USOO8425837B2

(12) United States Patent (10) Patent No.: US 8.425,837 B2

Carbone et al. (45) Date of Patent: Apr. 23, 2013

(54) DEVICE AND METHOD FOR GAS 5,650.442 A 7/1997 Mitchell et al.
STERILIZATION 5,665,077 A 9, 1997 Rosen et al.
5,683,668 A 11/1997 Hrabie et al.
(75) Inventors: Phil Carbone, North Reading, MA 35 A 28, R al al.
(US); Karen Benedek, Winchester, MA 5,718,892 A 2, 1998 Keeferet al.
(US); Michael O. Ruffo, Medford, MA 5,785,934. A 7/1998 Jacobs et al.
(US); Wade Luongo, Saugus, MA (US) 5,814,666 A
5,840,759 A
9, 1998 Green
11/1998 Mitchell et al.
(73) Assignee: Noxilizer, Inc., Baltimore, MD (US) 5,910,316 A 6/1999 Keefer et al.
(Continued)
(*) Notice: Subject to any disclaimer, the term of this FOREIGN PATENT DOCUMENTS
patent is extended or adjusted under 35 CA 2208754 C 12/2007
U.S.C. 154(b) by 369 days. CA 2582887 12/2007
(21) Appl. No.: 12/710,053 (Continued)
(22) Filed: Feb. 22, 2010 OTHER PUBLICATIONS
O O International Preliminary Report on Patentability mailed Sep. 1,
(65) Prior Publication Data 2011, for PCT/US2010/024925.
US 2011 FOO85938A1 Apr. 14, 2011 (Continued)
Related U.S. Application Data Primary Examiner — Sean E Conley
(60) Provisional application No. 61/154,625, filed on Feb. (74) Attorney, Agent, or Firm — Pillsbury Winthrop Shaw
23, 2009. Pittman, LLP
(51) Int. Cl. (57) ABSTRACT
A6IL 2/20 (2006.01) - -
(52) U.S. Cl A system for gas sterilization includes a sterilization cham
USPG 422/28: 422/33 ber, a source of sterilant gas, and a sterilant gas remediation
... T. grgrrr. s mechanism. Embodiments relate to systems and methods for
(58) Field of Classification Search .................... 2. delivering humidified air to a sterilization chamber, systems
S lication file f 1 hhi and methods for removing gaseous NO from an exhaust gas
ee application file for complete search history. stream of a sterilization chamber, systems and methods for
(56) References Cited removing and replacing a source of sterilant gas, an exhaust
gas scrubber and/or supplies for a humidification system.
U.S. PATENT DOCUMENTS Some embodiments relate to hardware and software for user
5,212.204 A 5, 1993 Keefer et al.
interface in a sterilizing device and hardware and software for
5,236,609 A 8, 1993 Smith control of a sterilization cycle. Some embodiments relate to
5,519,020 A 5, 1996 Smith et al. chamber, chassis and door configurations of a sterilizer.
5,632,981 A 5, 1997 Saavedra et al.
5,633,424 A 5, 1997 Graves 9 Claims, 8 Drawing Sheets

12
 US 8,425,837 B2
Page 2

U.S. PATENT DOCUMENTS EP 1704877 A1 9, 2006

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2009.0035350 A1 2/2009 Stankus

2009/0041845 A1 2/2009 Kleiner European Office Action issued in corresponding European Applica
FOREIGN PATENT DOCUMENTS tion No. 10705518.8, dated Nov. 21, 2011, 4 pages.
Ellies et al., “Crystallographic structure and Surface morphology of
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Page 3

Enomoto et al., “Inactivation of food microorganisms by high-pres Sharpless et al., “Impact of hydrogen peroxide on nitrite formation
Sure carbon dioxide treatment with or without explosive decompres during UV disinfections.” Water Res., 2003, 37(19):4730-6.
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disinfection.” Environ Sci. Technol., 2001, 35(14):2949-55. * cited by examiner
U.S. Patent Apr. 23, 2013 Sheet 1 of 8 US 8.425,837 B2
U.S. Patent Apr. 23, 2013 Sheet 2 of 8 US 8.425,837 B2
U.S. Patent Apr. 23, 2013 Sheet 3 of 8 US 8.425,837 B2
U.S. Patent Apr. 23, 2013 Sheet 4 of 8 US 8.425,837 B2
U.S. Patent Apr. 23, 2013 Sheet 5 of 8 US 8.425,837 B2

s
U.S. Patent Apr. 23, 2013 Sheet 6 of 8 US 8.425,837 B2

250 ENTERANTENANCE
CODE PLACENEW 270
CARTRIDGEN
SCRIBBERANDRE RECHECK
252 CONNECT, INSTALL INSTALATION OF
CORRECT CODE NEW SERVICETAG N0, CYLNDER
ENTERED YES
SNEW
YES SERVICETAG NOLEAK
INPACE DETECTED)
CLCSEWALVE
ONCY INDER
INSTANEWNO)
CYNDERAND
SEANSTA NEW
SERVICEFAG
SNEW
SERVICETAG
INPACE

OPENSUPPLY
VALEONNO
BOTTLE
260 PURGE
SEQUENCE
COMPETE
NOLEAKS
DETECTED)
SWITCHWACUU
262NEWIEEE
CYLNDER y
STORAGE AREA CLOSEDOORTO
264 STORAGE is:
NEWSERVICEA
AREANEGATIVE
PRESSURE

266 DISCONNECTAND
REVOVECYLINDER
AND SEAL
PRECYCLE
DISCONNECTAND COMPLETED
268 REMOVE USED
SCRUBBER YES
CARTRIDGE
SERVICECOMPLETE

FIG. 7
U.S. Patent Apr. 23, 2013 Sheet 7 of 8 US 8.425,837 B2

SURVIVORCURVES FOR NOAND NO2

OE-07 0 0.10% NO
1.OE-06 0.25% NO

1.
1.OE-05 to 0.10% NO2
g EB 0.25% NO2
t 10E-4
2 1.OE-03
m- o (0.10%
0.10% NONO)
Wr

S 10E-O2
-EXPON. (0.25% NO)
3 -EXPON. (0.10% NO2)
1.OE-0 -EXPON. (0.25% NO2)
OE+OO
-1 0 1 2 3 4 5 6 7 8 9 10 1 12 13 14 15 16 17 1819 20
TIME (MIN)

FIG. 8
U.S. Patent Apr. 23, 2013 Sheet 8 of 8 US 8.425,837 B2

D-WALUEWS. NO2 CONCENTRATION

EXPOSURE TIME 1.5 MIN.
1.OOE+06 (S
1.OOE-05
1.OOE-04 0 BALT, 0.01.09
1.OOE-03 X STUMBO MURPHY COCHRAN
1.OOE-02 -EXPON. (BALT, 01.01.09)
OOE+O1
cd OOE OO
- OOE-01
10OE-02
10OE-03
OOE-04
NO2CONC. (mg/l)
FIG. 9
 US 8,425,837 B2
1. 2
DEVICE AND METHOD FOR GAS Another aspect of the invention relates to a method for
STERILIZATION delivering gaseous NO to a sterilization chamber containing
one or more objects to be sterilized.
This application claims the benefit of U.S. Provisional Yet another aspect of the invention relates to a system
Application 61/154,625, filed Feb. 23, 2009, the contents of 5 configured to control the foregoing device or, method includ
which are incorporated by reference herein in their entirety. ing controlling one or more of sterilant gas concentration,
humidity, temperature, gas circulation, total or partial gas
FIELD OF THE INVENTION pressure and/or duration of exposure of the object or objects
to be sterilized.
10 Aspects of embodiments of the invention relate to machine
The invention relates generally to systems and methods for
sterilization using oxides of nitrogen. More particularly, it executable code embodied on a machine readable medium
relates to systems and methods for delivering gaseous NO to which, when executed, performs methods as described
a sterilization chamber containing one or more objects to be herein.
sterilized. Embodiments relate to systems and methods for These and other objects, features, and characteristics of the
15 present invention, as well as the methods of operation and
delivering humidified air to a sterilization chamber, systems functions of the related elements of structure and the combi
and methods for removing gaseous NO from an exhaust gas nation of parts and economies of manufacture, will become
stream of a sterilization chamber, systems and methods for more apparent upon consideration of the following descrip
removing and replacing a source of sterilant gas, an exhaust tion and the appended claims with reference to the accompa
gas scrubber and/or supplies for a humidification system. nying drawings, all of which form a part of this specification,
Embodiments relate to hardware and software for user inter
wherein like reference numerals designate corresponding
face in a sterilizing device and hardware and Software for parts in the various figures. It is to be expressly understood,
control of a sterilization cycle. Embodiments relate to cham however, that the drawings are for the purpose of illustration
ber, chassis and door configurations of a sterilizer, including and description only and are not intended as a definition of the
ornamental aspects thereof. 25 limits of the invention. As used in the specification and in the
DESCRIPTION OF THE RELATED ART
claims, the singular form of “a”, “an', and “the' include
plural referents unless the context clearly dictates otherwise.
Sterilization methods are known that rely on chemicals, BRIEF DESCRIPTION OF THE DRAWINGS
pressure and temperature to eliminate biological contami 30
nants such as bacteria, spores and fungi from a variety of FIGS. 1a and 1b are perspective views of a system for
Substrates including medical devices, medical compounds sterilization inaccordance with an embodiment of the present
and others. Alternately, radiation-based treatments may be invention;
used, avoiding some types of damage to the object to be FIG. 2 is a schematic diagram showing functional inter
sterilized that can result from heat and pressure. In another 35 connections for a system for sterilization in accordance with
approach, ethylene oxide, oZone and peroxide gas steriliza an embodiment of the present invention;
tion techniques have been used. FIG. 3 is a schematic diagram showing functional inter
In particular, pharmaceutical formulations may have a connections for a sterilant gas delivery Subsystem in accor
great deal of sensitivity to damage from heat and pressure, dance with an embodiment of the present invention;
leaving radiation as an option for Sterilization of these com 40 FIG. 4a is a front cutaway view of a sterilization chamber
pounds. However, radiation having appropriate energies and in accordance with an embodiment of the present invention;
penetration characteristics for sterilization may also have the FIG. 4b is a side cutaway view of a sterilization chamber in
effect of damaging the pharmaceutical, Substrate and/or accordance with an embodiment of the present invention;
delivery substrate itself. Likewise, shape memory materials FIG. 5 is an illustration of a Collison nebulizer for use in a
are susceptible to heat related phase transitions that may be 45 humidification Subsystem of a sterilizer in accordance with an
addressed using methods in accordance with embodiments of embodiment of the present invention;
the present invention. FIG. 6 is an illustration of a scrubber for removing sterilant
gas from an exhaust of a sterilizer in accordance with an
SUMMARY OF THE INVENTION embodiment of the present invention;
50 FIG. 7 is a flowchart illustrating a procedure for replace
One aspect of the invention relates to a device for deliver ment of consumables in accordance with an embodiment of
ing gaseous NO to a sterilization chamber containing one or the present invention; and
more objects to be sterilized. The device includes a steriliza FIGS. 8 and 9 are charts illustrating results using varying
tion chamber, a Source of sterilant gas, and a sterilant gas concentrations of sterilant gas in accordance with embodi
remediation mechanism. 55 ments of the present invention.
Aspects of embodiments relate to systems and methods for
delivering humidified air to a sterilization chamber, systems DETAILED DESCRIPTION
and methods for removing gaseous NO from an exhaust gas
stream of a sterilization chamber, systems and methods for In view of the issues raised with heat and radiation steril
removing and replacing a source of sterilant gas, an exhaust 60 ization approaches, the inventors have determined that gas
gas scrubber and/or Supplies for a humidification system. sterilization techniques based on oxides of nitrogen may pro
Aspects of embodiments relate to hardware and software vide good sterilization while mitigating damage to the steril
for user interface in a sterilizing device and hardware and ized substrate. In particular, the inventors have shown that
software for control of a sterilization cycle. nitrogen dioxide (NO) is an effective sterilization agent for a
Aspects of embodiments relate to chamber, chassis and 65 variety of biological targets.
door configurations of a sterilizer, including ornamental In an embodiment, a low concentration (<21 mg/L) of
aspects thereof. nitrogen dioxide gas in the presence of air and water vapor is
 US 8,425,837 B2
3 4
delivered to a sterilization chamber. In particular embodi stream such that the air delivered to the sterilizer, and in
ments, concentrations of between about 5 and 15 mg/L, and particular to the humidification system, is substantially
preferably between about 8 and 11 mg/L are used. Lower pathogen free. As will be appreciated, other sources of air
concentrations than 5 mg/L may be used, but as concentration may be substituted. For example, air may be provided by air
is reduced, dwell time should be extended. As described in tanks or a fixed air Supply system that provides pressurized air
greater detail below, the process may be performed at or near to the room in which the sterilizer is housed.
room temperature and entails evacuating air from the cham As shown, the air is supplied from the compressor 102 to an
ber, introducing the sterilant gas, and adding humidified air to accumulator 108 via a control valve 110. In the illustrated
a selected pressure. Depending on the physical characteristics embodiment, pressure in the accumulator 108 is controlled
and/or packaging of the item to be sterilized, the sequence of 10 via a feedback loop to the control valve 110 using a pressure
vacuum->sterilant injection->humid air injection, may be gage 112. Manual valves 114, 116 are optionally provided to
repeated several times or the sequence changed. Furthermore, allow pressure relief and water drain from the accumulator
additional sequence steps of dry air injection and dwell may 108 respectively. A water separator 109 may be included to
be included in one or all iterations of the sterilizing sequence. ensure that liquid water does not enter the air stream on the
At the ordinary operating temperatures and pressures of the 15 downstream side of the accumulator.
process, the NO remains in the gas phase and acts as an ideal Nitrogen dioxide is provided to the system from a liquid
gas. The cycle may include a check for water or humidity supply tank 118. A manual valve 120 and a valve 122 control
levels, and should the levels be above a threshold, a drying flow from the supply tank 118. A pressure gage 124 allows
sequence may be engaged. Drying may include heating of the monitoring of pressure in the lines and a pair of Solenoid
chamber, evacuating the chamber to pressures below the valves 126,128 control flow into a pre-chamber 130. Another
vapor pressure of water at the temperature of the chamber, pair of valves 132,134 control flow from the pre-chamber 130
and/or passing dry gas such as dry air or a dry inert gas to the sterilization chamber 136. Though illustrated in FIG.2
through the chamber. as a simple pipe connection, the flow into the chamber 136
An embodiment of a sterilizer that uses NO Sterilizing gas may alternately be provided using a manifold, allowing for
is illustrated generally in FIGS. 1a and 1b. The sterilizer 10 25 improved distribution of the sterilant gas within the chamber.
includes a housing 12. While the illustrated embodiment involves only transport of
In an embodiment, the housing 12 is sized such that a gaseous NO, it is envisioned that liquid NO could flow to
handle 14 for a door 16 for the sterilizing chamber 18 is at a the pre-chamber prior to vaporization. More detail of the
height Suited to use by an average standing user, for example, operation of the NO delivery sub-system is discussed below.
about 42". The overall height of such a system may be about 30 A sub-system for providing humidity to the sterilization
5 feet and the width, approximately 20". As shown, the hous chamber 136 begins with a Collison nebulizer 138 that pro
ing 12 may optionally be supported on a set of wheels 20, to duces aerosolized water in air to be provided to the steriliza
allow for easy portability of the sterilizer 10. tion chamber 136. The air for this process is provided by the
A second door 22 is located in a lower portion of the accumulator 108, similarly to the air used in the pre-chamber
housing 12 and allows access to serviceable portions of the 35 130. Water for humidification is stored in the reservoir 140,
sterilizer10. In particular, consumables may be stored in the and a solenoid valve 142 controls water flow from the reser
service area 24. In the embodiment shown, a sterilant gas voir 140 into the nebulizer 138. A level sensor 144 monitors
module 26 and a scrubber 28 are located in the service area, the water level in the nebulizer 138 and controls the opening
along with a reservoir 30 for storing water to be used by a of the solenoid valve 142. As the pressurized air enters the
humidification system, as described below. The sterilant gas 40 nebulizer, it generates a Sonic Velocity air jet in water held in
module includes a door 32 having a hinge 34 allowing it to be the nebulizer. The air jet aspirates the water, forming small
opened for access to replace a sterilant gas source (not droplets which then vaporize. A water separator 146 prevents
shown), as described in greater detail below. liquid water from entering the sterilization chamber 136
In an embodiment, the housing 12 may include an addi while allowing the humid air to pass through. An air vent 148
tional door (not shown) for accessing the sterilizing chamber 45 provides a vent pathway from the nebulizer allowing the
18, allowing for pass-through operation of the sterilizer 10. water to flow from the reservoir 140 to the nebulizer 138.
As an example, such a pass-through device may be mounted Suitable valves control the entry of the humidified air to the
into a wall opening between a clean room or a sterile area and sterilization chamber 136.
an area having less or no control over air quality, sterility or As illustrated, the sterilization chamber 136 includes
particle load. Such a device may find application, for 50 access via a set of valves 150 so that samples of the chamber
example, in a medical device manufacturing plant, in a phar atmosphere may be taken and analyzed. Analysis may be, for
maceutical plant, in product flow in a hospital sterile process example, by an FTIR, UV spectrophotometric, or other
ing department, or a controlled sterile laboratory. appropriate spectrometry system, not shown. Access for
FIG.2. is a schematic process and instrumentation diagram analysis has particular relevance to a test platform, and may
of an embodiment of a sterilizer 100 in accordance with the 55 be unnecessary in practice when the sterilizer is used in a
present invention. Note that while specific diameters are pro production environment.
vided for certain of the flow paths, these should not be taken The sterilization chamber 136 may include a fan 152 that
as limiting in any way, but are subject to variation in accor helps to circulate gases in the chamber. Circulation helps to
dance with specific applications. A first portion of the steril ensure both that the sterilant gas is well mixed with the
izer 100 is a source of air to be added to the nitrogen dioxide 60 humidified air, and that objects to be sterilized are well
gas in the chamber. A compressor 102 compresses air from exposed to the sterilant gas.
the ambient environment. Prior to compression, the ambient A pressure gage 154 and pressure relief valve 156 may be
airpasses through a muffler 104 and a filter 106. The filter 106 provided to control pressures in the sterilization chamber 136.
reduces dust and other particulate impurities that are gener As will be appreciated, in the case that exhaust from the
ally undesirable both for the compressor and the downstream 65 pressure relief pathway contains nitrogen dioxide, it should
use of the compressed air. Furthermore, the filter 106 may be controlled or processed to avoid contamination of the work
advantageously be designed to remove microbes from the air aca.
 US 8,425,837 B2
5 6
The primary exhaust pathway proceeds through a solenoid out any calculating steps. Thus, when a pressure threshold is
valve 158 to a scrubber 160, designed to eliminate and/or reached in the pre-chamber, the appropriate dose is present
capture nitrogen dioxide before the exhaust reaches the envi and the connection between the Source and the pre-chamber
ronment. A filter 162 removes particulates from the exhaust. may be closed. In an embodiment, there may be a table of
Pump 164 pushes scrubbed exhaust out of the system. 5 pressure set points, for example, stored in memory accessible
Another pump 166 provides a flow through an NO sensor to the controller, that correspond to desired dosages. In
168 for monitoring NO content of the exhaust gases. Should another embodiment, there may be a curve stored in memory
the NO levels exceed a selected threshold, solenoid valve accessible to the controller that associates dose with pressure
158 can be closed to ensure that NO, is not released into the set points. In either approach, the measured pressure during a
environment. As will be appreciated, the order between the 10 filling operation may be compared to the set point pressure
pump 166 and the sensor 168 may be reversed, allowing for derived from either the table or the curve. Where temperature
sensing prior to the control valve rather than after. is more variable, adjustments may be made based on a mea
FIG. 3 illustrates an embodiment of a sterilant delivery Sured temperature, and those adjustments may be calculated,
system similar in configuration to the sterilant delivery Sub or derived from a table or curve stored in a memory.
system of FIG. 2. A tank 118 containing liquid NO acts as the 15 As will also be appreciated, it is possible for other species
source of sterilant gas. A manual valve 120 provides a flow of of nitrogen oxides to form in the pre-chamber. As a result, it
gas from the tank 118. A manual valve 122 provides a sec may be useful to account for partial pressures of various
ondary control over flow from the tank. A pair of solenoid species in calculating the total deliverable dose of sterilant
valves 126, 128 are actuatable to allow flow from the valve to gas. The inventors have determined that the primary species
the sterilizing system. As illustrated, there are four separate present at the pressures observed is the dimer N.O. Because
valves that ultimately control flow from the tank 118. As will partial pressures of oxides of nitrogen in the (generally much
be appreciated, other valve arrangements are possible, and larger) sterilization chamber 136 are substantially lower than
redundancy may be reduced or eliminated, as desired. in the pre-chamber 130, the dimerization ofNO, is less preva
During use, sterilant gas is allowed to flow from the final lent and partial pressures remain at a low level and are not
solenoid valve 128 into a pre-chamber 130, where it expands 25 generally important. That is, the total mass of the NO and
and the dosage may be measured. As shown, the pre-chamber NO is generally available as NO in the sterilization cham
130 includes a pressure transducer 180 that allows measure ber 136.
ment of a total pressure which may be translated into dosage, After the pre-chamber 130 is pressurized, the valves 126
given appropriate knowledge of the size of the chamber and and 128 are closed, isolating the pre-chamber 130 from the
optionally, temperature data derived from a temperature sen 30 gas source. Valve 132 is opened, allowing the gas from the
sor, not shown. A solenoid valve 132 controls flow into the pre-chamber 130 to pass into the sterilizing chamber 136.
sterilizing chamber 136. An additional solenoid valve 182 Valve 182 is opened to allow dry air to enter into the steriliz
controls flow of dry air into the pre-chamber. ing chamber 136, and to push any remaining sterilant gas out
In one method of operating the illustrated embodiment, the of the pre-chamber 130 and into the sterilizing chamber 136.
chamber 136 and pre-chamber 130 are initially at low pres 35 Finally, valves 182 and 132 are closed, isolating the steriliz
Sure, for example, they may be evacuated using appropriate ing chamber from the other portions of the system.
vacuum pumps (for example, the pump 164 in the exhaust In an embodiment, the additional chamber, which may be
pathway illustrated in FIG. 2). In an embodiment, an evacu the pre-chamber, oran additional chamber, is used to circulate
ation cycle is repeated prior to injection of the sterilant gas. As the sterilizing gas into and out of the sterilizing chamber. For
an example, the chambers may be evacuated, re-filled with 40 example, a pre-chamber or co-chamber of sufficient size may
air, and then evacuated again prior to initiating the sterilant be used for recycling the sterilizing atmosphere. In this case,
gas Sequence. the sterilization cycle may be initiated in the manner
In order to begin delivery of sterilant gas, valve 128 is described with respect to the other embodiments. The pre
closed and 132 is opened, while valve 182 is held closed, chamber or co-chamber can be opened to the sterilizing
equalizing the pressure in the chamber 136 and pre-chamber 45 chamber, via a circuit that may include a pump for driving the
130 at a low pressure. Valve 132 is closed, isolating the gas from the sterilizing chamber to the alternative chamber
pre-chamber 130 from the sterilizing chamber 136. Valves Volume. Then, the gas can be re-introduced to the sterilizing
126 and 128 are then opened (valve 122 and manual valve 120 chamber. This re-introduction may occur one time, more than
having been already opened) and gas that has boiled off of the one time, or the gases may be continuously transferred from
liquid NO supply is allowed to enter the pre-chamber 130. 50 one chamber to the other. Each cycle may be the same as other
The pressure transducer 180 may be used in a feedback cycles, or each cycle may have different parameters includ
arrangement to control solenoid valve 126 such that a selected ing, for example, longer or shorter dwell times, greater or
total amount of NO is collected in the pre-chamber 130. lesser concentrations of sterilant gas, and higher or lower
As will be appreciated, if volume of the pre-chamber 130, pressures. The inventors have determined that repeated expo
pressure and temperature are known, for example via mea 55 sure cycles may be more effective for sterilization than a
Surements using the pressure transducer 180 and a tempera longer dwell, single exposure cycle. The removal and re
ture gage (not shown), the total amount of NO in the pre introduction of the sterilant gas may achieve the same ends as
chamber 130 may be calculated. By way of example, an would entirely cycling out the gas and cycling in new sterilant
operating pressure of 10-20 inHg may be generated in order to gas during repeated exposure cycles.
provide an approximately 0.5 gram dose of sterilant to a 60 The concentration of sterilant or the humidity of the gases
sterilization chamber 136 having a volume of about 60 liters. being transferred between the two chambers may be adjusted
In this approach, a concentration of about 10 mg/L of sterilant to maintain lethal exposure conditions. In particular, upon
gas is produced in the sterilization chamber 136. depressurization and re-pressurization of the gas in the cham
For a particular device in a particular setting, because the ber, it would be expected that humidity changes would occur.
Volume of the chamber does not change, and temperatures 65 As will be appreciated, other configurations and methods
will not fluctuate significantly, the process of preparing a dose may be used to provide the sterilant gas to the Sterilizing
may be controlled with pressure measurements alone, with chamber 136. For example, a gas source may be used in place
 US 8,425,837 B2
7 8
of the liquid source. The source may be a single use source, or In an alternate embodiment, water vapor may be directly
multiple use source as shown. Other Valving arrangements added to the Sterilization chamber. In another approach, the
and control sequences may replace those described herein. nebulizer may be replaced with a humidifier of another
Liquid or solid source material may be provided directly to design, Such as evaporative, steam, impeller or ultrasonic
the sterilizing chamber 136, without first being converted to a humidifiers. Finally, it is feasible to provide liquid water or
gas. As an example, a material that is known to produce NO water carried by a Substrate (such as a moist Sponge, towel or
(which may be converted to NO, in use) is described in U.S. other absorptive material) directly to the sterilization cham
patent application Ser. No. 11/052,745, filed Sep. 15, 2005, ber in order to provide humidity.
and herein incorporated by reference in its entirety. Likewise, Because relative humidity is dependent in part on tempera
gas may be delivered at varying concentrations to the cham 10 ture, it may be useful to use temperature data to determine an
ber. That is, while the described method provides a high amount of humidified air necessary to achieve a target humid
concentration sterilant gas to the chamber, there may be ity level in the chamber. In this regard, a temperature sensor,
greater or lesser degrees of mixing with air prior to delivery. not shown, may be provided in the sterilization chamber.
As described above, the exhaust pathway includes a scrub
In an embodiment, a non-reactive gas orgas mixture rather 15 ber 160 for removing sterilant gas from the exhaust stream,
than dry air is added to dilute the sterilant gas. For example, prior to venting to the exterior of the system. The scrubber
N gas may be used in place of air. In this approach, the Nagas 160 may be, for example, embodied in a cartridge filter type
may be used dry, humidified prior to adding to the steriliza of device as illustrated in FIG. 6. A cartridge of this type may
tion chamber 136, or may alternately be humidified in the be placed in-line in the exhaust pathway, such that gases
sterilization chamber 136, as with the embodiments using air. pulled out of the sterilization chamber 136 via the pump 164
FIGS. 4a and 4b illustrate an embodiment of a sterilization will pass through the cartridge.
chamber 136 in greater detail. In an embodiment, the steril In an embodiment, the cartridge is a cylinder having an
ization chamber 136 has a perfluoroalkoxy (PFA) coating on outer sleeve area where the gas to be treated enters. Perfora
its interior Surface. Because PFA coatings may be manufac tions in an inner sleeve allow the gas to flow through to the
tured to be non-porous and/or hydrophobic, heterogeneous 25 treating medium, thence to an outlet to the exhaust pathway.
liquid formation on Surfaces of the chamber may be reduced. The medium is selected to convert the reactive oxides of
Such reduction of liquid water formation may help to control nitrogen into non-reactive products or otherwise neutralize
humidity within the chamber, for example by ensuring that any hazard associated with the sterilant gas. The scrubber
humidity added to the sterilant atmosphere in the chamber material may be provided in granular form, Smaller granules
remains vaporized as a component of the atmosphere. Fur 30 providing a greater Surface area per unit volume of scrubbing
thermore, such a Smooth Surface can facilitate cleaning and material. In an embodiment, a sodium permanganate material
maintenance of a sterile environment within the chamber. As has been found to be suitable for oxidation of NO, to nitrate
will be appreciated, other materials having similar properties (i.e., NO to NO, and NO, to NO). In particular, granular
may be substituted, for example, stainless steel. Pura?il SP (14x28 mesh), a sodium permanganate including
As seen in FIG. 4a, the sterilization chamber 136 may 35 activated alumina has been found to be suitable. Once oxi
include a rack 200 for holding objects during sterilization. In dized, the nitrate bonds with sodium to form a solid salt which
the embodiment as shown, the rack 200 is slidably mounted is substantially non-toxic, non-corrosive, non-reactive and
on a pair of rails 202 for ease of access. A port 204 connects does not readily ignite. In an embodiment, the cartridge may
to the exhaust pathway and the scrubber 160, as shown in FIG. include a few kilograms of sodium permanganate at a density
2. 40 of about 50 lb/ft to provide up to about one month of scrub
Optionally, a motor 206 is operatively engaged with a fan bing capacity at typical usage rates. In embodiments, the
208 that may be driven to improve mixing and circulation exhaust gas may be considered to be remediated when NO.
within the sterilization chamber 160. A baffle 210 is posi levels are reduced below applicable safety standards, and
tioned in an upper region of the chamber. The baffle may be particularly, when reduced below about 5 ppm and more
configured and arranged to ensure that the fan does not 45 particularly, when reduced below about 1 ppm. In embodi
directly blow on objects being sterilized and also to assist in ments where the gas is exhausted directly outdoors, a higher
creating airflows that ensure good circulation of gases level of NO may be acceptable, and levels of 10 ppm may be
through the chamber. In particular, when used with a gener considered to be sufficiently remediated.
ally cylindrical chamber, the illustrated baffle, having open In an embodiment, the exhaust cycle may include a series
ings along upper sides of the chamber, will tend to create 50 of evacuations of the Sterilization chamber. In this approach,
airflows circulating along outer regions of the chamber, and the pressure in the sterilization chamber is reduced, for
returning along a central region. The arrow in FIG. 4a illus example, by 90%, exhausting all but 10% of the sterilant gas.
trates an example of such a flow circulating through the cham Next, a charge of air or other diluent gas is added to the
ber along a path originating at an edge of the baffle and chamber, and the exhausting is repeated. As will be appreci
continuing along the Surface of the cylinder and returning up 55 ated, each cycle reduces the amount of sterilant gas by 90%,
the center of the chamber. so that after three cycles, only 0.1% remains in the chamber.
In an embodiment, humidity is added to the sterilization This may be repeated as many times as necessary to render the
chamber 136 by way of a Collison nebulizer 138 as shown in interior of the chamber safe. For higher percentages of
FIG. 2. FIG. 5 is an illustration of a Collison nebulizer of a exhaust (e.g., 99%), fewer repetitions are needed while for
type that may be suitable for use in a system in accordance 60 lower percentages, more repetitions will be needed (e.g.,
with the present invention. In operation, the Collison nebu 80%) to reach a selected threshold. Using this approach, the
lizer is attached to a source of compressed air. As illustrated in exhaust cycle can be controlled based on pressure measure
FIG. 2, this may be an alternate path from the accumulator ments, and the interior NO levels may be known without
108. As will be appreciated, alternately a separate air source requiring additional NO monitoring equipment in the cham
may be employed. The nebulizer may include a fill adaptor 65 ber or at the outlet of the chamber.
that allows it to be continuously refilled from the reservoir 30 In an embodiment, replacement of the liquid NO bottle is
during use. controlled to improve safety. Interlocks may be provided to
 US 8,425,837 B2
10
restrict removal until all supply valves are closed and a purge What is claimed is:
sequence is performed. Optionally, the exhaust pump may be 1. A method of sterilizing an object comprising, in the
held on during cylinder disconnect to ensure that any remain following order:
ing sterilant gas is vented through the scrubber and exhaust depressurizing a pre-chamber in controllable fluid commu
pathway rather than backflowing through the inputside of the 5 nication with a liquid nitrogen dioxide supply:
system. Similar interlocking may be implemented to prevent allowing a controlled dose of nitrogen dioxide from the
removal/replacement of the scrubber when sterilant gas is liquid nitrogen dioxide supply to flow into the pre-cham
present in the lines. ber;
FIG. 7 is a flowchart illustrating an embodiment of a
replacement procedure for consumable elements of the 10 isolating Supply:
the pre-chamber from the liquid nitrogen dioxide
device. Inputs and outputs of this procedure may be, for opening a fluid communication channel between the pre
example, displayed on the graphical user interface described chamber and a depressurized sterilization chamber con
above or using other display and input devices. taining the object, and
The procedure begins as a maintenance code is entered exposing the object to the nitrogen dioxide in a gaseous
250, and checked 252. In response to the correct code, the 15
state for a selected duration, at a selected pressure and in
cylinder valve is closed 254 and checked 256. Once closed, a a selected concentration.
purge sequence is run 258. Upon a determination 260 that the
purge sequence is complete, a vacuum is activated 262 to ing2.the A method as in claim 1, further comprising, after open
fluid communication channel, providing pressurized
draw air from the cylinder storage area. When negative pres gas to the
Sure is detected in the storage area 264, the user may discon portion of pre-chamber, such that the pressurized gas and a
nect and remove the cylinder and seal 266. The scrubber pre-chamber flow into thenitrogen
an amount of dioxide remaining in the
sterilization chamber.
cartridge may also be removed 268 at this time. The user then
installs a new cartridge and corresponding service tag 270 and trolled3. A method as in claim 1, wherein the allowing a con
a new gas cylinder and seal 272. Once installed, the new bottle dioxide dose of nitrogen dioxide from the liquid nitrogen
supply to flow into the pre-chamber further com
is opened 274 and a leak check is performed 276. The service 25 prises:
door is closed 278 and a new service tag is installed. Note that measuring a pressure in the pre-chamber; and
though this procedure describes replacing both serviceable
items at once, they may likewise be replaced independently when the measured pressure reaches a threshold selected to
within the scope of the invention. provide a dose selected to achieve the selected concen
Control of the device may be implemented using a graphi 30 tration, isolating the pre-chamber from the liquid nitro
cal user interface. The graphical user interface can include, gen dioxide supply.
for example, controls for run parameters (e.g., dosage/con temperature4. A method as in claim3, further comprising measuring a
centration of sterilant gas, pressure limits, cycles, dwell adjusted based of the pre-chamber and wherein the threshold is
times, target pressures, etc.), readouts of metrology devices on the measured temperature.
(e.g., timers, thermometers, pressure transducers, etc.) and nitrogen dioxideasgasin isclaim
35 5. A method 1, wherein the concentration of
between about 5 mg/L and about 15
controls or status outputs for various of the valves and com mg/L.
pressors of the system. System warnings (e.g., interlock
6. A method as in claim 1, wherein the exposing further
warnings) can also be displayed via the graphical user inter comprises:
face. Alternately, the entire process may be automated such
that no user input is required and the user interface may 40 exposing the object a first time to the nitrogen dioxide for
a first selected duration, at a first selected pressure and in
simply be replaced by a display or other status indicators.
In an embodiment, in addition to an automated sterilization a first selected concentration;
cycle, the entire process including inserting and removing the after the first exposing, removing the nitrogen dioxide from
object to be sterilized may be automated. In this approach, a the sterilization chamber; and
robotic handler is provided that can convey the object to be 45 exposing the object a second time to the nitrogen dioxide
sterilized into the chamber, and remove it upon completion of for a second selected duration, at a second selected pres
Sure and in a second selected concentration.
the sterilization cycle. 7. A method as in claim 6, wherein the first selected time,
Although the invention has been described in detail for the
purpose of illustration based on what is currently considered pressure and concentration are the same as the second
to be the most practical and preferred embodiments, it is to be 50 8. A methodpressure
Selected time, and concentration.
understood that such detail is solely for that purpose and that evacuating the assterilization
in claim 6, wherein the removing comprises
the invention is not limited to the disclosed embodiments, but, the exposing a second time chamber into a co-chamber and
comprises allowing contents of
on the contrary, is intended to cover modifications and the co-chamber to flow into the sterilization chamber.
equivalent arrangements that are within the spirit and scope of
the appended claims. For example, it is to be understood that 55 time 9. A method as in claim 8, wherein, the exposing a second
the present invention contemplates that, to the extent pos humidity comprises adding humidity to the chamber to replace
sible, one or more features of any embodiment can be com lost to condensation during the removing.
bined with one or more features of any other embodiment. ck ck ck sk *k