Introduction

Batch adsorption technology has been successfully applied in a number of important protein separation processes. The principles of batch adsorption are used in a wide range of diverse applications, including several commercial-scale processes for the purification of protein products, a large number of biochemical assays (e.g., enzyme-linked immunosorbent assays), and design of biosensors and biomedical devices, where the aim could be to promote or retard protein adsorption. The focus of this article is on methods for recovery and purification of proteins, although the principles and considerations can be readily applied to the full range of applications.

Batch adsorption is considered here as a separation technique in which an entire protein-containing solution is contacted simultaneously with a fixed quantity of adsorbent. This is in contrast to adsorption in a fixed-bed column mode, where the feed stream flows through the column and is differentially contacted with the adsorbent. After adsorption, the wash and desorption procedures can be performed in a number of different ways. For example, elution may be performed in the original mixing vessel by changing the surrounding solution, in a different vessel after adsorbent recovery through an additional step such as cen-trifugation, or after transfer of the adsorbent into a column for ease of flowthrough operation. For desorption to be considered a batch operation, however, the elution must be performed in a manner consistent with single-stage solidliquid contact. This implies that the eluting solution will have uniform product concentration, which is in contrast to the differential elution characteristic of chromatogra-

phy.

Protein batch adsorption is often regarded as an outdated unit operation now superseded by modern column chromatography techniques incorporating a new generation of chromatographic supports. Before the introduction of rigid resins and high-performance liquid chromatogra-phy techniques, however, stirred tank batch contactors were the preferred configuration for scale-up of adsorptive separation steps, because the highly compressible resins could not even support their own weight when packed into process-scale chromatography columns. Nevertheless, an appropriate train of such stirred tanks could provide a moderate number of theoretical separation stages.

Although it is true that modern chromatographic techniques in many applications offer efficiencies and purification factors far superior to the stirred tank systems, there remain a number of applications where creative implementations of batch adsorption offer decided advantages. Because of the immediate and uniform contact of solution and adsorbent, batch adsorption can be performed faster than column-mode adsorption. Thus, it could offer an advantage in applications where a large volume of feed solution must be processed quickly to achieve efficient cycle times or where the limited stability or proteolytic susceptibility of protein products makes rapid processing essential. Batch adsorption may also be favored for handling crude feedstreams having high viscosity or debris that cannot be processed readily through column operations.

This review summarizes the physicochemical principles that define and control batch adsorption, describes a variety of classical and novel applications of these principles, and attempts to demonstrate that a widely overlooked unit operation still has significant utility in bioprocessing.

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