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Pharmaceutical Cell Capture and Cell Harvest

By: Darrell S. Ross Ph.D. – 2023


This article will attempt to explain generally what cell capture and cell harvest are, how they work, and their significance in the pharmaceutical industry.


Pharmaceutical cell capture and cell harvest are two essential steps in biopharmaceutical development. The pharmaceutical industry relies on biopharmaceuticals to diagnose, treat, and prevent diseases. Biopharmaceuticals are therapeutic proteins that are produced using living cells. The process involves isolating and purifying proteins from cellular sources like bacteria, animals, or plants. These processes of cell capture and cell harvest play a crucial role in every stage of biopharmaceutical production. Cell capture involves immobilizing cells, while cell harvest involves separating and collecting the proteins from cells.


Cell Capture


As stated, cell capture is the process of capturing and immobilizing cells. Cell capture plays a critical role in controlling the quality and productivity of cell-based biopharmaceutical production. The process involves immobilizing the cells so that they are stationary and can stay intact during the production process. Cell immobilization can be achieved by various methods such as adsorption, covalent binding, entrapment, and encapsulation. These methods utilize certain materials or processes to adhere or trap cells. The immobilization method chosen depends on several factors like cell type, size, and properties.


One of the commonly used immobilization methods is adsorption. Adsorption involves the attachment of the cells to a charged surface. The surface charge creates an electrostatic interaction between the cells and the surface. The surface can be a resin bead, a microcarrier, or a membrane. Adsorption is a simple, cost-effective, and efficient method for immobilizing cells. However, it may not be suitable for some cells that require specific conditions like growth factors or substrates.


Another immobilization method is covalent binding. Covalent binding involves attaching cells to a surface using chemical bonds. This method provides a stronger attachment between the cells and the surface. It can be achieved by coating the surface with a reagent that creates a covalent bond between the surface and the cells. Covalent binding is more stable than adsorption, making it suitable for some applications like tissue engineering. However, it is a more complicated process that requires specific chemical reagents.


Entrapment and encapsulation methods involve trapping the cells in a matrix or a capsule. This method provides a protective environment for the cells during the production process. The matrix or the capsule can be made of various materials like alginate, agarose, or polymeric beads. The material should be biocompatible and should allow the transfer of nutrients and waste products. Entrapment and encapsulation methods are suitable for sensitive cells that require specialized culture conditions.


Cell Harvest


Cell harvest is the process of separating and collecting protein products from cells. Cell harvest plays a vital role in the quality and yield of biopharmaceutical products. The process involves breaking the cell wall to release the protein products. The proteins are then separated from the cell debris and purified. Cell harvest can be achieved by various methods like mechanical methods, chemical methods, and enzymatic methods.


Mechanical methods of cell harvest involve disruption of the cell wall using physical forces. These methods include sonication, bead beating, and pressure cycling. Sonication involves the application of high-frequency soundwaves that lead to the cell wall's rupture. Bead beating is a process of grinding the cells using beads. Pressure cycling involves the application of high-pressure cycles to the cell suspension. Mechanical methods can be useful for large-scale production processes. However, they can also damage the proteins, making the purification process challenging.


Chemical methods of cell harvest involve the use of chemicals to disrupt the cell wall. The chemicals used include detergents, chaotropic agents, and organic solvents. These chemicals break down the cell wall, releasing proteins into the suspension. Chemical methods are suitable for small-scale production processes. However, they may also damage the proteins, reducing their quality.


Enzymatic methods of cell harvest use enzymes to degrade the cell wall. These enzymes, like lysozyme or papain, selectively break down the cell wall, releasing the proteins intact. Enzymatic methods are gentle and maintain protein quality. However, they are limited to certain cell types that have specific cell walls.


Cell capture and cell harvest play a crucial role in biopharmaceutical production. The processes ensure the quality and yield of protein products. Cell immobilization facilitates easy manipulation and monitoring of cell growth and activity. It also provides a protective environment for cell-based products. Cell harvest ensures the efficient recovery of proteins from cells and eliminates cell debris. Efficient cell harvest leads to high yield and quality of protein products.


In conclusion, pharmaceutical cell capture and cell harvest are essential processes in biopharmaceutical development. Cell capture and immobilization are crucial for efficient and effective control of cell-based biopharmaceutical production. The process of cell capture uses various methods like adsorption, covalent binding, entrapment, and encapsulation. Cell harvest, on the other hand, involves breaking the cell wall and separating the protein products from the cells. The process uses methods like mechanical methods, chemical methods, and enzymatic methods. Cell capture and cell harvest are critical for ensuring the quality and yield of biopharmaceutical products. Therefore, researchers and pharmaceutical companies should continue to develop new and more efficient cell capture and harvest methods to optimize biopharmaceutical production.


Citations:


1. Garcia-Jimenez, A., Barrios-Gonzalez, J., Fernandez-Lopez, L., & Gomez-Sobrino, A. (2019). Microbial cell immobilization: Evolution of techniques and applications. Applied Microbiology and Biotechnology, 103(7), 2837-2848.


2. Singh, R. P., Ramteke, P. W., & Oliveira, J. M. (2020). Bioprocess Engineering in the Manufacturing of Therapeutic Proteins. Springer.


3. Pareek, A., Khurana, S., & Kumar, V. (2018). Cell Immobilization and its Biotechnological Applications: An Overview. Journal of Microbiology and Biotechnology Reports, 2(1), 6-13.


4. Anjum, N., & Aslam, A. (2018). Bioprocess development for microbial production of therapeutic proteins: A review. Journal of Applied Biology & Biotechnology, 6(06), 1-16.


5. Karakaya, M. U., & Kavakli, I. H. (2017). Cell immobilization for microbial production of industrial enzymes. Molecular Biology Reports, 44(6), 655-664.

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