Building Blocks of Human Blood
Human blood is a remarkable fluid composed of several key components, each serving vital functions in maintaining our health. Red blood cells are responsible for transporting oxygen from the lungs to tissues throughout the body, ensuring that organs receive the oxygen they need to function properly. White blood cells act as the body's defence system, combating infections and foreign invaders. Platelets play a crucial role in blood clotting, preventing excessive bleeding when injuries occur. All these elements are suspended in plasma, the liquid portion of blood, which carries nutrients, hormones, and waste products, facilitating their distribution and removal.
Plasma fractionation: An irreplaceable pillar of modern medicine
Plasma fractionation is an essential and highly advanced process that isolates key proteins from human plasma to create therapies that cannot be replicated by synthetic alternatives. These plasma-derived treatments are critical for patients with immune deficiencies, bleeding disorders such as hemophilia, and a range of life-threatening neurological and autoimmune conditions.
Proteins derived from plasma fractionation cannot be produced through chemical synthesis or genetic engineering to the same extent as other pharmaceuticals, making the availability of plasma and its efficient processing critically important. As global demand rises, driven by an aging population and improved diagnostic capabilities, the role of plasma fractionation becomes increasingly essential.
How plasma fractionation works
Human plasma is first collected through plasmapheresis and rapidly frozen at −30°C or colder to preserve labile proteins such as coagulation factors and to prevent bacterial growth or protein degradation. When required for processing, the plasma is thawed slowly at 1–6°C, triggering the precipitation of certain cold-insoluble proteins- a step known as cryoprecipitation (Fig 1). The resulting cryoprecipitate contains medically valuable proteins such as fibrinogen (essential for clot formation), Factor VIII (critical for hemophilia A treatment), von Willebrand factor (vWF) (important for platelet adhesion and clot stabilization), and fibronectin (a key protein in wound healing and tissue repair). These proteins are separated out for targeted therapeutic use.
The remaining liquid portion, referred to as cryosupernatant, is then used in further fractionation processes. In some workflows, especially where large plasma volumes are handled, water removal techniques such as ultrafiltration or controlled evaporation may be applied to concentrate plasma proteins and reduce processing volume (Fig 1). This improves the efficiency of downstream purification steps, whether via ethanol precipitation (e.g., the Cohn process) or modern chromatographic techniques.
The remaining plasma is used for further fractionation through the Cohn process, which separates plasma proteins by gradually adjusting ethanol concentration, temperature, pH, and ionic strength. Each step causes specific proteins to precipitate while others remain in solution. The precipitated proteins are collected by centrifugation or filtration, yielding several fractions: Fraction I includes residual fibrinogen, Fraction II is rich in immunoglobulin G (IgG), and Fraction V contains albumin, which remains soluble even under harsh ethanol conditions (Fig 1).
Fig. 1 Schematic and simplified illustration of how the process works in reality.
Each of these fractions undergoes additional purification steps to ensure the proteins are safe, pure, and effective for therapeutic use (Fig 2). These include:
Through this combination of cold ethanol fractionation and advanced purification, essential plasma-derived medicines are produced, including coagulation factors, immunoglobulins, and albumin—each vital in treating bleeding disorders, immune deficiencies, and conditions requiring blood volume restoration.
Fig. 2 Downstream of plasma fractionation process.
Why mixing matters
In the realm of biopharmaceutical manufacturing, the mixing process is a delicate operation, especially when handling protein-based products. Proteins are complex molecules that can be sensitive to physical forces; improper mixing can lead to their denaturation or aggregation, compromising the efficacy and safety of the final product. Therefore, employing mixing technologies that provide gentle and uniform agitation is paramount to preserve the integrity of protein formulations and ensure consistent therapeutic outcomes.
Choosing the right mixing technology
Traditional magnetic mixers are using slide bearings for the mix head and uses the mixed product as a lubricant. This might cause heat and/or shear stress to the protein, that could lead to loss of function of the product or aggregates and filter clogging.
Metenova's Truelev mixer represents a significant advancement in mixing technology, particularly for applications requiring low shear forces. Its fully levitating, bearing-less design allows the mixing head to float freely, delivering exceptionally gentle mixing ideal for shear-sensitive products like proteins. This innovative approach minimizes the risk of damaging delicate molecules during the mixing process. Additionally, Truelev's design eliminates wear and moving parts in the motor, resulting in a maintenance-free operation that enhances reliability and reduces downtime in critical manufacturing processes.
Fig. 3 Metenova’s bearing less Truelev mixer. The mixer head is completely levitating without any contact to the tank plate.
Click here to learn more about the bearing less Truelev mixer.