Method of freeze-drying

Abstract

A method of freeze-drying comprising rapidly freezing either liquid or supercritical carbon dioxide in and around a material having pores at a rate of at least 0.2° C./min to limit the size of crystals formed from the carbon dioxide so as to avoid the formation of gas bubbles and damage to the pores and exposure of the material to gas-liquid interfaces. During freezing a solid layer primarily of solid carbon dioxide is formed on and surrounding the material by transferring heat with a cryogenic liquid circulating about the material. This solid layer protects the material from gas-liquid interfaces and surface tension before decreasing pressure about the material by venting carbon dioxide.

What is claimed is: 
     
         1 . A method of preserving a material in contact with a first fluid comprising the steps of;
 replacing the first fluid with a first non-gaseous fluid,   cooling the first non-gaseous fluid to cause the first non-gaseous fluid to freeze to form a solid, and   characterized by:   forming a solid layer of the solid on and surrounding the material,   then decreasing pressure about the material by expanding the first non-gaseous fluid to form a gas.   
     
     
         2 . The method of  claim 1  wherein the decreasing pressure is at a rate of at least 0.001 Mpa/min and less than or equal to 2.0 Mpa/min. 
     
     
         3 . The method of  claim 1  wherein the forming a solid layer of the solid on and surrounding the material comprises transferring heat with a liquid circulating about the material. 
     
     
         4 . The method of  claim 1  wherein the first fluid is non-gaseous. 
     
     
         5 . The method of  claim 4  wherein the replacing the first fluid with the first non-gaseous fluid comprises flushing the first fluid from the material with the first non-gaseous fluid. 
     
     
         6 . The method of  claim 4  comprising subliming the solid from the material. 
     
     
         7 . The method of  claim 6  including;
 preserving a material containing at least one pore, 
 subjecting the material to an impregnating agent with the impregnating agent being non-gaseous at the temperature and pressure conditions at which the first non-gaseous fluid is sublimed and with the impregnating agent being soluble in the first non-gaseous fluid, and 
 depositing the impregnating agent into at least one pore in the material. 
 
     
     
         8 . The method of  claim 1  wherein the first non-gaseous fluid is carbon dioxide. 
     
     
         9 . The method of  claim 8  comprising;
 reacting amines of the material comprising of one of primary amines, secondary amines, and a combination of primary and secondary amines with carbon dioxide to form carbamate groups, and 
 forming amines by removing carbon dioxide from the material. 
 
     
     
         10 . A method of drying and sterilizing and preserving and impregnating a material comprising the steps of:
 (a) flushing an original liquid from a material having pores and non-tertiary amines with an intermediate liquid having higher solubility with carbon dioxide than the original liquid to replace the original liquid with the intermediate liquid in the pores and around the material to protect the material from chemical reactions and expedite eventual replacement of the intermediate liquid with non-gaseous carbon dioxide;   wherein the intermediate liquid is selected from the group consisting of acetone, acetonitrile, acetic acid, amyl alcohol, benzene, carbon tetrachloride, cholrobenzene, cholroform, cyclo-cresylic acid, hexane, isopropyl alcohol, di-methyl formamid, ethanol, ethyl acetate, furfural, furfural alcohol, methanol, N-butane, N-heptane, N-hexane, pyridine, and combinations thereof; and   wherein the non-tertiary amines comprise of one of primary amines, secondary amines, and a combination of primary and secondary amines.   (b) evaporating the intermediate liquid to form a saturated vapor,   (c) surrounding the material and the intermediate liquid with the saturated vapor to impede evaporation of the intermediate liquid,   (d) heating the material and the saturated vapor and the intermediate liquid to at least the critical temperature of carbon dioxide,   (e) applying gaseous carbon dioxide at a rate that prevents turbulent fluid motion around the material to increase the pressure around the material to just below the critical pressure of carbon dioxide,   (f) maintaining pressure around the material at just below the critical pressure of carbon dioxide for at least ten minutes,   (g) applying non-gaseous fluid carbon dioxide and a co-solvent to the material,   (h) submerging the material in the non-gaseous fluid carbon dioxide and the co-solvent thereby causing the non-tertiary amines of the material to reversibly react with the non-gaseous fluid carbon dioxide to form carbamate groups which protect the material from surface tension,   (i) flushing the material with the non-gaseous fluid carbon dioxide and the co-solvent to remove the intermediate liquid surrounding the material and any gas from around the material to avoid moisture in the gas rehydrating the material while avoiding gas-liquid interfaces,   (j) subjecting the material to an impregnating agent with the impregnating agent being non-gaseous at the temperature and pressure conditions at which carbon dioxide is sublimed during part (p) and with the impregnating agent being soluble in liquid and supercritical carbon dioxide and insoluble in gaseous carbon dioxide,   (k) flushing the material with the non-gaseous fluid carbon dioxide and the co-solvent and the impregnating agent while avoiding gas-liquid interfaces,   (l) simultaneously with step (k) agitating the material and the non-gaseous fluid carbon dioxide and the co-solvent with ultrasonic irradiation,   (m) simultaneously with steps (l) and (k) mixing the non-gaseous fluid carbon dioxide and the co-solvent and the impregnating agent to establish shear forces to extract the intermediate liquid from the pores of the material,   (n) cooling the material and the non-gaseous fluid carbon dioxide and the co-solvent and the impregnating agent to below the freezing point of carbon dioxide to cause the non-gaseous fluid carbon dioxide and the co-solvent to freeze by transferring heat with a cryogenic liquid having a freezing point below the freezing point of carbon dioxide,   (o) simultaneously with step (n) expanding the non-gaseous carbon dioxide thereby reforming gaseous carbon dioxide to decrease pressure about the material at a rate greater than or equal to 0.001 Mpa/min and less than or equal to 2.0 Mpa/min to precipitate the impregnating agent into the pores and to produce a matrix of the material encased in solid carbon dioxide and the co-solvent and the impregnating agent,   (p) subliming solid carbon dioxide in the solid phase from the matrix and forming the non-tertiary amines by changing the environment of the matrix to one of little humidity and a temperature between room temperature and about 400° C. and a pressure above ambient pressure and at which carbon dioxide sublimes thereby producing a dried and sterilized material that contains the impregnating agent, and   characterized by:   (q) prior to step (o) cooling the non-gaseous fluid carbon dioxide around the material to form a solid layer primarily of solid carbon dioxide on and surrounding the material by transferring heat with a cryogenic liquid to protect the material from gas-liquid interfaces and surface tension before forming gaseous carbon dioxide in step (o),   (r) cooling at a rate of at least 0.2° C./min in steps (n) and (q) to limit the size of crystals formed when carbon dioxide freezes and for avoiding the formation of gas bubbles and for avoiding damage to the pores and exposure of the material to gas-liquid interfaces.