阅读说明：本技术 等离子体灭菌及干燥系统和方法 (Plasma sterilization and drying system and method ) 是由 萨拉·J·达维斯 卡尔布·T·尼尔森 约迪·L·康奈尔 乔舒亚·D·埃里克森 杰弗里·D·史 于 2018-12-26 设计创作，主要内容包括：本发明公开了用于对污染制品、具体地是医疗制品、更具体地是医疗器械的中空内部区域或医疗内窥镜的管腔进行消毒和干燥的系统和方法。该系统包括等离子体发生器,该等离子体发生器具有电极、屏蔽件以及电极与屏蔽件之间的介电间隙。连接到等离子体发生器的电功率源在电极与屏蔽件之间施加电极能量密度。灭菌气体前体源通过等离子体发生器提供灭菌气体前体流以生成等离子体,从而形成包含酸性物质和/或氧化物质的灭菌气体。使污染制品暴露于灭菌气体足够时间以实现期望灭菌程度。在污染制品暴露于灭菌气体时,使用干燥气体的湍流交替地干燥污染制品。(Systems and methods for disinfecting and drying a contaminated article, particularly a medical article, more particularly a hollow interior region of a medical instrument or a lumen of a medical endoscope are disclosed. The system includes a plasma generator having an electrode, a shield, and a dielectric gap between the electrode and the shield. An electrical power source connected to the plasma generator applies an electrode energy density between the electrode and the shield. The sterilizing gas precursor source provides a flow of sterilizing gas precursor through a plasma generator to generate a plasma to form a sterilizing gas comprising an acidic species and/or an oxidizing species. The contaminated article is exposed to the sterilizing gas for a sufficient time to achieve the desired degree of sterilization. The contaminated articles are alternately dried using a turbulent flow of drying gas while the contaminated articles are exposed to the sterilizing gas.)

1. A system for sterilizing a soiled article comprising:

a drying gas source configured to provide a turbulent flow of drying gas to dry the soiled article;

a plasma generator having:

an electrode is arranged on the base plate and is provided with a plurality of electrodes,

a shield, and

a dielectric gap between the electrode and the shield;

an electrical power source connected to the plasma generator for applying an electrode energy density between the electrode and the shield; and

a sterilizing gas precursor source comprising water vapor, oxygen and nitrogen and configured to provide a flow of sterilizing gas precursor between the electrode and the shield through the plasma generator to form a plasma, wherein a temperature at a surface of the shield is maintained below 150 ℃ when the electrode energy density is greater than 0.05 eV/molecule of sterilizing gas precursor passing between the electrode and the shield, further wherein the plasma forms a sterilizing gas comprising an acidic species and/or an oxidizing species from the sterilizing gas precursor, and further wherein the contaminated article is exposed to a flow of sterilizing gas, further wherein optionally the system further comprises means for delivering the contaminated article through a chamber fluidly connected to the flow of sterilizing gas.

2. The system of claim 1, wherein the sterilizing gas comprises one or more substances selected from the group consisting of molecular oxygen, molecular nitrogen, nitric oxide, nitric acid, and nitrous oxide.

3. The system of claim 1 or 2, wherein the sterilizing gas precursor comprises air, optionally wherein the relative humidity of the sterilizing gas precursor is at least 21%.

4. The system of any one of claims 1 to 3, further comprising one or more valves configured to apply a flow of drying gas and a flow of sterilizing gas alternately to the contaminated article.

5. The system of any one of claims 1 to 4, further comprising a cooling device.

6. The system of any of claims 1 to 4, wherein the electrical power source is a pulsed DC source with a high dV/dT.

7. The system of any one of claims 1 to 6, further comprising a filter for removing the acidic species and/or oxidizing species from the sterilizing gas.

8. A method of sterilizing a soiled article comprising:

providing a sterilizer, the sterilizer comprising:

a drying gas source configured to provide a turbulent flow of drying gas to dry the soiled article;

a plasma generator, the plasma generator comprising:

an electrode is arranged on the base plate and is provided with a plurality of electrodes,

a shield, and

a dielectric gap between the electrode and the shield;

an electrical power source connected to the plasma generator for applying an electrode energy density between the electrode and the shield; and

a sterilizing gas precursor source comprising water vapor, oxygen and nitrogen and configured to provide a flow of sterilizing gas precursor between the electrode and the shield through the plasma generator to form a plasma comprising acidic species and/or oxidizing species from the sterilizing gas precursor;

providing a flow of the sterilizing gas precursor between the electrode and the shield by the plasma generator to form a plasma, wherein the temperature at the surface of the shield is maintained below 150 ℃ when the electrode energy density is greater than 0.05eV per molecule of the sterilizing gas precursor passing between the electrode and the shield, further wherein the plasma causes the flow of sterilizing gas precursor to form a flow of sterilizing gas comprising the acidic species and/or oxidizing species;

directing the sterilizing gas stream comprising the acidic and/or oxidizing species from the plasma generator through an enclosure enclosing at least a portion of the contaminated article;

exposing the soiled article to a sterilizing gas comprising the acidic species and/or oxidizing species for a sufficient exposure time to achieve a desired degree of sterilization of the soiled article, optionally wherein the time sufficient to achieve the desired degree of sterilization of the soiled article does not exceed one hour; and

directing a turbulent flow of the drying gas into the enclosed space to dry the soiled article.

9. The method of claim 8, further comprising removing at least a portion of the acidic species and/or oxidizing species from the sterilizing gas after directing the sterilizing gas through the enclosed space.

10. The method of claim 9, wherein removing at least a portion of the acidic and/or oxidizing species from the sterilizing gas is performed by a filter comprising one or more materials selected from the group consisting of activated carbon, a species having a basic functional group, a species providing a basic adsorbent, a reducing species, and a molecular sieve.

11. The method of any one of claims 8 to 10, wherein the enclosed space is a sterilization chamber in which the soiled article is placed.

12. The method of any one of claims 8 to 11, wherein directing the flow of sterilizing gas through the enclosed space is for a duration of at least 10 seconds and no more than 5 minutes, and thereafter directing the flow of drying gas through the enclosed space for a duration of at least 10 seconds and no more than 10 minutes, optionally wherein alternately directing the flow of sterilizing gas and directing the flow of drying gas are repeated at least twice.

13. The method of any of claims 8 to 12, wherein at least one of the drying gas, the sterilizing gas precursor, or the sterilizing gas has a temperature of 10 ℃ to 60 ℃.

14. The method of any one of claims 8 to 13, wherein the drying gas is selected from the group consisting of oxygen, nitrogen, helium, neon, argon, krypton, or combinations thereof, optionally wherein the drying gas is substantially free of water.

15. The method of any one of claims 8 to 14, wherein the sterilizing gas comprises one or more substances selected from the group consisting of molecular oxygen, molecular nitrogen, nitric oxide, nitric acid, and nitrous oxide.

16. The method of any of claims 8 to 15, wherein the sterilizing gas precursor comprises air, optionally wherein the relative humidity of the sterilizing gas precursor entering the plasma generator is at least 21%.

17. The method of any of claims 8 to 16, wherein the electrical power source is a pulsed DC source with a high dV/dT.

18. The method of any one of claims 8 to 17, wherein the soiled article is a medical device and the enclosed space is a hollow region of the medical device.

19. The method of claim 18, wherein the medical device is an endoscope and the hollow region is a lumen of the endoscope, further wherein the sterilizing gas containing the acidic and/or oxidizing species is passed from the plasma generator through the lumen of the endoscope.

20. The method of claim 18, wherein the medical device is a medical instrument and the hollow region is at least one internal cavity of the medical instrument.

21. The method of any one of claims 8 to 20, wherein the soiled article is soiled with at least one of: a biofilm consisting of a plurality of microorganisms, a biofilm consisting of a plurality of microbial spores, a biofilm consisting of a plurality of fungi, or a plurality of fungi.

22. The method of claim 21, wherein the biofilm comprises a plurality of microorganisms selected from the group consisting of: bacillus stearothermophilus, Bacillus subtilis, Bacillus atrophaeus, Bacillus megaterium, Bacillus coagulans, Clostridium sporogenes, Bacillus pumilus, Aspergillus brasiliensis, Aspergillus oryzae, Aspergillus niger, Aspergillus nidulans, Aspergillus flavus, Clostridium difficile, Mycobacterium georgium, Mycobacterium tuberculosis, Mycobacterium bovis, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Staphylococcus epidermidis, Staphylococcus lugdunensis, Staphylococcus saprophyticus, enterococcus faecium, enterococcus faecalis, Propionibacterium acnes, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis, Salmonella enterica, Salmonella typhi, Streptococcus mutans, Shigella flexneri, and combinations thereof.

23. The method of any one of claims 21 to 22, wherein the contaminated article is contaminated with a biofilm comprising a plurality of microorganisms, further wherein the exposure time is at least 5 minutes and the number of colony forming units of a sterilized article is reduced by 4 to 9 log steps relative to the contaminated article, optionally wherein the exposure time is at most one hour.

24. The method of any one of claims 21 to 23, wherein the contaminated article is contaminated with a biofilm comprising a plurality of microbial or fungal spores, further wherein the exposure time is at least 2 minutes and the number of colony forming units of a sterilized article is reduced by 6 to 10 log orders relative to the contaminated article, optionally wherein the exposure time is at most one hour.

Technical Field

The present disclosure relates generally to sterilization or disinfection and drying of medical devices and articles, and more particularly to alternating application of gas plasma to effect sterilization or disinfection of medical articles such as medical instruments or medical endoscope lumens and turbulent gas flow to effect drying.

Background

Reliable supply of sterile equipment, instruments and supplies is critical to modern medical practice. Various types of equipment for sterilizing reusable items in a hospital environment are known, including for example steam autoclaves. U.S. patent 4,301,113(Alguire et al), U.S. patent 4,294,804(Baran), U.S. patent 5,317,896(Sheth et al), U.S. patent 5,399,314(Samuel et al), U.S. patent 3,571,563(Shulz), U.S. patent 3,054,270(Huston), and U.S. patent 3,564,861(Andersen et al) discuss sterilization apparatus and its control system. Items that cannot withstand autoclaving temperatures can be sterilized with a sterilizer using a biocidal gas such as ethylene oxide.

While ethylene oxide is an excellent sterilant and penetrates well into, for example, the lumen of an endoscope, ethylene oxide also exhibits undesirable toxicity and flammability, and for at least these reasons the art has sought alternatives.

Disclosure of Invention

The present disclosure provides a sterilization or disinfection and drying system that employs an oxygen/nitrogen plasma to effect sterilization or disinfection of a medical article, such as a medical instrument or medical endoscope lumen, and a turbulent gas flow to effect drying. The disclosed embodiments allow for high electrode energy density while minimizing unwanted heat generation. In addition to demonstrating effective sterilization by obtaining complete kill (6 to 7 log scale) of representative model organisms associated with endoscope reprocessing, the disclosed embodiments of the present invention also achieve removal of all visible moisture from the luminal passage of a medical endoscope.

Accordingly, in one aspect, the present disclosure is directed to a system for sterilizing a soiled article, the system comprising: a drying gas source configured to provide a turbulent flow of drying gas to dry the soiled article; a plasma generator having an electrode, a shield, and a dielectric gap between the electrode and the shield; an electrical power source connected to the plasma generator for applying an electrode energy density between the electrode and the shield; and a sterilizing gas precursor source comprising water vapor, oxygen and nitrogen and configured to provide a flow of sterilizing gas precursor between the electrode and the shield through the plasma generator to form a plasma. The temperature at the surface of the shield is maintained below 150 ℃ when the electrode energy density is greater than 0.05eV per molecule of the sterilizing gas precursor passing between the electrode and the shield. The plasma forms a sterilizing gas comprising an acidic species and/or an oxidizing species from the sterilizing gas precursor. The contaminated article is exposed to a flow of sterilizing gas.

In an exemplary embodiment of the system, the sterilizing gas comprises one or more selected from the group consisting of molecular oxygen, molecular nitrogen, nitric oxide, nitric acid and nitrous oxide. Preferably, the sterilizing gas precursor comprises water vapor, molecular oxygen and molecular nitrogen. In some exemplary embodiments, the sterilizing gas precursor comprises air. Preferably, the relative humidity of the sterilizing gas precursor entering the plasma generator is at least 21%.

In some presently preferred embodiments, the temperature at the surface of the shield is maintained below 150 ℃ when the electrode energy density is greater than 0.05eV per molecule of the gas passing between the electrode and the shield. In some exemplary embodiments, the electrical power source is a pulsed DC source with a high dV/dT.

Optionally, the system further comprises means for transporting the contaminated article through a chamber fluidly connected to the flow of sterilizing gas. In certain exemplary embodiments, the system additionally comprises a cooling device. In some exemplary embodiments, the system includes a filter for removing acidic species and/or oxidizing species from the sterilizing gas.

In a second aspect, the present disclosure describes a method of sterilizing a soiled article using a sterilizer, the method comprising: providing a sterilizer, the sterilizer comprising: a drying gas source configured to provide a turbulent flow of drying gas to dry the soiled article; a plasma generator comprising an electrode, a shield, and a dielectric gap between the electrode and the shield; an electrical power source connected to the plasma generator for applying an electrode energy density between the electrode and the shield; and a sterilizing gas precursor source comprising water vapor, oxygen and nitrogen and configured to provide a flow of sterilizing gas precursor between the electrode and the shield through the plasma generator to form a plasma comprising acidic species and/or oxidizing species from the sterilizing gas precursor. The method also includes providing a flow of a sterilizing gas precursor between the electrode and the shield through a plasma generator to form a plasma, wherein a temperature at a surface of the shield is maintained below 150 ℃ when an electrode energy density is greater than 0.05eV per molecule of the sterilizing gas precursor passing between the electrode and the shield. The plasma causes the sterilizing gas precursor stream to form a sterilizing gas stream comprising acidic species and/or oxidizing species. The method also includes directing a flow of sterilizing gas containing an acidic species and/or an oxidizing species from the plasma generator through an enclosed space enclosing at least a portion of the soiled article, exposing the soiled article to the sterilizing gas containing an acidic species and/or an oxidizing species for a sufficient exposure time to achieve a desired degree of sterilization of the soiled article, and directing a turbulent flow of drying gas into the enclosed space to dry the soiled article.

In some particular exemplary embodiments, the soiled article is exposed to the gas comprising the acidic species and/or the oxidizing species for a sufficient exposure time to achieve the desired degree of sterilization of the soiled article, the exposure time preferably not exceeding one hour.

In certain presently preferred embodiments, directing the flow of sterilizing gas through the enclosed space is for a duration of at least 10 seconds and no more than 5 minutes, and then directing the flow of drying gas through the enclosed space for a duration of at least 10 seconds and no more than 10 minutes. Preferably, this process of alternately directing a flow of sterilizing gas through the enclosed space and directing a flow of drying gas through the enclosed space is repeated at least twice.

In further exemplary embodiments, the sterilizing gas precursor comprises water vapor, oxygen, and nitrogen, and the temperature at the surface of the shield is maintained below 150 ℃ when the electrode energy density is greater than 0.05 eV/molecule of the gas passing between the electrode and the shield. In further exemplary embodiments, the drying gas is selected from the group consisting of oxygen, nitrogen, helium, neon, argon, krypton, or combinations thereof, optionally wherein the drying gas is substantially free of water. In certain exemplary embodiments, at least one of the drying gas, the sterilizing gas precursor, or the sterilizing gas has a temperature of 10 ℃ to 60 ℃.

In some particular exemplary embodiments, the soiled article is a medical device and the enclosed space is a hollow region of the medical device. In some such embodiments, the medical device is an endoscope and the hollow region is a lumen of the endoscope, further wherein a sterilizing gas comprising an acidic substance and/or an oxidizing substance from the plasma generator is passed through the lumen of the endoscope. In other exemplary embodiments, the medical device is a medical instrument and the hollow region is at least one internal cavity of the medical instrument.

In certain exemplary embodiments, the soiled article is soiled with at least one of: a biofilm consisting of a plurality of microorganisms, a biofilm consisting of a plurality of microbial spores, a biofilm consisting of a plurality of fungal spores, or a plurality of fungal spores. These organisms may be present with biofouling such as blood, feces, mucus, and the like. In some such exemplary embodiments, the biofilm comprises a plurality of microorganisms selected from the group consisting of: bacillus stearothermophilus (Geobacillus stearothermophilus), Bacillus subtilis (Bacillus subtilis), Bacillus atrophaeus (Bacillus atrophaeus), Bacillus megaterium (Bacillus megaterium), Bacillus coagulans (Bacillus coagulogenes), Clostridium sporogenes (Clostridium sporogenes), Bacillus pumilus (Bacillus pumilus), Aspergillus brasiliensis (Aspergillus braziliensis), Aspergillus oryzae (Aspergillus oryzae) Aspergillus oryzae (Aspergillus oryzae) Aspergillus niger, Aspergillus nidulans (Aspergillus nidulans), Aspergillus flavus (Aspergillus flavus), Clostridium difficile (Clostridium difficile), Mycobacterium tuberculosis (Mycobacterium tuberculosis), Mycobacterium bovis (Staphylococcus aureus), Escherichia coli (Staphylococcus aureus), Staphylococcus aureus (Escherichia coli), Staphylococcus aureus (Staphylococcus aureus), Bacillus subtilis (Staphylococcus aureus), Bacillus subtilis (Bacillus subtilis), Bacillus subtilis (Staphylococcus aureus), Bacillus subtilis (Staphylococcus aureus), Bacillus subtilis (Staphylococcus aureus), Bacillus subtilis, Enterococcus faecalis (Enterococcus faecalis), propionibacterium acnes (Propionibacterium acnes), Klebsiella pneumoniae (Klebsiella pneumoniae), Enterobacter cloacae (Enterobacter cloacae), Proteus mirabilis (Proteus mirabilis), Salmonella enterica (Salmonella enterica), Salmonella typhi (Salmonella typhi), Streptococcus mutans (Streptococcus mutans), Shigella flexneri (Shigella flexirii), and combinations thereof.

In some exemplary embodiments, the contaminated article is contaminated with a biofilm comprising a plurality of microorganisms, further wherein the exposure time is at least 5 minutes and the number of colony forming units of the sterilized article is reduced by 4 to 9 log steps relative to the contaminated article, optionally wherein the exposure time is at most one hour.

In further exemplary embodiments, the contaminated article is contaminated with a biofilm comprising a plurality of microbial or fungal spores, further wherein the exposure time is at least 2 minutes and the number of colony forming units of the sterilized article is reduced by 6 log steps to 10 log steps relative to the contaminated article, optionally wherein the exposure time is at most one hour.

Additional exemplary embodiments within the scope of the present disclosure are provided in the following list of exemplary embodiments.

List of exemplary embodiments

A. A system for sterilizing a soiled article comprising:

a drying gas source configured to provide a turbulent flow of drying gas to dry the soiled article;

a plasma generator having:

an electrode is arranged on the base plate and is provided with a plurality of electrodes,

a shield, and

a dielectric gap between the electrode and the shield;

an electrical power source connected to the plasma generator for applying an electrode energy density between the electrode and the shield; and

a sterilizing gas precursor source comprising water vapor, oxygen and nitrogen and configured to provide a flow of sterilizing gas precursor between the electrode and the shield through the plasma generator to form a plasma, wherein a temperature at a surface of the shield is maintained below 150 ℃ when the electrode energy density is greater than 0.05 eV/molecule of sterilizing gas precursor passing between the electrode and the shield, further wherein the plasma forms a sterilizing gas comprising an acidic species and/or an oxidizing species from the sterilizing gas precursor, and further wherein the contaminated article is exposed to a flow of sterilizing gas, further wherein optionally the system further comprises means for delivering the contaminated article through a chamber fluidly connected to the flow of sterilizing gas.

B. The system of embodiment a, wherein the sterilizing gas comprises one or more substances selected from the group consisting of molecular oxygen, molecular nitrogen, nitric oxide, nitric acid, and nitrous oxide.

C. The system of embodiments a or B, wherein the sterilizing gas precursor comprises air, optionally wherein the relative humidity of the sterilizing gas precursor is at least 21%.

D. The system of any of embodiments a-C, further comprising one or more valves configured to apply alternating flows of a drying gas and the sterilizing gas to the contaminated article.

E. The system of any of embodiments a-D, further comprising a cooling device.

F. The system according to any of embodiments a-E, wherein the electrical power source is a pulsed DC source with a high dV/dT.

G. The system according to any of embodiments a-F, further comprising a filter for removing the acidic and/or oxidizing species from the sterilizing gas.

H. A method of sterilizing a soiled article comprising:

providing a sterilizer, the sterilizer comprising:

a drying gas source configured to provide a turbulent flow of drying gas to dry the soiled article;

a plasma generator, the plasma generator comprising:

an electrode is arranged on the base plate and is provided with a plurality of electrodes,

a shield, and

a dielectric gap between the electrode and the shield;

an electrical power source connected to the plasma generator for applying an electrode energy density between the electrode and the shield; and

a sterilizing gas precursor source comprising water vapor, oxygen and nitrogen and configured to provide a flow of sterilizing gas precursor between the electrode and the shield through the plasma generator to form a plasma comprising acidic species and/or oxidizing species from the sterilizing gas precursor;

providing a flow of the sterilizing gas precursor between the electrode and the shield by the plasma generator to form a plasma, wherein the temperature at the surface of the shield is maintained below 150 ℃ when the electrode energy density is greater than 0.05eV per molecule of sterilizing gas precursor passing between the electrode and the shield, further wherein the plasma causes the flow of sterilizing gas precursor to form a flow of sterilizing gas comprising the acidic species and/or oxidizing species;

directing a flow of sterilizing gas comprising the acidic species and/or oxidizing species from the plasma generator through an enclosed space enclosing at least a portion of the contaminated article;

exposing the soiled article to a sterilizing gas comprising the acidic species and/or oxidizing species for a sufficient exposure time to achieve a desired degree of sterilization of the soiled article, optionally wherein the time sufficient to achieve the desired degree of sterilization of the soiled article does not exceed one hour; and

directing a turbulent flow of the drying gas into the enclosed space to dry the soiled article.

I. The method of embodiment H, further comprising removing at least a portion of the acidic species and/or oxidizing species from the sterilizing gas after directing the sterilizing gas through the enclosed space.

J. The method of embodiment I, wherein removing at least a portion of the acidic and/or oxidizing species from the sterilizing gas is performed by a filter comprising one or more materials selected from the group consisting of activated carbon, a species having a basic functional group, a species providing a basic adsorbent, a reducing species, and a molecular sieve.

K. The method according to any one of embodiments H-J, wherein the enclosed space is a sterilization chamber in which the soiled article is placed.

L. the method of any of embodiments H-K, wherein directing the flow of sterilizing gas through the enclosed space is for a duration of at least 10 seconds and no more than 5 minutes, and then directing the flow of drying gas through the enclosed space for a duration of at least 10 seconds and no more than 10 minutes, optionally wherein alternately directing the flow of sterilizing gas and directing the flow of drying gas are repeated at least twice.

M. the method of any of embodiments H-L, wherein at least one of the drying gas, the sterilizing gas precursor, or the sterilizing gas has a temperature of 10 ℃ to 60 ℃.

N. the method of any one of embodiments H through M, wherein the drying gas is selected from the group consisting of oxygen, nitrogen, helium, neon, argon, krypton, or combinations thereof, optionally wherein the drying gas is substantially free of water.

O. the method according to any one of embodiments H to N, wherein the sterilizing gas comprises one or more substances selected from the group consisting of molecular oxygen, molecular nitrogen, nitric oxide, nitric acid and nitrous oxide.

P. the method of any of embodiments H through O, wherein the sterilizing gas precursor comprises air, optionally wherein the relative humidity of the sterilizing gas precursor entering the plasma generator is at least 21%.

The method of any of embodiments H-P, wherein the electrical power source is a pulsed DC source with a high dV/dT.

R. the method of any one of embodiments H-Q, wherein the contaminated article is a medical device and the enclosed space is a hollow region of the medical device.

S. the method of embodiment R, wherein the medical device is an endoscope and the hollow region is a lumen of the endoscope, further wherein a sterilizing gas comprising the acidic and/or oxidizing species from the plasma generator passes through the lumen of the endoscope.

T. the method of embodiment R, wherein the medical device is a medical instrument and the hollow region is at least one internal cavity of the medical instrument.

U. the method of any one of embodiments H-T, wherein the soiled article is soiled with at least one of: a biofilm consisting of a plurality of microorganisms, a biofilm consisting of a plurality of microbial spores, a biofilm consisting of a plurality of fungal spores, or a plurality of fungal spores.

V. the method of embodiment U, wherein the biofilm comprises a plurality of microorganisms selected from the group consisting of: bacillus stearothermophilus, Bacillus subtilis, Bacillus atrophaeus, Bacillus megaterium, Bacillus coagulans, Clostridium sporogenes, Bacillus pumilus, Aspergillus brasiliensis, Aspergillus oryzae, Aspergillus niger, Aspergillus nidulans, Aspergillus flavus (Aspergillus, Clostridium difficile, Mycobacterium georgium, Mycobacterium tuberculosis, Mycobacterium bovis, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Staphylococcus epidermidis, Staphylococcus lugdunensis, Staphylococcus saprophyticus, enterococcus faecium, enterococcus faecalis, Propionibacterium acnes, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis, Salmonella enterica, Salmonella typhi, Streptococcus mutans, Shigella flexneri, and combinations thereof.

W. the method of embodiment U or V, wherein the contaminated article is contaminated with a biofilm comprising a plurality of microorganisms, further wherein the exposure time is at least 5 minutes and the number of colony forming units of a sterilized article is reduced by 4 to 9 log steps relative to the contaminated article, optionally wherein the exposure time is at most one hour.

X. the method of any one of embodiments U-W, wherein the contaminated article is contaminated with a biofilm comprising a plurality of microbial or fungal spores, further wherein the exposure time is at least 2 minutes and the number of colony forming units of a sterilized article is reduced by 6 to 10 log steps relative to the contaminated article, optionally wherein the exposure time is at most one hour.

Various aspects and advantages of exemplary embodiments of the present disclosure have been summarized. The above summary is not intended to describe each illustrated embodiment or every implementation of the present certain exemplary embodiments of the present disclosure. The following drawings and detailed description more particularly exemplify certain preferred embodiments using the principles disclosed herein.

Drawings

The present disclosure may be more completely understood in consideration of the following detailed description of exemplary embodiments and the accompanying drawings, in which:

fig. 1 is a schematic view of an exemplary sterilization and drying system according to the present disclosure.

Fig. 2a is a cross-sectional view of a variation of the plasma generator taken along section line 2-2 in fig. 1.

Fig. 2b is a cross-sectional view of another variation of the plasma generator taken along section line 2-2 in fig. 1.

Fig. 2c is a cross-sectional view of another variation of the plasma generator taken along section line 2-2 in fig. 1.

In the drawings, like numbering represents like elements. While the above-identified drawing figures, which may not be drawn to scale, set forth various embodiments of the disclosure, other embodiments are also contemplated, as noted in the detailed description. In all cases, this disclosure describes the presently disclosed disclosure by way of representation of exemplary embodiments and not by express limitations. It should be understood that numerous other modifications and embodiments can be devised by those skilled in the art that will fall within the scope and spirit of the principles of this disclosure.

Detailed Description

The present disclosure describes an apparatus and method for sterilizing or disinfecting and drying articles using a gas plasma comprising oxygen, nitrogen, and reactive species generated from these gases. In some convenient embodiments, the plasma is directed into a chamber in which the contaminated article to be sterilized or disinfected is placed. In other convenient embodiments, the plasma is directed into a hollow region of the equipment or article to be sterilized or disinfected.

Glossary

Certain terms are used throughout the description and claims, and although mostly known, some explanation may be required. It should be understood that, as used herein, unless a different definition is explicitly provided in the claims or elsewhere in the specification (including the drawings):

as used herein, the term "sterilizing gas" refers to a gas having antimicrobial activity for treating a device or article, whether or not the treated device or article is actually sterilized. The sterilization will depend on many process parameters such as exposure time, initial bioburden, type of organisms present, presence or absence of fouling, etc., as taught herein.

As used herein, the term "disinfecting" or "disinfecting" refers to reducing the microbial load on an article by exposure to a sterilizing gas.

The term "about" or "approximately" with respect to a numerical value or shape means +/-5% of the numerical value or attribute or characteristic, but expressly includes the exact numerical value. For example, a viscosity of "about" 1Pa-sec refers to a viscosity of 0.95Pa-sec to 1.05Pa-sec, but also specifically includes a viscosity of exactly 1 Pa-sec.

As used in this specification and the appended embodiments, the singular forms "a", "an" and "the" include plural referents unless the content clearly dictates otherwise. Thus, for example, reference to a fine fiber comprising "a compound" includes mixtures of two or more compounds. As used in this specification and the appended embodiments, the term "or" is generally employed in its sense including "and/or" unless the content clearly dictates otherwise.

The term "substantially" refers specifically to an attribute or characteristic, meaning that the attribute or characteristic is more pronounced than it is to the contrary. For example, a substrate that is "substantially" transparent refers to a substrate that transmits more radiation (e.g., visible light) than it does not. Thus, a substrate that transmits more than 50% of visible light incident on its surface is substantially transparent, but a substrate that transmits 50% or less of visible light incident on its surface is not substantially transparent.

As used in this specification, the recitation of numerical ranges by endpoints includes all numbers subsumed within that range (e.g. 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.8, 4, and 5).

Unless otherwise indicated, all numbers expressing quantities or ingredients, property measurements, and so forth used in the specification and embodiments are to be understood as being modified in all instances by the term "about". Accordingly, unless indicated to the contrary, the numerical parameters set forth in the foregoing specification and attached list of embodiments can vary depending upon the desired properties sought to be obtained by those skilled in the art utilizing the teachings of the present disclosure. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claimed embodiments, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.

Various modifications and alterations may be made to the exemplary embodiments of the present disclosure without departing from the spirit and scope thereof. Therefore, it is to be understood that the embodiments of the present disclosure are not limited to the exemplary embodiments described below, but rather are controlled by the limitations set forth in the claims and any equivalents thereof.

Exemplary Sterilization apparatus and Process

The present disclosure describes a system for sterilizing a contaminated article, the system comprising: a drying gas source configured to provide a turbulent flow of drying gas to dry the soiled article; a plasma generator having an electrode, a shield, and a dielectric gap between the electrode and the shield; an electrical power source connected to the plasma generator for applying an electrode energy density between the electrode and the shield; and a sterilizing gas precursor source comprising water vapor, oxygen and nitrogen and configured to provide a flow of sterilizing gas precursor between the electrode and the shield through the plasma generator to form a plasma. The temperature at the surface of the shield is maintained below 150 ℃ when the electrode energy density is greater than 0.05eV per molecule of the sterilizing gas precursor passing between the electrode and the shield. The plasma forms a sterilizing gas comprising an acidic species and/or an oxidizing species from the sterilizing gas precursor. The contaminated article is exposed to a flow of sterilizing gas. In some embodiments, the system further comprises a means for transporting the contaminated article through a chamber fluidly connected to the flow of sterilizing gas, such as a conveyor belt.

The present disclosure also describes a method of sterilizing a contaminated article using a sterilizer, the method comprising: providing a sterilizer, the sterilizer comprising: a drying gas source configured to provide a turbulent flow of drying gas to dry the soiled article; a plasma generator comprising an electrode, a shield, and a dielectric gap between the electrode and the shield; an electrical power source connected to the plasma generator for applying an electrode energy density between the electrode and the shield; and a sterilizing gas precursor source comprising water vapor, oxygen and nitrogen and configured to provide a flow of sterilizing gas precursor between the electrode and the shield through the plasma generator to form a plasma comprising acidic species and/or oxidizing species from the sterilizing gas precursor.

The method also includes providing a flow of a sterilizing gas precursor between the electrode and the shield through a plasma generator to form a plasma, wherein a temperature at a surface of the shield is maintained below 150 ℃ when an electrode energy density is greater than 0.05eV per molecule of the sterilizing gas precursor passing between the electrode and the shield. The plasma causes the sterilizing gas precursor stream to form a sterilizing gas stream comprising acidic species and/or oxidizing species.

The method also includes directing a flow of sterilizing gas containing an acidic species and/or an oxidizing species from the plasma generator through an enclosed space enclosing at least a portion of the soiled article, exposing the soiled article to the sterilizing gas containing an acidic species and/or an oxidizing species for a sufficient exposure time to achieve a desired degree of sterilization of the soiled article, and directing a turbulent flow of drying gas into the enclosed space to dry the soiled article.

In some embodiments, the soiled article is a medical device and the enclosed space is a hollow region of the medical device. In some such embodiments, the medical device is an endoscope and the hollow region is a lumen of the endoscope, further wherein a sterilizing gas comprising an acidic substance and/or an oxidizing substance from the plasma generator is passed through the lumen of the endoscope. In other exemplary embodiments, the medical device is a medical instrument and the hollow region is at least one internal cavity of the medical instrument. In other embodiments, the enclosed space is an enclosed chamber, such as a sterilization chamber into which the contaminated article to be sterilized has been placed.

Various exemplary embodiments of the present disclosure will now be described with particular reference to the accompanying drawings.

Referring now to fig. 1, a schematic diagram of an exemplary sterilization or disinfection and drying system 20 of the present disclosure is shown. Sterilization/disinfection system 20 includes a sterilizing gas precursor source 22 that contains molecular oxygen and molecular nitrogen. The sterilizing gas precursor from source 22 may be air or a particular blend comprising molecular oxygen and molecular nitrogen in a specified ratio, and may or may not be pressurized when provided. If from an unpressurized source 22, a compressor 24 may be used to pressurize the sterilizing gas precursor to the appropriate pressure. The sterilizing gas precursor is then delivered via line 26 to a flow controller 28 to meter the mass flow of the sterilizing gas precursor into the remainder of the sterilization system 20. The flow controller 28 may take the form of a pressure regulator, bulb flow meter, electronic mass flow controller, or other similar device.

The sterilizing gas precursor is then delivered via line 30 to humidification device 32 to achieve a humidity of between about 1g/m of the sterilizing gas precursor³And 50g/m³Between 2g/m³And 40g/m³Between 3g/m³And 30g/m³Between 4g/m³And 20g/m³Between or even between 5g/m³And 15g/m³In the meantime. Various means such as bubblers, nebulizers, atomizers, ultrasonic and wicking type humidifiers are suitable. In the embodiment shown, humidified sterilizing gas precursor is delivered via line 34 to an optional humidity detector 36 to verify that the humidity level is within the desired range. In some convenient embodiments, feedback control via control line 38 is provided to properly operate humidification apparatus 30.

Humidified sterilizing gas precursor is delivered via line 40 to a plasma generator 50, which is discussed in more detail below. The plasma generator 50 facilitates the generation of a sterilizing gas containing various chemicals, including one or more of nitrous oxide, nitric acid, ozone, and nitrous oxide, from the humidified sterilizing gas precursor. The sterilizing gas is delivered to a remote location via line 52. Surprisingly, line 52 can be quite long without loss of sterilization efficacy; a distance of between about 0.5 and 90 meters has been found suitable.

Line 52 may, for example, deliver sterilizing gas directly to endoscope 60 to sterilize the internal lumen, or to another enclosed chamber, such as a sterilization chamber (not shown in fig. 1), in which the contaminated article to be sterilized is placed.

The source of dry gas is connected to a flow controller 59 which is connected by line 58 to an endoscope 60 or to another enclosed chamber, such as a sterilization chamber (not shown in fig. 1), in which the contaminated article to be sterilized is placed. The flow controller 59 may be any device for adjusting the flow rate of the drying gas 26. Suitable devices include pressure regulators, flow control valves, bulb flow meters (rotameters), electronic mass flow controllers, or other similar devices. The flow controller 59 is used to regulate the flow rate of the dry gas to ensure that the gas is turbulent as it passes through the endoscope 60 or through another enclosed chamber, such as a sterilization chamber (not shown in fig. 1), in which the contaminated article being subjected to sterilization is placed.

Turbulent flow is achieved when the flow rate of the drying gas through line 58 is such that the characteristic reynolds number is greater than about 2100. The Reynolds number is defined as:

re ═ (2Q ρ/. mu.π R) where: q is the volumetric flow rate of the drying gas;

ρ is the density of the dry gas;

μ is the viscosity of the drying gas;

and R is the radius of a line 58 having a circular cross-section

The flow of sterilizing gas and the flow of drying gas are alternately supplied to the endoscope 60 or to another enclosed chamber, such as a sterilization chamber (not shown in fig. 1), in which the contaminated articles to be sterilized are placed. The alternation of the sterile gas flow and the dry gas flow can advantageously be performed using three-way valves 54 and 54', which can advantageously be electronically controlled valves, such as three-way solenoid valves. In a first position of three-way valves 54 and 54', a flow of sterilizing gas is directed from line 52 through line 56 and into endoscope 60 or another enclosed chamber such as a sterilization chamber (not shown in FIG. 1); and the flow of dry gas is isolated from the endoscope 60 or another enclosed chamber. After passing through the endoscope 60 or another enclosed chamber, the sterilizing gas exits the endoscope 60 (or equivalently, an enclosed chamber) via line 62 and is delivered to a filter 64 to render the sterilizing gas harmless.

In the second position of three-way valves 54 and 54', the turbulent flow of dry gas passes through line 58 and into endoscope 60 or another enclosed chamber, and the sterilizing gas is directed from line 52 through line 57 and into filter 64. In convenient embodiments, filter 64 will include a basic material such as sodium bicarbonate, potassium carbonate, sodium phosphate, and the like to neutralize any remaining acidic species. Preferably, the alkaline material is a material having a pH greater than 8 at 23 ℃ when mixed with water at a concentration of 10% w/w in deionized water. Elements such as activated carbon may also be conveniently present to remove oxidizing species such as ozone. After filtration, the sterilizing gas may be released to ambient conditions via outlet 66.

In some embodiments, directing a flow of sterilizing gas through the enclosed space for a duration of at least 10 seconds (15 seconds, 20 seconds, 25 seconds, 30 seconds; 1 minute, 2 minutes, 5 minutes) and no more than 5 minutes (4 minutes, 3 minutes, 2.5 minutes, 2 minutes) and then directing a flow of drying gas through the enclosed space for a duration of at least 10 seconds (15 seconds, 20 seconds, 25 seconds, 30 seconds; 1 minute, 2 minutes, 5 minutes) and no more than 10 minutes (9 minutes, 8 minutes, 7 minutes, 6 minutes, 5 minutes, 4 minutes, 3 minutes). Preferably, the flow of sterilizing gas and the flow of drying gas are alternately repeated at least two times (three, four, five, six or more times) through the endoscope 60 or through another closed chamber.

In some embodiments, at least one of the drying gas, the sterilizing gas precursor, or the sterilizing gas has a temperature of 10 ℃ to 60 ℃.

The drying gas may be selected from oxygen, nitrogen, helium, neon, argon, krypton, or combinations thereof. Preferably, the drying gas is substantially or even completely free of water.

The sterilizing gas precursor comprises water vapor, oxygen and nitrogen. In some embodiments, the sterilizing gas precursor comprises air. Preferably, the relative humidity of the sterilizing gas precursor entering the plasma generator is at least 21%, 22%, 23%, 24%, 25% or even higher.

The sterilizing gas comprises one or more substances selected from the group consisting of molecular oxygen, molecular nitrogen, nitric oxide, nitric acid and nitrous oxide.

Referring now to fig. 2a, a cross-sectional view of a variation 50a of the plasma generator 50 is shown taken along section line 2-2 of fig. 1. In variation 50a, the sterilizing gas is delivered through lumen 70 in outer tube 72. The tube 72 is a dielectric, convenient glass. Within lumen 70 is an inner tube 74 having a lumen 76. The tube 74 is also a dielectric, convenient glass. Within the lumen 76 is a first electrode 80. The second electrode 82 surrounds the outer tube 72 and in some convenient embodiments has fins 84 for its additional function as a heat sink. Other means may be used to provide cooling (such as fans, fins, heat exchangers), piezoelectric cooling, and combinations thereof.

During operation, a potential difference must exist between the first electrode 80 and the second electrode 82. In some convenient embodiments, the first electrode 80 is a high voltage electrode and the second electrode 82 is a ground electrode. An AC voltage of between about 4kV to 12kV is conveniently applied to the first electrode 80, the AC voltage having a frequency of between about 4kHz to 30 kHz. The exact conditions depend on the gas flow rates required to effectively process the equipment to be sterilized, the available cooling capacity of the plasma generator 50, and the dimensions of the outer tube 72 and the inner tube 74, respectively. In any case, the electrical parameters must be such that the conditions exceed the breakdown voltage of the sterilizing gas precursor between the tubes.

Referring now to fig. 2b, a cross-sectional view of another variation 50b of the plasma 50 is shown, taken along section line 2-2 of fig. 1. In variation 50b, the sterilizing gas is transmitted through a lumen 90 in a tube 92. The tube 92 is conveniently a polymer tubing such as Polytetrafluoroethylene (PTFE). Also within the lumen 90 is, for example, a ribbon cable 94, the ribbon cable 94 including a first conductor 96, a second conductor 98, conveniently both within a dielectric insulation 100.

Referring now to fig. 2c, a cross-sectional view of another variation 50c of the plasma 50 is shown, taken along section line 2-2 of fig. 1. In variation 50c, the sterilizing gas is delivered through lumen 110 in tube 112. The tube 112 is conveniently a polymer tubing, such as Polytetrafluoroethylene (PTFE). Also within lumen 110 is an electrode subassembly 114 that includes an electrode 116, conveniently a high voltage electrode, surrounded by a dielectric layer 118. Surrounding the dielectric layer 118 is another electrode 120, conveniently a ground electrode. The fins 122 may conveniently be present to improve the generated electric field.

During operation, a potential difference should exist between the first conductor 96 and the second conductor 98. In some convenient embodiments, the first conductor 96 is a high voltage electrode and the second conductor 98 is a ground electrode. A DC voltage of at least 20kV, at least 30kV, at least 40kV and even at least 50kV but preferably not exceeding 100kV, 90kV, 80kV, 70kV or even 60kV is conveniently applied to the first conductor 96 in the form of pulses of very fast (i.e. high) dV/dt having a duration in the order of nanoseconds. This means that the highest instantaneous rate of change of the rising voltage of the pulse should reach at least 10 kV/nanosecond, at least 20 kV/nanosecond, at least 30 kV/nanosecond, at least 40 kV/nanosecond or even at least 50 kV/nanosecond. This type of charging allows for the generation of a plasma within the sterilizing gas precursor with relatively little heating.

Other exemplary embodiments of the present disclosure describe a method of sterilizing a contaminated article using the sterilization system as described above. The sterilization system includes: a plasma generator having an electrode, a shield, and a dielectric gap between the electrode and the shield; an electrical power source connected to the plasma generator for applying an electrode energy density between the electrode and the shield; and a sterilizing gas precursor source providing a flow through the plasma generator to form a plasma from the sterilizing gas precursor and generate a sterilizing gas comprising an acidic species and/or an oxidizing species. A sterilizing gas containing an acidic substance and/or an oxidizing substance is directed from a plasma generator to an enclosed area that includes a portion of an article undergoing sterilization.

In certain presently preferred embodiments, the sterilizing gas precursor comprises water vapor, oxygen, and nitrogen, and the temperature at the surface of the shield is maintained below 150 ℃ when the electrode energy density is greater than 0.05eV per molecule of the sterilizing gas precursor passing between the electrode and the shield. The contaminated article is exposed to a sterilizing gas comprising an acidic species and/or an oxidizing species for a sufficient exposure time to sterilize the contaminated article, preferably not more than one hour.

In certain exemplary embodiments, the method further comprises removing at least a portion of the acidic species and/or the oxidizing species from the sterilizing gas upon achieving a desired degree of sterilization of the article. The removal of the acidic species and/or the oxidizing species from the sterilizing gas may be performed with an apparatus comprising one or more adsorbents or adsorbing materials selected from the group consisting of: activated carbon, chemicals having basic functional groups (e.g., organic amines, sodium hydroxide, potassium hydroxide, lithium hydroxide, etc.), substances that provide basic adsorbents (e.g., basic ion exchange resins), reducing substances (e.g., one or more active metals such as platinum, palladium, etc.), and molecular sieves. In some exemplary embodiments, removing the acidic species and/or the oxidizing species from the sterilizing gas may be performed by directing the sterilizing gas through a catalytic reducer.

In further exemplary embodiments, the enclosed area is a sterilization chamber. In other exemplary embodiments, the article undergoing sterilization is a medical device and the enclosed region is a hollow region of the medical device. In some presently preferred embodiments, the medical device is an endoscope and the hollow region is a lumen of the endoscope, and the sterilizing gas from the plasma generator comprising the acidic substance and/or the oxidizing substance is passed through the lumen of the endoscope.

In other exemplary embodiments, the medical device is a medical instrument and the hollow region is at least one internal cavity of the medical instrument.

In some embodiments, the soiled article is soiled with at least one of: a biofilm comprising a plurality of microorganisms or a plurality of microbial spores or fungal spores. Exposing the soiled article to a sterilizing gas comprising an acidic substance and/or an oxidizing substance for a sufficient exposure time to sterilize the soiled article by achieving at least a 2 log reduction and optionally a maximum of 11 log reductions in the number of colony forming units of the sterilized soiled article relative to the soiled article.

In certain such exemplary embodiments, the article undergoing sterilization is a medical device and the enclosed region is a hollow region of the medical device. In some presently preferred embodiments, the medical device is an endoscope and the hollow region is a lumen of the endoscope, and the sterilizing gas from the plasma generator comprising the acidic substance and/or the oxidizing substance is passed through the lumen of the endoscope.

In some exemplary embodiments, the biofilm comprises a plurality of microbial species selected from, for example: geobacillus sp, such as Geobacillus stearothermophilus; bacillus (Bacillus sp.) such as Bacillus subtilis, Bacillus atrophaeus, Bacillus megaterium, Bacillus coagulans, Bacillus pumilus; clostridia (Clostridium sp.) such as Clostridium sporogenes and Clostridium difficile; aspergillus sp, Aspergillus braziliensis, Aspergillus oryzae, Aspergillus niger, Aspergillus nidulans, Aspergillus flavus; bacterial cells such as Mycobacterium terrae, Mycobacterium tuberculosis, and Mycobacterium bovis; and biofilm-forming bacteria such as escherichia coli, staphylococcus aureus, pseudomonas aeruginosa, staphylococcus epidermidis, staphylococcus lugdunensis, staphylococcus saprophyticus, staphylococcus epidermidis, enterococcus faecium, enterococcus faecalis, propionibacterium acnes, klebsiella pneumoniae, enterobacter cloacae, proteus mirabilis, salmonella enterica, salmonella typhi, streptococcus mutans, and shigella flexneri; and combinations thereof.

In certain exemplary embodiments, the contaminated article is contaminated with a biofilm comprising a plurality of microorganisms for an exposure time of at least 5 minutes, and the number of colony forming units of the contaminated article is reduced by 4 log to 9 log relative to the contaminated article. More preferably, the number of colony forming units of the contaminated product is reduced by 5 log to 9 log relative to the contaminated product; 6 log levels to 9 log levels; or even 6 log levels to 10 log levels.

Preferably, the exposure time to achieve a desired level of disinfection of a soiled article contaminated with a biofilm comprising a plurality of microorganisms is selected to be at most one hour. More preferably, the exposure time to achieve the desired level of disinfection is no more than 50 minutes, 40 minutes, 30 minutes, 20 minutes, or even 10 minutes. Most preferably, the exposure time selected to achieve the desired level of disinfection is at most 9 minutes, 8 minutes, 7 minutes, 6 minutes, 5 minutes, or as low as 4 minutes, 3 minutes, 2 minutes, or even 1 minute.

In other exemplary embodiments, the contaminated article is contaminated with a biofilm comprising a plurality of microbial or fungal spores, the exposure time is at least 2 minutes, and the number of colony forming units of the contaminated article is reduced by 6 log orders to 10 log orders relative to the contaminated article. More preferably, the number of colony forming units of the contaminated product is reduced by 7 log to 10 log relative to the contaminated product; 8 log stages to 10 log stages; or even 9 log levels to 10 log levels.

Preferably, the exposure time to achieve a desired level of disinfection of a contaminated article contaminated with a biofilm comprising a plurality of microbial or fungal spores is selected to be at most one hour. More preferably, the exposure time to achieve the desired level of disinfection is no more than 50 minutes, 40 minutes, 30 minutes, 20 minutes, or even 10 minutes. Most preferably, the exposure time selected to achieve the desired level of disinfection is at most 9 minutes, 8 minutes, 7 minutes, 6 minutes, 5 minutes, or as low as 4 minutes, 3 minutes, 2 minutes, or even 1 minute.

The operation of the exemplary embodiments of the present disclosure will be further described with reference to the non-limiting specific examples detailed below. These examples are provided to further illustrate various specific and preferred embodiments and techniques. It should be understood, however, that many variations and modifications may be made while remaining within the scope of the present disclosure.