Ultrasound enchancement of membrane permeability

• US 4,780,212 A
• Filed: 07/31/1987
• Issued: 10/25/1988
• Est. Priority Date: 07/31/1987
• Status: Expired due to Term

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Langer, Robert S., Kost, Joseph
• Primary Examiner(s): Sever, Frank
• Application Number:
  US07/080,325
• Time in Patent Office: 452 Days
• Field of Search: 210/651, 210/650, 210/652, 210/649, 210/748, 210/645-647, 204/180, 204/186, 204/149, 204/152
• US Class Current: 210/646
• CPC Class Codes: A61M 37/0092 using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis
• CPC Class Codes: B01D 61/00 Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor separation of gases or vapours by diffusion B01D53/22
• CPC Class Codes: B01D 61/243 Dialysis
• CPC Class Codes: B01D 63/16 Rotary, reciprocated or vibrated modules

Abstract

A method for enhancing or controlling permeability of large molecular weight molecules in a membrane system wherein molecules in solution are contacted with membranes and the system is exposed to ultrasound at a selected intensity and frequency and for a specific length of time. The method may be designed to insure that only reversible changes in the membrane result from exposure to the ultrasound or to enhance the rate of degradation of the membrane and/or selectivity of passage of molecules through the membrane. The method may include selection of the membrane composition and structure, including the pore size, thickness, crystallinity and molecular arrangement. Selection of the solvent or media in which the molecules are suspended may be used to further enhance or control permeability. The media may be either an aqueous or inorganic solution with the physical and chemical properties may be selected to attenuate sound transmission or to enhance stability of the molecule permeating the membrane.

Claims

1. A method comprising:

controlling transport of preselected species of molecules in a solution through a membrane, by, providing a membrane containing apparatus,

contacting a solution containing molecules with the membrane,

exposing the membrane containing apparatus to ultrasound, and

adjusting the intensity, frequency and time of exposure of the ultrasound sufficient to selectively pass said preselected species of molecules through the membrane.

2. The method of claim 1 wherein the frequency and intensity of the ultrasound is limited to produce predominantly reversible changes in the molecules and membrane.

3. The method of claim 1 further comprising removing molecules interspersed within the membrane by exposing the membrane to ultrasound.

4. The method of claim 1 wherein the frequency of the ultrasound is between about 10 kHz and 20 MHz and the intensity of the ultrasound is between about 0.05 watt/cm² and 30 watts/cm².

5. The method of claim 4 wherein the ultrasound frequency is between approximately 1 MHz and 3 MHz and the intensity is between approximately 0.05 and 3 W/cm².

6. The method of claim 1 wherein the molecules are selected from the group of large molecular weight compounds consisting of proteins, cofactors, chemical compounds, nucleic acid sequences, saccharides, peptides, polymers and combinations thereof.

7. The method of claim 1 further comprising selecting a membrane composition and structure having a selective effect on the passage of the molecules in solution upon exposure to ultrasound.

8. The method of claim 7 wherein the membrane is selected to have a specific molecular weight cut off range.

9. The method of claim 7 wherein the membrane is selected from the group of organic, inorganic and biological polymer compositions consisting of polyanhydrides, ethylenevinyl acetate polymers, silicone, hydroxyethylmethacrylate, vinyl alcohol, polylactides, polyglyclolides, polycaprolactone, lactic glycolic copolymers, polyorthoesters, polyamides, agarose, carbohydrates, celluloses, polypropylene, polyethylene, polyurethanes, and combinations thereof.

10. The method of claim 1 further comprising selecting a membrane composition which degrades in response to the ultrasound.

11. The method of claim 10 further comprising selecting the frequency, intensity and time of exposure of the membrane to the ultrasound to increase the rate of degradation of the membrane.

12. The method of claim 1 further comprising altering the three dimensional structure of said molecules by selection of the solvent for the molecules.

13. The method of claim 12 further comprising selecting the solvent for the degree of attenuation of the ultrasound by the solvent.

14. The method of claim 1 wherein application of the ultrasound directly to the membrane alters the passage of the molecules through the membrane.

15. The method of claim 1 wherein application of the ultrasound to the solution alters passage of the molecules through the membrane.

16. The method of claim 1 wherein the passage of molecules through the membrane is enhanced.

17. A method for enhancing membrane dialysis comprising controlling transport of preselected species of molecules in a solution through a membrane, by, exposing a kidney dialysis apparatus to ultrasound at a frequency between about 10 KHz and 20 MHz and at an intensity of between about 0.05 and 30 W/cm², wherein the frequency and intensity of the ultrasound is limited to avoid irreversible damage to the membrane and blood.

18. A method for enhancing the oxygenation of blood comprising controlling transport of preselected species of molecules in a solution through a membrane, by, exposing a solution to be oxygenated in a membrane oxygenator device to ultrasound at a frequency between about 10 KHz and 20 MHz and an intensity of between about 0.05 and 30 W/cm², wherein the frequency and intensity of the ultrasound is limited to avoid irreversible damage to the membrane and solution.

19. A method for controlling the rate of a separation process comprising controlling transport of preselected species of molecules in a solution through a membrane, by, selecting a separation system medium and exposing the molecules to be separated to ultrasound in the medium, wherein the molecules move within the medium as a function of the frequency and intensity of the ultrasound.

20. The method of claim 19 further comprising selecting the separation mediums from the group of solid matrices consisting of agarose, sepharose, polymethacrylate, polyacrylamide, cellulose, ceramics and derivatives thereof.