Related Experiment Video
Updated: Jul 6, 2026
04:49
Automated Counterflow Centrifugal System for Small-Scale Cell Processing
Published on: December 12, 2019
Advances in primary recovery: centrifugation and membrane technology
1BioPurification Development, Merck Research Laboratories, P.O. Box 2000, Mailstop RY805S-100, Rahway, New Jersey 07065, USA. david_roush@merck.com
Biotechnology Progress
|April 16, 2008
Summary
Upstream processing advances create primary recovery bottlenecks in biologics manufacturing. New chemical engineering approaches like membrane cascades are emerging to address challenges with impurities and cell debris.
Area of Science:
- Biopharmaceutical Manufacturing
- Chemical Engineering
- Process Development
Background:
- Advances in upstream bioprocessing enable higher cell densities and product titers.
- Increased product titers and lower cell viability lead to higher levels of process impurities.
- Cell culture media components like hydrolysates contribute to impurity profiles.
Purpose of the Study:
- To review the current state of primary recovery in biologics downstream processing.
- To identify challenges and emerging solutions in primary recovery.
- To discuss potential future research directions in primary recovery.
Main Methods:
- Review of current primary recovery techniques including microfiltration and centrifugation with depth filtration.
- Discussion of challenges posed by impurities (lipids, proteins, nucleic acids, colloids) and their impact on downstream steps.
- Exploration of advanced chemical engineering approaches such as membrane cascades and precipitation.
Main Results:
- Primary recovery is a significant bottleneck due to high cell densities and impurity levels.
- Existing methods like filtration and centrifugation face challenges with diverse particle sizes and fouling.
- Novel techniques, rooted in chemical engineering principles, are gaining traction as disruptive solutions.
Conclusions:
- Optimization of primary recovery has become more complex, necessitating innovative solutions.
- Classical chemical engineering principles are being revisited to address primary recovery challenges.
- Emerging technologies offer promise for improved efficiency and impurity removal in biologics manufacturing.
Related Concept Videos
01:29Downstream Processing
Downstream processing begins once fermentation is complete and involves a series of steps to recover and purify products such as acids, vitamins, antibiotics, or proteins.Cell HarvestingFor example, for intracellular protein-based products, the first step is harvesting the cells. This is typically achieved using centrifugation or filtration to separate the cells from the liquid phase.Cell Disruption for Intracellular ProductsIf the target product is intracellular, the harvested cells must be...
01:05Centrifugation
Centrifugation is a separation technique based on differences in density or size. It is commonly used to separate solids from aqueous interferents. During centrifugation, the sample is placed in centrifugation tubes and spun at high angular velocity, which allows centrifugal force to act differentially on the different densities or masses of the components. After spinning, the supernatant liquid is decanted. Depending on the specific application, either the pellet or the supernatant is retained...
01:20Overview Of Cell Separation And Isolation
Cell separation was first achieved in 1964 by S. H. Seal, who separated large tumor cells from the smaller blood cells using filtration. Two years later, Pohl and Hawk performed experiments on how cells respond differently to a nonuniform electric field based on the cell type. Such observations were the inception of cell separation methods, which allow isolating a single cell type from a heterogeneous sample.
01:32Subcellular Fractionation
The homogenate obtained after cell lysis contains various membrane-bound organelles that can be further separated into pure fractions by subcellular fractionation. These isolates are used to study specific cellular components, analyze localized protein activity, and are even employed in diagnostics. Fractionation is typically achieved using centrifugation methods, the most common being density-gradient and differential centrifugation.
Differential Centrifugation
Differential centrifugation is...
Differential Centrifugation
Differential centrifugation is...
01:18Detergent Purification of Membrane Proteins
Detergents are used to purify the integral proteins of the membrane. The hydrophobic portion of the detergent can replace membrane phospholipids while solubilizing the membrane proteins. When detergent monomers reach a specific concentration in a solution called critical micelle concentration (CMC), they form micelles. Above CMC, the concentration of the detergent monomers remains in equilibrium with the micelle. The number of detergent monomers present in the CMC varies for each detergent, and...
01:15Dialysis
Dialysis is a diffusion-based purification process that separates analyte molecules from a complex matrix. This is accomplished by allowing molecules in the solution to pass through a semipermeable membrane into a liquid on the other side. The membrane is usually made of cellulose acetate or cellulose nitrate, and the second liquid must be miscible with the solution. Ions (e.g., chloride or sodium) or organic molecules (e.g., glucose) can pass through the membrane pores, which generally have...