JPH06256977A - Method for cleaning, sterilizing and transplanting material by using high energy dense fluid - Google Patents

Abstract

PURPOSE: To provide a method for preparing a subsequent material working process for various inorg. and org. materials contg. biological materials for long-term preservation or characteristic intensification by simultaneously prepurifying and sterilizing these materials by using an acoustochemically or electrostatically energized dense fluid and adhering and transplanting physical or chemical drugs to both of the outside surfaces and microgaps of the materials.

CONSTITUTION: The dense fluid is mixed with the chemicals or physical drugs and the mixture is simultaneously exposed to nonuniform acoustoelectric extraction and high output acoustic radiation energy. Contaminants are removed from the inside and outside surfaces of the materials of the intricate constitution like biological materials, surgical appliances or dental transplants in the acoustoelectric extraction process. The cleaned materials are then exposed to the high energy dense fluid oxidation environment, by which the deep penetration, sterilization and biological removal of the contaminants of the materials are executed. Finally, the chemicals are transplanted by using the acoustical adhesion process to the cleaned and sterilized materials so as to be ready for long-term preservation or to impart an electrical insulation characteristic, electrical conductivity or the properties of high bioadaptability to the materials.

COPYRIGHT: (C)1994,JPO

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates generally to the use of liquefied supercritical gases (hereinafter referred to as dense fluids) for precleaning and sterilizing substrates. More specifically, the present invention is directed to the simultaneous pre-purification and sterilization of various inorganic and organic materials, including biological materials, using sonochemically or electrostatically energized dense fluids or dense fluid mixtures. The present invention relates to a method of preparing a material for a subsequent material processing process and a device for carrying out the method, in order to deposit or implant a physical or chemical agent on both the outer surface and the slit of the material for long-term storage or property enhancement.

[0002]

SUMMARY OF THE INVENTION In a first embodiment of the present invention, an undesired substance, eg, a material containing biological contaminants on its inner or outer surface, is exposed to a high energy dense fluid environment. Dense fluids suitable for use in the present invention include either supercritical or liquefied gases and chemical admixtures or agents dissolved in the dense fluid or dense fluid mixture. Unlike common solvents like water, hexane, isopropyl alcohol or carbon tetrachloride,
Dense fluids have unique chemical properties such as variable solvency or solubility for various substances, spontaneous wetting, strong permeability. One dense fluid is a gas or gas mixture that has been compressed into a supercritical, liquefied or multiphase state to obtain a liquid-like density.

The most suitable gases for use in the present invention are inorganics such as carbon dioxide, argon, krypton, xenon, nitrous oxide, oxygen, helium and mixtures thereof. Other gases, such as hydrocarbons and halogenated hydrocarbons, also serve as carrier media for detergents or chemicals under normal dense fluid conditions, but such gases deteriorate in high energy environments and are dangerous by-products. Which is not suitable for use in the present invention. Preferably, a suitable gas or gas mixture is preconditioned to remove gaseous impurities such as hydrocarbons, moisture and microscopic particles having a diameter of 0.2 micrometers or greater. Due to the cleaning, sterilization and dressing or deposition aspects of the present invention, the dense fluid or dense fluid mixture is chosen to be soluble upon actuation. This is compatible with melting, removing, migrating, implanting, adhering or chemically degrading unwanted residues of interest, where it is most effective.
Solubility parameters or cohesive energy parameters have been used in the present invention to provide a method of correlating and predicting the cohesive energetics of contaminants, substrates, chemical melts and dense phase gases or dense fluids. There is.

FIG. 1 shows the Giddings equation (J.
`` High Pressure Gas Chromatography '' by C. Giddings and others
of Nonvolatile Species ", SCIENCE, 162, 567.1
986) and the Hildebrand equation for liquefied carbon dioxide, showing the type of solubility spectrum curve for carbon dioxide in the liquid and supercritical phases as a function of temperature at or above the critical pressure. Cohesive energy values for subcritical fluids or liquefied gases are readily available in vapor pressure data (KLHoy's New Values of the Solubility Paramete
rs from Vapor Pressure Data '', JOURNAL OF PAINT T
ECHNOLOGY, Vol. 42, No. 541, February 1979) can be used to study using classic Hildebrand calculations. Finally, cohesive energy values for solid surfaces or materials with higher densities than liquids are readily available in surface tension data (L. Jackson's Surface Characteriz
Based on Solubility Parameters '', ADHESIVES
AGE, October 1976).

As shown in FIG. 1, when the temperature of the dense phase carbon dioxide is increased from 298 ° K (25 ° C) to 350 ° K (77 ° C) at the carbon dioxide critical pressure (73 atm), the dense fluid energy content becomes approximately 22MPa ^1/2 to 8MPa
Change to ^1/2 . This energy change is 305
When the critical temperature of ° K (32 ° C) is reached, there is a change from the liquid phase of the dense fluid state 14 to the supercritical phase. This change in internal cohesive energy is accompanied by an overall change in the dipole-dipole solubility (solvent spectrum) of dense-phase carbon dioxide that eliminates hydrogen bonds and the polar energy contribution that dense-phase carbon dioxide has nothing. . However, our research has shown that supercritical or subcritical carbon dioxide is not a good solvent for certain material processing applications.

[Means for Solving the Problems]

Therefore, according to the invention, a dense fluid or a dense fluid mixture (polar, which can be reformed with hydrogen bonding contributors) is acoustically and electrically energized into the subcritical fluid (cavitation side). By creating a localized supercritical fluid zone, a spectrum of dissolving power is created at the same time. In this method, various contaminants or chemicals with different solubilities provide a suitable solvent environment for a single dense fluid or dense fluid mixture.

Alternatively, nitrous oxide-carbon dioxide, xenon-carbon dioxide and argon-carbon dioxide formulations have enhanced solute loading capacity by altering the solubility range, and thus the contaminant or chemical selection range. give.

In the second embodiment, the material is a semipermeable membrane,
For example, TYVEK (product name of EIDuPont de Numbers Co.)
Prepackaged and processed according to the method of the invention. The packaged material has an extended shelf life,
It can be handled immediately from processing and is ready upon opening, for example for surgical implant applications. Steroids can also be implanted in pre-packaged substrates for biomedical applications. Therefore, the matrix will elute the steroids for a long time after implantation, helping to reduce swelling, protein aggregation, biological reactions, or to enhance bioadhesion and cell contact.

[0009]

DETAILED DESCRIPTION OF THE INVENTION Acoustic radiation for practicing the present invention is provided by a high power ultrasonic generator which converts electrical energy into mechanical energy or acoustic radiation via a piezoelectric transducer. The transducer is connected to a titanium metal surface, which transfers acoustic radiant energy into a dense medium such as a liquid, producing strong high and low acoustic pressure waves.
This effect is shown in FIG.

As shown in FIG. 2, a strong pressure differential causes a supercritical fluid implosion cavity, forming a process called supercritical cavitation in the present invention. Thus, in about 100 milliseconds, the cavitation site undergoes a cavity expansion, implosion cycle (cavitation) followed by a change from the liquid state 18 to the supercritical state 20 and back to the liquid state 22. This state change is
Accompanied by an overall cohesive energy change of 10 MPa ^1/2 or more.

In the present invention, the liquefied gas or mixture of liquefied gas and the chemical compound has a critical pressure (Pc).
It receives acoustic radiation at higher pressures and temperatures below the critical temperature (Tc). The dense gas molecules absorb acoustic energy, raising the cavitation temperature in these regions to a level above the critical temperature and thus increasing the internal energy content. Because the liquefied gas or gas mixture cannot evaporate under the pressure conditions of the process, the heat of expansion creates a supercritical fluid microenvironment in these localized regions. The heat in these areas is rapidly dissipated, causing reliquefaction of the gas.

This heating and cooling of the dense fluid to form the two phases simultaneously is referred to in the present invention as multiphase formation. If the acoustic radiant energy is applied continuously without internal temperature control, the temperature of the bulk dense fluid will rise steadily above the critical temperature, forming a single supercritical fluid phase. Thus, a wide range of solvent properties are produced with one dense fluid or dense fluid mixture. This effect promotes anti-contamination of the substrate and controls for implanting chemical agents into the material. The intermediate dense phase gas pressure or equilibrium pressure present in the present invention enhances the penetration effect of acoustic radiation.

FIG. 3 is a graph showing the general effect of equilibrium pressure on cavitation energy. Figure 3
As shown in, the cavitation energy increases significantly with the equilibrium energy. Increased cavitation energy facilitates the infiltration of dense fluids into double-ended closed microcavities, as is commonly found in amorphous polymers. However, the acoustic pressure must be maintained at 2 to 4 times the equilibrium pressure for maximum effect. This is done by increasing the power output applied to the acoustic amplifier to provide additional acoustic pressure to the titanium horn.

In the present invention, polyphase formation is controlled by varying the acoustic energy output (acoustic pressure), and
It is controlled by an internal temperature compensator, an externally supplied closed loop water / gas cooled / heated hot surface located in the process chamber (which in the present invention also acts as an electric field / ion collector and cold trap). By controlling the acoustic radiant energy intensity and the temperature compensator, a temperature gradient is created from the surrounding dense fluid towards the heat sink. The multiphase formation process becomes more pronounced when acoustic energy is applied to a suitable dense fluid liquefied mixture, such as a mixture of nitrous oxide and carbon dioxide or xenon and carbon dioxide. Due to the difference in critical temperature of the individual mixture components, a region of a two-phase two-component dense fluid is created during the acoustic cycle, improving the contaminant solubility range and hence the purification level of the dense fluid mixture. Thus, multi-phase formation can be done in one continuous process
By simultaneously providing a solvent environment range in a dense fluid or dense fluid mixture of a type, the need to provide a special compatible solvent-solute environment is eliminated.

In another aspect of the invention, the internal temperature compensator acts as a contaminant collector or cold trap. The temperature compensator condenses and traps contaminants removed from the material during the cleaning, electrostatic heat-vacuum operation of the present invention, and returns or recycles contaminants to the substrate surface during the acoustoelectric extraction cycle and room depressurization. Prevents adhesion.

The non-uniform ionizing electric field used in the present invention is used to remove contaminants from the substrate by electrophoresis and facilitate the implantation or attachment of chemicals to the substrate. One effect obtained by the non-uniform ionization electric field is that the charged agglomeration of ultrafine particles and the internal collector
Migration of aggregated contaminants towards the plate. An outlet is provided near the grounding plate to facilitate removal of collected contaminants from the purification chamber.

Another effect obtained by a non-uniform electric field is
Electrophoresis of agglomerated contaminants within the internal pores into a more dilute dense fluid surrounding the material being processed. This process is called zone electrophoresis. The electric field gradient further enhances the purification by causing migration of charged ion contaminants from the inner material pores towards the ground plate. The electric field is pulsed to impart a positive and negative electric field gradient to the dense fluid and the material being processed.

FIG. 4 shows the effect of a non-uniform electric field on contaminants, particles and molecules of a dense fluid. As shown in FIG. 4, the electric field concentrates near the collector plate 26. To achieve this, the ground collector plate 26
A larger pulsed switched electrostatic field generator 36 is used to electrostatically charge the field source plate 28. This promotes the attraction of both positive and negative charge species 30 towards the collector plate 26 via polarization, creating an electrostatic field energy field gradient 32. The neutral particles and the chemical species also move in this non-uniform electric field, and regardless of the sign, they migrate in a single direction in the direction of the electrostatic field 34 in which the chemical species of both positive and negative charges are concentrated. This effect is similar to the sedimentation of particles or macromolecules in the gravitational field. The nature of the dielectric medium between the oppositely charged plates has a significant effect on the electrophoresis of species dissolved or suspended in the medium or the material being treated. An electro-extraction medium with high dielectric strength and low viscosity maximizes electrophoretic or electrophoretic velocity in non-uniform electric fields.

Scientific formulas (BIOCHEMISTR) used to calculate the electrophoresis of dissolved or suspended species in various media.
Y, L. Stryer, WH Freeman and Co., 1981, p90) show that the high dielectric strength, low viscosity dense fluid medium used to practice the invention provides extremely high contaminant mobilities.

Thus, the material suspended in the dense fluid or dense fluid mixture between plates of opposite charge in a non-uniform electric field can be separated from various internal contaminants via a process called dense fluid electroextraction in the present invention. Get kicked out. The contaminants migrate from the inner surface of the material to the surrounding dense fluid and are either captured by an internal temperature compensator, or
It is discharged from the purification chamber during depressurization.

Non-uniform ionizing electrostatic fields for use in practicing the present invention include charged hemispherical ion / field source emission plates and hemispherical ground plates (ion /
Electric field collectors) and placing them on both sides of the material being processed. The ion / field source emission plate surface is much larger than the collector surface, causing non-uniform electric field density during electrostatic field pulse operation. +/- 1 per centimeter of direct current (DC)
A pulsed electrostatic charge of 00-+ /-10000 volts (volts / cm) is applied to the emitter plate. The dense fluid molecules and contaminants are charged or ionized in the electrostatic field and migrate toward the ground collector plate.

The simultaneous application of acoustic and electrostatic energy provides the high energy environment required to cleanse and sterilize complex materials in preparation for subsequent attachment or implantation processes. Since the effects of acoustic and electrostatic energy propagate through complex materials, these effects are internalized within the material and promote rapid contaminant removal via the solubility and electrophoretic mechanisms described above.

FIGS. 5 and 6 show each of the preferred acoustic and electrostatic sequences used to create the energy polyphase forming environment of the present invention. As shown in FIG. 5, the pulsed acoustic radiant energy is turned on / off for several minutes in combination with internal temperature control.
Optimum contaminants for various contaminants, substrates, applied in cycle 40, altering the overall solubility of the dense fluid.
Provides conditions for chemical transfer, purification, attachment or implantation. As shown in Figure 6, the pulsed electrostatic field produces 5 + 5000 volts / cmDC and -5000 volts / cmD during the acoustic cycle sequence.
It can be changed in both positive and negative charge cycles 42 between C. The combination of acoustic energy and non-uniform electrostatic fields provides a wide range of contaminant / chemical solubility, unidirectional contaminant removal, chemical mobility or immobility (adhesion).

Chemicals can be implanted in the material according to the present invention to modify its properties. For example, electrostatically safe materials can be made by implanting static dissipative organics such as surfactants.

Thus, the present invention uses a high energy source to generate a combination of thermal, acoustic, electrostatic energy environments and solute concentration gradients. These energy sources are applied to the dense fluids, dense fluid mixtures and gases under negative pressure in a single continuous process to remove organic, inorganic, ionic, particulate and biological contaminants, and internal and external surfaces. It attaches or implants beneficial chemicals to provide optimal material preparation conditions for improving end product properties. Further, the present invention provides a material treatment step for a material that is pre-packaged with a semi-permeable thin film to prevent mixed contamination of the following steps according to the method of the present invention.

Hydrogen peroxide improves the dense carbon dioxide purification level under both high and low energy conditions, is an excellent insecticide, and decomposes into harmless by-products during high energy decomposition, so the pre-purification of the present invention. , A preferred chemical formulation for performing sterilization operations. Hydrogen peroxide is an inorganic,
It is highly soluble in both organic matrices and is therefore an excellent infiltration formulation. In addition, unlike carbon dioxide, hydrogen peroxide has a large dipole and a low dielectric strength. Mixtures of carbon dioxide and hydrogen peroxide in various ratios therefore contribute over a wide range to hydrogen bonding, polar, dipole energy and thus solubility. Carbon dioxide-hydrogen peroxide fluid mixtures have been found in our study to have significant cleaning capabilities for many organic, inorganic and ionic residues under high energy conditions. Hydrogen peroxide chemically decomposes into the highly active atomic oxygen, hydroxyl, and hydrogen radicals under the high-energy conditions used in the present invention, rapidly degrading biological and other organic contaminants into water and gaseous by-products. Disassemble into. Thus, hydrogen peroxide serves in the present invention as a dense fluid medium modifier, a purifying solvent, an oxidant and an insecticide.

Finally, the exemplary preclean, sterilization, chemical implant system uses analog-to-digital controller 70 and computer control software 72, along with its network of valves, sensors, pumps, mixers and high energy systems. Integrated with computer system 68. Information such as dense fluid energy calculations, special material pre-cleaning, process parameters for sterilization and chemical implant processes for post-processed end product requirements are interrelated and stored in the material process computer software library. It is remembered and used to do a complete and consistent processing of materials,
It will serve as a reference database for new material processing applications. The entire processing system described above, with the exception of the computer system 68, is preferably housed in an environmental control enclosure (not shown) to prevent recontamination of materials processed in accordance with the present invention.

FIG. 8 is a detailed view showing an example of a material processing chamber for use in carrying out the precleaning, sterilizing, chemical implanting or deposition processes of the present invention. As shown, the system includes an inlet 74 used to deliver a dense fluid or a dense fluid-chemical formulation to the interior 76 of the material processing chamber 78. This material processing chamber 78
At this point, the material 80 to be processed according to the present invention is affixed to the rack 81 and the outlet 84 to reduce pressure during the vacuum, dense fluid-chemical refill, or electrostatic thermal vacuum processing sequence of the present invention. , Emit pollutants or excess chemicals. Material processing chamber 78,
The closure 86 used to seal the process chamber during the process sequence, as well as all internal mouth energy system components, are capable of withstanding the high energy, temperature, pressure conditions of the present invention and in processing materials. Made of materials that are chemically compatible with the appropriate dense fluids, dense fluid formulations and chemicals used.

The non-uniform electrostatic field used in the present invention is generated by delivering a pulsed DC charge to the inner hemispherical ion emitter plate 90 via electrical connections and high pressure through holes 88. The ion emitter plate is connected to an external refrigerant or heat transfer medium delivery system 92 using a closed loop high pressure heat coil 96 of the purification and sterilization chamber and has an oppositely charged internal hemisphere on the side to be heated or cooled. It has a larger surface area than the ion collector plate 94.

A smaller hemispherical ion collector plate 94 is connected to the thermal coil 96 and acts as an internal temperature compensator, ion collector, cold trap in accordance with the process of the present invention. A titanium radiator or horn 98 is inserted through the bottom of the material processing chamber 78, which is secured to the processing chamber 78 using high pressure compression fittings to provide the acoustic energy needed to raise the internal energy level. In addition, multiphase formation is performed according to the present invention. The titanium horn 98 includes a transducer assembly 100 and an adjustable high power variable frequency (20
.About.40 kilohertz) connected to the generator 102.

Finally, the inner surface of the material processing chamber 78 is TEFLON.
Covered with an electrically insulative non-staining coating or sleeve such as (registered trademark of EIDuPont de Numbers Co.).
The non-conductive coating controls temperature and insulation against electric field loss between electrostatic field plates. Finally, purification /
The outer shell of the sterilization chamber is a ceramic heating band (not shown) adapted to be used to heat the processing chamber during the electrostatic thermal vacuum precleaning or post-implantation cycle of the present invention.
Equipped with.

FIG. 9 is a detailed view showing an example of a chemical injection system used for carrying out the sixth embodiment of the present invention. As shown, the chemical injector includes a chemical reservoir 104, which contains the chemical or mixture of chemicals to be added to the chemical injection chamber 106, which is suitable. It is mixed with the dense fluid carrier medium, introduced through an inlet 108 provided below the chemical injection diffuser 110, and transferred to a material processing chamber (not shown) by a high pressure pump (not shown). The diffuser assembly 110 is used to disperse the chemicals as fine droplets in the injection mixing chamber 112 to help dissolve a mole fraction of the chemicals in the dense fluid carrier solvent. Material pre-purification / sterilization (material preparation)
The dense fluid used in the cycle, which is also used as a chemical carrier solvent, is pumped by a high pressure pump (not shown) into the injection mixing chamber 112 through the injection port 108. At this time, the dense fluid and chemical mixture rises up through a column of fine mesh stainless steel scrubbing medium 114 or other suitable scrubbing medium.

The saturated dense fluid-chemical formulation rises vertically through the chemical injection chamber and into the saturation zone 116, where insoluble chemicals separate and settle to the bottom of the injection chamber 112, from which the chemical is removed. It is returned to the chemical reservoir 104 through the chemical return line 118. The saturated dense fluid-chemical blend is then returned to the material processing chamber (not shown) through outlet 120. Alternatively, a magnetically driven mixer (not shown) or an acoustic horn (not shown) may be integrated with the injection chamber to help dissolve and disperse the chemical in a suitable dense fluid in the injection mixing zone 112. In addition, a cooling / heating device such as a cooling coil (not shown), a ceramic heating band (not shown) or a radio frequency (microwave) generator may be provided integrally with the chemical injection chamber 106 to calculate the cohesive energy. On the basis, it is possible to provide the most suitable internal chamber energy state for dissolving the desired rate of chemicals in the dense carrier fluid or dense fluid mixture. The injection chamber is equipped with a pin or bolt closure 122 that allows periodic opening and cleaning of its cavity.
The internal and external surfaces of the exemplary chemical injection system, all of the components, are materials that are both chemically and physically compatible with the pressures, temperatures, suitable dense fluids and suitable chemicals used to practice the invention. Composed of.

FIGS. 10, 11, 12, 13, and 14 are front, rear, and top surfaces of a rack for loading, mounting, and unloading materials in a specific material processing chamber (not shown). FIG. 2 is a schematic view of a bottom surface and side surfaces.

As shown in FIGS. 10 and 13, an opening is provided on the side surface of the rack, and hemispherical ion emitters of various sizes are provided in the purification / sterilization chamber 20 (not shown).
Plate 124 and ion collector plate 12
It can accommodate 5 (only one shown).

As shown in FIG. 14, a titanium horn (not shown) can be inserted into the circular opening 126 provided at the bottom of the rack. However, the loading racks shown here do not have shelves, but can be equipped with suitable loading racks with shelves designed to not interfere with acoustic and electrostatic energy sources so that multiple materials can be processed simultaneously. You may It should be appreciated here that many other rack configurations can be designed to accommodate materials having different geometric shapes. The rack must be made of materials that are both chemically and physically compatible with the dense fluids, dense fluid-chemical formulations, pressure, temperature and high energy conditions of the present invention.

As shown in FIGS. 11 and 12, the top surface 128 of the processing rack is made of an electrically and thermally insulating material, and the material processing chamber wall is electrically insulated (not shown). )
There is a tight fit between. The rack top surface 128 serves as an electrical thermal insulator between the process chamber closure (not shown) and the hemispherical ion emitter collector plate (not shown).

Finally, as shown in FIGS. 11 and 12, the illustrated material processing rack is mounted on the top surface of the rack 128 for loading and unloading the rack and materials in a material processing chamber (not shown). Handle 1 to help you in doing
Have 30.

FIG. 15 shows an example of an environmental control enclosure used to house the preferred cleaning, sterilization and chemical implant system. Upon removal of the closure from the purification and sterilization chamber after treatment of the material according to the invention, the material is exposed to the external environment. Treated materials can be contaminated by airborne organic and inorganic contaminants such as vapors and particles if they are not prepackaged within the semipermeable membrane or protected by other techniques There is. The environmental control enclosure houses the purification, sterilization and implantation system and is preferred for carrying out the process of the present invention. The exemplary enclosure protects the unpacked, sterilized, and transplanted material after removal from the material processing chamber from biological, organic, and inorganic contaminants contained in the air.

As shown in FIG. 15, the environmental control enclosure illustrated here has a high efficiency particle (HEPA) filtration system 134.
Vertical or horizontal draft laminar workbench with 1
Achieving better than 99.9% removal rate of airborne particulate matter having a diameter of 0.25 micron or greater in workstation 136, including line 32 and line of sight work surface 1
A UV light source 138 having a dominant output emission wavelength of about 3 nanometers for sterilizing 40 is included. Finally, a preferred integrated structure with the illustrated environmental control enclosure of the material processing chamber 142 is shown in FIG. A computer control system (not shown) will be installed adjacent to or remote from the environmental control enclosure.

Although the purification / sterilization / transplantation system components necessary to carry out the various embodiments of the present invention have been described, the above system components will be described below for each sequence of pre-purification, sterilization, and transplantation. A detailed description will be given with appropriate reference.

A flow chart showing the steps in the material purification phase of the present invention is shown in FIG. This process is
The entire purification and sterilization system is carried out in the material processing chamber containing the material to be processed, which is installed in the material loading rack.
Protected in a particle purification and sterilization environment using an environmental control enclosure.

As shown in FIG. 16, the material is first loaded and fixed in the material processing chamber. At this time, the material processing chamber
Sealed using the preferred enclosure 86 (FIG. 8), purged with helium or nitrogen for a few minutes, then purged with the selected process gas at a pressure of 10-100 atm for a few minutes. The gas purging operation removes volatile impurities such as moisture in the chamber and preconditions the material before pressurizing it to an operating pressure above the critical pressure of the selected process gas or gas mixture. After the purge cycle, the material processing chamber is pressurized to a critical pressure with the selected process gas or gas mixture at a temperature below the critical temperature of the dense gas or gas mixture.

Next, the material is simultaneously subjected to the acoustic energy cycle and the electrostatic energy cycle shown in FIGS. During the acousto-electric extraction cycle, the internal chamber temperature is kept below the critical temperature of the dense fluid for several minutes using the internal temperature compensator 94 (FIG. 8). The internal temperature is then raised to the critical temperature of the dense fluid or dense fluid mixture. At that time, the acoustic energy source is stopped and the chamber is refilled with the preconditioned dense fluid at a pressure above the critical pressure. During the cleaning and sterilization sequence, the AC non-uniform electric field generator 56 (FIG. 7) is continuously on.

This acousto-electrical extraction and dense fluid refilling process is based on predetermined performance tests or based on data from in-line real-time chamber dense fluid tests such as supercritical gas chromatography. Repeated to achieve the desired clean level. Following the precleaning-acoustic-electric extraction sequence, the chamber is evacuated to ambient pressure (1 atm) in preparation for the subsequent sterilization sequence.

A flow chart showing the steps of the material sterilization phase is shown in FIG. This process is performed in the same chamber as the cleaning sequence above. As shown in FIG. 17, the chamber has a chemical injection system outlet 120 (FIG. 9).
Refilled with a dense fluid mixture of carbon dioxide, hydrogen peroxide, or other suitable chemical compound coming through
This is left in contact with the material for a few minutes. After this, the acousto-electric extraction cycle is repeated as described above for the cleaning sequence with periodic chemical compound refills until a sterilization level of the material is achieved. The frequency of chemical refills is empirical, but when hydrogen peroxide is used as the chemical formulation, hydrogen peroxide breaks rapidly under high energy conditions, so at least once per acoustic-electric extraction cycle. Refill of chemicals is required.

After the material sterilization phase, the chamber is refilled with a dense fluid to remove residual chemicals and then purged with nitrogen or helium for a few minutes. The clarification chamber and materials are then evacuated to ambient pressure by slowly venting the dense fluid and residual gas through vent 84 (FIG. 8), ready for the next implant or attachment sequence. Alternatively, the material processing chamber may remain pressurized with the dense fluid in preparation for the next chemical implant operation.

This process is carried out in the same material processing chamber as the sterilization sequence described above. As shown in FIG.
The mixture of the dense phase gas and the chemical is injected into the material processing chamber at a pressure higher than the critical pressure and a temperature lower than the critical temperature. The mixture then contacts and wets the material for several minutes, ensuring a homogeneous distribution of the material processing chamber and material. After the contact period, acoustic and electrostatic energy sources
Without internal temperature control

It can be operated simultaneously as described with reference to FIGS. The internal chamber fluid mixture temperature rises sharply to a critical temperature during energization, reducing the total cohesive energy content (solubility) of the dense carrier fluid. At this time, a large proportion of chemicals adheres to the inner and outer surfaces of the material. As mentioned above, the level of chemical deposition, the rate of deposition, can be controlled by adjusting the process pressure, ie, the pressure above the critical pressure that triggers the acoustic energy source. In addition, by pulsing or adjusting the power output on the acoustic amplifier, the chemical deposition level, deposition rate can be controlled.

Finally, depending on the difference in solubility at various temperatures, the internal temperature compensator 94 (FIG. 8) allows the acoustic--dense fluid--before or during the electrostatic energy cycle.
A coolant or heat transfer medium may be provided to regulate the temperature of the chemical formulation. Once the critical temperature of the dense fluid-chemical formulation is obtained, the acoustic and electrostatic energy sources are turned off. The dense fluid-chemical formulation is then cooled to below the critical temperature using an internal closed loop temperature compensator 94 (FIG. 8). Once the desired temperature is reached, depending on the chemistry and the solubility of the dense fluid, the supply of refrigerant to the temperature compensator is stopped and the acousto-electrostatic energy cycle is restarted. Using this temperature and energy control sequence, chemicals are implanted or attached to the inner surface of the material in individual coatings or layers.

The material processing chamber is refilled with the dense fluid-chemical formulation and the above acoustic deposition cycle is repeated to obtain the desired deposition level. Once the desired level of chemicals has been implanted or adhered to the material, the material processing chamber is evacuated to ambient pressure (1 atm) and purged with preconditioned nitrogen or helium. The material is then removed from the quality and packaged or used as desired.

According to a second embodiment of the invention, the material may be packaged in a semipermeable membrane and implanted with a chemical according to the process described above.

Examples of the present invention are as follows. Example 1 This example illustrates the removal of organic contaminants from a liquid oxygen valve using one embodiment of the present invention. Oxygen valves can be contaminated with organic and inorganic substances such as oil and particles. If these contaminants are not removed, the valve seal may be damaged or contaminants may cause contaminant-induced detonation of the valve during operation. The material was fine cleaned using a dense phase carbon dioxide / hydrogen peroxide mixture (90:10) in combination with acoustic energy cycles and electrostatic energy cycles. The valve was loaded into the purification and sterilization chamber, stuck, and purged with preconditioned nitrogen gas at 10 atm for several minutes. After gas purging, the chamber was filled with 90:10 v: v mixture of carbon dioxide and hydrogen peroxide at 25 at 150 atm.
The pressure was increased to. The valve was contacted with the mixture for a few minutes. The acoustic energy source was then started on a titanium horn at 20 kilohertz with an input power of approximately 250 watts and the ion emitter plate was +5000 volts / cmD every 10 seconds.
Pulsed at C, -5000 volts / cmDC. This continued until the internal temperature rose to 35 ° C. The energy source was then turned off, the chamber depressurized to purge the extracted contaminants, and refilled with the dense carbon dioxide-hydrogen peroxide mixture as described above. This process was repeated several times over 20 minutes. Following the sonoelectric extraction cycle, the chamber was refilled with 150 atm, 25 ° C. dense phase carbon dioxide and the acoustoelectric extraction cycle was repeated as described above while periodically refilling the dense phase carbon dioxide, leaving any residual excess. Hydrogen oxide and supercritical oxidation byproducts were removed. After this, the chamber was purged with preconditioned argon, depressurized to 0.0001 Torr using a high vacuum pump, and heated to 60 ° C. using an external ceramic band heater. Next, +5000 volts /
cmDC, -5000 volts / cmDC voltage is applied to the ion emitter
Applied to the plate (the ion collector plate was grounded in series with the static electricity generator). The internal temperature compensator (ion collector plate) was cooled to a temperature lower than -50 ° C with liquid nitrogen for 30 minutes. Following the thermostatic vacuum operation, the chamber pressure was returned to 1 atm with preconditioned nitrogen. Subsequently, a small oxygen valve was subjected to hexane solvent extraction, but no hydrocarbon contaminant was detected.

Example 2 In this example, the precleaning and sterilization process of the present invention was used to clean titanium clips packaged in TYVEK semipermeable membranes for use in attaching bone and tissue in surgical applications. There is. The same cleaning and sterilization sequence as in Example 1 was carried out with a 2% v: v loading of hydrogen peroxide, but it was visually clean even when treated with clean and sterilized titanium clips according to standard microbial culture techniques. And the bacterial count was negative.

Example 3 In this example, the cleaning and sterilization process of the present invention is used to prepare a human denture. According to the purification / sterilization process of the present invention, dense phase carbon dioxide, nitrous oxide, sodium 2-ethylhexyl sulphate (surfactant / penetrant) at a ratio of 85: 10: 5 v: v of 15
Energy was applied acoustically and electrostatically at 0 atm and 25 ° C. for several cycles. The critical temperature of nitrous oxide is about 37 ° C, so the mixture was energized according to the acoustoelectric extraction cycle of the present invention, and finally the temperature of the mixture was 40 ° C. At this time, the mixture was discharged and the chamber was refilled and reenergized. After this, a mixture of dense phase carbon dioxide / hydrogen peroxide 90:10 v: v at 150 atm and 25 ° C. was used for several acoustoelectric extraction cycles to extract residual organic contaminants for deep sterilization. After this treatment, the denture was visually clean and no microbial growth was found in the bacterial culture test.

Example 4 This example uses the precleaning, sterilization, and chemical implantation processes of the present invention to prepare a silicone artificial vocal cord for biological use. This silicone artificial vocal cord was cleaned and sterilized by the same procedure as in Example 2,
After pre-cleaning and sterilization sequence using a high energy carbon dioxide-hydrogen peroxide mixture, n-octyl alcohol was transplanted according to the above transplantation process. Microbial culture tests on various parts of the silicone artificial vocal cords showed no microbial activity for several weeks after implantation.

Example 5 In this example, the sterilization and implantation process of the present invention is used to treat plant products such as senna and cinnamon for long term storage. A large amount of plant product was sterilized using the same sonoelectric extraction cycle as in Example 1 except that a 95: 5 v: v mixture of liquid carbon dioxide and n-octyl alcohol was used. Following the sterilization process of the present invention, residual n-octyl alcohol was removed and recovered from the plant product for subsequent reuse using the hot vacuum degassing operation of the present invention.

Example 6 In this example, the pre-purification of the present invention was applied to treat foamed rubber for use in environments where static dissipative properties were required.
It uses a porting process. The foamed rubber was precleaned using the same sonoelectric extraction cycle as in Example 1 except for a 90:10 v: v mixture of liquid carbon dioxide and liquid nitrous oxide. The foamed rubber was then grafted with a percentage of surfactant using a 95: 5 v: v mixture of liquid carbon dioxide and trimethylamine surfactant to render the foamed rubber static dissipative according to the implanting process of the present invention. .

While specific embodiments of the present invention have been described, it will be apparent to those skilled in the art that this disclosure is illustrative only and that various other alternatives, applications and modifications may be made within the scope of the present invention. . Therefore, the present invention should not be limited to the specific embodiments described herein, but only by the claims.

[0060]

The method of the present invention has numerous material preparation and processing applications. Biomedical, space engineering, high energy environment (material cleanliness and end product properties are important issues)
A wide range of materials can be prepared for, including biomaterials, prosthetic materials, precision valves, mini-valves, surgical tissue and surgical aids. The particular processing parameters used in this method will depend on the nature of the material, the type of contaminants to be removed and the desired cleanliness, sterilization level. This method is well suited for preparing materials with complex internal and external geometries and with many different constituent materials.

[Brief description of drawings]

FIG. 1 is a graph showing the effect of temperature change on the internal energy content of dense phase carbon dioxide.

FIG. 2 is a graph showing the effect of acoustic radiant energy on the solubility of dense phase carbon dioxide as measured by the cohesive energy content of the applied acoustic radiant energy versus time (microseconds).

FIG. 3 is a graph showing the effect of equilibrium pressure (Po) on acoustic pressure (Pa) or cavitation energy intensity.

FIG. 4 shows the effect of pulsed inhomogeneous electric fields on contaminants, particles and molecules of dense fluids.

FIG. 5 is a diagram illustrating an acoustic cycle sequence and an electrostatic cycle sequence that are simultaneously used to perform a dense gas multiphase formation effect and an electroextraction cleaning effect according to the present invention.

FIG. 6 is a diagram illustrating an acoustic cycle sequence and an electrostatic cycle sequence used simultaneously to perform a multiphase formation effect and an electrical extraction cleaning effect of a dense phase according to the present invention.

FIG. 7 illustrates the major components and integral structure of a preferred purification, sterilization, chemical injection system, including computerization, for use with the present invention.

FIG. 8 is a partial cross-sectional view of a preferred preclean, sterilization, chemical injection system for use with the present invention.

FIG. 9 is a partial cross-sectional view of a preferred preclean, sterilization, and chemical injection system for use with the present invention.

FIG. 10 is a cross-sectional view of a rack used to load and support a substrate to prepare it for implantation or attachment according to the present invention.

FIG. 11 is a cross-sectional view of a rack used to load and support a substrate to prepare it for implantation or attachment according to the present invention.

FIG. 12 is a cross-sectional view of a rack used to load and support a substrate to prepare it for implantation or attachment according to the present invention.

FIG. 13 is a cross-sectional view of a rack used to load and support a substrate to prepare it for implantation or attachment according to the present invention.

FIG. 14 is a cross-sectional view of a rack used to load and support a substrate to prepare it for implantation or attachment according to the present invention.

FIG. 15 is a partial cross-sectional view of an environmental control enclosure containing a preferred purification, sterilization, implantation system and used to practice the method according to the present invention.

FIG. 16: Pre-cleaning, sterilization (material preparation) according to the invention,
It is a flow chart explaining various processes of transplantation (material processing).

FIG. 17: Pre-cleaning, sterilization (material preparation) according to the invention,
It is a flow chart explaining various processes of transplantation (material processing).

FIG. 18: Pre-cleaning, sterilization (material preparation) according to the invention,
It is a flow chart explaining various processes of transplantation (material processing).

[Explanation of symbols]

 68 ... Computer system 70 ... Analog-digital controller 72 ... Computer control software 74 ... Injection port 78 ... Material processing chamber 80 ... Material 82 ... Rack 84 ... Discharge port 86 ... Closed body 88 ... Through hole 90 ... Ion emitter plate 94 ... Ion collector plate 96 ... Closed loop high-pressure heat coil 98 ... Titanium horn 100 ...・ Transducer assembly 102 ・ ・ ・ Adjustable high output variable frequency generator 104 ・ ・ ・ Chemical agent reservoir 106 ・ ・ ・ Chemical agent injection chamber 108 ・ ・ ・ Injection port 110 ・ ・ ・ Chemical agent injection diffuser 112 ・ ・ ・ Injection Mixing chamber 114 ... Scrubbing medium 118 ... Chemical agent return line 120 ... Discharge port 122 ... Closed body 1 24 ... Ion emitter plate 125 ... Ion collector plate 126 ... Opening 134 ... High efficiency particle filtration system 136 ... Workstation 138 ... UV light source 140 ... Outlook Line work surface 142 ・ ・ ・ Material processing room

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification code Office reference number FI technical display location C23C 22/00 C23G 3/00 9351-4K

Claims (16)

[Claims] 1. A method for processing a material (hereinafter referred to as a substrate) by adhesion or implantation of a physical or chemical agent, which comprises: a) a specific method in a processing chamber, that is, preparatory purification or sterilization. The step of pre-cleaning or sterilizing the substrate, which may contain one or more contaminants, in the following order: 1) the substrate containing the contaminants being critical Contacting a dense fluid at a pressure above the pressure and a temperature below the critical temperature, 2) simultaneously or subsequently exposing the dense fluid to a high energy acoustic radiation source or a non-uniform electrostatic energy field, in a process called acoustoelectric extraction. Contact of the energized dense fluid with the substrate containing the contaminant for a period of time at a pressure higher than a critical pressure of the dense fluid and lower than a critical temperature thereof. Maintaining the temperature and simultaneously creating a wide range of solvent environments in a process called multi-phase formation, causing the dissolution and migration of contaminants from the substrate, in one continuous process from the substrate Further removal of contaminants; b) introducing a physical or chemical agent into the dense fluid by injection, dissolution or reaction methods, and c) simultaneously introducing said dense fluid and into it Process parameters (eg,
High energy acoustic radiation, non-uniform electric field strength, temperature of the substrate or dense fluid medium, etc., and contacting the substrate with the energized dense fluid for a period of time to induce a physical or chemical agent. Causing the precipitation, dissociation, dissolution or activation of the substrate, resulting in the attachment of a physical or chemical agent on the substrate or the implantation into the interstitial space of the substrate; Torr) and intermediate temperature (60
C.) to remove residual contaminants or excess physical or chemical agents during the processing steps of precleaning, sterilization and transplantation. 2. The method of claim 1, wherein the high energy acoustic radiation is provided at an internal temperature kept below a critical temperature of the dense fluid. 3. The method of claim 1, wherein the temperature is raised above a critical temperature and then the temperature is below the critical temperature. 4. The method of claim 1, wherein the acoustic energy is pulsed at 200-400 Watts for a few minutes. 5. The method of claim 4, wherein the acoustic energy is varied within the range of 20-40 kilohertz. 6. A method according to claim 1, characterized in that the acoustic emission is carried out in a liquefied gas and is stopped once the critical temperature of the dense fluid is reached. 7. The method of claim 1, wherein the non-uniform electrostatic field occurs in a combination of charge plates located parallel to and corresponding to a corresponding charge plate at a finite distance. how to. 8. The method according to claim 7, wherein the non-uniform electrostatic electric field is from +10000 volts / cm to -10000 volts / c.
A method characterized in that it is charged in the range of m DC. 9. The method of claim 1 wherein the non-uniform electrostatic field is constantly on during acoustic work. 10. The method of claim 8 wherein the non-uniform electrostatic field is constantly on under high vacuum and intermediate temperatures to improve volatile contaminant removal. 11. The method of claim 1, wherein the dense fluid is carbon dioxide, nitrous oxide, krypton,
A method characterized in that it is selected from the group consisting of inorganic substances such as xenon, argon, oxygen, helium, nitrogen, ammonia and mixtures thereof. 12. The method according to claim 11, wherein
A method wherein the dense fluid is selected from a mixture of carbon dioxide and nitrous oxide or other suitable dense fluid mixture. 13. The method according to claim 11, wherein
The method, wherein the dense fluid is mixed with a chemical agent to improve the dense fluid purification effect. 14. The method according to claim 1, wherein the physical or chemical agent is an organometallic compound, an insecticide, a surfactant, an alcohol, a dye, a reducing agent, an oxidizing agent,
A method comprising the group consisting of steroids and odorants. 15. The method of claim 13, wherein the dense fluid chemical mixture comprises liquefied carbon dioxide and hydrogen peroxide. 16. The method of claim 1, wherein the physical or chemical agent is a unique material, eg,
Biocompatibility, long-term residual sterilization and physical properties of the substrate (eg, chemical durability, conductivity, degassing or volatility, abrasion resistance, electrical resistance, appearance, mechanical properties such as odor). Such a characteristic) is introduced so as to improve the method.