An Economical, Scaled-Down, Suction-Based Tangential Flow Ultrafiltration System for Biological Process and Product Development Applications

Scaled-down ultrafiltration systems are frequently needed at various stages of protein biologics product and process development. In this paper, an economical and easy-to-use scaled-down tangential flow filtration (TFF) system that is suitable for concentration and buffer exchange of protein solutions, is described and discussed. One or more syringes connected to the permeate side of the membrane module with their plungers pulled out and appropriately clamped were used to generate the pressure drop for filtration by suction. The pumping requirement was therefore significantly less demanding than that in conventional TFF systems. An inexpensive single-purpose pump could easily be used in the proposed TFF system for generating the required tangential flow, as there was no need for generating high pressure on the feed side of the membrane. Also, a feed-side pressure control valve was not required. The hold-up volume of the proposed TFF system was 300 microliters, and feed solutions having volumes as low as 1 mL could easily be processed using it. Its suitability for conducting concentration and buffer exchange experiments was demonstrated by ultrafiltering human immunoglobulin G (HIgG) solutions. An order of magnitude increase in protein concentration (from 10 mg/mL to more than 100 mg/mL) could easily be achieved in 180 min. The highest protein concentration that could be obtained in this study was 152 mg/mL. Buffer exchange of a 50 mg/mL HIgG solution from phosphate buffered saline to low pH acetate buffer and vice-versa could be achieved in 2.5 diafiltration volumes. The specific mechanisms involved in permeate generation in such suction-driven ultrafiltration processes are examined. The role of evaporation under vacuum on the permeate side of the membrane and its potential impact on the process is hypothesized.