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Updated: Jun 26, 2026

Three-Dimensionally Printed Microfluidic Cross-flow System for Ultrafiltration/Nanofiltration Membrane Performance Testing
Published on: February 13, 2016
Small molecule clearance in ultrafiltration/diafiltration in relation to protein interactions:Study of citrate
C Harinarayan1, K Skidmore, Y Kao
1Genentech, Inc., South San Francisco, California 94080, USA.
Abstract:
Ultrafiltration/diafiltration (UFDF) is commonly utilized in the purification of recombinant proteins to concentrate and buffer exchange the product. It is often the final step in the purification process, placing the protein in its final formulation and clearing small molecules introduced in upstream purification steps. This article presents a case study of reduced small molecule clearance in ultrafiltration/diafiltration of an antigen-binding fragment of a monoclonal antibody. Citrate, a commonly utilized small molecule in downstream processes, is shown to have reduced clearance due to specific interactions with the protein product. The study presents process solutions and utilizes a simple model to characterize clearance of small molecules which exhibit interactions with product protein.
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