少了与理论板(RHETP)的降低的高度降低了44%。对于聚甲基丙烯酸酯颗粒,实现了18%的进一步填充固结,并将RHETP降低25%。因此,表明施加机械振动导致更有效地堆积的柱。振动的应用进一步可能适用于原位消除柱壁附近的流动通道。

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