Hollow Fiber Technology: How To Protect The Activity Of Biological Products With Low Shear Force?

Hollow Fiber (HF) is a fibrous material with a hollow cavity structure, featuring an internal hollow channel and an outer wall made of porous or dense polymer membranes. This unique structure provides a high specific surface area, excellent mass transfer performance, and mechanical strength. Driven by tangential pressure, hollow fibers filter out particles, bacteria, or intercept target substances with selective permeability, making them widely applicable in biomedicine, bioengineering, and environmental protection.

 

Product Advantages

● Open flow channels with high dirt-holding capacity

● Uniform membranes with comprehensive pore size options

● Flexible modular design for linear scalability

● Low shear force, especially suitable for sensitive protein-based products and viral processing

Shear force in hollow fiber systems significantly impacts the production, purification, and stability of biological products, particularly in biopharmaceuticals (e.g., monoclonal antibodies, vaccines, recombinant proteins) and cell therapy. Appropriate shear force enhances mass transfer and mixing, but excessive shear force may lead to inactivation, aggregation, or cell damage. Shear force is primarily influenced by three categories of factors: hydrodynamic parameters, fiber structural parameters, and operating conditions. Flow rate (Q) is directly proportional to shear force, while increased fluid viscosity (μ) significantly elevates shear force levels. Fiber inner diameter (Di) is the most critical structural parameter, as it inversely correlates with shear force cubed-minor changes in Di can drastically alter shear force.

 

(1) Hydrodynamic Parameters

Factor	Impact
Flow rate (Q)	Higher flow rates increase wall shear stress
Viscosity (μ)	High-viscosity fluids (e.g., concentrated cell culture media) exhibit higher shear stress at the same flow rate
Flow mode	Laminar flow (low shear) vs. turbulent flow (high shear, risk of cell damage or protein denaturation)

 

(2) Hollow Fiber Structural Parameters

Factor	Impact
Inner diameter (Di)	Smaller Di increases velocity and shear stress at the same flow rate
Length (L)	Increased length elevates pressure drop, indirectly affecting shear stress distribution
Fiber packing density	Dense packing increases inter-fiber flow resistance, potentially raising local shear stress

 

(2) Operating Conditions

Factor	Impact
Transmembrane pressure (TMP	High pressure differences may increase membrane surface shear stress, causing fouling or deformation
Pulsatile flow	Periodic flow reduces fouling but may introduce transient shear stress peaks

 

Formulas for Calculating Shear Force in Hollow Fibers

(1) Wall Shear Stress (τw)

Applicable to laminar flow (low Reynolds number Re < 2100) in straight fiber tubes:

τw: Wall shear stress (Pa or dyn/cm²)

μ: Fluid viscosity (Pa·s)

Q: Volumetric flow rate (m³/s)

Di: Fiber inner diameter (m)

 

(2) Reynolds Number (Re) for Flow Regime Determination

ρ: Fluid density (kg/m³)

v: Flow velocity (m/s)

Di: Fiber inner diameter (m)

Laminar flow: Re < 2100 (predictable shear stress)

Turbulent flow: Re > 4000 (complex shear stress, requiring CFD simulation)

 

(3) Relationship Between Pressure Drop (ΔP) and Shear Stress

Hagen-Poiseuille equation (laminar flow):

High pressure drop may indirectly increase shear stress, especially in long fibers or systems with small Di.

 

Direct Effects of Shear Force on Biological Products

Application	Shear Force Risk	Typical Tolerance Threshold
mAb production	Aggregation (medium-high sensitivity)	＜1000s-1 (ultrafiltration)
CHO cell culture	CHO cell damage (high sensitivity)	＜50-100dyn/cm²
AAV purification (UF)	Viral particle rupture (high sensitivity)	＜500s-1
Hemodialysis	Hemolysis (extremely high sensitivity)	＜1500s-1
Exosome isolation	Vesicle rupture (high sensitivity)	＜1500s-1
Traditional Alum adjuvant	Particle breakage, pore collapse (high sensitivity	＜1000s-1(Low-risk threshold) 1000-3000s-1(medium-risk threshold) ＞3000s-1(high-risk threshold)

 

(1) Protein/Antibody Denaturation or Aggregation

Mechanism:

High shear forces (e.g., turbulence, cavitation) may induce conformational changes in proteins, exposing hydrophobic regions and triggering aggregation. During filtration, ultrafiltration, or perfusion culture, shear forces can disrupt native protein structures.

Case:

Monoclonal antibodies (mAb) are prone to aggregation during high-speed pumping or membrane filtration, compromising efficacy and safety.

 

(2) Cell Damage (Mammalian/Microbial Cells)

Mechanism:

Mammalian cells (e.g., CHO cells) are shear-sensitive; high shear forces may cause membrane rupture, apoptosis, or metabolic dysfunction. Microbes (e.g., E. coli) may lyse under high shear, releasing endotoxins.

Critical Thresholds:

Mammalian cells: Typically tolerate <50–100 dyn/cm² (perfusion culture).

Red blood cells: >1500 s⁻¹ may induce hemolysis (e.g., hemodialysis).

 

(3) Disruption of Viruses/Exosomes (Nanoparticles)

Mechanism:

Viral vectors (e.g., AAV, lentivirus) or exosomes may rupture under shear stress, reducing infectivity or therapeutic efficacy.

Case:

In gene therapy, viral vectors require shear force control during hollow fiber purification to avoid titer loss.

 

(4) Membrane Fouling and Product Loss

Mechanism:

High shear forces may cause cell debris or protein deposition on membranes, blocking pores and reducing mass transfer efficiency. Shear-induced adsorption (e.g., nonspecific antibody binding) may lower product recovery.

 

Optimization Strategies: Mitigating Shear Force Impact

(1) System Design Optimization

Reduce flow rate: Use low-shear pumps (e.g., peristaltic pumps) or optimize flow path design (e.g., tapered channels).

Fiber selection: Increase Di to reduce wall shear stress (balance with mass transfer efficiency).

Use surface-modified membranes (e.g., hydrophilic coatings) to minimize protein adsorption.

(2) Process Parameter Control

Perfusion culture: Control perfusion rate (e.g., 1–3 RV/day) to avoid cell damage.

Implement alternating tangential flow (ATF) technology to reduce sustained high shear.

Purification stages: Use low TMP (<1 bar) and low flow rates during ultrafiltration/dialysis.

(3) Additive Protection

Stabilizers: Add sugars (e.g., trehalose) or surfactants (e.g., Pluronic F68) to reduce protein aggregation.

Cell protectants: Use serum or polymers (e.g., polyvinyl alcohol) to lower shear sensitivity.

(4) Real-Time Monitoring and Modeling

Sensor monitoring: Real-time detection of shear stress (e.g., wall shear stress sensors).

CFD simulation: Predict high-shear zones and optimize flow fields via computational fluid dynamics.

Hollow fiber technology demonstrates significant advantages in biological product applications due to its low-shear design, making it ideal for shear-sensitive substances (e.g., proteins, viral vectors, cells). Its tangential flow filtration (TFF) reduces transmembrane pressure (TMP) via parallel flow, minimizing fluid shear stress to prevent product denaturation or damage. The laminar flow characteristics of fiber lumens and optimized flow rates enable efficient mass transfer while maintaining gentle operation, widely applied in mAb concentration, vaccine purification, and other precision processes. Modular designs support linear scalability, ensuring consistent shear force parameters from lab to production scale, thereby preserving product activity. Furthermore, hydrophilic membrane materials (e.g., PES, PVDF) and low-shear pumps (e.g., diaphragm pumps) synergistically reduce friction and adsorption, improving recovery rates (e.g., >90% for AAV purification). In summary, hollow fiber technology, with its low shear, high controllability, and scalability, is an ideal choice for downstream bioprocessing, particularly for high-value, shear-sensitive products.

 

About Guidling

Guidling Technology is a production-oriented and high-tech enterprise focusing on the downstream clarification, separation and purification of biopharmaceuticals. The products are widely used in the filtration process of MAB, vaccine, diagnosis, blood products, serum, endotoxin and other biological products; Guidling Technology has "cassettes filter and tangential flow filtration device", "hollow fiber membrane", "virus filter", "deep membrane", "sterilizaation filter", "centrifugal filter devices" and other products, and has a large number of product lines, from small disposable laboratory filtration to production filtration system, meet the needs of testing and production. Guidling Technology is looking forward to cooperating with you!