1. Advanced Techniques for Pore Structure Characterization of Biomedical Materials Akshaya Jena and Krishna Gupta Porous Materials, Inc. 20 Dutch Mill Road Ithaca, NY 14850

2. Topics ê Important Pore Structure Characteristics ê Innovative Extrusion Techniques for Characterization ê Examples of Applications ê Advantages of the Techniques ê Summary and Conclusion ê Need For Structure Characterization of Biomedical Materials

3. Need For Structure Characterization of Biomedical Materials ê Performance is determined by pore structure characteristics. ê Many modern biomedical materials are porous

4. Need for Pore Structure Characterization of Biomedical Materials ê Powder drugs ê Drug delivery system ê Hydrophobic/hydrophilic mixtures ê Dialysis membranes Examples ê Synthetic Skin ê Hydrogels ê Substrate for tissue growth ê Dialysis membranes

5. Need for Pore Structure Characterization of Biomedical Materials ê Cosmetic powders ê Blood clotting material Examples ê Arterial grafts ê Blood delivery systems ê and many more

6. Important Pore Structure Characteristics Pore throat diameterPore Volume (Barrier properties)(Holding capacity) Largest diameterPore distribution (Barrier properties)(Barrier & flow)

7. Important Pore Structure Characteristics Mean diameterSurface area (Barrier & flow)(Barrier, rate & flow) Liquid permeability Gas permeability (Rate of process)(Rate of process)

8. Innovative Extrusion Techniques for Characterization  Pores of sample spontaneously filled with a wetting liquid g sample/liquid <g sample/gas Principle

9. Innovative Extrusion Techniques for Characterization  Differential pressure, p of gas on one side of sample increased to displace liquid from pore p = 4 g cos q/D g = liquid surface tension q = liquid contact angle D = Diameter of pore such that: (dS/dV)pore = (dS/dV)cylindrical opening of diameter, D S = gas/solid surface area in pore V = volume of gas in pore

10. Innovative Extrusion Techniques for Characterization ê Differential pressure and flow rate of liquid displaced from pores measured  Extrusion porosimetry (Liquid Extrusion Porosimetry) ê Differential pressure and gas flow rates through wet and dry samples measured  Extrusion flow porometry (Capillary Flow Porometry)

11. Innovative Extrusion Techniques for Characterization Extrusion Flow Porometry Extrusion Porosimetry (Capillary Flow Porometry) (Liquid Extrusion Porosimetry)

12. Instrument ê Fully automated & computer controlled Liquid Extrusion Porosimeter Capillary Flow Porometer ê Highly accurate, reliable & objective

13. Examples of Applications ê Primary function: Filtration ê Important requirements: ë The largest pore diameter ë Mean pore diameter ë Pore distribution ë Flow Rate Dialysis membrane

14. Dialysis membrane Test results using Capillary Flow Porometry Differential pressure and flow rates through wet and dry samples of a dialysis membrane. The half-dry curve is computed from dry curve to yield half of flow rate through dry sample

15. Dialysis membrane Pore Structure Characteristics  Mean flow pore diameter  From mean flow pressure = 0.458 mm ê Pore distribution  Distribution function: f =-d[(f w /f d )x100]/dD f w = wet flow f d = dry flow  The largest pore diameter  From pressure for flow initiation = 1.023 mm

16. Normalized Pore distribution function Dialysis membrane Pore Structure Characteristics  Area in a pore size range = % Flow through pores in the range. Almost 80% flow is through 0.2-0.7mm pores

17. Liquid flow rate measured as a function of pressure ê Liquid permeability computed from measured liquid flow rates ê Dry curve yields gas permeability Dialysis membrane Pore Structure Characteristics

18. ê All required characteristics including very small pore diameters were measured by capillary flow porometry Dialysis membrane Pore Structure Characteristics

19. Hydrogels ê Promotes healing of wounds & burns when used as dressings Requirements: ê Pore volume for holding capacity ê Pore size & distribution for barrier ê High permeability to promote healing of wounds Primary function: ê Hormone & drug delivery

20. Hydrogels Test results using Water Extrusion Porosimetry Pore volume of hydrogel measured using water intrusion porosimeter

21. Hydrogels Pore Structure Characteristics ë Porosity  67.12% ê Pore Volume Distribution  Distribution function, fv = -(dV/dD) V = pore volume D = pore diameter ê Pore Volume ë Total pore volume  0.421 cm 3 /g

22.  Pores have a narrow range  5-20 mm For a given range: Area = pore volume Hydrogels Pore Structure Characteristics

23. Typical Plot of flow rate of water vs pressure Hydrogels Pore Structure Characteristics ê Liquid flow rate yields permeability

24. ê Pore volume, pore volume distribution and liquid permeability were successfully measured in a water extrusion porosimeter. No other technique can measure these properties. Hydrogels Pore Structure Characteristics

25. Artificial Skin ê Be breathable Requirements: ê Pore size & distribution to promote blood vessel growth ê Gas and vapor permeability to be breathable Primary function: ê Promotes and allows growth of blood vessels

26. Artificial Skin Test results using Capillary Flow Porometry Differential pressure and flow rates through wet and dry samples of a sample of synthetic skin. The half-dry curve is computed from dry curve to yield half of flow rate through dry sample

27. Artificial Skin Pore Structure Characteristics  Mean flow pore diameter  From mean flow pressure = 31.489 mm ê Pore distribution  Distribution function: f = -d[(f w /f d )x100]/dD f w = wet flow f d = dry flow  The largest pore diameter  From pressure for flow initiation = 4.932 mm

28. Normalized Pore Distribution function vs pore diameter Artificial Skin Pore Structure Characteristics

29. ê Dry flow rate yields permeability ê Largest constricted pore diameters, broad distribution and high permeability were measured by capillary flow porometry  A board & uniform distibution: About 5 to 70 mm Artificial Skin Pore Structure Characteristics

30. Nanofiber Mats for Tissue and Organ Culture ê Suitable pore diameter in x, y & z directions ê Ability to be shaped in desired manner Primary function: ê Sufficient pore volume to supply adequate nutrients

31. Nanofiber Mats for Tissue and Organ Culture ê Pore size & distribution ê x, y & z direction pore structure Requirements ê Pore volume

32. Techniques & measurable Characteristics ë Pore diameter ê Extrusion Flow Porometry ë Constricted pore diameter ë Pore distribution ê Extrusion Flow Porometry (In-plane) ë x & y direction pore diameter ë x & y direction pore distribution ê Extrusion porosimetry ë Pore volume Nanofiber Mats for Tissue and Organ Culture

33. Advantages of the Techniques ê Samples not contaminated, reusable and can be saved ê Low test pressures ê Small test duration ê Only through pores measured ê No toxic material is used: No heath hazard, No environmental pollution

34. Summary and Conclusion ê An innovative extrusion technique was used for characterization. Two variations of the technique were employed ë Extrusion flow porometry ë Extrusion porosimetry ê Performance of many pharmaceutical and biotech products depend upon their pore structure characteristics

35. Summary and Conclusion ê A variety of products including dialysis membranes, artificial skins, hydrogels, were successfully tested ê The technique was successfully used to measure pore structure characteristics including constricted pore diameter, the largest pore diameter, mean flow pore diameter, flow distribution, pore volume and permeability

36. Summary and Conclusion ê The technique had a number of advantages including absence of the need for use of any toxic material, ability for the sample to be reused or saved, use of low pressures and small test duration.

37. Thank You