11 Development of a Recirculation Tangential Flow Filtration System as a Teaching Module Based on Bovine Serum Albumin Concentration

Faculty Mentor: Mikhail Skliar (Department of Chemical Engineering, University of Utah)

Abstract

Biological macromolecules such as proteins are necessary to several industrial sectors, including food, biotechnology, pharmaceuticals, and cosmetics (Labrou, 2014). In the biopharmaceutical industry, monoclonal antibodies (mAbs) have become major therapeutic products. The global market for antibody-based therapies expanded from approximately $0.3 billion in 1997 to $186 billion in 2021, with projections of reaching $445 billion by 2028 (Lyu et al., 2022). Along with mAbs, other important products include recombinant proteins, COVID-19 vaccines, biosimilars, and nucleic acid- or cell-based therapies (Walsh & Walsh, 2022).

Commercial use of proteins requires purification processes that can achieve the high purity levels necessary for downstream applications while maintaining yield and biological activity (Labrou, 2014). Industrial-scale purification typically involves several chromatography steps that separate biomolecules according to molecular size, charge, hydrophobicity, or specific binding interactions (Pires & Palmer, 2022; Freitag & Horváth, 1996). Despite its selectivity, chromatography is limited by the high cost of resins and low volumetric throughput, which restricts scalability (Fan et al., 2018).

Over the past two decades, improvements in upstream biomanufacturing have led to a significant imbalance between production and purification capacities. The rate of protein synthesis per unit volume of culture now frequently exceeds purification throughput, making downstream operations a major cost contributor, often accounting for 50–80% of total production costs (Gottschalk, 2008; Labrou, 2014). These limitations have increased the demand for alternative purification technologies that are more cost-effective and scalable. Membrane-based separations, particularly tangential flow filtration (TFF), have been identified as viable options due to their simplicity, reduced cost, and potential for continuous operation (Fan et al., 2018).

This study reports the development of a low-cost TFF system designed for educational use in bioprocessing. The system was constructed within a $250 budget and includes a sealable acrylic housing, pressure-resistant design, modular membrane replacement, and integrated pressure monitoring. The filtration channel measures 3 × 1 × 0.5 in. (L×W×H). Bovine serum albumin (BSA) was used as the model protein because of its well-known characteristics and ease of quantification by UV–Vis spectrophotometry at 278 nm. A hydrophilic polyethersulfone membrane with a 30 kDa molecular weight cut-off was chosen based on BSA’s average molecular weight of 66 kDa.

Performance evaluation followed a design of experiments framework that varied initial protein concentration (500–1000 mg/L), volumetric flow rate (33–60 L/h), transmembrane pressure (15–35 psi), processing time (1–4 h), membrane area (2.25–3 in²), and channel volume (0.74–1.50 in³). The system operated under laminar flow conditions (Re < 2000), and the pressure drop followed the Hagen–Poiseuille relationship. Complete protein retention (R = 1) was observed in all experiments, with the highest retentate concentration reaching 1082.76 mg/L under optimal conditions. Multiple linear regression (R² = 0.97) indicated that membrane area and transmembrane pressure were the most influential parameters affecting system performance.

The results confirm that a functional, low-cost tangential flow filtration unit can be developed for educational purposes. The system provides a simple and reproducible model for demonstrating membrane filtration principles and can serve as a basis for further development of scalable purification systems applicable to research and industrial environments.

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