Hollow Fibers

1. Hollow Fibers

2. Hollow Fibers • Definition- materials capable of conducting flow in an axial direction or providing a conduit to guide the regeneration of tissue, and generally capable of separating soluble molecules on the basis of size and in certain specialized cases on the basis of charge (semipermeable), in other cases the separation is not molecular but cellular.

3. Filtration • Hollow Fiber Membranes (HFM); • Selective Separation; Materials • Thermoplastics-PS, PAN, PAN-PVC, CA, CN • Polyurethane

4. Separation Based on Size Exclusion

5. D æ ö c = = D ç ÷ J D P ( c ) s x è ø Increased Number of Pores Concentration Concentration Concentration Concentration Gradient Gradient Gradient Gradient Fick’s Law Fick’s Law Fick’s Law Fick’s Law

6. Hollow Fiber Modules

9. Applications • Blood gas oxygenators • Plasmapheresis • Dialysis • Liquid sterilization • Bioartificial liver • Bioartificial kidney • Drug delivery-cell encapsulation • Biotechnology-bioreactors • Vascular grafts • Nerve repair

10. Hemodialysis External procedure 3 sessions of 4 hrs a week Filtration process only Hollow Fiber Dialyzer Blood flows in and is cleaned using the process of diffusion and ultrafiltration.

11. Cell Culture Bioreactor and Purification of Biologics

12. Bioartificial liver Based on pig hepatocytes attached to collagen microcarriers

13. Nerve Track Repair: Bridging Substrates

14. Nerve Repair-Entubulation

15. Huntington’s Alzheimer’s Therapeutic Targets Affective Disorders Parkinson’s Central Nervous System Disorders Endocrine and Metabolic Disorders Tissue Reconstruction or Repair Epilepsy Pituitary Disorders Hypercalcemia Connective Tissues Cardiac Tissue Skin Blood Vessels Liver Failure Intractable Pain Diabetes Anemia Nerves Muscles Applications of Cell Replacement Therapy

16. Problems with Conventional Cell Replacement Therapies • Immune rejection • Shortage of donor cells • Pathogenicity • Tumor formation • Non-reversible treatment

17. Cell Encapsulation Technology “Immunoisolation” Waste Products Nutrients Immune Response Cell Secretions Encapsulation Membrane

19. Huntington’s Alzheimer’s Therapeutic Targets Affective Disorders Parkinson’s Central Nervous System Disorders Endocrine and Metabolic Disorders Tissue Reconstruction or Repair Epilepsy Pituitary Disorders Hypercalcemia Connective Tissues Cardiac Tissue Skin Blood Vessels Liver Failure Intractable Pain Diabetes Anemia Nerves Muscles Applications of Cell Replacement Therapy

20. Tag Active Segment Distal Segment Diffusion of Metabolites Immune Exclusion Device Concept

21. Cell Encapsulation Therapy Harvested Tissue Purification and/or Isolation Stem/Precursor Cells Transformed Cell line Genetic Engineering In Vitro Expansion PrimaryCells Implantation of device Cell Encapsulation device loading

22. Retrievable Cell Delivery Products

24. HFM Fabrication-Fiber Spinning

25. Phase Inversion • Controlled precipitation • Solution--> porous solid that is interconnected and traversed by an interpenetrating pore structure which provides channels across the wall structure

26. Required Elements • A polymer of sufficient Mw that is, enough length to provide inter chain entanglement following precipitation and adhesive force to provide the appropriate mechanical properties for a particular application • Polymer & solvent • Miscible non-solvent

27. Note: Picture not drawn to scale Nonsolvent Polymer Stream Solution Stream Outflow Stream Anatomy of a Spinneret Spinneret HFM

28. Dry-Jet Wet Spinning Spinnerette Nonsolvent Stream Note: Picture not drawn to scale Nonsolvent Polymer Stream Solution Stream Polymer Solution Stream Outflow Stream Nonsolvent Bath

29. Polymer Solution

30. The Addition of Non-solvent

31. Precipitation with Chain Entanglement

32. Note: Picture not drawn to scale Nonsolvent Polymer Stream Solution Stream Outflow Stream Anatomy of a Spinneret Spinneret HFM

33. Various Stages in the Early Life of a HFM HFM

34. Polymer Rich Zone Dense Skin Lumen of Hollow Fiber

36. Laser Photodiode Cantilever and Probe Tip XYZ piezotranslator Topography of Selective Skin Layer

37. Inner Skin Ultra-topography

38. 4° C - 100% H20 Quench 22° C - 100% H20 Quench 35 1000 x 1000 nm 54° C - 100% H20 Quench 54° C - 50/50 DMF/H20 Quench nm 0

39. Polymer Rich Zone Dense Skin Lumen of Hollow Fiber

40. Production Spinning Line

41. Molecular Separation Reverse osmosis-Ion selective Ultrafiltration-rejection of molecules >100kD Microporous-rejection of cells Macroporous-cell permeable

43. 1000.0 1000.0 Water Water PAN - PVC PAN - PVC 100.0 100.0 cm/sec) cm/sec) 10.0 10.0 6 6 Hindered Transport Model Hindered Transport Model Km (x 10 Km (x 10 1.0 1.0 0.1 0.1 1 10 100 1000 1 10 100 1000 Molecular Weight ( kDa ) Molecular Weight ( kDa ) Diffusive Transport Characteristics

44. D æ ö c = = D ç ÷ J D P ( c ) s x è ø Increased Number of Pores Concentration Concentration Concentration Concentration Gradient Gradient Gradient Gradient Fick’s Law Fick’s Law Fick’s Law Fick’s Law

45. C A G D E B F H On a Larger Scale Various Structures are Apparent and can be controlled by changing Fabrications conditions A PAN-PVC Li et al. 1998 B PAN-PVC Li et al. 1998 C Polyimide Chung et al. 1992 D Polysulfone Valette et al.1999 E Cellulose acetate Hao et al. 1996 F PAN copolymer Valette et al.1999 G AN69 Valette et al.1999 H PMMA Valette et al.1999