U.S. patent application number 14/818545 was filed with the patent office on 2017-06-22 for devices, systems and methods for zone sterilization.
The applicant listed for this patent is Burkert Contromatic Corp., Burkert Werke GMBH. Invention is credited to Heinz Duemmler, Ray M. Frey, Harm Stratman.
Application Number | 20170173197 14/818545 |
Document ID | / |
Family ID | 58053429 |
Filed Date | 2017-06-22 |
United States Patent
Application |
20170173197 |
Kind Code |
A9 |
Stratman; Harm ; et
al. |
June 22, 2017 |
DEVICES, SYSTEMS AND METHODS FOR ZONE STERILIZATION
Abstract
A gas transfer system including a housing, a pressurized gas
canister held by the housing, a first passageway in fluid
communication with the pressurized gas canister and configured to
supply pressurized pre-sterilization gas from the pressurized gas
canister to a fluid flow component, a gas discharge canister held
by the housing; and a second passageway in fluid communication with
the gas discharge canister and configured to supply
post-sterilization gas from the fluid flow component to the gas
discharge canister. Additional related devices, systems and methods
are provided.
Inventors: |
Stratman; Harm; (Davidson,
NC) ; Duemmler; Heinz; (Indian Trail, NC) ;
Frey; Ray M.; (Fort Mill, SC) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Burkert Contromatic Corp.
Burkert Werke GMBH |
Charlotte
Ingelfingen |
NC |
US
DE |
|
|
Prior
Publication: |
|
Document Identifier |
Publication Date |
|
US 20170035922 A1 |
February 9, 2017 |
|
|
Family ID: |
58053429 |
Appl. No.: |
14/818545 |
Filed: |
August 5, 2015 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
14283814 |
May 21, 2014 |
9125960 |
|
|
14818545 |
|
|
|
|
13623331 |
Sep 20, 2012 |
8992853 |
|
|
14283814 |
|
|
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|
61538124 |
Sep 22, 2011 |
|
|
|
61564898 |
Nov 30, 2011 |
|
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|
61650625 |
May 23, 2012 |
|
|
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61L 2/202 20130101 |
International
Class: |
A61L 2/20 20060101
A61L002/20 |
Claims
1. A method for sterilizing a fluid flow member, comprising:
supplying pressurized ozone gas from a gas transfer device to the
fluid flow member; dispersing the pressurized ozone gas at the
fluid flow member; receiving at the gas transfer device
post-sterilization gas supplied from the fluid flow member; and
detecting the level of ozone in the received post-sterilization
gas.
2. The method of claim 1, further comprising: positioning a gas
dispersion device at the fluid flow member; dispersing the
pressurized ozone gas at the fluid flow component using the gas
dispersion device; and receiving at the gas transfer device
post-sterilization gas supplied from the gas dispersion device.
3. The method of claim 2, wherein the gas dispersion device
comprises: a housing defining a fluid flow path; and a gas flow
member held in the housing, the gas flow member having an upper
portion and a lower portion, the gas flow member comprising a
supply gas passageway extending from the top portion to first and
second gas dispersion openings at the lower portion, the gas flow
member further comprising first and second return gas passageways
extending from the bottom portion to the top portion; wherein the
gas flow member is movable between a sterilization position wherein
the gas flow member lower portion is disposed in the fluid flow
path and a product flow position wherein the lower portion is
withdrawn from the fluid flow path; and wherein positioning a gas
dispersion device at the fluid flow component comprises positioning
the gas dispersion device at the fluid flow component with the gas
flow member in the sterilization position.
4. The method of claim 3, further comprising: determining whether
the fluid flow component has been adequately sterilized based on
the detected level of ozone in the received post-sterilization
gas
5. The method of claim 3, further comprising: moving the gas flow
member to the product flow position; locking the gas flow member in
the product flow position; and flowing material through the fluid
flow path.
6. The method of claim 1, further comprising: determining that the
fluid flow component has been adequately sterilized based on the
detected level of ozone in the received post-sterilization gas; and
halting the supply of pressurized ozone gas from a gas transfer
device to the fluid flow component.
7. The method of claim 4, wherein determining whether the fluid
flow component has been adequately sterilized based on the detected
level of ozone comprises determining whether a Sterility Assurance
Level (SAL) of 10.sup.-6 has been achieved.
8. The method of claim 1, further comprising converting the
received post-sterilization gas to oxygen at the gas transfer
device.
9. A method for sterilizing a zone defined by a fluid flow
component, comprising: supplying pressurized ozone gas from a gas
transfer device to the zone; dispersing the pressurized ozone gas
through the zone; receiving at the gas transfer device
post-sterilization gas from the zone; and detecting the level of
ozone in the received post-sterilization gas.
10. The method of claim 9, further comprising determining whether
the zone has been adequately sterilized based on the detected level
of ozone.
11. The method of claim 9, wherein the zone is defined by a
manifold including a first connection end through which the
pressurized ozone gas is supplied, a second connection end from
which the post-sterilization gas is received at the gas transfer
device, the method further comprising: after determining that the
zone has been adequately sterilized, clamping the manifold at the
first and second connection ends and the capped connection points
to seal the manifold having the sterilized zone.
12. The method of claim 9, wherein the zone is defined by a
discrete device having a first connection end through which the
pressurized ozone gas is supplied and a second connection end from
which the post-sterilization gas is received at the gas transfer
device, the method further comprising: after determining that the
zone has been adequately sterilized, clamping the discrete at the
first and second connection ends to seal the discrete device having
the sterilized zone.
13. A gas transfer system, comprising: a housing; a pressurized gas
canister held by the housing; a first passageway in fluid
communication with the pressurized gas canister and configured to
supply pressurized pre-sterilization gas from the pressurized gas
canister to a fluid flow component; a gas discharge canister held
by the housing; and a second passageway in fluid communication with
the gas discharge canister and configured to supply
post-sterilization gas from the fluid flow component to the gas
discharge canister.
14. The gas transfer system of claim 13, further comprising a
sensor disposed adjacent the second passageway upstream of the gas
discharge canister, the sensor configured to detect a
characteristic of the post-sterilization gas.
Description
RELATED APPLICATIONS
[0001] This is a continuation of U.S. patent application Ser. No.
14/283,814, filed May 21, 2014, which is a continuation-in-part of
U.S. patent application Ser. No. 13/623,331, filed Sep. 20, 2012,
which claims priority to U.S. Provisional Patent Application No.
61/538,124, filed Sep. 22, 2011, to U.S. Provisional Patent
Application No. 61/564,898, filed Nov. 30, 2011, and to U.S.
Provisional Patent Application No. 61/650,625, filed May 23, 2012,
the disclosures of which are incorporated by reference herein in
their entireties.
FIELD OF THE INVENTION
[0002] This invention relates to devices, systems and methods for
sterilization of components, containers and fluid passageways in
fluid flow components.
BACKGROUND
[0003] Today's market demand for new drugs, combined with the
difficult economic climate, is challenging bioprocessors to review
their manufacturing systems and seek ways to make them more
flexible, reliable and cost effective. Increasingly,
biomanufacturers are turning to single-use aseptic processing
systems to meet or beat aggressive product introduction timeframes
while controlling cost.
[0004] In the pharmaceutical fluid drug processing and
manufacturing industry, there is a need for aseptic sterile
conditions in the direct fluid product transfer path to minimize
bacteria contamination, which results in contamination of the
product batches at various stages of production. With the costs to
manufacture a single drug approaching $1 billion and time-to-market
ranging from 8 to 12 years, bioprocess manufacturers need to
minimize all bio-burden contamination risk points in their process.
By introducing a localized non-encumbering sterilization process at
each process connection with optional sterilant level verification,
the contamination risk concerns of bioprocess manufacturers would
be addressed.
[0005] It is known to use localized steam sterilization, and steam
sterilization is approved by the FDA. However, the use of steam
suffers from several drawbacks. First, steam production has
recurring costs. Also, there are thermal safety issues regarding
the handling of steam by floor personnel. Moreover, concerns arise
over the collection, recycling, or reprocessing of steam condensate
after sterilization.
[0006] Ozone sterilization of medical and pharmaceutical devices
has also been approved by the FDA. It is currently used on large
scale batch sterilization of components used in sterile processing.
However, small localized connector or small device "point-of-use"
(POU) and zone ozone sterilization is not known to be in use.
SUMMARY
[0007] Some embodiments of the invention are directed to a portable
gas transfer device for point-of-use sterilization at a
sterilization site. The device includes: a housing; a pressurized
gas canister held by the housing; a first passageway in fluid
communication with the pressurized gas canister and configured to
supply pressurized pre-sterilization gas from the pressurized gas
canister to the site; a gas discharge canister held by the housing;
and a second passageway in fluid communication with the gas
discharge canister and configured to supply post-sterilization gas
from the site to the gas discharge canister.
[0008] In some embodiments, the device includes a sensor disposed
in the second passageway upstream of the gas discharge canister,
the sensor configured to detect a characteristic of the
post-sterilization gas. The device may include at least one
controller configured to receive a detection signal from the sensor
and determine whether the site has been adequately sterilized based
on the received detection signal. The controller may be configured
to determine whether the site has been sterilized to a Sterility
Assurance Level (SAL) of 10.sup.-6. The device may include at least
one indicator on the housing to provide visual feedback that the
site has been adequately sterilized based on a determination that
the site has been adequately sterilized. The device may include a
memory for storing data related to the received detection signal
and/or the determination of whether the site has been adequately
sterilized.
[0009] The pressurized pre-sterilization gas may be ozone. The
detected characteristic may be an ozone level in the
post-sterilization gas and the controller may be configured to
determine whether the site has been adequately sterilized based on
the ozone level over a period of time. The gas discharge canister
may be a gas discharge catalyst canister including a catalyst
material held therein, with the catalyst material configured to
convert waste ozone in the post-sterilization gas to oxygen. The
catalyst material may comprise manganese dioxide/copper oxide,
activated charcoal or a molecular sieve. The device may include a
vent on the housing for the expulsion of oxygen from the gas
discharge catalyst canister.
[0010] In some embodiments, the device includes a gas fill port
valve on the housing, with the gas fill port valve configured to
receive pressurized gas from a recharging station to refill the
pressurized gas canister. In some embodiments, the device includes
an electrical interface on the housing, with the electrical
interface configured to connect with an electrical connection to:
recharge a battery pack of the portable gas transfer device; and/or
transfer data to a database, including sterilization validation
data.
[0011] Other embodiments of the invention are directed to a gas
dispersion device. The device includes a housing and a gas flow
member held in the housing. The housing defines a fluid flow path
along an axis. The fluid flow path has first and second opposite
ends. Each of the first and second ends is configured to
operatively connect with at least one flow component. The gas flow
member has an upper portion and a lower portion. The gas flow
member includes a supply gas passageway extending from a gas supply
port at the upper portion to first and second gas dispersion
openings at the bottom portion. The gas flow member further
includes first and second return gas passageways, with each return
gas passageway extending from a return gas opening at the bottom
portion to a return discharge port at the upper portion. The gas
flow member is positionable in a sterilization position with the
gas flow member lower portion disposed in the fluid flow path. In
the sterilization position, the gas dispersion openings are
configured to disperse pressurized pre-sterilization gas received
from the gas supply port to sterilize flow components operatively
connected with the first and second ends of the fluid flow path. In
the sterilization position, the return gas discharge ports are
configured to discharge post-sterilization gas received from the
return gas openings. The gas dispersion device may be single-use
disposable.
[0012] In some embodiments, the fluid flow path comprises a chamber
and a pair of conduits extending away from the chamber, with each
conduit including a flange at a distal end thereof, with the
flanges defining the first and second ends of the fluid flow path.
In some embodiments, at least one flow component is operatively
connected with each of the first and second ends of the fluid flow
path. The at least one flow component is at least one of a
connector, a fitting, a flow passageway, a sensor and a
transmitter. In some embodiments, in the sterilization position,
the dispersion openings are configured to disperse gas received
from the gas supply port around and/or past the flow components to
achieve a Sterile Assurance Level (SAL) of 10.sup.-6 for the flow
components. In some embodiments, in the sterilization position, the
first and second gas dispersion openings are generally aligned with
the axis.
[0013] The gas flow member may be movable between the sterilization
position and a product flow position. In the product flow position,
the lower portion of the gas flow member may be withdrawn out of
the fluid flow path. In the product flow position, the fluid flow
path may be configured to receive bioprocessing fluid flow
therethrough. The lower portion of the gas flow member may include
a seal configured to seal the fluid flow path. The device may
include a locking mechanism to lock the device in product flow
position.
[0014] In some embodiments, the device includes a shear key held in
the housing and at least one shear cutter access port on the
housing. The at least one shear cutter access port is configured to
receive a shear cutter therethrough to cut the shear key. When the
shear key is cut, the gas flow member moves from the sterilization
position to the product flow position.
[0015] Other embodiments of the invention are directed to a system
for sterilizing a process connection or joint. The system includes
a gas dispersion device positioned in the process connection or
joint and a portable gas transfer device. The gas dispersion device
includes a housing defining a fluid flow path and a gas flow member
held in the housing. The gas flow member has an upper portion and a
lower portion disposed in the fluid flow path. The gas flow member
includes a supply gas passageway extending from a gas supply port
at the upper portion to at least one gas dispersion opening at the
lower portion, and the gas flow member further includes at least
one return gas passageway extending from a gas return opening at
the lower portion to a gas discharge port at the upper portion. The
portable gas transfer device includes: a supply gas canister
containing pressurized gas; a gas discharge canister; and a gas
transport member in fluid communication with the supply gas
canister and the gas discharge canister, with the gas transport
member held in a guided opening configured to receive the upper
portion of the gas dispersion device. When the upper portion of the
gas flow member is received in the guided opening, the portable gas
transfer device is configured to: supply pre-sterilization
pressurized gas from the supply gas canister to the at least one
gas dispersion opening such that gas is dispersed in the fluid flow
path to sterilize the process connection or joint; and receive
post-sterilization gas in the gas discharge canister from the at
least one gas return opening.
[0016] In some embodiments, when the upper portion of the gas flow
member is received in the guided opening, the gas flow member and
the gas transport member mate such that the supply gas passageway
of the gas flow member is aligned with a supply passageway of the
gas transport member and the at least one return gas passageway of
the gas flow member is aligned with at least one discharge gas
passageway of the gas transport member.
[0017] The portable gas transfer device may include: a gas sensor
disposed in a passageway between the gas transport member and the
gas discharge canister, with the sensor configured to detect a
characteristic of the post-sterilization gas; and a controller
configured to monitor the detected characteristic and validate that
the process connection or joint has been sterilized based on
detected characteristic. The portable gas transfer device may be
configured to halt the supply of pre-sterilization gas to the gas
dispersion device after validation that the process connection or
joint has been sterilized. The portable gas transfer device may
include an indicator to provide visual feedback after validation
that the process connection or joint has been sterilized.
[0018] Other embodiments of the invention are directed to a
sterilization gas supply and refilling system for portable gas
transfer devices. The system includes a portable gas transfer
device, a portable gas transfer device docking station and a gas
supply manifold. The portable gas transfer device includes: a
housing; a pressurized gas canister held by the housing, with the
pressurized gas canister configured to supply pressurized
pre-sterilization gas to a sterilization site; a gas discharge
canister held by the housing, with the gas discharge canister
configured to receive post-sterilization gas from the sterilization
site; and a gas fill valve on the housing. The docking station
includes a docking area configured to receive the portable gas
transfer device, with the docking area including a gas supply
connection for attachment with the portable gas transfer device
fill valve. The gas supply manifold is configured to supply
pressurized gas through the gas supply connection to the portable
gas transfer device pressurized gas canister, thereby refilling the
pressurized gas canister. The system may include a plurality of
portable gas transfer devices and a plurality of docking areas,
with each docking area configured to receive one of the gas
transfer devices.
[0019] In some embodiments, the portable gas transfer device
includes an electrical interface on the housing, and the docking
area includes an electrical connection configured to: charge a
battery pack of the portable gas transfer device; and receive data
from memory of the portable gas transfer device, wherein the data
includes sterilization validation data from at least one past
sterilization event.
[0020] In some embodiments, the system includes a gas supply unit
configured to supply pressurized gas to the gas supply manifold.
The gas supply unit may include an ozone generation unit configured
to generate ozone from an oxygen supply and/or a secondary gas
supply. The system may include a gas catalytic converter in fluid
communication with the gas supply manifold and the docking area,
with the gas catalytic converter configured to: receive ozone gas
that has been held in the portable gas transfer device and/or the
gas supply manifold past a time limit; convert the received ozone
gas to oxygen; and discharge the oxygen to atmosphere.
[0021] Other embodiments of the invention are directed to a method
for sterilizing a bioprocessing connection or joint. The method
includes: supplying pressurized ozone gas from a portable gas
transfer device to the connection or joint; dispersing the
pressurized ozone gas at the connection or joint; receiving at the
portable gas transfer device post-sterilization gas supplied from
the connection or joint; detecting the level of ozone in the
received post-sterilization gas; and determining whether the
connection or joint has been adequately sterilized based on the
detected level of ozone.
[0022] In some embodiments, the method includes: positioning a gas
dispersion device at the connection or joint; dispersing the
pressurized ozone gas at the connection or joint using the gas
dispersion device; and receiving at the portable gas transfer
device post-sterilization gas supplied from the gas dispersion
device. The gas dispersion device may include: a housing defining a
fluid flow path; and a gas flow member held in the housing, the gas
flow member having an upper portion and a lower portion, the gas
flow member comprising a supply gas passageway extending from the
top portion to first and second gas dispersion openings at the
lower portion, the gas flow member further comprising first and
second return gas passageways extending from the bottom portion to
the top portion. The gas flow member may be movable between a
sterilization position wherein the gas flow member lower portion is
disposed in the fluid flow path and a product flow position wherein
the lower portion is withdrawn from the fluid flow path. The method
may include positioning the gas dispersion device at the connection
or joint with the gas flow member in the sterilization position.
The method may include: determining that the connection or joint
has been adequately sterilized based on the detected level of ozone
in the received post-sterilization gas; then moving the gas flow
member to the product flow position; locking the gas flow member in
the product flow position; and flowing bioprocessing fluid and/or
material through the fluid flow path.
[0023] In some embodiments, the method includes: determining that
the connection or joint has been adequately sterilized based on the
detected level of ozone in the received post-sterilization gas; and
halting the supply of pressurized ozone gas from a portable gas
transfer device to the connection or joint. In some embodiments,
the method includes determining whether a Sterility Assurance Level
(SAL) of 10.sup.-6 has been achieved. In some embodiments, the
method includes converting the received post-sterilization gas to
oxygen at the portable gas transfer device.
[0024] Other embodiments of the invention are directed to a system
including a sealable local environment and an ozone source operably
coupled to the sealable local environment. The sealable local
environment is configured to receive two or more fluid path members
and to sealingly contain the two or more fluid path members. The
sealable local environment is further configured to be manipulated
to interconnect the two or more fluid path members within the
sealable local environment while the sealable local environment
remains sealed. The two or more fluid path members sealingly
contained within the sealable local environment may be exposed to
ozone to sterilize the two or more fluid path members prior to
interconnecting the two or more fluid path members. In some
embodiments, the sealable local environment includes a membrane
configured to receive the ozone source, and the ozone source
includes a syringe configured to inject ozone past the membrane.
The sealable local environment may include a rigid structure
configured to contain the two or more fluid path members, and the
rigid structure may include an assembly chamber including one or
more manipulators enabling the two or more fluid path members to be
interconnected from outside the assembly chamber.
[0025] Other embodiments of the invention are directed to a system
for point-of-use sterilization, including: a pressurized gas
source; and a gas dispersion device. The gas dispersion device
includes a housing defining a chamber; first and second flow
conduits in fluid communication with the chamber, with each conduit
extending away from the chamber, and with each conduit including a
distal end portion configured to operatively connect with at least
one fluid flow component; and a gas flow member held at least
partially in the housing, with the gas flow member having a gas
inlet port configured to operatively connect with the pressurized
gas source and first and second dispersion openings in fluid
communication with the gas inlet port. When the pressurized gas
source is operatively connected with the gas inlet port, the
dispersion openings are configured to disperse gas received from
the pressurized gas source throughout the chamber and through the
conduits to sterilize fluid flow components connected thereto.
[0026] In some embodiments, the pressurized gas source is a
portable gas transfer device. In some embodiments, the pressurized
gas source is or includes a syringe.
[0027] In some embodiments, the gas flow member includes a
butterfly valve element. The butterfly valve element includes main
faces and is adapted for rotational movement in the chamber between
a closed position and an open position. The butterfly valve
includes an inlet for introduction of gas, with the inlet
communicating with a central gas dispersion opening extending
transversely through a medial portion of the valve element for
outward dispersion of gas at both main faces of the valve element.
The butterfly valve element includes gas return ports at opposite
marginal portions on opposite main faces of the butterfly valve
element communicating with gas discharge ports at an end portion of
the valve element.
[0028] In some embodiments, the gas flow member is movable between
a sterilization position wherein the gas dispersion openings are
disposed in the chamber and a product flow position, wherein the
gas flow member is retracted from the chamber and/or rotated within
the chamber to reach the product flow position.
[0029] It is noted that any one or more aspects or features
described with respect to one embodiment may be incorporated in a
different embodiment although not specifically described relative
thereto. That is, all embodiments and/or features of any embodiment
can be combined in any way and/or combination. Applicant reserves
the right to change any originally filed claim or file any new
claim accordingly, including the right to be able to amend any
originally filed claim to depend from and/or incorporate any
feature of any other claim although not originally claimed in that
manner. These and other objects and/or aspects of the present
invention are explained in detail in the specification set forth
below.
BRIEF DESCRIPTION OF THE FIGURES
[0030] FIG. 1 is a top perspective view of a gas dispersion device
according to some embodiments.
[0031] FIG. 2 is a partially transparent top perspective view of
the device of FIG. 1.
[0032] FIG. 3 is a partially transparent bottom perspective view of
the device of FIG. 1.
[0033] FIG. 4 a partially transparent end view of the device of
FIG. 1.
[0034] FIG. 5 is a cross-sectional side view of the device of FIG.
1.
[0035] FIG. 6 is a cross-sectional end view of the device of FIG.
1.
[0036] FIG. 7 is a cross-sectional side view of the device of FIG.
1 in a post-sterilization or product flow position.
[0037] FIG. 8 is a cross-sectional end view of the device of FIG. 1
in a post-sterilization or product flow position.
[0038] FIG. 9 is a schematic view illustrating various exemplary
sensor/transmitter mounting configurations to point-of-use
connection points and employing the device of FIG. 1.
[0039] FIG. 10 is an enlarged schematic view illustrating one of
the exemplary sensor/transmitter mounting configurations of FIG.
9.
[0040] FIG. 11 is an enlarged schematic view illustrating one of
the exemplary sensor/transmitter mounting configurations of FIG.
9.
[0041] FIG. 12 is a top perspective view of a portable gas transfer
device according to some embodiments.
[0042] FIG. 13 is an enlarged bottom perspective view of the
portable gas transfer device of FIG. 12.
[0043] FIG. 14 is an enlarged bottom perspective view of the
portable gas transfer device of FIG. 12.
[0044] FIG. 15 is an enlarged bottom perspective view of the
portable gas transfer device of FIG. 12.
[0045] FIG. 16 is a cross-sectional front view of a portion of the
portable gas transfer device of FIG. 12.
[0046] FIG. 17 is top perspective view of a fixed housing member of
the portable gas transfer device of FIG. 12.
[0047] FIG. 18 is a side perspective view of the member of FIG.
17.
[0048] FIG. 19 is bottom perspective view of a movable gas transfer
member of the portable gas transfer device of FIG. 12.
[0049] FIG. 20 is a transparent perspective view of the member of
FIG. 19.
[0050] FIG. 21 is a top perspective view of the member of FIG.
19.
[0051] FIG. 22 is an enlarged partially transparent view
illustrating interior components of the portable gas transfer
device of FIG. 12.
[0052] FIG. 23 is an enlarged partially transparent view
illustrating portions of gas flow passageways of the portable gas
transfer device of FIG. 12.
[0053] FIG. 24 is an enlarged partially transparent view
illustrating portions of gas flow passageways of the portable gas
transfer device of FIG. 12.
[0054] FIG. 25 is an enlarged partially transparent view
illustrating portions of gas flow passageways of the portable gas
transfer device of FIG. 12.
[0055] FIG. 26 is a partial perspective view of the portable gas
transfer device of FIG. 12.
[0056] FIG. 27 is an enlarged partially transparent view
illustrating interior components of the portable gas transfer
device of FIG. 12.
[0057] FIG. 28 is a partial perspective view of the portable gas
transfer device of FIG. 12 positioned over the gas dispersion
device of FIG. 1.
[0058] FIG. 29 is an end view of the portable gas transfer device
of FIG. 12 coupled to the gas dispersion device of FIG. 1.
[0059] FIG. 30 is a partial top perspective view of the portable
gas transfer device of FIG. 12.
[0060] FIG. 31 is schematic illustrating a sterilization gas
supply/refilling system for use with the portable gas transfer
device of FIG. 12.
[0061] FIG. 32 is a front view of a sterilization apparatus
according to some embodiments.
[0062] FIG. 33 is a perspective view of a sealable local
environment of the apparatus of FIG. 32.
[0063] FIG. 34 is a cross-sectional front view of the sealable
local environment of FIG. 33.
[0064] FIG. 35 is an enlarged perspective view of the sealable
local environment of FIG. 33 showing a membrane configured to
receive a pressurized gas source.
[0065] FIG. 36 is an enlarged perspective view of the sealable
local environment of FIG. 35 showing the pressurized gas source
inserted into or past the membrane.
[0066] FIG. 37 is an enlarged perspective view of an injection
member of the pressurized gas source of FIG. 35.
[0067] FIG. 38 is a top perspective view of a sterilization
apparatus according to other embodiments.
[0068] FIG. 39 is a flow diagram of a method of sterilizing an open
portion of a fluid path according to some embodiments.
[0069] FIG. 40 is a flow diagram of a method of sterilizing two or
more fluid path connectors according to some embodiments.
[0070] FIG. 41 is a schematic perspective view of a gas dispersion
device according to other embodiments.
[0071] FIG. 42 is a front elevation view of a valve element of the
gas dispersion device of FIG. 41.
[0072] FIG. 43 is a top perspective view the gas dispersion device
of FIG. 41.
[0073] FIG. 44 is a transparent side view of a gas dispersion
device according to other embodiments.
[0074] FIG. 45 is a transparent end view of the gas dispersion
device of FIG. 44.
[0075] FIG. 46 is an enlarged perspective view of the gas
dispersion device of FIG. 44.
[0076] FIGS. 47A and 47B are elevation views of the gas dispersion
device of FIG. 1 with alternative connection features.
[0077] FIG. 48 is a perspective view of a portable gas transfer
device according to other embodiments.
[0078] FIG. 49 is an enlarged partial perspective view of the
device of FIG. 48.
[0079] FIGS. 50A and 50B are perspective views of a mounting head
of the device of FIG. 48 with alternative connection features.
[0080] FIGS. 51A and 52A are perspective views of the mounting head
of FIG. 50A positioned over the gas dispersion device of FIG.
1.
[0081] FIGS. 51B and 52B are perspective views of the mounting head
of FIG. 50B positioned over the gas dispersion device of FIG.
1.
[0082] FIG. 53 is a cross-sectional front view of a portion of the
mounting head of FIG. 50A.
[0083] FIG. 54 is a schematic illustrating point-of-use
sterilization according to some embodiments.
[0084] FIG. 55 is a schematic illustrating zone sterilization of a
manifold according to some embodiments.
[0085] FIG. 56 is a schematic illustrating zone sterilization of a
manifold connected to a process tank according to some
embodiments.
[0086] FIG. 57 is a schematic illustrating zone sterilization of a
discrete device according to some embodiments.
DETAILED DESCRIPTION
[0087] The present invention now will be described more fully with
reference to the accompanying drawings, in which embodiments of the
invention are shown. However, this invention should not be
construed as limited to the embodiments set forth herein. Rather,
these embodiments are provided so that this disclosure will be
thorough and complete, and will fully convey the scope of the
invention to those skilled in the art. In the drawings, like
numbers refer to like elements throughout. Thicknesses and
dimensions of some components may be exaggerated for clarity.
[0088] As used herein, the term "comprising" or "comprises" is
open-ended, and includes one or more stated features, integers,
elements, steps, components or functions but does not preclude the
presence or addition of one or more other features, integers,
elements, steps, components, functions or groups thereof. As used
herein, the term "and/or" includes any and all combinations of one
or more of the associated listed items.
[0089] As used herein, the common abbreviation "e.g.," which
derives from the Latin phrase "exempli gratia," may be used to
introduce or specify a general example or examples of a previously
mentioned item, and is not intended to be limiting of such item. If
used herein, the common abbreviation "i.e.," which derives from the
Latin phrase "id est," may be used to specify a particular item
from a more general recitation.
[0090] The terminology used herein is for the purpose of describing
particular embodiments only and is not intended to be limiting of
the invention. As used herein, the singular forms "a," "an" and
"the" are intended to include the plural forms as well, unless the
context clearly indicates otherwise.
[0091] Well-known functions or constructions may not be described
in detail for brevity and/or clarity.
[0092] Unless otherwise defined, all terms (including technical and
scientific terms) used herein have the same meaning as commonly
understood by one of ordinary skill in the art to which this
invention belongs. It will be further understood that terms, such
as those defined in commonly used dictionaries, should be
interpreted as having a meaning that is consistent with their
meaning in the context of the relevant art and will not be
interpreted in an idealized or overly formal sense unless expressly
so defined herein.
[0093] In addition, spatially relative terms, such as "under,"
"below," "lower," "over," "upper," "downward," "upward," "inward,
"outward" and the like, may be used herein for ease of description
to describe one element or feature's relationship to another
element(s) or feature(s) as illustrated in the figures. It will be
understood that the spatially relative terms are intended to
encompass different orientations of the device in use or operation
in addition to the orientation depicted in the figures. For
example, if the device in the figures is turned over, elements
described as "under" or "beneath" other elements or features would
then be oriented "over" the other elements or features. Thus, the
exemplary term "under" can encompass both an orientation of over
and under. The device may be otherwise oriented (rotated 90 degrees
or at other orientations) and the spatially relative descriptors
used herein interpreted accordingly.
[0094] It will be understood that when an element is referred to as
being "attached," "coupled" or "connected" to another element, it
can be directly attached, coupled or connected to the other element
or intervening elements may also be present. In contrast, when an
element is referred to as being "directly attached," directly
coupled" or "directly connected" to another element, there are no
intervening elements present.
[0095] It is noted that any one or more aspects or features
described with respect to one embodiment may be incorporated in a
different embodiment although not specifically described relative
thereto. That is, all embodiments and/or features of any embodiment
can be combined in any way and/or combination. Applicant reserves
the right to change any originally filed claim or file any new
claim accordingly, including the right to be able to amend any
originally filed claim to depend from and/or incorporate any
feature of any other claim although not originally claimed in that
manner. These and other objects and/or aspects of the present
invention are explained in detail in the specification set forth
below.
[0096] As used herein, the terms "flow component" and "fluid flow
component" mean a component that is attachable or operatively
attachable to a gas dispersion device and/or to another fluid flow
component that is in fluid communication with the gas dispersion
device. Alternatively, the fluid flow component may be integrated
with the gas dispersion device. The flow component has one or more
interior surfaces that are to be exposed to product fluid, such as
bioprocessing fluid. The interior surface(s) may include hidden
and/or occluded areas. The gas dispersion device is configured to
disperse gas around, into and/or through the fluid flow component
such that the interior surfaces including the hidden/occluded areas
are sterilized to a predetermined level (e.g., a Sterility
Assurance Level of 10.sup.-6). Exemplary fluid flow components
include, but are not limited to: connectors, fittings, fluid flow
members such as tubes, sensors, transmitters and valves. The
sterilization gas dispersed from the gas dispersion device may flow
past or through the flow component (e.g., in the case of certain
fittings and fluid flow members) or may flow adjacent or around the
flow component (e.g., in the case of certain sensors and
transmitters).
[0097] The gas dispersion devices of the present invention
effectively sterilize the fluid flow members, which may be located
at or near process connections or joints. The gas dispersion
devices may be disposed at these connections or joints to
effectively sterilize the connection/joint and/or any nearby or
attached fluid flow component. It will be understood that any of
the fluid flow components described above (e.g., connectors,
fittings, sensors, transmitters, etc.) may be disposed at or near
(or integrated with) a "process connection or joint" as the term is
used herein.
[0098] A gas dispersion interconnect device 10 according to some
embodiments is illustrated in FIGS. 1-8. The gas dispersion device
10 includes a housing 12. At least a portion of the housing 12
defines an internal cavity or chamber 14. The housing 12 includes
an upper portion 16 and a lower portion 18. As illustrated, the
chamber 14 is defined in the lower portion 18 of the housing 12
(FIG. 5).
[0099] First and second flow conduits 20 are in fluid communication
with and extend outwardly away from the chamber 14. As illustrated
in FIG. 5, the first and second conduits 20 are diametrically
opposed and extend away from the chamber along an axis A1. The
chamber 14 and the conduits 20 may be collectively referred to as a
fluid flow path 15 (FIGS. 7 and 8). A distal end portion of each
conduit 20 includes a flange 22 configured to connect or
operatively connect to a fluid flow component (for example, via a
sanitary clamp). As will be described in detail below, the gas
dispersion device 10 is configured to disperse pressurized gas to
sterilize the fluid flow components connected thereto.
[0100] The gas dispersion device 10 includes an elongated gas flow
member 24. The gas flow member 24 has an upper portion 26 and a
lower portion 28. The gas flow member upper portion 26 includes a
gas supply/inlet port or opening 30 and the gas flow member lower
portion 28 includes first and second gas dispersion openings 32. A
gas inflow or supply passageway 34 extends between the inlet port
30 and the gas dispersion openings 32.
[0101] The gas flow member 24 includes first and second gas return
passageways 36 (FIG. 2). Each gas return passageway 36 extends
between a gas return opening or port 38 at the gas flow member
lower portion 28 (FIGS. 3 and 4) and a gas discharge opening or
port 40 at the gas flow member upper portion 26 (FIG. 1).
[0102] The gas flow member 24 is positionable in a sterilization
position, as illustrated in FIGS. 1-6. In the sterilization
position, the gas flow member lower portion 28 is disposed in the
chamber 14 or the fluid flow path 15. In this regard, the gas
dispersion openings 32 are positioned and configured to effectively
and rapidly disperse pressurized gas received from the gas inlet
port 30 through the conduits 20 and adjacent and/or past fluid flow
components attached to the flanges 22. In some embodiments, the gas
dispersion openings 32 are generally or substantially aligned with
the axis A1 in the sterilization position (FIGS. 2 and 4). It will
be understood that, in use, the device 10 may be positioned such
that the axis A1 is defined as a longitudinal (horizontal) axis, a
latitudinal (vertical) axis or any angle or axis therebetween.
[0103] In the sterilization position, the gas return openings or
ports 38 are also disposed in the chamber 14 or the fluid flow path
15. As illustrated, the gas return openings 38 may be offset from
the axis A1 (FIG. 4).
[0104] The gas dispersion device 10 may be temporarily locked in
the sterilization position via a locking mechanism. As shown in
FIG. 6, an opening 41 extends inwardly from an outer surface of the
gas flow member 24, and a pin 42 is received in the opening 41 to
retain the gas flow member 24 in the sterilization position. The
pin 42 is part of a "shear key assembly" described in more detail
below.
[0105] Also as shown in FIG. 6, the gas dispersion device 10
includes a main actuator spring 44. In the sterilization position,
the spring 44 is held within a main actuator spring containment
body 46; the spring containment body 46 is disposed within the
housing 12. A flat washer 48 is positioned above the spring 44 and
a retaining ring 50 is positioned above the washer 48. At least one
of the washer 48 and the retaining ring 50 is attached to the outer
surface of the gas flow member 24. In the sterilization position,
the spring 44 is compressed and held in place by the washer 48 and
the retaining ring 50.
[0106] Still referring to FIG. 6, a first annular seal 52 is
provided in a groove 54 of the spring containment body 46. The seal
52 inhibits the passage of pre- and post-sterilization gas as well
as bioprocessing fluid/material that flows through the fluid flow
path after sterilization has taken place.
[0107] Again, in the sterilization position, the gas dispersion
device 10 is configured to rapidly disperse gas from the gas
dispersion openings 32. The gas is dispersed throughout the chamber
14, through the conduits 20, and adjacent and/or past flow
components attached to the flanges 22, thereby efficiently
sterilizing these components. The gas is received from a
pressurized gas source through the gas supply port 30 and flows
through the gas passageway 34 before being dispersed from the gas
dispersion openings 32. As will be described in more detail below,
the pressurized gas source may be received on a collar 55 (FIG. 1)
at the top portion of the housing 12.
[0108] In some embodiments, the housing 12 is a one-piece housing.
In some embodiments, the housing upper portion 16 and the housing
lower portion 18 are discrete components. This may accommodate the
placement of the spring containment body 46 within the housing 12.
As illustrated in FIG. 5, the housing lower portion 18 may include
at least one locating guide pin 58 and the spring containment body
46 may include at least one opening 60 sized and configured to
receive the at least one guide pin 58. There may be a plurality of
guide pins 58 and openings 60 or the guide pin 58 may be an annular
or semi-annular protrusion and the opening 60 may be a
corresponding annular or semi-annular groove. The housing upper and
lower portions 16, 18 may be welded (e.g., ultrasonically welded)
at joint 56. In some embodiments, most or all of the components of
the gas dispersion device 10 are formed of an inert polymer. In
some embodiments, the spring 44, the washer 48 and/or the retaining
ring 50 are formed of a metallic material such as stainless
steel.
[0109] The gas dispersion device 10 is movable between the
sterilization position, described above, and a post-sterilization
or product flow position, as illustrated in FIGS. 7 and 8. In the
product flow position, the gas flow member lower portion 28 is
withdrawn from the chamber 14 after flow components attached to the
flanges 22 have been adequately sterilized. With the gas flow
member 24 withdrawn from the chamber 14, the chamber 14 and the
conduits 20 define an open flow path 15 (e.g., along the axis A1).
The open flow path provides a low resistance path for product, such
as bioprocessing fluid/material, to flow, including along or past
flow components attached to the flanges 22 that were sterilized
when the gas dispersion device 10 was in the sterilization
position.
[0110] As illustrated in FIG. 8, the movement from the
sterilization position to the product flow position is initiated by
cutting a shear key 58; the process for cutting the shear key 58
will be described in more detail below. According to some
embodiments, the shear key 58 comprises a brittle ceramic or
polymeric material that crumbles, shatters or otherwise fractures
when cut. In some embodiments, the shear key is made of brittle
polystyrene. After the shear key 58 is cut, previously compressed
spring 60 expands and retaining pin 42 retracts away from the gas
flow member 24 and clear of the opening 41 therein. At this point,
previously compressed spring 44 expands and forces the washer 48
and the retaining ring 50 upward, and in turn forces the gas flow
member 24 upward.
[0111] The gas dispersion device 10 may include a locking mechanism
to lock the gas dispersion device 10 or the gas flow member 24 in
the product flow position. In the illustrated embodiment, first and
second post-sterilization locking cams 62 are disposed in the
housing upper portion 16. A spring 64 biases each cam 62 inwardly
toward the gas flow member 24. Each cam 62 has a side surface 66
that tapers inwardly from bottom to top. Each cam 62 also has a
flat or substantially flat top surface 68. As noted above, the
spring 44 forces the washer 48 and/or the retaining ring 50
upwardly after the pin 42 becomes disengaged with the opening 41 in
the gas flow member 24. As the washer 48 travels upwardly, the
washer 48 engages the cam side surface 66 and compresses the spring
64 such that the washer 48 can extend upwardly past the top portion
of the cam side surface 66. After the washer 48 has cleared the top
portion of the cam side surface 66, the spring 64 urges the cam 62
inwardly such that the washer 48 may rest on the cam top surface
68. The gas dispersion device 10 or the gas flow member 24 is now
locked in place in the post-sterilization or product flow
position.
[0112] The gas flow member lower portion 28 includes a second seal
70. The second seal 70 may take the form of an annular seal or
o-ring positioned below the gas dispersion openings 32. For
example, as shown in FIG. 8, the gas flow member lower portion 28
may include a seat 72 on which the second seal 70 may be
positioned, with the seal positioned below the gas dispersion
openings 32 and the return gas flow ports 38.
[0113] As illustrated in FIGS. 7 and 8, in the product flow
position, the second seal 70 is brought into contact with a lower
portion of the spring containment body 46. In this regard, a
"double seal" is provided with the first and second seals 52, 70 to
inhibit upward flow of bioprocessing or product fluid/material that
flows through the fluid flow pathway 15.
[0114] Referring back to FIG. 6, in the sterilization position, the
gas flow member 24 (or the upper portion 26 thereof) extends a
first distance d1 from a top portion of the threaded collar 55. As
shown in FIG. 8, in the post-sterilization or product flow
position, the gas flow member 24 (or the upper portion 26 thereof)
extends a second distance d2 from a top portion of the threaded
collar 55, with the second distance d2 being greater than the first
distance d1. In some embodiments, the second distance d2 is less
than about 1 inch greater than the first distance d1. In some
embodiments, the second distance d2 is between about 0.5 and about
0.75 inches greater than the first distance d1. The difference
between the distances d2 and d1 represents the amount of upward
travel of the gas flow member 24 between the sterilization position
and the product flow position.
[0115] Referring again to FIG. 3, a bottom portion of the gas
dispersion device 10 may include a well 84 (i.e., below the chamber
14). The well 84 may be used to accommodate a sensor/transmitter to
be attached or integrated to the gas dispersion device 10. The well
84 may be of varying size depending on the size or type of
sensor/transmitter to be accommodated. Where used, a through-hole
86 provides fluid communication for a probe or the like of the
sensor/transmitter. The through-hole 86 may also be of varying size
depending on the application.
[0116] The gas interconnect dispersion device 10 may be employed to
efficiently disperse low-temperature gases/vapors for localized
sterilization of fluid flow components at point-of-use connection
sites. As described above, the fluid flow components (including
connectors, fittings, fluid flow paths such as tubing and the like,
sensors and/or transmitters) may be connected or operatively
connected to the conduits 20 or the flanges 22 of the gas
dispersion device 10.
[0117] Current technology employs "pre-sterilized" flow components
such as connectors, fittings, fluid flow paths,
sensors/transmitters and the like. However, during the process of
connecting such flow components to a drug manufacturing or
processing system, the sterile connectors, fittings and
sensors/transmitters are often exposed to an ambient non-sterile
atmosphere that has the potential to cause microbial contamination.
The gas dispersion interconnect device 10 helps ensure that after a
"pre-sterilized" aseptic flow component is exposed to an ambient
non-sterile atmosphere, any residual microbial contamination can be
reduced to the necessary level.
[0118] Low-temperature gas/vapor sterilants include: ozone gas,
ethylene oxide (EO or EtO), vaporized hydrogen peroxide (VHP or
HPV), hydrogen peroxide gas plasma, vaporized formaldehyde, gaseous
chlorine dioxide and vaporized peracetic acid.
[0119] Pressurized ozone gas may be advantageously used because it
is an efficient FDA-approved sterilant, because it leaves no
residual surface coatings, because it is safe and inexpensive to
produce, because of its low pressure handling characteristics
and/or because it is easily reverted back to oxygen using a
chemical catalyst. While the discussion herein largely focuses on
the use of ozone gas as the sterilant, it will be appreciated that
other low-temperature gases/vapors, such as those listed above, may
be employed.
[0120] As pressurized ozone gas dispersed by the gas dispersion
device 10 migrates through joints or process connections joined by
the dispersion device 10 and/or flow components operatively
connected to the gas dispersion device 10, it sterilizes all
internal surfaces, including occluded or hidden areas of the flow
components where bacteria or microbial populations can grow, to
achieve a Sterility Assurance Level (SAL) of 10.sup.-6 as mandated
by the FDA. That is, the gas dispersion device 10 can effectively
sterilize connected or operatively connected connectors, fittings,
fluid flow paths, sensors and/or transmitters including occluded
portions thereof to a SAL of 10.sup.-6. The gas dispersion device
10 may effectively disperse the gas to sterilize further downstream
areas, including downstream occluded areas, as well.
[0121] The gas dispersion interconnect device 10 is typically
"single-use" and can be used to sterilize connection points in the
fluid product transfer path in drug processing and manufacturing
systems, for example. In addition, the gas interconnect device 10
can be used to sterilize single-use and reusable aseptic disposable
sensors/transmitters, as described below.
[0122] Sensors/transmitters can be integrated with and mounted to
the gas dispersion device 10. Thus, the present invention
contemplates the integration and mounting of various types of
single-use or reusable sensors and transmitters into a drug
manufacturing system, and their subsequent sterilization using
ozone gas at the point-of-use (POU) connection point. The types of
sensors and transmitters that may be sterilized include, but are
not limited to: pressure sensors and transmitters, flow rate
sensors and transmitters, temperature sensors and transmitters,
CO.sub.2 sensors and transmitters, O.sub.2 sensors and
transmitters, pH sensors and transmitters, conductivity sensors and
transmitters and redox and O.R.P. sensors and transmitters. By
exposing the sensor mounting at aseptic connection points to a
calculated concentration of ozone gas, the majority of the
microbial population is killed to achieve a SAL of 10.sup.-6.
[0123] According to some embodiments, a sensor/transmitter mounting
and fitting assembly includes a single-use or reusable
sensor/transmitter, a single-use mounting fitting and an ozone gas
dispersion sterilization device, such as the device 10 described
above. Two or more of the sensor/transmitter mounting and fitting
assemblies may be integrated to form an integrated, single-use
assembly.
[0124] Exemplary embodiments of such assemblies are shown in FIGS.
9-11. Three exemplary configurations are illustrated together in
FIG. 9. As best shown in FIGS. 9 and 10, a first configuration 300
includes the gas dispersion sterilization device 10, a mounting
fitting 302 and a long probe sensor/transmitter 304. The fitting
302 is T-shaped and includes a first run portion 302a extending
between first and second ends and a second run portion 302b
extending outwardly from the first run portion 302a.
[0125] The first end of the first run 302a is operatively connected
to one of the conduits 20 (or one of flanges 22) the gas dispersion
device 10 via a sanitary clamp 306. The opposite end of the first
run 302a is operatively connected to the sensor/transmitter 304 via
another sanitary clamp 306. The length of the first run 302a can be
selected to accommodate the length of the long probe sensor 304. In
some embodiments, the length of the first run 302a is selected to
accommodate sensor probes having lengths of 9-10 inches or
greater.
[0126] The second run 302b of the fitting 302 is operatively
connected to a vessel V (such as a bioreactor) via another sanitary
clamp 306. This connection point is adjacent an isolation valve
associated with the bioreactor or product vessel V. The isolation
valve is movable between open and closed positions.
[0127] With the isolation valve in the closed position, a
pressurized ozone gas source, such as a syringe or a hand-held or
portable ozone gas supply canister (described in detail below), is
provided. The portable ozone gas supply canister is configured to
connect with the gas flow member top portion 26 of the gas
dispersion device 10 and supply pressurized ozone through the gas
inlet port 30 (FIG. 1), thereby effectively and rapidly dispersing
the ozone gas through the dispersion openings, as described above.
All internal cavities and components including the
sensor/transmitter 304, mounting fitting 302 and other attached
components are exposed to the ozone gas and sterilized to the
requisite SAL of 10.sup.-6. As will be described below, excessive
amounts of "post-sterilization" ozone gas will be passed through
the gas outlet ports 40 of the gas dispersion device 10 and through
a catalytic filter associated with the portable ozone canister to
convert the waste ozone gas to oxygen before it reenters the
atmosphere. Also as described below, the "post-sterilization" gas
may be monitored and analyzed before or during the conversion
process to ensure that the required log 6 reduction of microbial
species has occurred; the portable ozone gas supply canister
includes the catalytic device and a measuring and/or monitoring
device to measure and/or indicate that an SAL of 10.sup.-6 has been
achieved with respect to components connected or operatively
connected to the gas dispersion device 10.
[0128] Referring to FIG. 9, a second exemplary configuration 310 is
shown. An in-line sensor/transmitter 312 and a mounting fitting 314
are operatively connected to one of the conduits or flanges 20, 22
of the gas dispersion device 10 via a sanitary clamp 306. The other
one of the conduits or flanges 20, 22 of the gas dispersion device
10 is operatively connected to the vessel V. Thus, an in-line
sensor/transmitter mounting assembly is formed. In the manner
described above, an isolation valve associated with the vessel V is
closed, and a portable ozone gas supply canister is attached to the
gas dispersion device 10. All internal cavities including the
sensor/transmitter 312, mounting fitting 314 and other attached
components are exposed to the ozone gas and sterilized to the
requisite SAL of 10.sup.-6.
[0129] A third exemplary configuration 320 is shown in FIGS. 9 and
11. Here, the gas dispersion device 10 is configured to receive the
sensor/transmitter 322 via the well 84, thereby forming a direct
sensor/transmitter mounting configuration. One of the flanges 22 of
the gas dispersion device 10 is operatively connected to the vessel
V via a fitting 324 and a sanitary clamp 306. Again, an isolation
valve associated with the vessel V is closed, and a portable ozone
gas supply canister is attached to the gas dispersion device. All
internal cavities including the sensor/transmitter 322 and the
fitting 324 and other attached or nearby components are exposed to
the ozone gas and sterilized to the requisite SAL of 10.sup.-6.
[0130] In the third configuration 320, a sanitary clamp 306
connects the other one of the flanges 22 of the gas dispersion
device 10 with a flow blocking member 326. It is contemplated that
the gas dispersion device 10 may alternatively be formed or
manufactured with a closed conduit, or with no conduit at this
location (e.g., the gas dispersion device 10 includes only one
conduit 20). Further, it is noted that, in place of the flow
blocking member 326, a fluid flow path such as a fitting or a tube
could be connected to the flange 22 via the sanitary clamp 306. The
fluid flow path may be connected to another container or vessel,
for example. In this configuration, the gas dispersion device 10
would be configured to further sterilize this additional fluid flow
path running to the other container or vessel.
[0131] For all of the above-described configurations, all or some
of the gas dispersion device, the sensor/transmitter and any
associated mounting fittings or flow components may be integrated
so as to form a single-use disposable assembly that may be
integrated to the bioprocessing system. The above described
sterilization/product flow processes may take place, after which
point the entire integrated assembly is removed and the vessel is
cleaned around the isolation valve area. It is noted that the
vessel may also be single-use disposable and, in some embodiments,
may also be integrated with the assembly.
[0132] As discussed above, the gas dispersion device 10 is
configured to receive pressurized gas through the gas supply port
30 from a pressurized gas supply source. Various pressurized gas
sources, such as a syringe or the like, are contemplated as
described below. One such source is included in the portable gas
canister assembly or portable gas transfer device 100 shown in
FIGS. 12-27. The device 100 includes a housing 101 having an upper
portion 102 and a lower portion 104. A carry handle 106 may be
provided between the housing upper and lower portions 102, 104. The
device 100 includes a gas supply canister 108 and a gas discharge
canister or gas discharge catalyst canister 110. As illustrated,
the gas supply canister 108 and the gas discharge catalyst canister
110 may each extend between the housing upper and lower portions
102, 104. One or more support columns 112 may also extend between
the housing upper and lower portions 102, 104 to provide strength.
According to some embodiments, the canisters 108, 110 are metallic.
According to some embodiments, the gas supply canister 108 is
nickel plated aluminum. According to some embodiments, the gas
discharge catalyst canister 110 is stainless steel. According to
some embodiments, the gas supply canister 108 has an internal
volume of about 0.5 liters. According to some embodiments, the gas
supply canister is configured to hold ozone at a pressure of about
100 psig.
[0133] Disposed on the housing upper portion 102 are a plurality of
status indicator lights 114, a display 116 and an operator
interface 118. Also disposed on the housing upper portion 102 is a
gas discharge vent 120. The vent 120 is in fluid communication with
the gas discharge catalyst canister 110. The functionality of these
components will be described below.
[0134] Attached to the housing lower portion 104 is a mounting nut
122. Referring to FIG. 13, the mounting nut 122 includes an opening
124 sized and configured to receive therethrough the gas flow
member 24 of the gas dispersion device 10. The mounting nut opening
124 is also sized and configured to receive and engage the collar
55 of the gas dispersion device 10. The interior of the mounting
nut opening 124 may be threaded such that the mounting nut 122
threadingly engages the collar 55. Alternatively, the mounting nut
opening 124' may include pins 81' for engaging L-shaped slots 133'
on a collar 55' for creating a bayonete-type engagement (as shown
in FIGS. 50B, 51B, 52B, and 53).
[0135] A guide bar 126 is provided on each side surface of the
housing 101 (only one guide bar 126 is visible in FIG. 13). The
guide bars 126 may be received in guide tracks of a recharging
station, which is described in greater detail below. Gas refill
supply valve 128 (e.g., a check valve) and electrical interface 130
are also disposed on the housing 101. These components are
connected to the recharging station.
[0136] An alignment key 132 is located on the housing lower portion
104. The alignment key 132 is aligned with and received within a
locating guide 80 of the gas dispersion device 10 (FIG. 1). The
alignment key 132 is shown in greater detail in FIG. 14. The
alignment key 132 includes first and second shear cutter ports 134.
First and second shear cutters 136 are located within the alignment
key 132 with each shear cutter 136 aligned with a respective shear
cutter port 134. When the alignment key 132 is matingly received in
the locating guide 80, the shear cutter ports 134 are in alignment
with shear cutter access ports 82 of the gas dispersion device 10
(FIG. 1).
[0137] As illustrated in FIGS. 15 and 16, above the mounting nut
opening 124 is a guided opening 138. The guided opening 138 is
sized and configured to receive the gas flow member 24 of the gas
dispersion device 10. The guided opening 138 has a similar shape or
profile to that of the gas flow member 24 such that the gas flow
member 24 can be matingly received in the guided opening 138. The
guided opening 138 may have a polygonal and/or an oblong shape or
profile to inhibit rotation of components therein, including the
gas flow member 24 of the gas dispersion device 10.
[0138] A fixed housing portion 140 is illustrated in FIG. 16. The
fixed housing portion 140 may be part of the housing 101 or
attached thereto. At or near the bottom of the fixed housing
portion 140 is an annular groove 142 that is configured to receive
a retaining ring 144 therein. A top portion of the mounting nut 122
rests on the retaining ring 144.
[0139] The fixed housing portion 140 defines the guided opening
138. Referring to FIGS. 17 and 18, the fixed housing portion 140
includes a relatively larger upper bore 146 with a sill 148 defined
at the top of the guided opening 138.
[0140] A gas flow or transfer member 150 is movable within the
fixed housing member 140. As shown in FIGS. 19-21, the movable gas
flow member 150 includes a lower stem portion 152 and an upper head
portion 154. The lower stem portion 152 is shaped and configured to
fit within the guided opening 138 of the fixed housing portion 140.
The upper head portion 154 is shaped and configured to fit within
the upper bore 146 of the fixed housing portion 140. The head
portion 154 sits on the sill 148 with the gas flow member 150 in a
"seated" position. As will be explained in more detail below, when
the gas dispersion device 10 and the gas transfer device 100 are
initially coupled, the gas flow member 150 is in the seated
position when the gas dispersion device 10 is in the sterilization
position. Also, the gas flow member 150 moves upward into a
"raised" position when the gas dispersion device 10 moves to the
post-sterilization or product flow position.
[0141] One gas supply passageway 156 and first and second gas
return or discharge passageways 158 extend through the gas flow or
transfer member 150. A counterbore forms a ledge or sill 156L, 158L
in each passageway 156, 158 near a bottom surface 160 of the stem
portion 152 (FIG. 19). As illustrated in FIGS. 15 and 16, a
stainless steel tube or fitting 166 is inserted into the passageway
156 such that one end of the tube 166 abuts the ledge 156L and the
other end of the tube 166 extends outwardly from the lower surface
160 of the stem portion 152. Similarly, a stainless steel tube or
fitting 168 is inserted into each passageway 158 such that one end
of the tube 168 abuts the ledge 158L and the other end of the tube
168 extends outwardly from the lower surface 160.
[0142] A face seal 169 is adhered or otherwise attached to the
lower surface 160 of the gas flow member 150. The face seal 169 has
generally the same shape or profile as the guided opening 138 and
the gas flow member stem portion 152. The face seal 169 includes
apertures that are aligned with the gas flow member passageways
156, 158. When attached, the stainless steel tubes 166, 168 extend
downwardly past the face seal 169.
[0143] As shown in FIGS. 20 and 21, each of the passageways 156,
158 extends upwardly through the stem portion 152, then makes a
pair of 90 degree turns in the head portion 154. This configuration
allows for the passageways to be spaced apart a greater radial
distance such that tubes connected thereto may wrap around a
compression spring, as described below. An opening 162 may be
formed from one of the 90 degree runs of the passageway 156 and
openings 164 may be formed from one of the 90 degree runs of the
passageways 158. The openings 162, 164 may be filled with plugs 167
(FIG. 22).
[0144] An opening 166 is formed from the other of the 90 degree
runs of the passageway 156 and openings 168 are formed from the
other of the 90 degree runs of the passageways 158. The openings
166, 168 are located in alcoves 170. The alcoves 170 provide
tooling space for the attachment of fittings 172, such as barbed
fittings, to the openings 166, 168 (FIG. 22).
[0145] Turning to FIG. 22, a flexible tube 174 is attached to the
fitting 172 attached to the opening 166. A flexible tube 176 is
attached to the fitting 172 attached to each opening 168. The
flexible tubes 176 receive return or discharge gas that flows
upwardly through the passageways 158 of the gas transfer member
150. The flexible tube 174 ultimately supplies pressurized gas to
the passageway 156 of the gas transfer member 150 such that the
pressurized gas may flow downwardly therethrough.
[0146] The tubes 174, 176 extend upwardly and wrap around a
compression spring 178. The tubes 174, 176 may be wrapped around
the spring 178 in a helical configuration, for example. Again, the
gas transfer member 150 is configured to move upward from its
seated position; for example, the gas transfer member 150 may move
upward after a "successful sterilization event" has been performed
by the gas dispersion device 10 and detected or validated by the
gas transfer device 100. In FIG. 22, the gas transfer member 150 is
shown in its "seated" or down position. The compression spring 178
is received in a central valley 171 of the gas flow member head 154
(FIG. 21) and helps urge the gas transfer member 150 in the seated
position. Further, the gas flow member head 154 includes an opening
180 sized and configured to receive a pin 182. The pin 182 is
extendable and retractable, for example by a solenoid valve 184.
The solenoid valve 184 may be received in an opening 185 of the
fixed housing member 140 (FIG. 18). In FIG. 22, the pin 182 is
shown in its extended position, engaging the opening 180, thereby
further urging the gas flow member to remain the down or seated
position.
[0147] FIG. 23 illustrates a portion of the gas transfer device 100
above the compression spring 178. As illustrated, the tubes 174,
176 terminate near a top portion of the spring 178, at which point
they connect with gas flow passageways (via barbed connectors, for
example). Pressurized gas is supplied from the gas supply canister
108, as shown by the arrows indicated SG. The pressurized supply
gas travels along passageway 190 to a first port of a solenoid
valve and then travels along a different passageway 192 from a
second port of the solenoid valve. The solenoid valve is described
in further detail below. The gas that travels through passageway
192 enters the supply tube 174 and travels downwardly to the gas
transfer member 150, where the supply gas enters the supply gas
passageway 156.
[0148] The return or discharge gas flowing upwardly through the
tubes 176 is routed to a common return gas passageway 194 and
travels in a path shown by the arrows RG. Face seals 196, 198 may
be provided to seal the supply gas and return gas passageways,
respectively.
[0149] FIG. 24 shows the path of the pressurized supply gas SG in
greater detail. A solenoid valve 200 is provided. Supply gas
passageway 190 is attached to a first port 202 of the solenoid
valve 200 and supply gas passageway 192 is attached to a second
port 204 of the solenoid valve. The solenoid valve 202 is "normally
off" or "normally closed" such that supply gas typically will not
flow into or through the passageway 192. The valve 202 may be
energized or otherwise receive a signal to open when supply gas is
needed (i.e., when sterilization is to begin at the gas dispersion
device 10). At this point, the supply gas will flow into and
through the passageway 192, through the tube 174 and downwardly
through the passageway 156 of the gas flow or transfer member
150.
[0150] FIG. 25 shows the path of the discharge or return gas RG in
greater detail. The return gas passageway 194 ultimately branches
into two segments. A first segment 206 directs a portion of the
discharge or return gas RG to a gas level monitor sensor 210. The
gas level monitor sensor 210 is configured to monitor
characteristics of the return gas such that a determination can be
made as to whether a successful sterilization has taken place. For
example, if ozone is used as the pressurized gas, the sensor 210
may monitor the amount of oxygen or ozone in the return gas such
that a concentration over time (e.g., ppm ozone/time) can be used
to determine or validate whether sterilization is complete. Also
shown in FIG. 25 are printed circuit boards 212. A lesser or
greater number of circuit boards may be provided in various
embodiments. The printed circuit board(s) 212 may include or be
associated with at least one controller. The printed circuit
board(s) and/or the controller may control certain operations such
as supplying power to the solenoid valves, monitoring the sensors,
validating sterilization events and other operations that are
described herein.
[0151] A second segment 208 directs a portion of the return gas RG
to the gas discharge catalyst canister 110. Referring to FIG. 26,
return gas is supplied to a gas diffuser tube 214 located in the
gas discharge catalyst canister 110. The gas diffuser tube 214
includes a plurality of apertures 216 on an outer surface thereof
such that return gas is diffused in the area surrounding the
diffuser tube 214. A suitable catalyst material 218 is positioned
around the gas diffuser tube 214 to convert the return gas to
oxygen, which is then released through the gas vent 120 (FIG. 12).
For example, if ozone is used as the sterilization gas, manganese
dioxide/copper oxide, activated charcoal or a molecular sieve may
be supplied around the gas diffuser tube 214 such that waste ozone
is converted to oxygen.
[0152] A shear cutter assembly 220 is illustrated in FIG. 27. The
shear cutter assembly 220 is positioned inside the housing 101. The
assembly includes first and second spur gears 222, 224 having a 2:1
gear reduction. The first gear 222 is driven by a DC motor 226 and
a planetary gear reducer 228 (these components are hidden from view
by respective casings or housings). An eccentric cam 230 having an
extended portion 232 is driven by gear 224 via a cam shaft 234. A
cam follower 236 engages the cam 230. Attached to the cam follower
236 are the shear cutters 136 (see FIG. 14). A spring 238 surrounds
at least a portion of each shear cutter 136; the springs 238 are
also attached to the cam follower 236. The springs 238 are biased
such that the cam follower 236 is urged toward the cam 230.
[0153] The motor 226 drives the gear 222, which in turn drives the
gear 224, which in turn rotates the cam shaft 234 and the eccentric
cam 230. As the eccentric cam 230 rotates, the springs 238 compress
and the cam follower 236 and the shear cutters 136 are pushed away
from the cam shaft 234. Eventually, when the cam extended portion
232 engages the cam follower 236, the shear cutters 136 fully
extend from the shear cutter ports 134 (FIG. 14). As noted above,
the alignment key 132 of the canister assembly 100 may be matingly
received in the locating guide 80 of the gas dispersion device 10
such that the shear cutter ports 134 are aligned with shear cutter
access ports 82 of the gas dispersion device 10 (FIG. 1). As such,
with the shear cutters 136 extended, the shear key 58 of the gas
dispersion device 10 is cut, allowing the gas dispersion device 10
(or the gas flow member 24 thereof) to move from the sterilization
position to the product flow position, as discussed further
below.
[0154] Connection of the gas dispersion device 10 and the gas
transfer device 100 and the ensuing operation of the combined
system will now be described in greater detail. As shown in FIG.
28, the gas transfer device 100 is positioned over the gas
dispersion device 10; specifically, the mounting nut 122 is
centered over the collar 55 and the gas flow member upper portion
26. As shown in FIG. 29, the alignment key 132 of the transfer
device 100 is matingly received in the locating guide 80 of the gas
dispersion device 10. In some embodiments, the mounting nut 122 is
then rotated to threadingly engage the collar 55 of the gas
dispersion device. In some embodiments, the mounting nut 122 is
then rotated to engage the collar 55' for creating a bayonete-type
engagement (as shown in FIGS. 50B, 51B, 52B, and 53). Although not
illustrated in FIGS. 28 and 29, flow components (e.g., connectors,
fittings, sensors, tubes, etc.) will typically be operatively
connected to the flanges 22 of the gas dispersion device 10 for
subsequent sterilization before the gas transfer device 100 is
introduced.
[0155] The gas transfer device 100 is connected with the gas
dispersion device 10 in the sterilization position. This is
apparent from FIG. 29, wherein the gas dispersion and gas return
ports 32, 38 are visible through the conduit 20. As such, the gas
flow member 24 is in its lowered position when the gas canister
assembly 100 is coupled to the gas dispersion device 10.
[0156] Referring to FIGS. 1, 2, 15 and 16, the gas flow member
upper portion 26 of the gas dispersion device 10 is received in the
guided opening 138 of the gas transfer device 100. The top surface
of the gas flow member upper portion 26 contacts the face seal 169.
The tube 166 is received in the gas supply passageway 34 through
the gas supply port 30 and the tubes 168 are received in the gas
return passageways 36 through the return discharge gas ports 40.
The ends of the tubes 166, 168 may be seated on a ledge in
respective passageways 34, 36 similar to the opposite ends of the
tubes 166, 168 seated on the ledges 156L, 158L in the passageways
156, 158 (FIG. 19). The insertion of the tubes 166, 168 into the
passageways along with the face seal 169 help to ensure a sealed
connection between the gas dispersion device 10 and the gas
transfer device 100.
[0157] In this position, the gas supply passageway 34 of the gas
dispersion device 10 is in fluid communication with the gas supply
canister 108 and the gas return passageways 36 of the gas
dispersion device 10 are in fluid communication with the gas
discharge catalyst canister 110, with the exception of any flow
blocking mechanisms disposed therebetween (e.g., the solenoid valve
200 shown in FIG. 24).
[0158] With the portable gas transfer device 100 coupled to the gas
dispersion device 10 as described above, an operator may use the
display 116, the operator interface 118 and/or the indicator lights
114 to initiate and monitor a sterilization process. As shown in
FIG. 30, the display 116 may display data including, but not
limited to, a date and time stamp 250, an identification of the gas
supply canister assembly 252, a connection or joint identification
254 and an operator identification 256.
[0159] The date and time 250 may be dynamically updated by at least
one onboard controller of the gas transfer device 100. The gas
canister assembly identification 252 may also be provided by the
onboard controller. These data may be automatically displayed on
the display 116 without any user input. In some embodiments, these
data are displayed before the gas transfer device 100 is connected
to the gas dispersion device 10 as well as after the gas transfer
device 100 is connected to the gas dispersion device 10.
[0160] The connection or joint identification 254 identifies the
connection or joint in the bioprocessing system that is to be
sterilized. Specifically, this is the connection or joint at which
a particular gas dispersion device 10 is attached (e.g., a specific
connection or joint in a bioprocessing system). The connection or
joint identification 254 may be displayed on the display 116
without any user input and/or before the gas canister assembly 100
is connected with the gas dispersion device 10. In this regard, the
connection or joint identification 254 may direct the operator to
the proper connection or joint to be sterilized. In some other
embodiments, the operator may use the operator interface 118 to
input the connection or joint identification, which may be marked
on or near the connection or joint or on a map, for example. The
operator may depress the arrow keys 260 to scroll between various
displays or lists, one of which may include a list of possible
connections or joints. The operator may depress the "enter" key 262
when the correct connection or joint identification is found or
highlighted. Other configurations for the operator interface 118
are contemplated. As just one example, the display 116 may be a
touch-sensitive display to supplement or replace the operator
interface 118.
[0161] The operator identification 256 generally must be input by
the operator. The operator may use the operator interface 118 to
enter a password or other identifying information. Once the
operator has been identified, the gas transfer device 100 may
"unlock" to allow the sterilization process to begin.
[0162] The operator may press the "start" button 264 to begin the
sterilization process. The indicators 114 provide visual feedback
to the operator throughout the process. The indicators 114 may be
differently colored LEDs or the like to provide the visual
feedback. For example, the indicator 114a may be an amber LED that
indicates that sterilization is in progress, the indicator 114b may
be a green LED that indicates that a successful sterilization has
taken place and the indicator 114c may be a red LED that indicates
an unsuccessful sterilization or that a sterilization "fault" has
occurred.
[0163] At the beginning of the sterilization process, power or a
signal is supplied to the solenoid valve 200 (FIG. 24). The
solenoid valve 200 turns on or opens, allowing the pressurized
supply gas SG to exit the port 204 and flow along the passageway
192. The supply gas SG flows in the tube 174 downwardly and around
the spring 178 (FIG. 22). The supply gas SG enters the movable gas
transfer member 150 at port 166 (FIG. 21) and flows downwardly
through the passageway 156 of the gas transfer member 150 (FIGS. 19
and 20). The supply gas SG enters the gas dispersion device 10
through the gas supply port 30 of the gas flow member 24 (FIG. 1).
The supply gas flows downwardly, then outwardly through the gas
flow member supply gas passageway 34, at which point the supply gas
is rapidly dispersed via the gas dispersion openings 32 (FIG. 5).
The dispersed supply gas flows through the conduits 20 and past or
adjacent flow components operatively attached to the flanges 22, as
described in detail above.
[0164] "Post-sterilization" or return gas is received in the gas
return openings 38 (FIGS. 3 and 4) and flows upwardly through the
gas flow member return gas passageways 36 (FIG. 2). The return gas
flows upwardly through the movable gas flow member passageways 158
(FIGS. 19-21). The return gas then enters the tubes 176 and flows
therethrough upwardly and around the spring 178 (FIG. 22). As shown
in FIG. 23, the return gas RG flows through a pair of short
passageways which converge into the single return gas passageway
194. As shown in FIG. 25, the return gas RG flows through the
passageway 194 toward the gas discharge catalyst canister 110 and
the gas level monitor sensor 210. Segments 206 and 208 branch from
the passageway 194. A portion of the return gas RG is directed
through the segment 208 into the gas discharge catalyst canister
110, where it is converted into a safe and/or stable discharge gas,
which is then discharged through the vent 120, as described
above.
[0165] A portion of the return gas RG is direction through the
segment 208 to contact the gas level monitor sensor 210. The sensor
210 continuously detects a characteristic, such as a level of a
substance, of the return gas RG. The signal detected by the sensor
210 is provided to a controller, which continuously monitors the
detected characteristic. For example, if the pressurized
sterilization gas is ozone, the sensor 210 detects the level of
ozone present in the return gas. The controller determines the
level of ozone over time (e.g., ppm of ozone over time). A
threshold value of level of ozone over time is known to correlate
to a predetermined required sterilization level, such as a SAL of
10.sup.-6. When this threshold value is reached, the controller
determines that a "good sterilization" has taken place. A good
sterilization indicates that all components in fluid communication
with the gas dispersion device 10 have been adequately
sterilized.
[0166] After it has been determined or validated that a "good
sterilization" has taken place, the sterilization process ends. The
controller sends a signal to the solenoid 184 and the pin 182 is
retracted from the opening 180 in the head portion 154 of the
movable gas flow member 150 (FIG. 22). At this point, the movable
gas flow member 150 remains in position; the weight of the spring
178 continues to urge the movable gas flow member 150 downward such
that the head portion 154 remains seated on the sill 148 of the
fixed housing member 140 (FIG. 17).
[0167] Referring to FIG. 27, the controller then sends a signal to
turn on the motor 226. The motor 226 drives the gear 222, which in
turn drives the gear 224. The motor turns the gear 222 one full
revolution, which corresponds to one half revolution of the gear
224 due to the 2:1 reduction. The rotation of the gear 224 results
in a corresponding rotation of the cam shaft 234 and eccentric cam
230. The extended portion 232 of the cam 230 fully engages the cam
follower 236 after 180 degrees of rotation. As a result, the cam
follower 236 and the shear cutters 136 attached thereto are pushed
against the force of the spring 238 such that the shear cutters 136
extend out of the shear cutter ports 134 of the alignment key 132
(FIG. 14) and into the shear cutter access ports 82 of the gas
dispersion device 10 (FIG. 1).
[0168] The shear cutters 136 cut the shear key 58 of the gas
dispersion device 10 such that the pin 42 retracts from the opening
41 in the gas flow member 24 and the gas flow member 24 moves to
the product flow position due to the force of the spring 44 (FIGS.
6 and 8). As illustrated in FIG. 7, the gas dispersion device 10 or
the gas flow member 24 is locked in the product flow position by
the locking cams 62. The gas dispersion device 10 is typically
single-use disposable; accordingly, this locking action will
advantageously hinder or prevent the gas dispersion device 10 from
being reused for sterilization purposes.
[0169] Although not illustrated in FIG. 16, as discussed above, the
gas dispersion device gas flow member 24 engages the gas canister
assembly movable gas flow member 150 at the face seal 169. The tube
166 extends into the gas dispersion device gas supply port 30 and
the tubes 168 extend into the gas return openings 40 (FIG. 1). When
the gas dispersion device gas flow member 24 moves upward into the
product flow position, the movable gas flow member 150 moves upward
a corresponding distance. In some embodiments, the upward travel is
less than about 1 inch. In some embodiments, the upward travel is
between about 0.5 and about 0.75 inches.
[0170] As described above, at least one of the indicators 114 (FIG.
30) may provide visual feedback to the operator that the
sterilization process is complete and/or that a successful or
"good" sterilization event has been validated. After the
sterilization process, the operator may loosen the mounting nut 122
and disconnect the gas transfer device 100 from the gas dispersion
device 10.
[0171] A sterilization gas supply/refilling system 300 according to
some embodiments is illustrated in FIG. 31. The system 300 includes
a portable gas transfer device docking station 302. The docking
station has a plurality of docking areas, with each area configured
to receive one of a plurality of portable gas transfer devices
100.sub.1, 100.sub.2, 100.sub.3, 100.sub.4. Although not
illustrated, each docking area may include guide tracks to receive
the portable gas transfer device guide bars 126 shown in FIG. 13.
This configuration provides audible and/or tactile feedback that
the portable gas transfer device has been properly seated in the
docking area. Each docking area includes a gas supply connection
for the gas refill supply valve 128 and an electrical connection
for the electrical interface 130.
[0172] The portable gas transfer devices 100.sub.1, 100.sub.2,
100.sub.3, 100.sub.4 are refilled through the valve 128 with
pressurized sterilization gas supplied from the gas supply manifold
304. Various transmitters may be integrated into the gas supply
manifold 304, including a pressure transmitter (PT) 306, a relative
humidity transmitter (RHT) 308, and/or a gas concentration monitor
transmitter (GCMT) 310. Other sensors or transmitters may be
incorporated as needed. Signals from the transmitters are fed to an
electrical control interface system 314.
[0173] In some embodiments, the gas supply manifold 304 is supplied
with an existing sterilization gas supply. Alternatively, a
sterilization gas generation and/or supply system 320 may be
provided to supply gas to the gas supply manifold 304. In the
illustrated embodiment, the system 320 generates ozone gas from a
separate oxygen supply. The system 320 pressurizes and supplies the
gas to the manifold 304. Pressure levels (e.g., 90-100 psig) are
controlled by a pressure regulator (PR).
[0174] In some embodiments, a relative humidity (RH) generating
system 322 is provided. The effectiveness of certain sterilization
gases in achieving a (log 6) pathogen kill rate is enhanced by
increased RH levels. The RH system 322 may supply clean moisture
(at a controlled RH) to sterilization gas steam, for example.
[0175] Certain sterilization gases (such as ozone) have relatively
short "half-life" gas concentration reduction due to
pressurization. As such, a gas catalytic converter system 312 may
be provided; any portable gas transfer devices 100 that have been
docked past the allowable "half-life" time limit may be discharged
to the gas catalytic converter system 312. The gas catalytic
converter system 312 converts harmful or toxic sterilization gases
to a safe discharge gas. In the case of ozone (O.sub.3), it is
converted to (O.sub.2) by the catalytic converter. The discharged
portable gas transfer devices may then be refilled from the gas
supply manifold system 304. Furthermore, unused sterilization gas
from the gas supply manifold 304 may be directed to the gas
catalytic converter system 312. These actions may all be controlled
automatically from the electrical control interface system 314.
[0176] As noted above, the docking station 302 also includes an
electrical connection for the electrical interface 130 of each
portable gas transfer device 100. Each portable gas transfer device
100 includes at least one battery pack to provide power to various
components (e.g., the display, the controller, etc.). The
electrical connection at the docking station recharges the battery
pack. In addition, the electrical connection transfers electronic
validation data from the portable gas transfer devices to a central
data base 318 via a data transfer interface 316.
[0177] Specifically, the data transfer interface 316 controls the
transfer of electronic sterilization validation protocol data from
the portable gas transfer devices to the main central data base
318. Each time a portable gas transfer device 100 sterilizes a
single-use aseptic connection or joint in a bioprocess system, an
electronic signature of the portable gas transfer device ID, the
single-use connection ID, the operator ID (all described above in
connection with the display 116), as well as the gas concentration
per time (e.g., ppm of ozone/time) is stored on an EPROM in the
portable gas transfer device controller. Other data such as
relative humidity may also be included as each bio-process system
warrants.
[0178] As indicated above, the electrical control interface 314 is
the overall system control hub. It controls each subsystem
function, sensor/transmitter monitoring, and data transfer to the
central database computer. It is noted that, when the gas transfer
devices are docked in the docking areas, they are effectively
"reset" for future use. This includes not only refilling the
pressurized gas canister, but also sending a signal to the solenoid
184 such that the pin 182 engages the opening 180 of the gas
transfer member 150 (FIG. 22), for example.
[0179] A power supply/distribution system 324 system supplies the
AC/DC power requirements of the overall system.
[0180] Pressurized gas, such as ozone, may be injected in a
single-use connection site or joint in a number of ways. Examples
include, but are not limited to: a gas syringe injection; a
single-use valve system (e.g., the gas dispersion interconnect
device 10 described above); a rotating gas dispersing tube; and a
gas dispersing spray ball.
[0181] A sterilization apparatus 400 according to some embodiments
is illustrated in FIG. 32. Generally, the sterilization apparatus
400 includes two portions: a sealable local environment 410 and a
pressurized gas (e.g., ozone) source 420, the form and function of
each of which are described in detail with reference to FIGS.
32-40. An aseptic connection point (not shown in FIG. 32), such as
an open portion of a fluid path or two or more fluid flow
components or connectors, may be received within the sealable local
environment 410. Although the aseptic connection point may have
been pre-sterilized, for purposes of this description, it is
assumed that an ambient environment 430 may not be sufficiently
sterile. Accordingly, to effect an aseptic connection, the aseptic
connection point is received within the sealable local environment
410 which is then sealed against the ambient environment 430.
[0182] After the sealable local environment 410 is sealed, the
ozone source 420 is used to introduce a supply of ozone (not shown
in FIG. 32) into the sealable local environment 410. Exposure to
the supply of ozone, for example at a predetermined concentration
and for a predetermined duration, enables the sealable local
environment 410 and the aseptic connection point therein to reach a
predetermined sterilization level. As a result, an aseptic
connection may be made within an ambient environment 430 that may
not be sterile. The ozone source 420 may include a pneumatic
injection device, such as a syringe, adapted to penetrate a
membrane described with reference to FIG. 35 to introduce the
supply of ozone into the interior of the sealable local environment
410. Alternatively, the ozone source 420 may include another type
of pump or may include an ozone generator, such as a water
electrolysis ozone generator. Alternatively, the ozone source 420
may take the form of the portable gas transfer device 100 described
above or a similar device.
[0183] FIG. 33 is a perspective view of a sealable local
environment 410 of the sterilization apparatus 400 of FIG. 32 in
which the sealable local environment 410 includes a rigid
structure. As further described with reference to FIG. 38, the
sealable local environment may alternatively comprise a flexible
body. The sealable local environment 410, shown in a closed
position, may be configured to receive the aseptic connection point
(not shown in FIG. 33) which, for sake of example, may include a
pair of more fluid path connectors or fluid flow components
(referred to below as "connectors"). As previously described, the
connectors may be pre-sterilized but may need to be coupled in a
non-sterile ambient environment 430 (FIG. 32). To allow the
connectors to be aseptically coupled within the non-sterile ambient
environment 430, each of the connectors may be received in chambers
440 and 450 of the sealable local environment 410. The chambers 440
and 450 may include openings 442 and 452, respectively, to enable
connection lines (not shown in FIG. 33) to extend from the sealable
local environment 410 to fluid lines or fluid sources (also not
shown in FIG. 33) to which the connectors are coupled.
[0184] Once the connectors are in place in the sealable local
environment 410, the sealable local environment may be sealed by
securing a closure device 460. The closure device 460 may be in the
form of a screw-driven closure that may be closed and secured by
turning a knob 462. Once the connectors have been sterilized within
the sealable local environment 410, as further described below, the
sealable local environment 410 may be manipulated to enable the
connectors enclosed therein to be coupled together while the
sterile, sealable local environment 410 remains sealed. The
sealable local environment 410 may include a manipulator 470, such
as a screw-driven manipulator, that enables the chambers 440 and
450 of the sealable local environment to be drawn together without
unsealing the sealable local environment 410. In some embodiments,
an actuator 472, such as a knob, may be turned to drive the
chambers 440 and 450 together so as to forcibly interconnect the
connectors within the sterile, sealable local environment 410. Once
the connectors have been interconnected, the closure device 460 may
be released and the joined connectors (or other secured connection
point) may be removed from the sealable local environment 410. The
connection point may then be exposed to a potentially non-sterile
environment without exposing the fluid path to contamination.
[0185] FIG. 34 is an internal cross-sectional view of the sealable
local environment 410 of FIG. 33. As previously described with
reference to FIG. 33, the sealable local environment 410 includes
chambers 440 and 450 to receive parts of the connection point, such
as a pair of fluid path connectors or fluid flow components (not
shown in FIG. 34). The chambers 440 and 450 may include end
portions 444 and 454, respectively, to forcibly engage portions of
the fluid path connectors. By forcibly engaging ends of the fluid
path connectors, when the actuator 472 is manipulated to drive the
chambers 440 and 450 together, the fluid path connectors will be
forcibly interconnected at a central point 480 of the sealable
local environment 410. It is noted that, before the actuator 472 is
manipulated to interconnect the fluid path connectors, the fluid
path connectors or other connection point may not be joined
together at the central point 480. As described with reference to
FIG. 35, the supply of ozone or other gas is introduced near the
central point 480 to facilitate sterilization of interior portions
of the fluid path connectors or other connection point before the
connection point is closed.
[0186] As previously described with reference to FIG. 33, once the
aseptic connection has been made within the sealable local
environment 410, the sealable local environment 410 may be unsealed
and the aseptically sealed fluid path connectors or other
connection point may be removed and exposed to the ambient
environment without risk of contamination of the fluid path.
[0187] FIG. 35 is a perspective view of the sterilization apparatus
400 of FIG. 32 showing a membrane 500 in the sealable local
environment 410 configured to receive a supply of ozone (not shown)
from the ozone source 420. As previously described with reference
to FIG. 34, according to some embodiments, the membrane 500 is near
the central point 480 (FIG. 34) of the sealable local environment
410 so that the supply of ozone may reach interior portions of the
fluid path connectors or other connection point to sterilize
interior portions of the connection point that may engage the fluid
within.
[0188] In some embodiments, the membrane 500 may define a small
opening sized to closely engage sides of a needle or other
injection member 422 of the ozone source 420. Having the membrane
500 and the injection member 422 closely match in size may prevent
leakage at the membrane 500. The membrane 500 may be comprised of a
penetrable material to enable the injection member 422 to penetrate
the membrane 500 while the membrane sealingly engages sides of the
injection member 422. As previously described with reference to
FIG. 32, the ozone source may include a pneumatic device, such as a
syringe or other pump. Alternatively, the ozone source may include
an ozone generator that is securable to the membrane 500 or a
similar port formed in the sealable local environment 410 to
receive the supply of ozone. An exemplary "ozone generator" is the
portable gas transfer device 100 described above.
[0189] FIG. 36 is another perspective view of the sterilization
apparatus 400 of FIG. 32 showing the ozone source 420 upon
insertion into the membrane 500. As previously described, the
injection member 422 may penetrate and puncture the membrane 500,
facilitating a tight seal between the membrane 500 and the
injection member 422. In some embodiments, the tight seal between
the membrane 500 and the injection member 422 prevents microbial
contamination of the interior of the sealable local environment 410
while containing the supply of ozone within the interior of the
sealable local environment 410.
[0190] FIG. 37 is a cutaway view of the ozone source 420 showing
details of the injection member 422 according to some embodiments.
In some embodiments, the sealable local environment 410 permits the
injection member 420 to be inserted into the sealable local
environment 410 to a depth sufficient to enable one or more
orifices 424 of the injection member 422 to enter into the sealable
local environment 410. The supply of ozone (not shown) is presented
into the sealable local environment 410 through the orifices
424.
[0191] In some embodiments, after sterilization, the supply of
ozone may be captured from the sealable local environment 410 prior
to unsealing the sealable local environment. The captured ozone may
thus be stored or disposed of as desired. For example, the captured
supply of ozone may be passed through a catalytic converter to
convert the ozone to oxygen, and then released.
[0192] FIG. 38 is a top perspective view of a sterilization
apparatus according to other embodiments in which a sealable local
environment 510 comprises a flexible body. The sealable local
environment 510 may be in the nature of a glove box that includes
flexible openings in a more rigid shell to receive a user's hands
520. Alternatively, the sealable local environment 510 overall may
include a flexible body allowing the user's hands 520 to manipulate
the sealable local environment 510 to enable connection of fluid
path connectors or fluid flow components or some other connection
point within a sterile sealable local environment 510. The sealable
local environment 510 may include one or more membranes or other
orifices 530 to receive an ozone source (not shown in FIG. 38). The
sealable local environment 510 also may include one or more outlets
540 to enable fluid lines coupled to the fluid path connectors or
other connection point to extend outwardly through sides of the
sealable local environment 510.
[0193] FIG. 39 is a flow diagram of a method 600 of sterilizing an
open portion of a fluid path according to some embodiments. At
block 602, an open portion of a fluid path is received in a
sealable local environment. As previously described with reference
to FIG. 34, for example, the open portion of the fluid path may
include fluid path connectors to be interconnected in a potentially
non-sterile environment. The sealable local environment 410 may be
opened and the fluid path connectors may be inserted within the
sealable local environment 410. At block 604, the sealable local
environment is sealed. As described with reference to FIG. 33, the
sealable local environment 410 may be sealed through the use of a
closure device 460. At block 606, a supply of ozone is received
into the sealable local environment, where the portion of the fluid
path is exposed to the ozone. As described with reference to FIGS.
34-37, for example, an ozone source, such as a syringe or other
pneumatic device or an ozone generator may be coupled to the
sealable local environment 410 and a supply of ozone thus may be
introduced into the sealable local environment 410. As also
previously described, by introducing the supply of ozone into the
sealable local environment before the fluid path connectors are
interconnected, the fluid path is exposed to and sterilized by the
ozone.
[0194] FIG. 40 is a flow diagram of a method 700 of sterilizing an
open portion of a fluid path according to some embodiments. At
block 702, two or more fluid path connectors are received in a
sealable local environment, where the two or more fluid path
connectors are configured to be used in an aseptic fluid
environment, and where the two of more fluid path connectors are
received in the sealable local environment prior to interconnecting
the two or more fluid path connectors. As previously described with
reference to FIG. 34, the two or more fluid path connectors may
need to be interconnected in a potentially non-sterile environment.
The sealable local environment 410 may be opened and the fluid path
connectors may be inserted within the sealable local environment
410. At block 704, the sealable local environment is sealed. As
described with reference to FIG. 33, the sealable local environment
410 may be sealed through the use of a closure device 460.
[0195] At block 706, a supply of ozone is received into the
sealable local environment, where the supply of ozone is supplied
at a combination of a concentration and for a duration configured
to cause the sealable local environment to reach a predetermined
sterilization level. As described with reference to FIGS. 34-37,
for example, an ozone source, such as a syringe or other pneumatic
device or an ozone generator may be coupled to the sealable local
environment 410 and a supply of ozone thus may be introduced into
the sealable local environment 410. As also previously described,
by introducing the supply of ozone into the sealable local
environment before the fluid path connectors are interconnected,
the fluid path is exposed to and sterilized by the ozone. The
concentration of ozone may be calculated based on the duration for
which the fluid path connectors are to be exposed or based on the
ozone source selected. At block 708, after the predetermined
sterilization level is reached, the two or more fluid path
connectors are interconnected within the sealable local
environment. As described with reference to FIGS. 33 and 34, in a
rigid sealable local environment 410, a manipulator or actuator 472
may be used to forcibly interconnect the fluid path connectors
within the sealable local environment. As described with reference
to FIG. 38, when the sealable local environment includes a flexible
body, a user may manipulate the flexible body to interconnect the
fluid path connectors.
[0196] Although the component 420 is described herein as an ozone
source, it is contemplated that the component 420 could be a source
of other pressurized gas/vapor, including low-temperature gas/vapor
sterilants such as, but not limited to: ethylene oxide (EO or EtO),
vaporized hydrogen peroxide (VHP or HPV), hydrogen peroxide gas
plasma, vaporized formaldehyde, gaseous chlorine dioxide and
vaporized peracetic acid.
[0197] It is noted that the ozone source 420 (or other pressurized
gas/vapor source) could be used in connection with the gas
dispersion device 10 described above or a similar device. For
example, referring to FIG. 1, the ozone source 420 could be
inserted into the gas supply port 30. A membrane similar to the
membrane 500 could be positioned at or near the gas supply port 30,
and the membrane could receive the ozone source injection member
422 therethrough. Thus, the gas dispersion device 10 may be used
with other pressurized gas/vapor sources, such as a syringe. The
gas dispersion device 10 may provide advantages as the internal
portions of the interconnected process connection or joint, or
fluid flow components attached to the gas dispersion device 10,
need not be disconnected and exposed to an ambient and potentially
non-sterile atmosphere after sterilization and before a fluid, such
as bioprocessing fluid, flows therethrough.
[0198] A gas interconnect dispersion device 800 according to some
other embodiments is illustrated in FIGS. 41-43. The gas dispersion
device 800 is similar to the gas dispersion device 10; however, the
gas dispersion device 800 includes a rotatable gas flow member
rather than a retractable gas flow member. Other differences
between the gas dispersion devices 10 and 800 will be apparent from
the description below.
[0199] The gas dispersion interconnect device 800 shown in FIG. 41
includes a cylindrical valve body 802 defining a valve cavity 804
therein, in which is disposed a butterfly valve element 806 (e.g.,
a rotatable gas flow member). The interconnect device 800 includes
a first inlet/discharge port assembly 840 including inlet/discharge
conduit 842, and connection flange 846 having central opening 848
therein communicating with the interior bore of conduit 842. The
bore in conduit 842 communicates with the interior volume of the
valve cavity 804.
[0200] In like manner, the interconnect device 800 includes a
second inlet/discharge port assembly 850, comprising
inlet/discharge conduit 852 coupled to connection flange 856 having
an inlet/discharge opening that communicates with the bore of
conduit 852. The bore in conduit 852 communicates with the interior
volume of valve cavity 804.
[0201] The butterfly valve element 806 includes a cylindrical
collar 816 having an open bore 818 therein communicating with an
interior passage (not shown) in the main body portion 810 of the
valve element. The main body portion as shown has a top surface 814
containing gas discharge ports at its lateral portions, by which
previously used sterilization gas (e.g., ozone gas) can be
discharged from the valve in the direction indicated by arrows
B.
[0202] Depending downwardly from the main body portion 810 is a
lower collar member 820, which may be journaled or otherwise
secured in the valve assembly, being coaxial with the upper collar
member 816, whereby the valve in operation can be bi-directionally
rotated in the directions indicated by the bi-directional arrow
A.
[0203] The butterfly valve 806 is shaped so that it has a
cross-sectional profile that is taperingly convergent from the
central axis defined by collar members 816 and 820, to the lateral
edges 812 of the valve element. The main body 810 of the valve
element thus may have a flattened or flap-like character.
[0204] The main body 810 of the butterfly valve 806 has a central
opening extending transversely through the main body 810
(transverse to the central axis of the valve element, as defined by
the center line of the valve element extending longitudinally
through the main body 810 and upper collar 816 and lower collar
820) and outwardly from the respective faces of the valve element.
The transverse dispersion opening 822 communicates by an interior
passage (not shown in FIG. 41) with the bore 818 of upper collar
816, so that ozone gas introduced into the bore 818, in the
direction indicated by arrow C, flows through the upper collar 816
and the internal passage of main body 810 and is discharged at both
faces of valve element from the transverse opening 822 into the
valve cavity 804, so that the dispersed sterilant fluid is
thereafter distributed throughout the valve cavity 804 and passages
in conduits 842 and 852.
[0205] Such gas introduction can be carried out so that the gas
dispersion interconnect device 800 that is coupled with flow
circuitry elements at each of the flanges 846 and 856, e.g., to
tubing, piping, conduits, or other flow passage structure or fluid
flow components achieves a sterile connection.
[0206] The main body 810 of the valve element 806 is also provided
with lateral gas return ports 826 and 830 on one face of the main
body (on the front face of the valve element in the view shown in
FIG. 41), with lateral gas return ports 834 and 836 on the opposite
face and opposite marginal portion of the valve element 806 (i.e.,
the right-hand marginal portion on the back face of the valve
element in the view shown in FIG. 41).
[0207] The front face gas return ports 826 and 830 in the view
shown communicate with the return gas discharge port at the top
face 814 at the left-hand portion thereof, and the return gas ports
834 and 836 communicate with the return gas discharge port at the
right-hand portion of the top surface 814 of the valve element
806.
[0208] In this manner, each of the front and rear main faces of the
butterfly valve element 806 present gas return discharge port
openings communicating with interior passages in the main body 810,
so that gas following contact with interior surfaces of the valve
chamber and associated flow circuitry structure enters the gas
return port openings, flows through the interior passage structure
of the valve element and is discharged from the valve at the gas
discharge ports on the top surface 814 of the valve element,
flowing in the direction indicated by arrows B in FIG. 41.
[0209] The valve element 806 may be rotatable as shown by the arrow
A between a sterilization position and a product flow position. In
the sterilization position, the dispersion opening 822 may be
aligned or generally aligned with the bores of the conduits 842,
852. In the product flow position, the valve element 806 may be
rotated (e.g., by 90 degrees or about 90 degrees) so as to provide
additional fluid flow space in the valve cavity 804.
[0210] FIG. 42 is a front elevation view of the valve element 806.
As illustrated, the dispersion opening 822 extends through the body
of the valve element. The dispersion opening 822 is configured to
rapidly disperse "pre-sterilization" pressurized gas received from
the upper collar bore 818 in the direction C (FIG. 41). Also shown
are gas return openings or ports 826, 830. The gas return openings
826, 830 are configured to receive "post-sterilization" gas, which
is then directed upward in the direction B (FIG. 41). Gas return
openings 834, 836 (FIG. 41) are disposed on the opposite side of
the valve element 806 and are not visible in FIG. 42.
[0211] As shown in FIGS. 41 and 43, at least a portion of the valve
element 806 may be contained in the valve cavity 804 by a lid 870.
The lid 870 may include openings or ports 872 that may be aligned
with the gas discharge openings at the valve element top surface
814. The upper collar 816 may extend upwardly past the lid 870.
[0212] The gas dispersion device 800 may be configured to receive a
device similar to the portable gas transfer device 100 described
above which may supply pressurized gas to the gas dispersion device
800 and/or may receive discharged post-sterilization gas from the
gas dispersion device 800. Further, the ozone source 420 of FIG. 32
(or other pressurized gas/vapor source) could be used in connection
with the gas dispersion device 800 or a similar gas dispersion
device. For example, referring to FIG. 41, the ozone source 420
could be inserted into the upper collar bore 818. A membrane
similar to the membrane 500 (FIG. 35) could be positioned at or
near the upper collar bore 818, and the membrane could receive the
ozone source injection member 422 therethrough. Thus, the gas
dispersion device 800 may be used with other pressurized gas/vapor
sources, such as a syringe.
[0213] A gas interconnect dispersion device 900 according to some
other embodiments is illustrated in FIGS. 44-46. The device
includes a housing 910, with the housing defining an internal
cavity or chamber 912. A top portion 914 includes a gas inlet port
916 and a pair of gas outlet ports 918. Two flow conduits 920 are
in fluid communication with the chamber 912, with each of the
conduits 920 extending away from the chamber 912 at different sides
of the housing 910. The housing may be generally cylindrical in
shape, and the conduits 920 may be diametrically opposed.
[0214] A rotatable gas flow tube assembly 930 (FIG. 46) is at least
partially disposed within the chamber 912. The rotatable tube
assembly 930 includes a pair of dispersion openings 932 in fluid
communication with the gas inlet port 916. The dispersion openings
932 are configured to effectively and rapidly disperse pressurized
"pre-sterilization" gas received from the gas inlet port 916
throughout the chamber 912 and through the conduits 920. The
rotatable tube assembly 930 is rotatable between a sterilization
position and a product flow position, as described in more detail
below.
[0215] The device 900 also includes a pair of return tubes 934
(FIG. 45) at least partially disposed within the chamber 912. Each
return tube 934 is in fluid communication with a respective gas
outlet port 918. The tubes 934 are configured to receive
"post-sterilization" gas; as described above, "post-sterilization"
gas means gas that has already been dispersed and sterilized
various components and/or has sterilized various components to a
Sterile Assurance Level (SAL) of 10.sup.-6. The ends or tips of the
tubes 934 disposed in the chamber 912 may be beveled, as best seen
in FIG. 45.
[0216] Like the devices 10 and 800 described above, the device 900
is connectable or operatively connectable to various components,
such as connectors, fittings, flow passageways and
sensors/transmitters (e.g., fluid flow components), via the
conduits 920. Specifically, a distal end portion of each conduit
920 is configured to connect or operatively connect with at least
one fluid flow component. As illustrated, the distal end portion of
each conduit 920 includes a flange 940 to accommodate connection
with such components, such as by a sanitary clamp. When the device
900 is connected to fluid flow components, the rotatable tube
dispersion openings 932 are configured to disperse gas received
from the gas inlet port 916 through or past the conduits 920 and
adjacent or past the fluid flow components to sterilize these
components (e.g., to achieve a SAL of 10.sup.-6 for these
components).
[0217] In some embodiments, at least a portion of the housing 910,
the conduits 920 and the flanges 940 form a monolithic structure.
The rotatable tube assembly 930 may include a T-shaped member that
defines the dispersion openings 932. The rotatable tube assembly
930 may be at least partially enclosed within the chamber 912 by a
lid 950. Extending from or through the lid 950 is a collar 952 that
defines the gas inlet port 916. The lid 950 may also include
through-holes that align with the gas outlet ports 918. As
illustrated, the rotatable tube assembly 930 and/or the lid 950
include one or more o-rings or other seals to effectuate a seal
between the various components and to hinder the passage of pre- or
post-sterilization gas or other fluid (e.g., bioprocessing
fluid).
[0218] In some embodiments, the lid 950 is ultrasonically sealed or
welded to the housing 910. Again, the rotatable tube assembly 930
is free to rotate from a sterilization position to a product flow
position (a rotation of approximately 90 degrees).
[0219] FIG. 45 illustrates the gas dispersion interconnect device
900 wherein the rotatable tube assembly 930 is in the sterilization
position. It can be seen that the dispersion opening 932 is aligned
with and substantially centered with the bore of the conduit 920 to
provide effective dispersion and sterilization.
[0220] After components connected or operatively connected to the
gas dispersion device 900 have been adequately sterilized (i.e., to
an SAL of 10.sup.-6), the rotatable tube assembly 930 may be
rotated 90 degrees or about 90 degrees to a product flow position
and bioprocessing fluid may pass through the conduits 920 and/or
the chamber 912 of the gas dispersion device. Bioprocessing fluid
passes through the sterilized path and past the sterilized flow
components so that it can be measured and/or transferred with
little to no contamination. In the product flow position, the
dispersion openings 932 may be sealed by sidewalls of the housing
910 or chamber 912.
[0221] The gas dispersion device 900 may be configured to receive a
device similar to the portable gas transfer device 100 described
above which may supply pressurized gas to the gas dispersion device
900 and/or may receive post-sterilization gas from the gas
dispersion device 900. Further, the ozone source 420 of FIG. 32 (or
other pressurized gas/vapor source) could be used in connection
with the gas dispersion device 900 or a similar gas dispersion
device. For example, referring to FIG. 45, the ozone source 420
could be inserted into the gas inlet port 916. A membrane similar
to the membrane 500 (FIG. 35) could be positioned at or near the
gas inlet port 916, and the membrane could receive the ozone source
injection member 422 therethrough. Thus, the gas dispersion device
900 may be used with other pressurized gas/vapor sources, such as a
syringe.
[0222] It will be understood that various components or features of
the gas dispersion interconnect devices 10, 800 and 900 may be
combined. By way of example, the rotatable tube assembly 930 of the
device 900 may also be retractable. By way of further example, the
extendable/retractable gas flow member 24 of the gas dispersion
device 10 may also be rotatable.
[0223] As described above, and as shown in FIG. 1, the gas
dispersion device 10 may include a pair of conduits 20 and a flange
22 at a distal end of each conduit 20. The flange 22 may be used to
connect a fluid flow component (for example, using a sanitary
clamp). The gas dispersion device 10 may include other connection
features. For example, referring to FIGS. 47A and 47B, the gas
dispersion device 10 may include a barbed connector 23 extending
from at least one of the conduits 20 without a flange 22. The
barbed connector 23 may be configured to receive a tube (e.g.,
plastic tubing). As illustrated, the gas dispersion device 10 may
include a flange 22 on one end and a barbed connector 23 on the
other (FIG. 47A), or may include a pair of barbed connectors 23
(FIG. 47B). The barbed connector(s) 23 may be provided in a variety
of sizes to accommodate differently sized tubing.
[0224] Turning now to FIGS. 48-53, a portable gas transfer device
100' is illustrated. The portable gas transfer device 100' includes
the same features and operates the same way as the portable gas
transfer device 100 except as described below.
[0225] The portable gas transfer device 100' includes an umbilical
assembly 270 that extends between a connection or mounting head 123
(which includes the mounting nut 122) and the housing 101 of the
portable gas transfer device 100'. The mounting head 123 may
include components and features as described above in connection
with the portable gas transfer device 100. In some embodiments, the
mounting head 123 includes an opening 124 (FIGS. 50A and 51A) sized
and configured to receive therethrough the gas flow member 24 of
the gas dispersion device 10; the opening 124 is also sized and
configured to engage the collar 55 of the gas dispersion device 10
(FIG. 1) with a threaded connection. In some embodiments, the
mounting head 123 includes an opening 124' (FIGS. 50B and 51B)
sized and configured to receive therethrough the gas flow member 24
of the gas dispersion device 10; the opening 124' is also sized and
configured to engage the collar 55' of the gas dispersion device 10
(FIG. 1) with a bayonete-type connection.
[0226] The umbilical assembly 270 includes a gas supply passageway
or tube 272 and at least one gas return passageways or tubes 274
(as illustrated, the umbilical assembly 270 includes two gas return
tubes 274). The gas supply tube 272 is in fluid communication with
the gas supply canister 108 and the gas return tubes 274 are in
fluid communication with the gas discharge catalyst canister 110
(see FIG. 12; these components are hidden from view by the housing
101 in FIGS. 48 and 49).
[0227] The portable gas transfer device 100' includes a strap 276
for carrying the device 100', for example for carrying the portable
gas transfer device 100' over a user's shoulder. This configuration
allows the user to have two hands free while connecting the
portable gas transfer device 100' to a gas dispersion device 10.
This may be particularly useful for point-of-use connection points
that are difficult to access; for example, point-of-use connection
points that are confined and/or require the user to be upside down
or in some other awkward position.
[0228] As shown in FIGS. 51A, 51B, 52A and 52B, the mounting head
123 of the portable gas transfer device 100' may be positioned over
the gas flow member 24 of the gas dispersion device 10. As
described above in some embodiments (FIGS. 50A and 51A), the
mounting head opening 124 receives the gas flow member 24 and the
collar 55 of the gas dispersion device 10. In some embodiments
(FIGS. 50B and 51B), the mounting head opening 124' receives the
gas flow member 24 and the collar 55' of the gas dispersion device
10.
[0229] As shown in FIG. 50A, the mounting head 123 may include one
or more locating guides 80' disposed in the opening 124. The
locating guide(s) 80' may be matingly received in one or more
alignment keys 132' of the gas dispersion device 10 (FIG. 52). As
illustrated in FIG. 52A, the gas dispersion device 10 includes
first and second alignment keys 132' located on opposite sides of
the gas flow member 24, with each alignment key 132' sized and
configured to receive a respective one of the locating guides 80'
of the portable gas transfer device 100'.
[0230] In some embodiments, the gas dispersion device collar 55 and
an inside surface of the mounting nut 122 may be threaded such that
the two components threadingly engage one another as the opening
124 of the mounting nut 122 is positioned over and tightened onto
the gas flow member 24 and the collar 55. In some embodiments, the
gas dispersion device collar 55' and an inside surface of the
mounting nut 122 may include pins 81' for engaging L-shaped slots
133' on a collar 55' for creating a bayonete-type engagement (as
shown in FIGS. 50B, 51B, 52B, and 53) such that the two components
securely engage one another as the opening 124' of the mounting nut
122 is positioned over and secured onto the gas flow member 24 and
the collar 55'.
[0231] FIG. 53 is a cross-sectional front view of a portion of the
mounting head 123 of FIG. 50A. As shown in FIG. 53, the mounting
head 123 includes a mounting nut 122 including an opening 124'
(shown in FIGS. 50B and 51B) sized and configured to receive
therethrough the gas flow member 24 of the gas dispersion device
10. The mounting nut opening 124' may include pins 81' for engaging
L-shaped slots 133' on the collar 55' for creating a bayonete-type
engagement. Once the pins 81' of mounting nut 122 are aligned with
the L-shaped slots 133' on the collar 55', the mounting nut may be
tightened down in a direction towards the gas dispersion device 10
and tightened perpendicularly until the pins 81' engage a seat 135'
at the end of the L-shaped slots 133'.
[0232] When the mounting nut 122 is securely engaged to the gas
dispersion device 10, the gas supply passageway 34 of the gas
dispersion device 10 may be in fluid communication with the gas
supply canister 108 via the gas supply tube 272 of the umbilical
assembly 270. In some embodiments, the gas return passageways 36 of
the gas dispersion device 10 may be in fluid communication with the
gas discharge catalyst canister 110 via the gas return tubes 274 of
the umbilical assembly 270. Other intermediate components may be
present in the housing 101 as described above in connection with
the portable gas transfer device 100.
[0233] Referring again to FIG. 48, the portable gas transfer device
100' may include a bar code reader or scanner 280. The reader 280
may be used to read a bar code at a connection or joint that is to
be sterilized. The reader 280 may be releasably held on and/or
tethered to the housing 101. Other identifying mechanisms are
contemplated; as just one example, the gas transfer device 100' may
include an RFID reader for reading an RFID chip or tag at the
connection or joint.
[0234] As shown in FIG. 49, the gas refill supply valve 128 and/or
the electrical interface 130 may be tethered to the housing 101. As
illustrated, the gas refill supply valve 128 and the electrical
interface 130 are connected to the housing 101 via a tube 282 and a
cord 284, respectively. The gas refill supply valve 128 and the
electrical interface 130 may be connected to the portable gas
transfer device docking station 302, described above in reference
to FIG. 31.
[0235] It will be understood that any of the components or features
described and shown in connection with the portable gas transfer
device 100 may be employed with the portable gas transfer device
100' and vice versa. That is, various components or features of the
portable gas transfer devices 100 and 100' may be combined and/or
omitted.
[0236] The gas dispersion devices and portable gas transfer devices
described herein may be used in a variety of applications. FIGS.
54-57 show exemplary applications using the portable gas transfer
device 100'; it will be understood that the portable gas transfer
device 100 may also be used in these applications.
[0237] FIG. 54 is a schematic illustration of the gas dispersion
device 10 and the portable gas dispersion device 100' used for
point-of-use localized sterilization at a connection point P. In
the illustrated embodiment, the connection point P is disposed
between a pair of tubes 550, 552 through which bioprocessing fluid
or the like will flow after the connection point P is sterilized.
Each tube 550, 552 is clamped closed by a tube pinch clamp or pinch
valve 554 prior to sterilization of the connection point P. The
mounting head 123 of the portable gas transfer device 100' is
connected to the gas dispersion device 10. Pressurized
sterilization gas is supplied from the gas transfer device 100'
through the umbilical assembly 270 and the connection point P is
sterilized. Post-sterilization gas is returned to the gas transfer
device 100' through the umbilical assembly 270. After the
connection point P is sterilized, the mounting head 123 is removed
from the gas dispersion device 10 and the gas flow member 24 of the
gas dispersion device 10 retracts as shown in FIG. 7. The pinch
clamps 554 are removed and fluid passes through the tube 550,
through the gas dispersion device 10 and through the tube 552.
[0238] The systems illustrated in FIGS. 54-56 use an adapter
assembly 610 for "zone sterilization" applications. The term "zone
sterilization" as used herein means sterilization of one or more
areas adapted to be connected to the portable sterilization gas
dispensing supply unit 100' including, but not limited to, a
manifold 651, an adaptor assembly 610, or a discrete device (e.g.,
point-of-use connection point). The adapter assembly 610 includes a
zone sterilization adapter 620. The adapter 620 includes a first or
upper portion 622 and a second or lower portion 624. The adapter
first portion 622 is sized and configured to receive the mounting
head 123 of the portable gas transfer device 100'. The adapter
assembly 610 includes first and second adapter connections 626,
627. A first tube 628 extends between and fluidly connects the
adapter second portion 624 and the first adapter connection 626. A
second tube 630 extends between and fluidly connects the adapter
second portion 624 and the second adapter connection 627.
[0239] The zone sterilization adapter 620 is configured to receive
sterilization or supply gas from the portable gas transfer device
100' and disperse it through a "zone" which may be or include a
manifold or a discrete device, for example. The zone sterilization
adapter 620 is configured to receive post-sterilization or return
gas after it has passed through the zone and as it is being
returned to the portable gas transfer device 100'.
[0240] Referring to FIG. 55, the adapter assembly 610 may be used
with a connector manifold assembly 650. The manifold assembly 650
includes a manifold 651 having first and second connection ends
652, 654. As illustrated, the first adapter connection 626 is
connected to the manifold first connection end 652 and the second
adapter connection 627 is connected to the manifold second
connection end 654.
[0241] In the system shown in FIG. 55, the manifold 651 defines the
zone that is sterilized using the portable gas transfer device 100'
and the adapter assembly 610. This zone is shown as the shaded area
in FIG. 55.
[0242] The manifold assembly 650 includes a plurality of capped or
terminated connection points T. After the manifold 651 is
adequately sterilized, pinch clamps 554 may be positioned adjacent
each of the capped or terminated connection points T as well as
adjacent each of the first and second connection ends 652, 654 of
the manifold 651. The adapter connectors 626, 627 are disconnected
from the manifold 651. The manifold 651 may be transported to
another location (e.g., a bioreactor room) for connection in a
fluid flow system (e.g., a bioprocessing system).
[0243] For example, one of the first and second connection ends
652, 654 of the manifold 651 may be connected to a bioreactor. The
other one of the first and second connection ends 652, 654 of the
manifold 651 as well as one or more of the terminated connection
points T having the pinch clamps 554 may be locally sterilized
using a process like the one described above in connection with
FIG. 54. For example, a gas dispersion device 10 may be positioned
between the manifold 651 and another fluid flow component (e.g., a
sensor, a tube, etc.) at one or more of the capped or terminated
connection points T. The gas dispersion devices 10 may be used for
point-of-use sterilization at these connection points after the
"zone sterilization" of the manifold 651. This may be useful
because the area outside the pinch clamp 554 may become
contaminated while transporting the manifold and/or while uncapping
the connection points T. The pinch clamps 554 may then be removed
after the connection point has been adequately sterilized using the
gas dispersion device 10.
[0244] FIG. 56 is an illustration of a system including the
portable gas transfer device 100', the adapter assembly 610 and the
manifold assembly 650. A process tank V has a process tank
connection 660 that is connected to the first connection 652 of the
manifold 651.
[0245] The process tank and the manifold assembly 650 may be
pre-attached prior to zone sterilization. A pinch clamp 554 is
applied to the manifold 651 near the first connection end 652. The
area to the left of this pinch clamp 554 (e.g., including manifold
first connection end 652, the process tank connection 660 and/or
the process tank V) may be pre-sterilized (for example, using gamma
or steam sterilization).
[0246] As illustrated, the first adapter connection 626 is
connected to a third connection end 655 of the manifold 651 and the
second adapter connection 627 is connected to the second connection
end 654 of the manifold 651. The portable gas transfer device 100'
and the adapter assembly 610 are configured to sterilize the zone
defined by the manifold 651 as described above. The zone is shown
as the shaded area in FIG. 56.
[0247] After the manifold 651 is adequately sterilized, pinch
clamps 554 may be positioned adjacent each of the capped or
terminated connection points T as well as adjacent the second
connection end 654 of the manifold 651. The adapter connections
626, 627 are disconnected from the manifold 651. The second
connection end 654 of the manifold 651 as well as one or more of
the terminated connection points T having the pinch clamps 554 may
be locally sterilized using a process like the one described above
in connection with FIG. 54. For example, a gas dispersion device 10
may be positioned between the manifold 651 and another fluid flow
component (e.g., a sensor, a tube, etc.) at one or more of the
capped or terminated connection points T and/or at the second
connection end 654. The gas dispersion devices 10 may be used for
point-of-use sterilization at these connection points after the
"zone sterilization" of the manifold 651. The pinch clamps 554 may
be removed after the connection point has been adequately
sterilized. The pinch clamp 554 adjacent the manifold first
connection end 652 may be removed to allow fluid flow from/to the
process tank V and through the sterilized zone and sterilized
point-of-use connection points.
[0248] FIG. 57 illustrates a system including the portable gas
transfer device 100', the adapter assembly 610 and an inline or
discrete device 670 that is to be sterilized. The inline or
discrete device 670 may be, for example, a filter, a pre-assembled
sensor assembly (e.g., a sensor and a fitting or pipe connection),
or some other device that is used in a bioprocessing system.
Connectors 672 are provided at opposite ends of the device 670. The
connectors 672 may be included as part of the device 670 or may be
attached to the device 670. The connectors 672 may be flexible
(e.g., such that a pinch clamp can be applied thereto).
[0249] The first adapter connection 626 is connected to one of the
connectors 672 of the device 670 and the second adapter connection
627 is connected to the other one of the connectors 672 of the
device 670. The portable gas transfer device 100' and the adapter
assembly 610 are configured to sterilize the zone defined by the
device 670 in the manner described above. The zone is shown as the
shaded area in FIG. 57.
[0250] Pinch clamps 554 may be positioned at the connectors 672 to
seal the sterilized zone. The mounting head 123 of the portable gas
transfer device 100' and the adapter connections 626, 627 are
removed. The device 670 may be transported to an appropriate
location where it is to be added in and/or connected to a
bioprocessing system. A gas dispersion device 10 may be positioned
between each connector 672 of the device 670 and another fluid flow
component for point-of-use sterilization at these connection
points.
[0251] Sterilization of certain instrumentation using ozone or
other suitable sterilization gas may provide advantages beyond
those discussed above. For example, certain sterilization
techniques (e.g., gamma or steam sterilization) can damage or
destroy silicon-based electronics and their programming
characteristics. The instrumentation is not damaged in this way
using ozone sterilization, such as with the system shown in FIG.
57.
[0252] Many alterations and modifications may be made by those
having ordinary skill in the art, given the benefit of present
disclosure, without departing from the spirit and scope of the
invention. Therefore, it must be understood that the illustrated
embodiments have been set forth only for the purposes of example,
and that it should not be taken as limiting the invention as
defined by the following claims. The following claims, therefore,
are to be read to include not only the combination of elements
which are literally set forth but all equivalent elements for
performing substantially the same function in substantially the
same way to obtain substantially the same result. The claims are
thus to be understood to include what is specifically illustrated
and described above, what is conceptually equivalent, and also what
incorporates the essential idea of the invention.
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