Effects of Membrane Morphology on Separation Efficiency

1. Effects of Membrane Morphology on Separation Efficiency Mark Hurwitz, Ajay Lajmi, David Grzenia, Anil Kumar June 23, 2014

2. Pall CorporationGlobal leader in high-tech filtration, separation, and purification • Fiscal Year 2013: • $1.3 billion Life Sciences • 33% BioPharmaceuticals • 9% Food & Beverage • 8% Medical • $1.3 billion Industrial • 31% Process Technologies • 10% Microelectronics • 9% Aerospace

3. The Problem • Competing requirements: Fine separation with low power consumption • Obvious Resolution: Use largest pore size and void fraction consistent with separation requirement • Complication: Fouling depends on many parameters, not just pore size and void fraction. • Challenge:Devise a common mathematical description of membrane morphology which • Distinguishes common membrane types • Connects to separation and fouling performance

4. Sieving – the simplest capture mechanism • Some filters are simple screens or sieves. • Particles retained by “Direct Interception.” • Particles form a filter “cake” which acts as a finer filter.

5. Depth Filtration • The thickness of most filter media is important for filtration. • Depth creates a “Tortuous Path” which helps trap particles. • Depth filters are often constructed of randomly oriented fibers.

6. Single Fiber Capture • In addition to being blocked by size, particles contact media by • Inertial impaction: • Brownian motion: • Particles adhere by: • Electric charge • van der Waals forces • Chemical bond

7. Membranes • Cast porous structures • Usually sub-micron pore sizes • Mostly direct interception capture at membrane surface • Other mechanisms play a role in macro-molecule capture

8. Summary of Membranes

9. Asymmetric 0.2 µm PES E4 Membrane Tight Side Surface View, 200 x Magnification Open Side Surface View, 2000 x Magnification 250 µm 0 µm Cross Section View, 350 x Magnification

10. Symmetric 0.2 µm PES E1 Membrane Tight Side Surface View, 5000 x Magnification Open Side Surface View, 5000 x Magnification

11. Symmetric 0.2 µm PES E4 Membrane Surface -1 View, 5000 x Magnification Surface -2 View, 4000 x Magnification

12. Symmetric 0.45 µm PES E5 Membrane 3.13 µm 3.13 µm Surface -2 View, 3200 x Magnification Surface -1 View, 3200 x Magnification

13. 0.2 Micron Track Etched Membrane Side 1 Side 2

14. Effect of PES Membrane Morphology on BSA Throughput using 0.2 µm E4 Hydrophilicity (1) Tests performed under constant pressure condition

15. Effect of PES Membrane Morphology on BSA Throughput using 0.2 µm E4 Hydrophilicity(2) Tests performed under constant pressure condition

16. Effect of Membrane Morphology (3) Tests performed under constant flow condition, E4 Hydrophilicity

17. Effect of Membrane Morphology (4) Tests performed under constant flow condition, E4 Hydrophilicity Effect of Membrane Morphology (3) Tests performed under constant flow condition

18. Typical Test Proteins IgG 150 KD (7 nm*) Isoelectric point: Mab1: pH 5.5, Mab2: pH 7.7 Cytochrome C 12 KD (3 nm*) Isoelectric point: pH 10 BSA 60 KD (5 nm*) Isoelectric point: pH 5.3 “Top” View “Side” View *Size in nm is diameter of a sphere of the given mass & typical protein density (1.37 g/cm3) See: http://www.springerprotocols.com/Abstract/doi/10.1007/s12575-009-9008-x

19. Non-destructive Testing • Forward Flow, Pressure Hold and Bubble Point Tests are all based on the same physics: • Flow rate of a gas through a wetted membrane depends on: • The pore structure of the membrane. • The surface tension of the liquid. • Diffusivity of the gas. • Water Intrusion Test is the Opposite: • Flow rate of a liquid through an initially dry membrane also depends on pore structure and surface tension.

20. Bubble Point of a Wetted Membrane • Surface tension keeps fluid in pores. • When air pressure is high enough, fluid is blown out of the largest pores. • Smaller pores open at higher pressure. • Diffusive flow masks opening of small pores – very difficult to measure pore size distributions!

21. Pressurized Gas Flow Across a Wetted Membrane • Pressure Hold test: • Set Test Pressure upstream. • Measure slow pressure decay by diffusion. • Fast decay = problem. • Forward Flow test: • Maintain Test Pressure upstream. • Measure flow rate downstream. • High flow rate = problem. Example: 10” Cartridge with 0.2 micron membrane.

22. 60 User Test Value 50 First Non Sterility 40 30 Forward Flow (ml/min) 20 10 0 Filter Cartridges Correlation of Forward Flow Values with Bacteria Retention Sterile Non Sterile

23. An Integrity Test Tells You • The filter is undamaged and properly assembled. • The filter is the same as those used to produce the correlation with bacterial retention. • The filter is the same as those normally produced. • The purpose of integrity testing is to confirm filter integrity, not to measure pore size

24. The Problem (again) • Devise a common mathematical description of membrane morphology which • Distinguishes common membrane types • Connects to separation and fouling performance

25. Thank you!