Note: Descriptions are shown in the official language in which they were submitted.
DISPERSAL AND EXPOSURE CHAMBER SYSTEMS AND METHODS
FIELD OF THE INVENTION
[001] This patent application relates to allergen evaluations and assessments
and more
particularly to naturalistic exposure chambers and allergen aerosolization
systems to provide
controlled allergen dispersal / dosing within environments representative of
the user's normal
exposure scenario.
BACKGROUND OF THE INVENTION
[002] Allergen exposure chambers (AECs) can be used to produce controlled
exposure to
allergenic and non-allergenic airborne particles in an enclosed environment,
in order to
characterize the pathological features of respiratory diseases and inform and
accelerate the clinical
development of pharmacological treatments and allergen immunotherapy for
allergic disease of
the respiratory tract (such as allergic rhinitis, allergic conjunctivitis, and
allergic asthma).
[003] However, to date AECs cannot be used for the pivotal, double-blind,
placebo-controlled,
randomized clinical trials currently required by regulatory authorities.
Amongst the factors
requiring addressing in order to establish AECs at the required levels are
aspects including, but
not limited, to dimensions and structure of the AEC; AEC staff; air flow, air
processing, and
operating conditions; particle dispersal; pollen/particle counting; safety and
non-contamination
measures; procedures for symptom assessments and tested allergens/substances
and validation
procedures.
[004] Accordingly, it would be beneficial to provide naturalistic exposure
chambers (NECs)
which are AECs designed to mimic the environment(s) within which a typical
user / individual is
exposed rather than typical clinical settings. It would be further beneficial
for the NECs to be
portable allowing their deployment widely with relative low cost to enable
enhanced data
acquisition, evaluation of regional / territorial / climate factors etc.
[005] It would be further beneficial to provide both AECs and NECs with a
reproducible means
to aerosolize and distribute the allergen / dander within the AECs / NECs
relative to the ad-hoc /
haphazard prior art methodologies.
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[006] Other aspects and features of the present invention will become apparent
to those ordinarily
skilled in the art upon review of the following description of specific
embodiments of the invention
in conjunction with the accompanying figures.
SUMMARY OF THE INVENTION
[007] It is an object of the present invention to mitigate limitations within
the prior art relating to
allergen evaluations and assessments and more particularly to naturalistic
exposure chambers and
allergen aerosolization systems to provide controlled allergen dispersal /
dosing within
environments representative of the user's normal exposure scenario.
[008] In accordance with an embodiment of the invention there is provided a
method comprising:
providing a body housing a motor, an impeller, an exhaust and a controller;
providing the motor coupled to the impeller for generating an exhaust air
flow;
providing the controller coupled to the motor for adjusting a rate of the
exhaust air flow exhausted
through the exhaust; and
providing an exhaust allergen dispenser (EAD) assembly, coupled to the
exhaust, containing an
allergen; wherein
the allergen is distributed within an environment through the allergen in the
EAD assembly being
exhausted from the EAD assembly by the exhaust air flow.
[009] In accordance with an embodiment of the invention there is provided a
system comprising:
a body housing a motor, an impeller, an exhaust and a controller;
the motor coupled to the impeller for generating an exhaust air flow;
the controller coupled to the motor for adjusting a rate of the exhaust air
flow exhausted through
the exhaust; and
an exhaust allergen dispenser (EAD) assembly, coupled to the exhaust,
containing an allergen;
wherein
the allergen is distributed within an environment through the allergen in the
EAD assembly being
exhausted from the EAD assembly by the exhaust air flow.
[0010] Other aspects and features of the present invention will become
apparent to those ordinarily
skilled in the art upon review of the following description of specific
embodiments of the invention
in conjunction with the accompanying figures.
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BRIEF DESCRIPTION OF THE DRAWINGS
[0011] Embodiments of the present invention will now be described, by way of
example only,
with reference to the attached Figures, wherein:
[0012] Figure 1 depicts an exemplary network environment within which
configurable electrical
devices according to and supporting embodiments of the invention may be
deployed and operate;
and
[0013] Figure 2 depicts an exemplary wireless portable electronic device
supporting
communications to a network such as depicted in Figure 1 and configurable
electrical devices
according to and supporting embodiments of the invention;
[0014] Figure 3 depicts an exemplary allergen exposure chamber (AEC) according
to an
embodiment of the invention and/or within which embodiments of the invention
can operate
together with particle counts showing that these are strongly and linearly
correlated over a wide
range of concentrations;
[0015] Figure 4 depicts pollen particle counts over extended periods of time
with and without set-
point corrections within an AEC according to an embodiment of the invention;
[0016] Figure 5 depicts a naturalistic exposure chamber (NEC) AEC from the
outside according
to an embodiment of the invention together with a layout schematic;
[0017] Figure 6 depicts a robotic allergen aerosolization system (robotic AAS)
according to an
embodiment of the invention;
[0018] Figure 7 depicts a large room NEC AEC according to an embodiment of the
invention;
[0019] Figure 8 depicts particle size distributions at various times during a
two hour aerosolization
test within a small room NEC AEC according to an embodiment of the invention;
[0020] Figure 9 depicts representative particle size distribution in terms of
particle count and
particle volume for one of the tests performed at t = 13 min within a small
NEC AEC according
to an embodiment of the invention;
[0021] Figure 10 depicts particle aerosolization via a robotic AAS according
to an embodiment of
the invention and prior art blanket shaking;
[0022] Figure 11 depicts particle concentrations versus time for a robotic AAS
according to
embodiments of the invention with and without an allergen extractor;
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[0023] Figure 12 depicts a test average (Fe! d 1> within a small NEC AEC
according to an
embodiment of the invention employing a robotic AAS according to an embodiment
of the
invention for varying vacuum suction levels (as percentage of maximum exhaust
flow rate),
performed without allergen extractors;
[0024] Figures 13 and 14 depict test averages (Fe! d 1> within a small NEC AEC
according to an
embodiment of the invention employing a robotic AAS according to an embodiment
of the
invention;
[0025] Figure 15 depicts the test average (Fe! d 1> within a small NEC AEC
according to an
embodiment of the invention employing a AAS according to an embodiment of the
invention as a
function of the cumulative count of particles with aerodynamic diameters
larger than 2 jim;
[0026] Figure 16 depicts exemplary staged suction level settings for an AAS
according to an
embodiment of the invention during a 2-hr dander aerosolization within a large
NEC AEC
according to an embodiment of the invention;
[0027] Figures 17 and 18 depicts the time and spatial distributions (Fel dl)
for experiments within
a large NEC AEC according to an embodiment of the invention employing a
robotic AAS
according to an embodiment of the invention;
[0028] Figure 19 depicts photographs of a field deployable AEC for use in
conjunction with an
AAS according to an embodiment of the invention;
[0029] Figure 20 depicts a view of a mesh debris filter for an AAS according
to an embodiment
of the invention;
[0030] Figure 21 depicts a prototype robotic AAS according to an embodiment of
the invention
with an exhaust fitting / dispersion assembly (EFDA) or exhaust allergen
dispenser (EAD)
assembly according to an embodiment of the invention;
[0031] Figure 22 depicts perspective and cross-sectional views of an exemplary
exhaust allergen
dispenser assembly for an AAS according to an embodiment of the invention;
[0032] Figure 23 depicts an exemplary allergen canister for a robotic AAS
according to an
embodiment of the invention disassembled with a vibration motor attached and
assembled with
mesh screen(s) inserted;
[0033] Figure 24 depicts average (Fe! d 1> within a field deployable AEC
employing a robotic
AAS according to an embodiment of the invention;
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[0034] Figure 25 depicts particle distributions at different times during and
after aerosolization for
very small particles (0.1 - 2 gm) and particles larger than 2 gm using a
robotic AAS according to
an embodiment of the invention;
[0035] Figure 26 depicts the total number of particles >2 pm over time for a
robotic AAS
according to an embodiment of the invention versus a prior art method of
dispersion;
[0036] Figure 27 depicts total particles versus time during and after
dispersal with a robotic AAS
according to an embodiment of the invention;
[0037] Figure 28 depicts total number of particles versus time for different
power levels and
with/without extractors within a robotic AAS according to an embodiment of the
invention;
[0038] Figure 29 depicts exhaust velocities versus control setting for a
robotic AAS according to
an embodiment of the invention under economical (ECO) and standard performance
(performance)
modes;
[0039] Figures 30 and 31 depict Fel d 1 concentration and particle level
versus time for tests using
varying carpet preload amounts for a robotic AAS within a portable AEC
according to
embodiments of the invention;
[0040] Figures 32 and 33 depict Fel d 1 concentration and particle level
versus time for tests using
varying canister preload amounts for a robotic AAS within a portable AEC
according to
embodiments of the invention;
[0041] Figures 34 and 35 depict Fel d 1 concentration and particle levels
versus time for tests using
varying power scaling patterns for a robotic AAS within a portable AEC
according to
embodiments of the invention;
[0042] Figure 36 depicts the results of varying the preload quantity on
average Fel d 1 levels in
the first hour of testing using a robotic AAS within a portable AEC according
to embodiments of
the invention;
[0043] Figure 37 depicts the overall effect of varying the canister quantity
on average Fel d 1
levels in the first hour of testing using a robotic AAS within a portable AEC
according to
embodiments of the invention;
[0044] Figures 38 and 39 depict the effect of varying the robotic AAS power
scaling on average
Fel d 1 levels in the first hour of testing using a robotic AAS within a
portable AEC according to
embodiments of the invention;
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[0045] Figure 40 to 43 depict different views in assembled, part assembled and
disassembled states
for an exhaust fitting / dispersion assembly (EFDA) or exhaust allergen
dispenser (EAD) assembly
according to an embodiment of the invention;
[0046] Figures 44 and 45 depict the EDFA/EAD assembly according to an
embodiment of the
invention fitted to a robotic AAS according to an embodiment of the invention;
[0047] Figures 46 and 47 depict the evolution of normalized particle count
with particle sizes
greater than 1 gm and 51.1m respectively from prototype testing of the
aerosolization of house dust
mites using the EFDA/EAD described and depicted with respect to Figures 40 to
43 with the
robotic AAS as depicted in Figures 44 and 45 within a FD-AEC according to an
embodiment of
the invention; and
[0048] Figure 48 depicts depict the distribution of Der p 1 allergen levels as
function of time from
samples collected at one side of a FD-AEC according to an embodiment of the
invention during
prototype testing of the aerosolization of house dust mites using the EFDA/EAD
described and
depicted with respect to Figures 40 to 43 with the robotic AAS as depicted in
Figures 44 and 45.
DETAILED DESCRIPTION
[0049] The present invention is directed to allergen evaluations and
assessments and more
particularly to naturalistic exposure chambers and allergen aerosolization
systems to provide
controlled allergen dispersal / dosing within environments representative of
the user's normal
exposure scenario.
[0050] The ensuing description provides representative embodiment(s) only, and
is not intended
to limit the scope, applicability or configuration of the disclosure. Rather,
the ensuing description
of the embodiment(s) will provide those skilled in the art with an enabling
description for
implementing an embodiment or embodiments of the invention. It being
understood that various
changes can be made in the function and arrangement of elements without
departing from the spirit
and scope as set forth in the appended claims. Accordingly, an embodiment is
an example or
implementation of the inventions and not the sole implementation. Various
appearances of "one
embodiment," "an embodiment" or "some embodiments" do not necessarily all
refer to the same
embodiments. Although various features of the invention may be described in
the context of a
single embodiment, the features may also be provided separately or in any
suitable combination.
Conversely, although the invention may be described herein in the context of
separate
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embodiments for clarity, the invention can also be implemented in a single
embodiment or any
combination of embodiments.
[0051] Reference in the specification to "one embodiment", "an embodiment",
"some
embodiments" or "other embodiments" means that a particular feature,
structure, or characteristic
described in connection with the embodiments is included in at least one
embodiment, but not
necessarily all embodiments, of the inventions. The phraseology and
terminology employed herein
is not to be construed as limiting but is for descriptive purpose only. It is
to be understood that
where the claims or specification refer to "a" or "an" element, such reference
is not to be construed
as there being only one of that element. It is to be understood that where the
specification states
that a component feature, structure, or characteristic "may", "might", "can"
or "could" be included,
that particular component, feature, structure, or characteristic is not
required to be included.
[0052] Reference to terms such as "left", "right", "top", "bottom", "front"
and "back" are intended
for use in respect to the orientation of the particular feature, structure, or
element within the figures
depicting embodiments of the invention. It would be evident that such
directional terminology
with respect to the actual use of a device has no specific meaning as the
device can be employed
in a multiplicity of orientations by the user or users.
[0053] Reference to terms "including", "comprising", "consisting" and
grammatical variants
thereof do not preclude the addition of one or more components, features,
steps, integers or groups
thereof and that the terms are not to be construed as specifying components,
features, steps or
integers. Likewise, the phrase "consisting essentially of", and grammatical
variants thereof, when
used herein is not to be construed as excluding additional components, steps,
features integers or
groups thereof but rather that the additional features, integers, steps,
components or groups thereof
do not materially alter the basic and novel characteristics of the claimed
composition, device or
method. If the specification or claims refer to "an additional" element, that
does not preclude there
being more than one of the additional element.
[0054] A "wireless standard" as used herein and throughout this disclosure,
refer to, but is not
limited to, a standard for transmitting signals and / or data through
electromagnetic radiation which
may be optical, radio-frequency (RF) or microwave although typically RF
wireless systems and
techniques dominate. A wireless standard may be defined globally, nationally,
or specific to an
equipment manufacturer or set of equipment manufacturers. Dominant wireless
standards at
present include, but are not limited to IEEE 802.11, IEEE 802.15, IEEE 802.16,
IEEE 802.20,
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UMTS, GSM 850, GSM 900, GSM 1800, GSM 1900, GPRS, ITU-R 5.138, ITU-R 5.150,
ITU-R
5.280, IMT-1000, Bluetoothim, Wi-Fi, Ultra-Wideband and WiMAXTm. Some
standards may be
a conglomeration of sub-standards such as IEEE 802.11 which may refer to, but
is not limited to,
IEEE 802.1a, IEEE 802.11b, IEEE 802.11g, or IEEE 802.11n as well as others
under the IEEE
802.11 umbrella.
[0055] A "wired standard" as used herein and throughout this disclosure,
generally refer to, but is
not limited to, a standard for transmitting signals and / or data through an
electrical cable discretely
or in combination with another signal. Such wired standards may include, but
are not limited to,
digital subscriber loop (DSL), Dial-Up (exploiting the public switched
telephone network (PSTN)
to establish a connection to an Internet service provider (ISP)), Data Over
Cable Service Interface
Specification (DOCSIS), Ethernet, Gigabit home networking (G.hn), Integrated
Services Digital
Network (ISDN), Multimedia over Coax Alliance (MoCA), and Power Line
Communication
(PLC, wherein data is overlaid to AC / DC power supply). In some embodiments a
"wired
standard" may refer to, but is not limited to, exploiting an optical cable and
optical interfaces such
as within Passive Optical Networks (PONs) for example.
[0056] A "sensor" as used herein may refer to, but is not limited to, a
transducer providing an
electrical outpupt generated in dependence upon a magnitude of a measure and
selected from the
group comprising, but is not limited to, environmental sensors, medical
sensors, biological sensors,
chemical sensors, ambient environment sensors, position sensors, motion
sensors, thermal sensors,
infrared sensors, visible sensors, RFID sensors, and medical testing and
diagnosis devices.
[0057] A "portable electronic device" (PED) as used herein and throughout this
disclosure, refers
to a wireless device used for communications and other applications that
requires a battery or other
independent form of energy for power. This includes devices, but is not
limited to, such as a
cellular telephone, smartphone, personal digital assistant (PDA), portable
computer, pager,
portable multimedia player, portable gaming console, laptop computer, tablet
computer, a
wearable device and an electronic reader.
[0058] A "fixed electronic device" (FED) as used herein and throughout this
disclosure, refers to
a wireless and /or wired device used for communications and other applications
that requires
connection to a fixed interface to obtain power. This includes, but is not
limited to, a laptop
computer, a personal computer, a computer server, a kiosk, a gaming console, a
digital set-top box,
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an analog set-top box, an Internet enabled appliance, an Internet enabled
television, and a
multimedia player.
[0059] A "server" as used herein, and throughout this disclosure, refers to
one or more physical
computers co-located and / or geographically distributed running one or more
services as a host to
users of other computers, PEDs, FEDs, etc. to serve the client needs of these
other users. This
includes, but is not limited to, a database server, file server, mail server,
print server, web server,
gaming server, or virtual environment server.
[0060] An "application" (commonly referred to as an "app") as used herein may
refer to, but is
not limited to, a "software application", an element of a "software suite", a
computer program
designed to allow an individual to perform an activity, a computer program
designed to allow an
electronic device to perform an activity, and a computer program designed to
communicate with
local and / or remote electronic devices. An application thus differs from an
operating system
(which runs a computer), a utility (which performs maintenance or general-
purpose chores), and a
programming tools (with which computer programs are created). Generally,
within the following
description with respect to embodiments of the invention an application is
generally presented in
respect of software permanently and / or temporarily installed upon a PED and
/ or FED.
[0061] An "enterprise" as used herein may refer to, but is not limited to, a
provider of a service
and / or a product to a user, customer, or consumer. This includes, but is not
limited to, a retail
outlet, a store, a market, an online marketplace, a manufacturer, an online
retailer, a charity, a
utility, and a service provider. Such enterprises may be directly owned and
controlled by a
company or may be owned and operated by a franchisee under the direction and
management of a
franchiser.
[0062] A "service provider" as used herein may refer to, but is not limited
to, a third party provider
of a service and / or a product to an enterprise and / or individual and / or
group of individuals and
/ or a device comprising a microprocessor. This includes, but is not limited
to, a retail outlet, a
store, a market, an online marketplace, a manufacturer, an online retailer, a
utility, an own brand
provider, and a service provider wherein the service and / or product is at
least one of marketed,
sold, offered, and distributed by the enterprise solely or in addition to the
service provider.
[0063] A "third party" or "third party provider" as used herein may refer to,
but is not limited to,
a so-called "arm's length" provider of a service and / or a product to an
enterprise and / or individual
and / or group of individuals and / or a device comprising a microprocessor
wherein the consumer
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and / or customer engages the third party but the actual service and / or
product that they are
interested in and / or purchase and / or receive is provided through an
enterprise and / or service
provider.
[0064] A "user" as used herein may refer to, but is not limited to, an
individual or group of
individuals. This includes, but is not limited to, private individuals,
employees of organizations
and / or enterprises, members of community organizations, members of charity
organizations, men
and women. In its broadest sense the user may further include, but not be
limited to, software
systems, mechanical systems, robotic systems, android systems, etc. that may
be characterised by
an ability to exploit one or more embodiments of the invention. A user may
also be associated
through one or more accounts and / or profiles with one or more of a service
provider, third party
provider, enterprise, social network, social media etc. via a dashboard, web
service, website,
software plug-in, software application, and graphical user interface.
[0065] "Biometric" information as used herein may refer to, but is not limited
to, data relating to
a user characterised by data relating to a subset of conditions including, but
not limited to, their
environment, medical condition, biological condition, physiological condition,
chemical
condition, ambient environment condition, position condition, neurological
condition, drug
condition, and one or more specific aspects of one or more of these said
conditions. Accordingly,
such biometric information may include, but not be limited, blood oxygenation,
blood pressure,
blood flow rate, heart rate, temperate, fluidic pH, viscosity, particulate
content, solids content,
altitude, vibration, motion, perspiration, EEG, ECG, energy level, etc. In
addition, biometric
information may include data relating to physiological characteristics related
to the shape and / or
condition of the body wherein examples may include, but are not limited to,
fingerprint, facial
geometry, baldness, DNA, hand geometry, odour, and scent. Biometric
information may also
include data relating to behavioral characteristics, including but not limited
to, typing rhythm, gait,
and voice.
[0066] "User information" as used herein may refer to, but is not limited to,
user behavior
information and / or user profile information. It may also include a user's
biometric information,
an estimation of the user's biometric information, or a projection /
prediction of a user's biometric
information derived from current and / or historical biometric information.
[0067] A "wearable device" or "wearable sensor" relates to miniature
electronic devices that are
worn by the user including those under, within, with or on top of clothing and
are part of a broader
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general class of wearable technology which includes "wearable computers" which
in contrast are
directed to general or special purpose information technologies and media
development. Such
wearable devices and / or wearable sensors may include, but not be limited to,
smartphones, smart
watches, e-textiles, smart shirts, activity trackers, smart glasses,
environmental sensors, medical
sensors, biological sensors, physiological sensors, chemical sensors, ambient
environment sensors,
position sensors, neurological sensors, drug delivery systems, medical testing
and diagnosis
devices, and motion sensors.
[0068] "Electronic content" (also referred to as "content" or "digital
content") as used herein may
refer to, but is not limited to, any type of content that exists in the form
of digital data as stored,
transmitted, received and / or converted wherein one or more of these steps
may be analog although
generally these steps will be digital. Forms of digital content include, but
are not limited to,
information that is digitally broadcast, streamed or contained in discrete
files. Viewed narrowly,
types of digital content include popular media types such as MP3, JPG, AVI,
TIFF, AAC, TXT,
RTF, HTML, XHTML, PDF, XLS, SVG, WMA, MP4, FLV, and PPT, for example, as well
as
others, see for example http://en.wikipedia.org/wiki/List of file formats.
Within a broader
approach digital content mat include any type of digital information, e.g.
digitally updated weather
forecast, a GPS map, an eBook, a photograph, a video, a VineTM, a blog
posting, a FacebookTM
posting, a TwitterTm tweet, online TV, etc. The digital content may be any
digital data that is at
least one of generated, selected, created, modified, and transmitted in
response to a user request,
said request may be a query, a search, a trigger, an alarm, and a message for
example.
[0069] A "profile" as used herein, and throughout this disclosure, refers to a
computer and/or
microprocessor readable data file comprising data relating to settings and/or
limits of an adult
device. Such profiles may be established by a manufacturer / supplier /
provider of a device,
service, etc. or they may be established by a user through a user interface
for a device, a service or
a PED/FED in communication with a device, another device, a server or a
service provider etc.
[0070] A "computer file" (commonly known as a file) as used herein, and
throughout this
disclosure, refers to a computer resource for recording data discretely in a
computer storage device,
this data being electronic content. A file may be defined by one of different
types of computer
files, designed for different purposes. A file may be designed to store
electronic content such as a
written message, a video, a computer program, or a wide variety of other kinds
of data. Some types
of files can store several types of information at once. A file can be opened,
read, modified, copied,
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and closed with one or more software applications an arbitrary number of
times. Typically, files
are organized in a file system which can be used on numerous different types
of storage device
exploiting different kinds of media which keeps track of where the files are
located on the storage
device(s) and enables user access. The format of a file is defined by its
content since a file is solely
a container for data, although, on some platforms the format is usually
indicated by its filename
extension, specifying the rules for how the bytes must be organized and
interpreted meaningfully.
For example, the bytes of a plain text file are associated with either ASCII
or UTF-8 characters,
while the bytes of image, video, and audio files are interpreted otherwise.
Some file types also
allocate a few bytes for metadata, which allows a file to carry some basic
information about itself.
[0071] "Metadata" as used herein, and throughout this disclosure, refers to
information stored as
data that provides information about other data. Many distinct types of
metadata exist, including
but not limited to, descriptive metadata, structural metadata, administrative
metadata, reference
metadata and statistical metadata. Descriptive metadata may describe a
resource for purposes such
as discovery and identification and may include, but not be limited to,
elements such as title,
abstract, author, and keywords. Structural metadata relates to containers of
data and indicates how
compound objects are assembled and may include, but not be limited to, how
pages are ordered to
form chapters, and typically describes the types, versions, relationships and
other characteristics
of digital materials. Administrative metadata may provide information employed
in managing a
resource and may include, but not be limited to, when and how it was created,
file type, technical
information, and who can access it. Reference metadata may describe the
contents and quality of
statistical data whereas statistical metadata may also describe processes that
collect, process, or
produce statistical data. Statistical metadata may also be referred to as
process data.
[0072] An "artificial intelligence system" (referred to hereafter as
artificial intelligence, Al) as
used herein, and throughout disclosure, refers to machine intelligence or
machine learning in
contrast to natural intelligence. An Al may refer to analytical, human
inspired, or humanized
artificial intelligence. An Al may refer to the use of one or more machine
learning algorithms
and/or processes. An Al may employ one or more of an artificial network,
decision trees, support
vector machines, Bayesian networks, and genetic algorithms. An Al may employ a
training model
or federated learning.
[0073] "Machine Learning" (ML) or more specifically machine learning processes
as used herein
refers to, but is not limited, to programs, algorithms or software tools,
which allow a given device
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or program to learn to adapt its functionality based on information processed
by it or by other
independent processes. These learning processes are in practice, gathered from
the result of said
process which produce data and or algorithms that lend themselves to
prediction. This prediction
process allows ML-capable devices to behave according to guidelines initially
established within
its own programming but evolved as a result of the ML. A machine learning
algorithm or
machining learning process as employed by an AT may include, but not be
limited to, supervised
learning, unsupervised learning, cluster analysis, reinforcement learning,
feature learning, sparse
dictionary learning, anomaly detection, association rule learning, inductive
logic programming.
[0074] An "allergen" as used herein, and throughout the disclosure, refers to
a material, e.g. a
microscopic material, which can trigger an allergic reaction within a user.
This allergen may
include, but not be limited to, dander, which typically refers to material
shed from the body of
humans and other materials that have fur, hair, or feathers within this
specification is employed to
mean any microscopic material capable of being aerosolized and distributed
which may or may
not trigger an allergic reaction within an individual, user, animal exposed
temporarily or over
extended periods to the aerosolized dander. An allergen within this broader
content may include
organic material(s), inorganic material(s), powder(s), droplet(s), mist(s),
airborne particle, and
pollen.
[0075] "Fed d 1" as referred to herein refers to a secretoglobin protein that,
in cats, is encoded by
the CH1 (chain 1/Fel d 1-A) and CH2 (chain 2/Fel d 1-B) genes. Among cats, Fel
d 1 is produced
largely in their saliva and by the sebaceous glands located in their skin. It
is the primary allergen
present on cats and kittens and causes an Immunoglobulin G (IgG) or
Immunoglobulin E (IgE)
reaction in sensitive humans (either as an allergic or asthmatic response).
[0076] A "chamber" as used herein, and throughout this disclosure, refers to
an environment
within which embodiments of the invention can be disposed / employed to
establish allergen
response(s) by one or more users. A chamber may include, but not be limited
to, a temporary
enclosure or structure installed within an indoor or outdoor environment, a
permanent enclosure
or structure, a room which can be closed off from one or more other rooms it
is connected to, an
environment under positive pressure relative to its surroundings, a series of
rooms, a house, a
factory, a retail environment, a dedicated test environment, and a temporary
test environment.
- 13 -
Date Recue/Date Received 2023-07-10
[0077] "Aerosolization" as used herein, and throughout this disclosure, refers
to a process or act
of dispersing a physical substance comprising particles small and light enough
to be carried by a
gas, e.g. air, into an aerosol.
[0078] An "aerosol" as used herein, and throughout this disclosure, refers to
a suspension of fine
solid particles or liquid droplets in air or another gas.
[0079] Referring to Figure 1 there is depicted a Network 100 within which
embodiments of the
invention may be employed supporting Naturalistic Exposure Chambers (NECs)
and/or Allergen
Aerosolization System (AASs) Systems, Applications and Platforms (NEC-AAS-
SAPs) according
to embodiments of the invention. As shown, first and second user groups 100A
and 100B
respectively interface to a telecommunications Network 100. Within the
representative
telecommunication architecture, a remote central exchange 180 communicates
with the remainder
of a telecommunication service providers network via the Network 100 which may
include for
example long-haul OC-48 / OC-192 backbone elements, an OC-48 wide area network
(WAN), a
Passive Optical Network, and a Wireless Link. The central exchange 180 is
connected via the
Network 100 to local, regional, and international exchanges (not shown for
clarity) and therein
through Network 100 to first and second cellular APs 195A and 195B
respectively which provide
Wi-Fi cells for first and second user groups 100A and 100B respectively. Also
connected to the
Network 100 are first and second Wi-Fi nodes 110A and 110B, the latter of
which being coupled
to Network 100 via router 105. Second Wi-Fi node 110B is associated with
commercial service
provider 160, e.g. UnitedHealthcare Group, comprising other first and second
user groups 100A
and 100B. Second user group 100B may also be connected to the Network 100 via
wired interfaces
including, but not limited to, DSL, Dial-Up, DOCSIS, Ethernet, G.hn, ISDN,
MoCA, PON, and
Power line communication (PLC) which may or may not be routed through a router
such as router
105.
[0080] Within the cell associated with first AP 110A the first group of users
100A may employ a
variety of PEDs including for example, laptop computer 155, portable gaming
console 135, tablet
computer 140, smartphone 150, cellular telephone 145 as well as portable
multimedia player 130.
Within the cell associated with second AP 110B are the second group of users
100B which may
employ a variety of FEDs including for example gaming console 125, personal
computer 115 and
wireless / Internet enabled television 120 as well as cable modem 105. First
and second cellular
APs 195A and 195B respectively provide, for example, cellular GSM (Global
System for Mobile
- 14 -
Date Recue/Date Received 2023-07-10
Communications) telephony services as well as 3G and 4G evolved services with
enhanced data
transport support. Second cellular AP 195B provides coverage in the exemplary
embodiment to
first and second user groups 100A and 100B. Alternatively the first and second
user groups 100A
and 100B may be geographically disparate and access the Network 100 through
multiple APs, not
shown for clarity, distributed geographically by the network operator or
operators. First cellular
AP 195A as shown provides coverage to first user group 100A and environment
170, which
comprises second user group 100B as well as first user group 100A.
Accordingly, the first and
second user groups 100A and 100B may according to their particular
communications interfaces
communicate to the Network 100 through one or more wireless communications
standards such
as, for example, IEEE 802.11, IEEE 802.15, IEEE 802.16, IEEE 802.20, UMTS, GSM
850, GSM
900, GSM 1800, GSM 1900, GPRS, ITU-R 5.138, ITU-R 5.150, ITU-R 5.280, and IMT-
1000. It
would be evident to one skilled in the art that many portable and fixed
electronic devices may
support multiple wireless protocols simultaneously, such that for example a
user may employ GSM
services such as telephony and SMS and Wi-Fi / WiMAX data transmission, VOIP
and Internet
access. Accordingly, portable electronic devices within first user group 100A
may form
associations either through standards such as IEEE 802.15 and Bluetooth as
well in an ad-hoc
manner.
[0081] Also connected to the Network 100 are Social Networks (SOCNETS) 165,
first and second
service providers 170A and 170B respectively, first and second third party
service providers 170C
and 170D respectively, and a user 170E. Also connected to the Network 100 are
first and second
enterprises 175A and 175B respectively, first and second organizations 175C
and 175D
respectively, and a government entity 175E. Also depicted first and second
servers 190A and 190B
may host according to embodiments of the inventions multiple services
associated with a provider
of contact management systems and contact management applications / platforms
(NEC-AAS-
SAPs); a provider of a SOCNET or Social Media (SOME) exploiting NEC-AAS-SAP
features; a
provider of a SOCNET and / or SOME not exploiting NEC-AAS-SAP features; a
provider of
services to PEDS and / or FEDS; a provider of one or more aspects of wired and
/ or wireless
communications; an Enterprise 160 such as UnitedHealthcare Group (a provider
of healthcare
insurance) exploiting NEC-AAS-SAP features; license databases; content
databases; image
databases; content libraries; customer databases; websites; and software
applications for download
to or access by FEDs and / or PEDs exploiting and / or hosting NEC-AAS-SAP
features. First and
- 15 -
Date Recue/Date Received 2023-07-10
second primary content servers 190A and 190B may also host for example other
Internet services
such as a search engine, financial services, third party applications and
other Internet based
services.
[0082] Also depicted in Figure 1 are Allergen Aerosolization Systems (AASs)
100 according to
embodiments of the invention such as described and depicted below in respect
of Figures 3 to 28.
As depicted in Figure 1 the AASs 100 communicate directly to the Network 100.
The AASs 100
may communicate to the Network 100 through one or more wireless or wired
interfaces included
those, for example, selected from the group comprising IEEE 802.11, IEEE
802.15, IEEE 802.16,
IEEE 802.20, UMTS, GSM 850, GSM 900, GSM 1800, GSM 1900, GPRS, ITU-R 5.138,
ITU-R
5.150, ITU-R 5.280, IMT-1000, DSL, Dial-Up, DOCSIS, Ethernet, G.hn, ISDN,
MoCA, PON,
and Power line communication (PLC).
[0083] Accordingly, a user may exploit a PED and / or FED within an Enterprise
160, for example,
and access one of the first or second primary content servers 190A and 190B
respectively to
perform an operation such as accessing / downloading an application which
provides NEC-AAS-
SAP features according to embodiments of the invention; execute an application
already installed
providing NEC-AAS-SAP features; execute a web based application providing NEC-
AAS-SAP
features; or access content. Similarly, a user may undertake such actions or
others exploiting
embodiments of the invention exploiting a PED or FED within first and second
user groups 100A
and 100B respectively via one of first and second cellular APs 195A and 195B
respectively and
first Wi-Fi nodes 110A. It would also be evident that a user may, via
exploiting Network 100
communicate via telephone, fax, email, SMS, social media, etc.
[0084] Now referring to Figure 2 there is depicted an Allergen Aerosolization
System 204 and
network access point 207 supporting NEC-AAS-SAP features according to
embodiments of the
invention. AAS 204 may, for example, be a PED and / or FED and may include
additional elements
above and beyond those described and depicted. Also depicted within the AAS
204 is the protocol
architecture as part of a simplified functional diagram of a system 200 that
includes an AAS 204,
such as a smartphone 155, an access point (AP) 206, such as first AP 110, and
one or more network
devices 207, such as communication servers, streaming media servers, and
routers for example
such as first and second servers 190A and 190B respectively. Network devices
207 may be coupled
to AP 206 via any combination of networks, wired, wireless and/or optical
communication links
such as discussed above in respect of Figure 1 as well as directly as
indicated. Network devices
- 16 -
Date Recue/Date Received 2023-07-10
207 are coupled to Network 100 and therein Social Networks (SOCNETS) 165,
first and second
service providers 170A and 170B respectively, first and second third party
service providers 170C
and 170D respectively, a user 170E, first and second enterprises 175A and 175B
respectively, first
and second organizations 175C and 175D respectively, and a government entity
175E.
[0085] The AAS 204 includes one or more processors 210 and a memory 212
coupled to
processor(s) 210. AP 206 also includes one or more processors 211 and a memory
213 coupled to
processor(s) 210. A non-exhaustive list of examples for any of processors 210
and 211 includes a
central processing unit (CPU), a digital signal processor (DSP), a reduced
instruction set computer
(RISC), a complex instruction set computer (CISC) and the like. Furthermore,
any of processors
210 and 211 may be part of application specific integrated circuits (ASICs) or
may be a part of
application specific standard products (ASSPs). A non-exhaustive list of
examples for memories
212 and 213 includes any combination of the following semiconductor devices
such as registers,
latches, ROM, EEPROM, flash memory devices, non-volatile random access memory
devices
(NVRAM), SDRAM, DRAM, double data rate (DDR) memory devices, SRAM, universal
serial
bus (USB) removable memory, and the like.
[0086] AAS 204 may include an audio input element 214, for example a
microphone, and an audio
output element 216, for example, a speaker, coupled to any of processors 210.
AAS 204 may
include a video input element 218, for example, a video camera or camera, and
a video output
element 220, for example an LCD display, coupled to any of processors 210. AAS
204 also
includes a keyboard 215 and touchpad 217 which may for example be a physical
keyboard and
touchpad allowing the user to enter content or select functions within one of
more applications
222. Alternatively, the keyboard 215 and touchpad 217 may be predetermined
regions of a touch
sensitive element forming part of the display within the AAS 204. The one or
more applications
222 that are typically stored in memory 212 and are executable by any
combination of processors
210. AAS 204 also includes accelerometer 260 providing three-dimensional
motion input to the
process 210 and GPS 262 which provides geographical location information to
processor 210.
[0087] AAS 204 is also depicted as comprising one or more Motors 280 which may
include, but
not be limited to, motors controlling motion of the AAS 204 within its
environment, motors
controlling acquisition and/or distribution of an allergen or allergens. The
one or more Motors 280
may be associated with an acquisition and/or dispersal method such that
discretely or in
combination with one or more allergen extractors, such as Allergen Extractors
630 in Figure 6, to
- 17 -
Date Recue/Date Received 2023-07-10
provide suction to draw the acquired allergens into the AAS 204 for storage
and/or dispersal.
Within other embodiments of the invention the one or more Motors 280 may be
associated with a
system that provides solely acquisition of the allergen or allergens. Within
other embodiments of
the invention the one or more Motors 280 may be associated with a system that
provides solely
distribution of the allergen or allergens such that the AAS 204 does not
acquire the allergen or
allergens through one or more allergen extractors but through its being loaded
with the allergen or
allergens. The one or more Motors 280 would be coupled to one or more
impellers in order to
provide an airflow for acquisition and/or dispersal method.
[0088] The AAS 204 may control the one or more Motors 280 through the
Processor 210 using
metadata, data, and/or applications stored within Memory 212 or these may be
controlled via data
/ instructions provided to the AAS 204 through the network connection(s) such
as from Enterprise
160, first and second service providers 170A and 170B respectively, first and
second third party
service providers 170C and 170D respectively, a user 170E, first and second
enterprises 175A and
175B respectively, first and second organizations 175C and 175D respectively,
and a government
entity 175E.
[0089] Further, the AAS 204 as depicted comprises one or more Sensors 290
which may acquire
additional information which is transmitted from the AAS 204 together with
data relating to its
motion, location, etc. Such data may be pulled from the AAS 204 or pushed from
the AAS 204 to
one or more of the Enterprise 160, first and second service providers 170A and
170B respectively,
first and second third party service providers 170C and 170D respectively, a
user 170E, first and
second enterprises 175A and 175B respectively, first and second organizations
175C and 175D
respectively, and a government entity 175E. Optionally, a Sensor 290 may
include a Laser Particle
counter (LPC) and/or a Rotational Impact Samplers (RIS) or other methods of
determining particle
counts / particle size etc.
[0090] Accordingly, an AAS 204 may acquire data from the Sensors 290, Motor(s)
280,
Accelerometer 260, GPS 262 etc. and communicate this via Front-End Tx/Rx &
Antenna 228
wirelessly to an Access Point 206 associated with the AEC (e.g. NEC AEC or
portable AEC as
described below in respect of embodiments of the invention). This data may be
stored in
association with data relating to the individual(s) tested, location, time,
date, etc. to provide data
for analysis, verification, compliance etc.
- 18 -
Date Recue/Date Received 2023-07-10
[0091] AAS 204 includes a protocol stack 224 and AP 206 includes a
communication stack 225.
Within system 200 protocol stack 224 is shown as IEEE 802.11 protocol stack
but alternatively
may exploit other protocol stacks such as an Internet Engineering Task Force
(IETF) multimedia
protocol stack for example. Likewise, AP stack 225 exploits a protocol stack
but is not expanded
for clarity. Elements of protocol stack 224 and AP stack 225 may be
implemented in any
combination of software, firmware and/or hardware. Protocol stack 224 includes
an IEEE 802.11-
compatible PHY module 226 that is coupled to one or more Front-End Tx/Rx &
Antenna 228, an
IEEE 802.11-compatible MAC module 230 coupled to an IEEE 802.2-compatible LLC
module
232. Protocol stack 224 includes a network layer IP module 234, a transport
layer User Datagram
Protocol (UDP) module 236 and a transport layer Transmission Control Protocol
(TCP) module
238.
[0092] Protocol stack 224 also includes a session layer Real Time Transport
Protocol (RTP)
module 240, a Session Announcement Protocol (SAP) module 242, a Session
Initiation Protocol
(SIP) module 244 and a Real Time Streaming Protocol (RTSP) module 246.
Protocol stack 224
includes a presentation layer media negotiation module 248, a call control
module 250, one or
more audio codecs 252 and one or more video codecs 254. Applications 222 may
be able to create
maintain and/or terminate communication sessions with any of devices 207 by
way of AP 206.
Typically, applications 222 may activate any of the SAP, SIP, RTSP, media
negotiation and call
control modules for that purpose. Typically, information may propagate from
the SAP, SIP, RTSP,
media negotiation and call control modules to PHY module 226 through TCP
module 238, IP
module 234, LLC module 232 and MAC module 230.
[0093] It would be apparent to one skilled in the art that elements of the AAS
204 may also be
implemented within the AP 206 including but not limited to one or more
elements of the protocol
stack 224, including for example an IEEE 802.11-compatible PHY module, an IEEE
802.11-
compatible MAC module, and an IEEE 802.2-compatible LLC module 232. The AP 206
may
additionally include a network layer IP module, a transport layer User
Datagram Protocol (UDP)
module and a transport layer Transmission Control Protocol (TCP) module as
well as a session
layer Real Time Transport Protocol (RTP) module, a Session Announcement
Protocol (SAP)
module, a Session Initiation Protocol (SIP) module and a Real Time Streaming
Protocol (RTSP)
module, media negotiation module, and a call control module. Portable and
fixed electronic
devices represented by AAS 204 may include one or more additional wireless or
wired interfaces
- 19 -
Date Recue/Date Received 2023-07-10
in addition to the depicted IEEE 802.11 interface which may be selected from
the group comprising
IEEE 802.15, IEEE 802.16, IEEE 802.20, UMTS, GSM 850, GSM 900, GSM 1800, GSM
1900,
GPRS, ITU-R 5.138, ITU-R 5.150, ITU-R 5.280, IMT-1000, DSL, Dial-Up, DOCSIS,
Ethernet,
G.hn, ISDN, MoCA, PON, and Power line communication (PLC).
[0094] Also depicted in Figure 2 are Allergen Aerosolization Systems (AASs)
100 according to
embodiments of the invention such as described and depicted below. As depicted
in Figure 2 an
AASs 100 may communicate directly to the Network 100. Other AASs 100 may
communicate to
the Network Device 207, Access Point 206, and AAS 204. Some AASs 100 may
communicate to
other AASs 100 directly. Within Figure 2 the AASs 100 coupled to the Network
100 and Network
Device 207 communicate via wired interfaces. The AASs 100 coupled to the
Access Point 206
and AAS 204 communicate via wireless interfaces. Each AAS 100 may communicate
to another
electronic device, e.g. Access Point 206, AAS 204 and Network Device 207, or a
network, e.g.
Network 100. Each AAS 100 may support one or more wireless or wired interfaces
including
those, for example, selected from the group comprising IEEE 802.11, IEEE
802.15, IEEE 802.16,
IEEE 802.20, UMTS, GSM 850, GSM 900, GSM 1800, GSM 1900, GPRS, ITU-R 5.138,
ITU-R
5.150, ITU-R 5.280, IMT-1000, DSL, Dial-Up, DOCSIS, Ethernet, G.hn, ISDN,
MoCA, PON,
and Power line communication (PLC).
[0095] Optionally, rather than wired and/or wireless communication interfaces
devices may
exploit other communication interfaces such as optical communication
interfaces and/or satellite
communications interfaces. Optical communications interfaces may support
Ethernet, Gigabit
Ethernet, SONET, Synchronous Digital Hierarchy (SDH) etc.
[0096] Referring to Figure 3 there is depicted an Allergen Exposure Chamber
300A
representative of typical fixed AECs within the prior art. AEC 300A being the
Red Maple TrialTm
Allergen Challenge TheatreTm located in Ottawa, Canada which measures 16
metres by 8 metres
(approximately 52 feet by 26 feet), giving a total surface area of 133 square
meters (approximately
1,430 square feet). The ceiling height in the chamber is 2.2 meters
(approximately 7 feet). The
walls and floor were designed and fabricated using clean-room material that is
repellent to
particles for ease-of-cleaning. The adjustable theatre-like seating 310 is
arranged in elevated rows
to optimize allergen exposure to the subjects faces. The chamber consists of
four independent
quadrants, each of which has a dedicated allergen/particle supply. For
consistency, the same
allergen is always used in the same quadrant. The largest quadrant (Zone 370
in Figure 3) has a
- 20 -
Date Recue/Date Received 2023-07-10
40-person capacity (five rows of eight seats). Observation windows enable the
theatre to be
monitored from an adjacent control room during trials. First and second Doors
320 and 340 provide
ingress/egress points for the trial subjects. In extended trials catering can
be provided through
Catering Entrance 350 whilst Emergency Exit 360 allows for rapid introduction
of a gurney,
wheelchair, etc. in the event of a requirement to move an individual partially
or fully incapacitated.
A series of Air Returns 330 draw air into and out of the AEC 300A through high-
efficiency
particulate air (HEPA) filters such that the direction of air flow within the
AEC 300A is across the
AEC 300A from top to bottom within the Figure.
[0097] Air is blown into the AEC 300A through selected vanes, not depicted, at
one side of the
room wherein the air flows across the AEC 300A before exiting through the Air
Returns 330. In
an exemplary embodiment the air flow is towards the faces of the participants
within the seats.
Accordingly, the air exits through the Air Returns 330, is HEPA-filtered to
remove the dander,
allergen, pollen, and is recirculated after the addition of new dander
particles. The AEC 300A is
maintained at a slight positive pressure, to ensure that no other allergens
enter the chamber during
testing.
[0098] Within the AEC 300A particle concentrations are measured using a number
of Laser
Optical Particle counters (LPCs) and a number of Rotational Impact Samplers
(RISs). The output
from one LPC (the driving LPC) is fed back to a programmable logic controller,
which adjusts (if
required) the amount of pollen injected into the airflow and thus maintains
the target level in the
AEC 300A. In validation studies, a linear relationship between LPC-derived and
RIS-derived
pollen counts over a wide range of concentrations were obtained for grass
pollen (first graph 300B
in Figure 3) where the regression coefficient of determination was R2=0.85 and
ragweed pollens
(second graph 300C in Figure 3) which had a regression coefficient of
determination of R2=0.93.
[0099] Typically, a physician and study coordinator are in the Allergen
Challenge Theatre
during challenges. Staff and study participants wear protective clothing which
is put on in an air
lock outside the entrance to the AEC 300A. Additional coordinators and
engineers remain in the
control room, observe through a window and communicate by two-way radio. An
emergency area
is located just outside the AEC 300A and is equipped with beds, a crash cart
and oxygen.,
[00100] As noted above, technical validation of the AEC 300A was performed for
Phleum
pratense grass pollen (timothy grass) and Ambrosia artemisiifolia pollen
(ragweed). The ragweed
and grass pollen concentrations were found to be (ii) stable over several
hours as evident from first
- 21 -
Date Recue/Date Received 2023-07-10
and second graphs 400A and 400B in Figure 4. Further, the AEC 300A is
responsive to changes
in the pollen setpoint as evident from the set-point change induced within the
measurements
depicted in second graph 400B. The achievable levels of the allergens being
sufficient to induce
symptoms within participants.
[00101] Within the AEC 300A one LPC 410 was designated as the driving LPC and
the results
measured with three other LPCs, left LPC 420, middle LPC 430 and right LPC
440. The
distribution of Phleum pratense in a single zone of the AEC 300A is presented
below in Table 1
whilst those for Ambrosia artemisiifolia pollen in a quadrant of the AEC 300A
are given in Table
2. The percentage deviations being 13% for ragweed and 17% for timothy grass.
These
measurements being performed with RISs in Table 1 and LPCs in Table 2.
Position Row 1 Row 2 Row 3 Row 4
Right RIS 4368 (867)
Middle RIS 3363 (492) 5039 (585) 4302 (236) 3333 (338)
Left RIS 3597 (176)
Table 1: Distribution of Phleum pratense grass pollen in a single zone of AEC
300A
Position Row 1 Row 2 Row 3 Row 4 Row 5
Mean (SD)
Right LPC 4554 5166 4802 4238 3625
4477 (523)
Middle 4947 5430 5508 4622 3988
4899 (559)
LPC
Left LPC 5401 4804 4229 3852 4163
4490 (550)
Mean (SD) 4967(346) 5133(257) 4846(523) 4237(315) 3925(224)
Overall mean (SD) all LPC data points 4622 (578)
Table 2: Distribution of Ambrosia artemisiifolia ragweed pollen in a single
zone of AEC 300A
[00102] Now referring to Figure 5 there is depicted a Naturalistic
Exposure Chamber (NEC)
allergen exposure chamber (AEC) operated by Red Maple TrialsTm. The NEC as
depicted in first
image 500A in Figure 5 consists of two cat rooms, one 2.8 meters by 2.1 meters
(approximately 9
feet by 7 feet) and the other 5.8 meters by 2.6 meters (approximately 19 feet
by 8.5 feet). An
observation area with windows provides views into the cat rooms and an air-
lock entrance controls
access. Two cats live in the rooms permanently to replicate a home
environment. The smaller
chamber is on the left with the larger chamber on the right.
- 22 -
Date Recue/Date Received 2023-07-10
[00103] Within the NEC depicted in first image 500A in Figure 5 air flow is
controlled by a
dedicated HVAC system, which supplies HEPA filtered air. The NEC is ventilated
with 10 air
changes per minute with the exhaust air ventilated to the building exterior.
The ventilation can be
reduced during challenges. In the NEC, allergen comes from the two cats that
are resident in the
cat rooms. Allergen levels in the NEC are measured using 3 sampling pumps
(firs to third pumps
510A, 510B and 510C in second image 500B in Figure 5). These are coupled to 25
mm glass fibre
filters located about 0.9 meters (approximately 3 feet) apart along the long
axis of the room and
1.2 meters (approximately 4 feet) above the floor. Subjects also wear a
sampling pump. Fel d 1 is
eluted from the filters and measured by enzyme-linked immunosorbent assay
(ELISA). During
challenges in the NEC, a physician and study coordinator are present in the
antechamber, observe
the subjects through the window and communicate by wireless headsets phones.
[00104] Accordingly, within the NEC AEC and as described below in respect of
portable AECs
it would be beneficial to provide an allergen aerosolization system (AAS)
without the requirements
for complex air handlers, air filtration system, HEPA filter, etc. but
providing reproducible
programmable allergen dispersal. Accordingly, the inventors have established
as depicted in
Figure 6 in first and second images 600A and 600B a robotic AAS. This being
depicted in second
image 500B in Figure 5 and robotic AAS 520B with a Docking Station 520A. Also
depicted within
the NEC in second image 500B in Figure 5 are a Doorway 540, Viewing Window 530
and Particle
Size Distribution Analyser (PSDA) 550.
[00105] The motivation to establish the robotic AAS arises, from the
consideration of cat
allergens although the motivations are common to a wide range of allergens,
due to limitations
within prior art approaches. For example, the development of new therapies for
cat allergies is
complicated by differences in patients' exposure to cats. Some patients choose
to avoid cats while
others keep cats at home and treat their symptoms. As a result, field studies
where patients report
their daily symptoms while receiving an experimental medication or placebo are
confounded by
variable and intermittent exposure and can fail. Environmental Exposure Units
(EEUs) such as
AEC 300A generate controlled levels of airborne allergen and thereby reduce
the variability in
exposure seen in field studies. Those developed for cat allergen either
aerosolize liquid allergen
extract or the dander and hair that is naturally shed from live cats. While
the latter provides a more
natural allergen exposure than with liquid extract (nebulized monodisperse
liquid droplets likely
deposit in the respiratory tract differently than irregular dander flakes and
absorption of the antigen
- 23 -
Date Recue/Date Received 2023-07-10
is likely faster), live cat exposure chambers which traditionally aerosolize
cat allergen by shaking
cats' bedding have highly variable allergen levels during individual exposures
and across different
exposures.
[00106] For example, in a study evaluating the efficacy of a pharmaceutical
solution for
preventing acute bronchoconstriction, Fel d 1 exposure ranged between 0
(undetectable) and
22,631 ng/m3 when subjects were exposed by blanket shaking at one of three
centres. The
variability associated with blanket shaking can arise from several factors
including variability in
cat shedding and salivary Fel d 1 production, inconsistent allergen
accumulation on bedding,
differences in blanket materials and their retention of dander, human
differences in performing
blanket shaking, and the intermittent nature of aerosolization. Accordingly, a
robotic AAS would
provide an EEU that provides exposure to natural cat dander, with allergen
concentrations
comparable to those found in homes with cats, but with a high degree of
control and repeatability.
[00107] First and second images 600A and 600B respectively depict upper and
lower perspective
views of the robotic AAS according to an embodiment of the invention. The
Robotic AAS depicted
can perform both allergen acquisition and allergen aerosolization. The robotic
AAS as depicted in
first image 600A has a Vent 610 disposed on the side of the Body 620 for
aerosolizing the allergen
into the surrounding environment where the air flow for the aerosolization is
provided by a motor
/ impeller assembly within the robotic AAS. An exemplary embodiment of the
invention provides
for a run time of 2 hours from a single battery charge and remote operability
as well as
programmatic based control. Optionally, the Vent 610 may be disposed in
another position relative
to the Body 620. Optionally, two or more Vents 610 may be provided.
Optionally, Vent 610 may
be supported on a tube / frame to place the exit of the Vent 610 at a
predetermined height from the
floor upon which the robotic AAS moves. Optionally, one or more attachments of
specific
geometry or geometries may be connected to the Vent 610, such as nozzles or
diffusers etc. to
change the diffusion characteristics of the allergen at the exhaust.
[00108] Referring to second image 600B the robotic AAS has a pair of Allergen
Extractors 630
disposed on its bottom surface, for example a pair of silicon brushes. During
operation of the
robotic AAS in an acquisition mode rather than a dispersal mode the robotic
AAS is operated such
that the pair of Allergen Extractors 630 rotate to induce removal of debris,
allergens, dander etc.
from the surface upon which the robotic AAS is operating. By applying a
filtering system within
the robotic AAS then the passage of fine allergen-carrying particulates is
allowed into a chamber
- 24 -
Date Recue/Date Received 2023-07-10
or chambers of the robotic AAS, such as described and depicted below in
respect of Figures 23-
25 and 26 but the passage of larger debris is blocked. See for example the
mesh depicted within
Figure 20 and the screens within the exhaust fitting / dispersion assembly
(EFDA), also referred
to as an Exhaust Allergen Dispenser (EAD), described and depicted in respect
of Figures 21-23.
[00109] The operation of the Allergen Extractors 630 may or may not be
included within a
dispersion or dispersal mode depending on the target level of dispersion. As
discussed below in
respect of Figure 2800B their concurrent operation in the dispersion or
dispersal mode results in
higher levels of allergen dispersal.
[00110] Within an embodiment of the invention the robotic AAS employs pulse
width
modulation (PWM) power regulation to adjust the speed of a fan within the
robotic AAS and hence
the suction generated. Within an embodiment of the invention the PWM control
allows for
operation from a maximum approximately 1700 Pa suction pressure to
approximately 250 Pa.
Additionally, the robotic AAS has drive wheels 640 coupled to a motor or
motors allowing the
robotic AAS to move forward, reverse, turn etc. such that the robotic AAS can
move throughout
the chamber, e.g. NEC AEC or field deployable AEC for the duration of
exposure, aerosolizing
the allergen that has either been placed within its allergen reservoir or that
has been naturally
collected on the floor.
[00111] Optionally, the robotic AAS may respond to various boundaries to
define a particular
area of operation. These boundaries may include, for example, physical
stoppers, virtual walls
defined by a beam the robotic AAS detects as it crosses it (e.g. infra-red
beam), triangulation based
upon, for example, wireless beacons, or the edges of a raised platform,
although it would be evident
that within other embodiments of the invention the area could be bounded by
other means.
[00112] Tests were initially performed within the small NEC AEC to establish
configuration and
dispersion settings in order to achieve even spatial distribution and temporal
stability of Fel d 1
within a target range of 40-100 ng/m3. In addition to measuring Fel d 1 air
concentrations
throughout the room, particle size distributions and concentrations were
measured to characterize
the aerosolized particulate and to facilitate more rapid evaluation of results
compared to Fel d 1
measurement (which takes several days to process following experiments).
Dander aerosolization
in the small chamber was tested for various vacuum suction levels, and with
and without
installation of the allergen extractors. Experiments were also performed
aerosolizing dander using
a standard blanket shaking protocol (shaking the cats' bedding), to compare
particle distributions
- 25 -
Date Recue/Date Received 2023-07-10
to the automated vacuum aerosolization. Dander aerosolization was then tested
within the larger
chamber and scaled using two vacuums simultaneously. In both the small and
large chambers
repeatability was demonstrated under the optimized settings.
[00113] Prior to each experiment, the cats and their furniture were removed
from the small NEC
AEC. Air sampling pumps were mounted 1.2 m (approximately 4 feet) above the
floor on stands
(approximately at the height of a patient's face while sitting), at the
midpoint of the left, back and
right walls of the small room, denoted as the "left", "centre" and "right"
measurement locations
510A, 510B and 510C in second image 500B in Figure 5, respectively. During
aerosolization, air
samples were collected every 20 minutes at 5 L/min onto glass fiber filters
(25 mm diameter, 2
gm pore size. Fel d 1 deposited on the filters was quantified afterwards using
enzyme-linked
immunosorbent assay (ELISA). Air Fel d 1 levels were calculated from the
volume of filtered air
sampled and the amount of Fel d 1 on the filter and expressed as ng/m3.
[00114] Counts and sizes of aerosolized dander particles were measured using a
time-of-flight
particle size distribution (PSD) analyzer and air particle concentrations were
expressed as
particles/m3 based on the volume of air sampled and sampling time. The PSD
analyzer was
positioned near the right air sampling pump as shown in second image 500B in
Figure 5. Every
three minutes during aerosolization air was sampled for two minutes at 1
L/min. Due to the
irregular shape of the allergen-carrying particles (namely dander flakes,
hairs and fibers), an
equivalent aerodynamic diameter D was used to characterize the particles:
defined as the diameter
of a spherical water particle settling with the same terminal velocity as the
particle. Baseline
measurements of particle count and Fel d 1 were measured at the start of each
test, prior to turning
on the vacuum.
[00115] The robotic AAS was turned on at t = 0 min and was run for 15-minute
on / 5-minute off
intervals for 60 or 120 minutes, depending on the specific experimental
procedure. During the 5-
minute off intervals, the vacuum was returned to its charging station at the
front of the room. This
on/off duty cycle was selected based on preliminary experiments, to maintain
airborne allergen
levels and prolong battery life. The air sampling pumps and the particle
analyzer also initiated at t
=0.
[00116] Dander aerosolization was also performed in the small chamber by
shaking the cat's
bedding for comparison to the vacuum method. Four tests were performed for
each method and
average particle counts were compared. In each test, a blanket having been
used as the cats'
- 26 -
Date Recue/Date Received 2023-07-10
primary bedding for four weeks was shaken vigorously for two minutes, followed
by 15 minutes
of settling. This was then repeated a second time. Particle measurements and
air sampling were
initiated at the start of shaking.
[00117] Results were evaluated for spatial distribution and temporal stability
of Fel d 1 levels
generated by the vacuum model with and without allergen extractors and for
various suction levels.
Repeatability was demonstrated under optimized settings.
[00118] Once validated in the smaller of the two chambers (3 subject
capacity), the aerosolizati on
system was scaled and tested for the larger chamber (8 subject capacity). In
this room, as depicted
in Figure 7, two carpets (identical to a rug in the small chamber) were
installed. During this testing
period, the same two cats that lived in the small room, resided in this larger
room. Again, the cats
and their furniture were removed prior to aerosolization tests. Eight chairs
were then set up around
the periphery of the room (Figure 7). Sampling pumps were hung from the
ceiling 1.2 meters above
the floor (approximately 4 feet) at the locations 710A to 710D respectively.
During each 2-hour
test, the robotic AAS moved about on each carpet (one robotic AAS per carpet),
while a third was
positioned on a battery charging station. Operating vacuums ran for 15-minute
on / 5-minute off
intervals, charging while off. At scheduled times, the third robotic AAS
replaced one of the two
operating robotic AAS which would then be docked to re-charge. This rotation
schedule extended
the maximum duration of tests, which was otherwise limited by the robotic AAS
battery capacity.
[00119] Figure 7 depicts a schematic of the large NEC AEC showing the
locations of the first to
fourth Pump 710A to 710D respectively, first to third robotic AAS 730A to 730C
respectively,
first and second carpets 720A and 720B respectively. Chairs 740 were also
provided for the users
to sit on.
[00120] Virtual walls were used to control the regions where each robotic AAS
operated. Fans
were placed in the front left and right corners of the room 1.0 m
(approximately 3 feet) above the
floor, facing towards the back center of the room. This was found to promote a
more uniform
allergen distribution throughout the room.
[00121] Carpet allergen levels were monitored regularly as part of all NEC
experiments,
measured regions of the carpets were passed over systematically using sampling
pumps and the
collected allergen quantified with ELISA, and a threshold Fel d 1 level (in
ng/m2) had been
identified to inform whether allergen supplementation was necessary in advance
of a test. To
account for the larger space of the large chamber, compared to the small
chamber, being loaded
- 27 -
Date Recue/Date Received 2023-07-10
with allergen from the same source (two cats), carpet allergen levels were
supplemented by
shaking cat bedding several days in advance of testing, and by adding
additional milled cat hair
samples directly to the carpets. In the case of the latter, weighed portions
of 10 or 20 grams of
milled cat hair were rubbed through a sieve evenly over the carpet area.
[00122] It would be evident that as a robotic AAS may "extract" and "disperse"
that the robotic
AAS may rove over the same area picking up allergens and re-dispersing them.
[00123] During 2-hr aerosolization tests, air samples were collected at the
four pump locations
for 30-minute sampling periods (4 L/min), resulting in four time points for
each location to assess
the temporal variation. Results were evaluated for spatial distribution and
temporal stability of Fel
d 1 levels. Repeatability was demonstrated under optimized settings.
[00124] The number of particles obtained using the time-of-flight method, NPSD
were
normalized by the volume of sampled air to obtain a particle concentration as
given by Equation
(1) where QpsD represents the sampling flowrate of the particle size
distribution analyzer and ts is
the sampling time. Fel d 1 was measured at locations x, and time intervals t,
as given by Equations
(2) to (5) where upper values are for small room and lower values for large
room.
Count/m3 = Npso 1 (Qpso x ts) (1)
=
{ [left, centre, right]
xi (2)
[left, left-centre, right-centre, right]
i=1...M (3)
where Mis the number of locations (3 - small room, 4 - large room)
¨
{ [10, 30, 50, 70, 90, 110] (4)
t.
¨ [15,45, 75,105]
j1. .N, where Nis the number of time intervals in the test. (5)
[00125] The values of times t are the mid-points of the air sampling period,
referenced from the
start of the aerosolization in minutes. The mass of Fel d 1 mf in ng,
collected on each filter and
determined by ELISA was normalized by the volume of sampled air to obtain the
air concentration
as given by Equation (6) where Qpump is the sampling pump suction flow rate.
Spatial averages of
Fel d 1 at each time ti were calculated using Equation (7). Time averages of
Fel d 1 at each location
xi were calculated using Equation (8) and the room average Fel d 1 was
calculated for each test
using Equation (9).
Fel di(xi,ti) = mf (xi, ti)1(Qpump x ts) (6)
- 28 -
Date Recue/Date Received 2023-07-10
(Fe! d1)ti = d1(x1,t1) (7)
N
(Fe! d1) = ¨E. Fe! d1(xi,ti)
Xi N j=i (8)
(Fe! dl) = ¨1 E lY (Fel d1)t. (9)
N
[00126] The particle size distribution of the cat dander was obtained every 3
minutes (sampling
the room for 2 minutes) during and after dispersion to assess the particles'
distribution in time.
First graph 800A in Figure 8 shows the particle size distribution as an
average of four consecutive
tests (performed under the same conditions) for five different time points
from the start of
aerosolization (t = 1 min) until the end of dispersion (t = 124 min). Second
graph 800B in Figure
8 focuses on the size distribution of particles with D > 2 gm. These larger
particles carry the
majority of antigen and are believed to be the most likely to deposit in the
respiratory system. The
error bars shown in second graph 800B represent the standard error determined
from the repeat
tests.
[00127] At all time-points during dispersion, a peak in particle count
occurred for particles at
approximately D = 0.7 gm (mode); the numbers of these smaller particles
increased over the period
of aerosolization. High standard errors were observed for the smaller
particles (D <2 gm) (not
shown). Particles of this size, with settling velocities <0.2 mm/s, are known
to remain suspended
for long durations (on the order of days). Large day-to-day variations in
their numbers were
therefore expected. The larger particles (D? 2 gm) (shown in second graph
800B) were detected
only during dispersion, and exhibited a smaller day-to-day variation. Having
greater mass and
higher settling velocities, their motion was more predominantly driven by the
robotic AAS
aerosolization and gravity, whereas smaller particles were affected by
additional factors.
[00128] Although small particles were detected in greater numbers, the
allergen associated with
them is expected to be minimal as these smaller particles represent only a
small portion of the bulk
sample volume. In Figure 9, the particle count and associated particle volume
are displayed and
compared for one of the tests performed (near the start of aerosolization).
Clearly, the larger
particles, although small in number, represent the largest portion of the bulk
sample volume. In
terms of the absolute numbers of particles dispersed, the arithmetic mean
particle diameter D(1,0)
was 0.76 gm; whereas in terms of volume contribution, the volume moment mean
diameter D(4,3)
was 4.34 gm.
- 29 -
Date Recue/Date Received 2023-07-10
[00129] The air concentration of the larger particles (second graph 800B in
Figure 8) reached a
maximum 10 minutes after the start of aerosolization, and then gradually
decreased in time. This
is better illustrated by the cumulative count of particles with D > 2 gm
versus aerosolization time
(Figure 11), where the distribution from the robotic AAS is compared to that
from the blanket
shaking method, each averaged from four tests.
[00130] The concentration of large particles increased within the first 10
minutes of robotic AAS
aerosolization, then gradually decreased over the remainder of the test period
(Figure 10). Particle
concentrations were very high during blanket shaking (t = 1 min and t = 16
min) but rapidly
decreased within 12 minutes after aerosolization, by which time all particles
D > 2 gm had settled.
[00131] The effect of the allergen extractors (second image 600B in Figure 6)
was measured by
performing aerosolization tests with and without them installed. Figure 11
shows the cumulative
particle concentrations (D > 2 gm) for tests with and without one extractor.
Two tests were
performed at the lowest suction setting without extractors and with one
extractor. A third test
performed at the highest suction setting without extractors is also shown to
compare the effect of
suction power to allergen extractors.
[00132] Even a single allergen extractor resulted in a 5-fold increase in
airborne particles,
summed over 60 minutes (74x106 vs. 13 x106 particles/m3). The extractor had a
much greater
effect on particle aerosolization than suction level. Without extractors, the
highest suction level
resulted in 2.6 times more total particles compared to the lowest suction
level (35x106 vs. 13x106
particles/m3) (Figure 11, black dots versus squares). Particle levels were
also much more variable
using the extractor. A large drop in particle levels at 45 minutes, followed
by a rapid rebound at
51 minutes was observed: while unclear as to the cause, this may have been the
result of an
accumulation of hair or allergen within the robotic AAS that was then
dislodged. Comparatively,
a continuous, but significant decline in particles was observed at the highest
power setting.
[00133] Extractors also resulted in significantly higher airborne Fel d 1
levels: At the lowest
suction level and using one extractor, (Fel d 1> was found to be 5.8 times
greater than the allergen
concentration seen with no extractor at the lowest suction level (238 ng/m3
vs. 41 ng/m3,
respectively). Again, this was a greater effect than of suction level alone:
with no extractors, (Fel
d 1> at the highest suction level was found to be 2.6 times higher than the
allergen concentration
at the lowest suction level (105 ng/m3 vs. 41 ng/m3, respectively). Because
the average Fel d 1
- 30 -
Date Recue/Date Received 2023-07-10
concentrations generated when using the extractor(s) exceeded our target
range, the subsequent
validation proceeded with the extractors removed from the vacuum.
[00134] Experiments were performed for a range of vacuum suction levels,
adjusted by regulating
the voltage to the vacuum. For each of four suction level tests, the exhaust
flow rate was calculated
from the velocity measured at the centerline of the exhaust flow using a flow
anemometer.
Experiments were done without the use of debris extractors for suction levels
that resulted in 52%
(N = 1), 62% (N = 4), 80% (N = 4), and 100% (N = 2) of maximum exhaust flow
rate. Despite
some day-to-day variation in Fel d 1 levels reflected by repeat tests at fixed
settings, there was a
positive correlation of test-averaged (Fel d 1> for increasing exhaust flow
rate, showing that the
added power control provides some degree of control over the aerosolized
allergen levels. These
results being depicted in Figure 12.
[00135] Based on these findings, the settings and configuration to achieve
stable allergen levels
in our target Fel d 1 range (40-100 ng/m3) were identified as:
= 15/5 minutes on/off duty cycling;
= Operating without installation of allergen extractors; and
= Operating at a power reduction that resulted in 80% of maximum exhaust
flow.
[00136] Four repeat tests were performed at these settings, showing good
temporal stability of
allergen levels over 2 hours (Figure 13) and even distribution across the room
(Figure 14). The
average (Fel dl > from the four tests was 55 ( 9 SD) ng/m3.
[00137] Averaged (Fel d 1> from tests performed using the robotic AAS in the
small NEC are
shown in Figure 15 as a function of their corresponding cumulative particle
count for particles
with D > 2 gm. The error bars indicate the standard error associated with the
Fel d 1 measurements.
A good correlation between the average (Fel d 1> and the particle count was
found (coefficient of
determination R2 = 0.89), especially for (Fel d 1> greater than 50 ng/m3. This
shows that particle
concentration may be used as an immediate indicator of airborne Fel d 1,
enabling a rapid response
to adjust levels for better control (rather than waiting a day or longer for
completion of ELISA
testing).
[00138] The large room validation procedure was adapted based on the results
of the small room
validation. Adjustments were made to account for the larger room volume (2.5
times larger). A
- 31 -
Date Recue/Date Received 2023-07-10
series of tests were done to identify the optimal test settings (power level
and dander
supplementation) to achieve Fel d 1 levels in the target range.
[00139] In the small room validation, a gradual decline of Fel d 1 and
particle concentration in
time had been observed (Figures 7 and 10). To correct for this, the protocol
for the large room tests
was adapted to increase the vacuum suction level gradually over the course of
aerosolization. The
staged suction levels chosen to achieve stable Fel d 1 levels over two hours,
following iterative
testing, are illustrated in Figure 16.
[00140] The settings and configuration that were identified through iterative
testing as optimal
for the large room aerosolization were:
= Two vacuums operating simultaneously in adjacent areas of the room.
= Carpet supplementation with milled cat hair and/or shaking cat bedding in
advance
of each test.
= Operating without installation of debris extractors.
= 15/5 minutes on/off duty cycling.
= Operating at a staged suction power level schedule starting at 67% of max
suction
flow rate at t = 0 minutes and gradually increasing to 92% max suction flow
rate at t
= 100 minutes, according to Figure 16.
[00141] Test mean (Fel d 1> from five repeat tests under these settings was 79
( 30 SD) ng/m3.
The results demonstrated excellent temporal stability of the allergen levels
(Figure 17) with 19%
maximum deviation from the mean. There was no systematic spatial gradient
observed within the
room (Figure 18) and the maximum spatial deviation from the average of five
tests was 11% from
the mean.
[00142] It is evident from the results above that the inventors have
successfully employed
particle counts and Fel d 1 measurements to configure a robotic AAS to
generate consistent dander
levels over time and space in two rooms. To characterize particle behaviour
during aerosolization
(Figures 8 and Figure 10), a threshold of 2 gm was used to differentiate small
and large particles.
This threshold is consistent with the pore size of the glass fiber filters (2
gm) used for air sampling.
Furthermore, it is these larger particles that will deposit in the upper and
lower airways and are
thus most significant for eliciting allergic symptoms in an EEU. At all
measurement times during
aerosolization, the mode of the average particle size distribution was
approximately D = 0.7 gm
(Figure 8). The majority of particles in this size range were likely non-Fel d
1 carrying particles
- 32 -
Date Recue/Date Received 2023-07-10
such as fine dust. The air concentrations of these smaller particles varied
significantly between
tests but were not correlated with aerosolized Fel d 1 (data not shown).
Particles sized between 1
and 2 gm were also numerous, as shown by Figure 8. To evaluate whether these
particles
contributed significantly to Fel d 1 levels, duplicate air samples were
collected using both 1 gm
and 2 gm pore size glass fiber filters and Fel d 1 was assessed by ELISA. No
significant difference
was found in the allergen concentration between the 1 gm and 2 gm pore size
filters (data not
shown), suggesting that particles in this size range did not significantly
contribute to aerosolized
allergen levels.
[00143] It is important to note that the diameters obtained using the particle
size distribution
analyzer (PSD) are aerodynamic particle diameters and do not accurately
reflect the dimensions
of the irregularly shaped dander particles (skin flakes). Therefore,
discrepancies between the
particle counts and Fel d 1 concentrations were expected. For example, the
time-of-flight method
for particle detection has been shown to underestimate the true aerodynamic
diameter of non-
spherical particles (with a dynamic shape factor of 1.19) by 20% to 27%.
Still, a correlation was
obtained (Figure 15) that can be used to coarsely predict Fel d 1 levels,
particularly for high levels
of dispersion.
[00144] The particle density of the aerosolized particulate was assumed to be
uniformly 10'
kg/m3 and was used in the time of flight calculation to estimate aerodynamic
equivalent particle
diameter. However, within the literature research with respect to the removal
rate of the dispersed
particles (dust) suggests lower settling velocities experimentally than
expected theoretically,
which suggests that the density of the dispersed particles may be less than
103 kg/m3. If the
assumption of density was in fact incorrect, i.e. overestimated, then this may
have resulted in an
underestimate of particle diameters.
[00145] Although the aerosolization method developed here produces more
consistent and
controlled allergen dispersion compared to traditional blanket shaking
methods, the allergen levels
within the NEC were also subject to some degree of natural variation. This is
largely attributed to
variation in cat shedding and Fel d 1 production, both of which have been
shown to be widely
variable between cats, by season, and from day to day. Accordingly, within
other embodiments of
the invention it may be beneficial to employ a first set of robotic AAS to
acquire the allergens,
consolidate the acquired material, and disperse the acquired material to a
second set of robotic
AAS such that the robotic AAS have consistent quantities of allergens for
dispersal. Optionally,
- 33 -
Date Recue/Date Received 2023-07-10
the allergens may be acquired by other means rather than a robotic AAS.
However, one benefit of
the robotic AAS is that these may be employed within an individual's home or
other environment
to acquire specific allergens to test the individual's response to the
allergens at higher levels and/or
effectiveness of pharmaceutical treatment(s) etc. Air humidity levels may also
affect dander
production, as well as its aerosolization. The relative humidity in the NEC
varied between 38-68%
during these experiments.
[00146] Allergen aerosolization within an NEC AEC of portable AEC relies on
dander
accumulation on the floor surface, e.g. carpet, rug, etc. For this reason,
frequency and rigor of
carpet cleaning must be carefully regulated and balanced (e.g. to provide a
sanitary environment
for the resident cats within the NEC) while avoiding depletion of the allergen
source. These carpet
allergen levels can be monitored regularly to identify the need for dander
supplementation, which
(when required) was achieved by shaking the cats' blankets in advance of
testing (adding variable
quantities of Fel d 1) or, for the large NEC only, by evenly distributing
weighed amounts of milled
cat hair onto the carpets. The timings and degree of cleaning, the level and
location of cat activity,
natural variations in the cats' allergen production, and changes in human foot
traffic are all likely
to contribute to the variability in Fel d 1 measured in repeat tests performed
on different days.
[00147] It was initially expected that all large airborne particulate would
fall back to the floor,
becoming available for recirculation in a closed system; however, a decline in
particle and Fel d 1
concentrations was observed over the course of aerosolization when operating
at constant suction
level (Figure 11), especially under high dispersion settings, indicating that
there were system
losses. This is consistent with the findings in the literature that allergens
in a carpet become
depleted after a few cycles of resuspension activities (5-minute disturbance
using a vacuum with
no filter). In the present case, particulates may also have been deposited
onto surfaces where it was
unavailable for recirculation such as the walls, ceiling or furniture.
Furthermore, accumulation of
particulate, especially cat hair, within the vacuum's dust bin likely impeded
the flow of subsequent
particulate. Periodically unblocking this accumulation was found to alleviate
the observed decline
of airborne allergen. In the large room validation, allergen levels were kept
steady in time by
incrementally increasing the suction level over the course of the 2-hour
tests. Such a protocol may
be defined for the smaller NEC as well as the portable AEC etc.
[00148] The presented results show that dander aerosolization using the robot
vacuum generates
much more stable allergen and particle levels in time compared with the
blanket shaking method
- 34 -
Date Recue/Date Received 2023-07-10
which was used by other investigators. It has been previously shown that for
blanket shaking, due
to the rapid settling of particulate after shaking, repeated intermittent
shaking is required to
maintain adequate allergen levels during a one-hour exposure. This frequent
intervention by the
investigator (typically every 15 minutes) is impractical for clinical study
protocols and increases
allergen spread outside of the exposure room due to frequent door openings.
The remote
operability of the robotic AAS affords minimal intervention from the operator
as compared to
blanket shaking.
[00149] The maintenance of Fel d 1 levels within a narrow range that mimics
levels found in
homes etc. permits evaluation of new medications in a controlled but homelike
setting. The use of
allergen extracts in exposure chambers permits the dispersion of spherical
particles with a narrow
size range and better control over the antigen levels. However, this is not
the natural exposure and
may alter the response profile. Furthermore, while we measured the major cat
allergen Fel d 1,
other cat antigens have been identified and may contribute to an individual
patient's allergic
response (e.g. Fel d 4). While extracts used in EECs normally only contain Fel
d 1, patients in the
NEC are exposed to all types of cat allergen as they would be in a home
environment, hence a
more realistic representation of the patient's experience during an allergic
reaction is achieved.
[00150] Now referring to Figure 19 there are depicted first to fifth images
1900A to 1900E of a
field deployable AEC according to an embodiment of the invention. The field
deployable AEC
(FD-AEC) is based upon a portable plastic structure, e.g. a greenhouse tent or
a tent for example,
which may be self-erecting or erectable. The FD-AEC provides a self-contained
AEC which can
be readily transported, deployed and employed to acquire data rather than
relying upon dedicated
fixed location AECs for example. First to fifth image 1900A to 1900E
depicting:
= First image 1900A depicting a rear door to the FD-AEC closed and secured
(the FD-
AEC depicted having front and rear doors but another FD-AEC may have only a
single door);
= Second image 1900B depicting a barrier and cable port structure to allow
power /
cables etc. to be run in / out of the FD-AEC as well as providing a physical
barrier
for the robotic AAS to detect rather than a distortable flexible wall of the
FD-AEC;
= Third image 1900C depicting the FD-AEC within an indoor environment with
entry
open;
- 35 -
Date Recue/Date Received 2023-07-10
= Fourth image 1900D depicting an inner view of the FD-AEC showing the
robotic
AAS 1910, robotic AAS Charging Station 1920, table, carpet, virtual wall and
handheld LPC 1930; and
= Fifth image 1900E depicting air sampling pumps in position with filter
cartridges
attached.
[00151] Whilst the description above with respect to robotic AAS and FD-AEC
has been
described and presented with respect to internal environments and/or
extracting allergens from
carpets and other surfaces it would be evident that the methods, systems and
processes described
and depicted may be similarly applied within external environments and/or with
external surfaces.
[00152] The following sections describe an exemplary sequence of actions /
steps with respect to
the set-up and operation of the exemplary FD-AEC depicted in Figure 19. Within
the following
description a greenhouse tent (tent) was employed as the external housing the
steps, and milled cat
hair was used as an exemplary allergen source. Many of the steps described
being specific to the
SpringHouseTM tent and allergen source employed which it would be evident of
one of skill in the
art would vary according to the FD-AEC housing / shell and embodiment of the
invention
employed. The exemplary FD-AEC in Figure 19 being approximately 1.8 meters x
1.8 meters x 2
meters (6 feet x 6 feet by 6 feet 6 inches high).
[00153] Chamber Setup
= Set up the tent.
= With the tent in position, tape the outside and inside tent flaps to the
floor along the entire
edge to create a seal.
= Zip both entrances closed. Hereafter, all personnel must be gowned and
chamber entrances
should remain closed whenever possible.
= Lay out the carpet (cut to size) on the floor inside the chamber.
= Unzip the front- and rear-entrance mesh screen doors, roll them up and
secure them to the
side using the hook-and-loop straps where the door connects to the tent wall.
= Duct-tape cardboard barriers into the inside front-left and front-right
corners of the tent
near the floor (to prevent the robotic AAS from becoming stuck on the tent
cross-poles).
= Set up the sampling pump mount (as seen in Figure 19 fifth image 1900E;
sampling pumps
and cartridges to be added later):
o Tie a mesh bag to the tent ceiling crossbar.
- 36 -
Date Recue/Date Received 2023-07-10
o Hang a cardboard sampling cartridge support using wire so the sampling
cartridges
will hang approximately 48 in. from the floor, in a line parallel to the front
and rear
tent walls.
o Attach three sampling pump tubes to the cardboard support using their
attached
alligator clips: one each on the right, middle, and left of the support (their
ends will
dangle for now, and will be attached to sampling pumps later).
= Place a subject chair against the middle of the rear tent wall (see
fourth image 1900D in
Figure 19).
= Place an overbed table over the chair, with its front-facing edge
approximately aligned
(vertically) with the front edge of the chair (see fourth image 1900D in
Figure 19).
o Adjust the table height to be ¨30 in. from the floor (measured from the
tabletop;
the lowest position for the table).
o Lock the table casters if possible.
= Place robotic AAS Virtual Walls on opposite sides of the chamber, facing
each other, to
create a line just where the chair's front legs end (-1/3rd of the tent from
the rear wall) (see
Figure 3, middle; only one virtual wall is shown but the other is in the
corresponding
location on the opposite side of the tent).
o Leave the virtual walls switched off until ready for testing.
= Place the robotic AAS charger on the floor against the middle of the
front wall (under the
front entrance) (see fourth image 1900D in Figure 19).
o Run the power cable from the home-base along the front wall (tucked under
the
carpet edge if possible) through the cable/hose port in the front wall to the
right* of
the entrance.
o Tape the cable against the tent wall interior underneath the port to
prevent snags.
o Plug the cable into power outside the chamber.
[00154] Throughout this description with respect to the FD-AEC "right" and
"left" are oriented
as when facing into the chamber from the front.
[00155] Test Setup
= Wipe tent interior (walls, ceiling, doors) with Lysol wipes or other
protein-denaturing
cleaner to remove residual allergen from previous tests.
- 37 -
Date Recue/Date Received 2023-07-10
o Allow at least 30 minutes before test start for surfaces to dry (or at
least 2 hours for
particles to settle if a spray cleaner is used).
= For each hour of testing planned, prepare 3 sampling cartridges with
21.1m Millipore glass-
fibre filters and support pads as per the SOP: RMT-ClinOps10-Air Sampling Pump
Operation and Procedure [3].
o Label the cartridges with, for example, the study identity, test
identity, and sample
identity.
= Set up the sampling pumps:
o Remove the pumps (typically RMT pumps A, B and C for example) from their
charging station, turn them on and clear them if necessary.
o Program each pump as follows (pump numbers A, B and C will be used
hereafter
to index individual pumps; if other pumps are used substitute their pump IDs
throughout):
= Flow rate: 5000 cc/min
= Delay: 42 min (pump C), 22 min (pump B), or 2 min (pump A)
= Run 1: 20 min
= Hold: 40 min
= Run 2: 20 min
o Place the pumps in the mesh bag.
o Affix the pump tubes (hanging from the cartridge support) to the pump
inlets
according to their position (i.e. the tube on the left of the support goes to
the pump
on the left and so on).
o Remove the red caps from sample cartridges 1 through 3 and place on the
tubes as
follows:
= Pump A: sample 1
= Pump B: sample 2
= Pump C: sample 3
o With the indicated programs, the pumps will take turns sampling for
sequential 20-
minute blocks of time from the start of the test (2 minutes after program
start) for
the duration ¨ samples IDs are indexed according to this order.
- 38 -
Date Recue/Date Received 2023-07-10
= Weigh out the desired amounts of allergen source, e.g. milled cat hair.
With milled cat hair
as the allergen source for the preload and canister loads the following values
were
employed within exemplary robotic AAS experiments. Accordingly, the following
description whilst referring to cat hair should be read as referring to the
allergen source in
other embodiments of the invention.
o For the technical validation repeats, allocation was as follows (all
10%):
= Preload: 3 g
= Canister hour 1: 0.5 g
= Canister hour 2: 1 g
o Record actual measured weights.
= Preload the carpet:
o Empty the allocated cat hair into a mesh sieve and begin shaking it
evenly across
the front 2/3rds of the carpet (the entire area in front of the chair and
table) using a
"flour dusting" motion until most of the free dust has been shaken out.
o Force remaining cat hair through the sieve by rubbing it against the mesh
by hand
¨ continuing to spread the resulting hair/dust over the area of the carpet
until most
of the milled cat hair has been distributed (and the rate of distribution
slows).
o Evenly distribute remaining clumps of hair across the same area of the
carpet.
o Hereafter, avoid stepping on the preloaded area as much as possible.
o Allow at least 2 hours before test start for aerosolized particles to
settle. Preloading
can be done the day before testing if desired.
= For a 2-hour or longer test, two robotic AASs will be required:
o Ensure all robotic AASs are accounted for and charged (typically RMT
Robotic
AASs 2 and 3; robotic AAS numbers 2 and 3 will be used hereafter to index
individual robotic AASs, if different robotic AASs are used substitute their
IDs
throughout).
o Remove both extractors from underneath each robotic AAS by squeezing the
yellow extractor frame release tabs to open the bottom compaiiment, then
gently
remove the extractors.
o Verify that the bins have been emptied and the robotic AASs are clean:
- 39 -
Date Recue/Date Received 2023-07-10
= Remove each bin from the robotic AAS by squeezing the bin release button
on
the back of the robotic AAS and then pulling the dust collection bin from the
back.
= Open all compaiiments of the bin and clean it out thoroughly. Make sure
to
remove all dirt and debris that may be trapped in the pump fan.
= Wipe along the bottom surface of each robotic AAS, including the sensors
and
charging contacts with damp cloth or antiseptic wipe.
= Wipe the inside of the bottom compartment that houses the extractors and
remove any debris.
= Wipe clean the inside of the exhaust fitting.
o Plug in a second robotic AAS home-base outside the chamber and set
Robotic AAS
2 on it to charge.
o Ensure that the filter has been removed from the bin of robotic AAS 3 and
that the
mesh covering has been mounted in the filter's place. A 6 mm diamond mesh was
used for all FD-AEC validation tests.
o Mount the exhaust fitting on robotic AAS 3 aligned with the exhaust hole
on the
back of the vacuum bin. Using duct tape, thoroughly seal the spaces around
where
the fitting meets the robotic AAS body (Figure 7). Note that it is important
to get a
good seal resistant to blow-out as there is increased resistance downstream in
the
allergen canister. A poor seal can result in significantly reduced allergen
aerosoli zati on.
o Prepare the allergen canister and vibration motor circuit:
= Insert the bottom mesh into the bottom cap. A 6 mm diamond mesh was used
for both the bottom and top meshes for FD-AEC validation repeats.
= Assemble the bottom cap and body (with the bottom mesh inset between
them,
not shown).
= Load the initial canister cat hair allocation into the partially
assembled canister
(it is a good idea to have the canister sitting in a weigh boat to catch any
allergen
that falls through the mesh).
= Insert the top mesh into the canister top cap. The top cap has a
vibration motor
affixed.
- 40 -
Date Recue/Date Received 2023-07-10
= Screw the top cap onto the canister body. Be careful not to jostle the
canister
excessively to avoid allergen loss.
= Screw the filled canister onto the robotic AAS exhaust fitting.
= Connect the vibration motor to the vibration motor power supply
o Place robotic AAS 3 inside the chamber on its home-base to charge.
o Set robotic AAS 3 to its starting power level (eco mode 5 for FD-AEC
validation
testing repeats).
[00156] Test Start
= Take a baseline particle count with the handheld LPC:
o Program the LPC (for example):
= Cycles: 2
= Delay: 00:02:00
= Hold: 00:01:00
= Sample: 00:02:00
= Take note of the current location setting, or set to L00001
o Affix LPC inlet nozzle and temperature and humidity sensor.
o Place the LPC on the chamber table upright (supported by its swivel
stand) aligned
with the middle axis of the chamber directly above the edge of the chair.
o Start the LPC program and exit the chamber for the sampling duration. Do
not
disturb the chamber while the baseline measurement is underway.
o If one or both the baseline measurements are higher than expected (e.g. >
500
particles > 5 gm dia.), you may want to allow extra time for particles to
settle before
starting a test. If so, take a new set of baseline measurements before the new
test
start.
= Reprogram the LPC for 20 cycles per hour of testing (i.e. 40 cycles for a
2-hour test; the
rest of the program is unmodified).
= Check that all robotic AASs are connected wireless to controller and
fully charged.
= Check that robotic AAS 3 is set to the correct starting power level and
set the robotic
AAS to performance or eco mode in the controller application as appropriate
(eco 5 for
FD-AEC validation testing repeats).
= Make sure the pumps are turned on and ready to start.
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Date Recue/Date Received 2023-07-10
= Remove the inlet caps from sampling cartridges 1 through 3.
= Start all three sampling pumps, the LPC, and the stopwatch as close to
one another as
possible (within 10-15 seconds). The 2-minute pre-test delay has now begun.
= Exit the chamber.
= 10-15 seconds before the end of the pre-test delay (stopwatch will read
1:45-1:50), toggle
the vibration motor on.
= After the 2-minute pre-test delay (the stopwatch will read 2 minutes),
approximately
simultaneously:
o Start Robotic AAS 3 from the app ¨ observe the initial plume of allergen
ejected
from the canister.
o Restart the stopwatch (this is t = 0).
o Listen to make sure the sampling pumps and LPC have started sampling.
[00157] Test Operation
= Enter the chamber only when necessary.
= Monitor robotic AAS status throughout, intervening if it becomes stuck.
= Ensure the robotic AAS stops/restarts approximately every 5 minutes:
o The robotic AAS will take 4-8 minutes to complete a program on its own.
Stop and
restart it from the app if 5 minutes have passed since the last power cycle.
o When the robotic AAS stops, check to make sure the bulk of the cat hair
has
dropped from the top of the canister to the bottom before restarting it (it
may take
a few seconds for most of the hair to drop, and some small clumps may remain
stuck against the top mesh). If the bulk of the hair remains stuck against the
top
mesh:
= Ensure the vibration motor is on and properly affixed.
= Tap the top of the canister with a finger to dislodge the hair, or use a
paperclip
or something similar to poke it down.
o Observe the plume of allergen ejected from the canister on robotic AAS
restart. If
very little is observed (particularly for multiple power cycles
consecutively), stop
the vacuum and mix up the hair using a paperclip or something similar.
= Scale the vacuum power level according to the testing regime. For FD-AEC
validation
testing repeats, power scaling was as follows:
-42 -
Date Recue/Date Received 2023-07-10
o 0-20 min: eco 5
o 20-40 min: performance 4
o 40-60 min: performance 5
o 60-120 min: performance 6
= For tests longer than 1 hour (such as FD-AAE validation testing repeats):
= At t = 48 min, exchange samples 1 and 2 for samples 4 and 5, respectively
(so sample 4
is on pump 10, and sample 5 is on pump 9). Cap samples 1 and 2 and place them,
outlet
side down, in the cartridge rack.
= At t = 50 min, prepare to swap robotic AAS 3 for robotic AAS 2:
o Stop robotic AAS 3 (and the vibration motor) and remove it from the
chamber.
o Disconnect the vibration motor from the battery pack and remove the
battery pack
from robotic AAS 3.
o Unscrew the allergen canister from the exhaust fitting (be careful not to
jostle the
canister excessively) and remove the remaining cat hair from the canister.
Completely disassemble the canister to ensure cat hair is removed from between
the various components. Put the collected hair aside to be weighed later.
o Load the canister with the hour 2 allocated cat hair (as outlined in
section 2, steps
6.g.i through v; 1 g for FD-AEC validation testing repeats).
o Remove the exhaust fitting from robotic AAS 3.
o Remove the dustbin from robotic AAS 3. Open the bin and ensure all
collected cat
hair is in the bottom compartment of the bin (underneath the mesh). Make sure
to
remove hair caught in the impeller. Mix up the hair with a pair of forceps,
then close
the bin and place it in Robotic AAS 2.
o Mount the exhaust fitting on robotic AAS 2 (as described in section 2,
step 6.f;
Figure 7).
o Screw the allergen canister onto the exhaust fitting.
o Tape the vibration motor battery pack onto robotic AAS 2 and reconnect
the
vibration motor circuit. Tape down the circuit connectors as done previously.
o Place robotic AAS 2 in the chamber on the home-base to charge.
o Set robotic AAS 2 to the correct power level for t = 60 min (performance
6 for FD-
AEC validation testing repeats).
- 43 -
Date Recue/Date Received 2023-07-10
= 10-15 seconds before t = 60 min, toggle the vibration motor on.
= At t = 60 min, start robotic AAS 2. Observe the initial plume of allergen
ejected from
the canister.
= After pump 8 stops sampling (at approximately t = 60 min), swap sample 3
for sample
6. Cap sample 3 and place it, outlet side down, in the cartridge rack.
= Record the current battery level of both robotic AAS 3 and robotic AAS 2.
= Place robotic AAS 3 on the home-base outside the chamber to charge.
= Continue monitoring robotic AAS status and power cycling as outlined in
steps 2-3 for
the remainder of the test duration.
[00158] Test End and Cleanup
= Toggle the vibration motor off.
= Secure testing samples/measurements:
o Cap air sampling cartridges and place them, outlet side down, in the
cartridge rack.
o Record robotic AAS battery levels.
o Remove remaining cat hair from the allergen canister and set it aside to
be weighed.
o Remove collected cat hair from the robotic AAS dustbin, including that
stuck in the
impeller, and set it aside to be weighed.
o Remove the LPC from the chamber.
o Document each air sample on an Air Sampling Pump Log (they should be 20
minutes and 100 L each).
= Disassemble the allergen canister and wipe all components and the exhaust
fitting.
= Turn off and wipe the virtual walls.
= Wipe, clear, and power off the pumps.
= Wipe the chair and table and remove them from the chamber.
= Install the allergen extractors and a filter into a robotic AAS with at
least 60% battery
remaining. With all other furnishings removed from the chamber, vacuum the
carpet
by running the robotic AAS at max power (performance mode 10) for 30 minutes.
Afterward, dispose of any material collected and remove the filter and
extractors again.
= Use a damp paper towel or alcohol wipe to wipe all robotic AASs used.
Wipe the interior
of the bin, making sure to reach all corners and collect any remaining dust
and dander
- 44 -
Date Recue/Date Received 2023-07-10
before replacing the mesh grid inside the bin. Wipe the bottom extractor
compaiiment
as well as the sensors and charging contacts.
= Weigh all allotments of cat hair set aside previously (canister hour 1,
canister hour 2,
bin) and record. Store used cat hair in the labelled container (optionally
within a
freezer).
= Extract LPC data.
[00159] Package and store air samples for ELISA analysis according to
protocol.
[00160] Allow at least two hours before subsequent testing.
[00161] Within the preceding sections a low complexity robotic AAS is
described requiring
additional user input. Within other embodiments of the invention the robotic
AAS may automate
many of the additional steps, provide robotic handling mechanisms etc.
[00162] Figure 20 depicts a cover of the robotic AAS according to an
embodiment of the
invention showing a mesh for large debris filtering. Whilst a square mesh is
depicted embodiments
of the invention may employ other meshes such as diamond, rectangular,
triangular, circular etc.
Within the following descriptions with respect to a robotic AAS according to
embodiments of the
invention a 6mm (0.25 inch) diamond mesh was employed.
[00163] Figures 21 to 23 depict an exemplary exhaust fitting / dispersion
assembly (EFDA), also
referred to as an Exhaust Allergen Dispenser (EAD) for a robotic AAS according
to embodiments
of the invention. Figure 21 depicts a prototype robotic AAS according to an
embodiment of the
invention with the EFDA 2110 together with Vibratory Motor 2120 and Suction
Control 2130. It
would be evident that within other embodiments of the invention the Suction
Control 2130 may
be integrated to the robotic AAS and controlled through programming of the
robotic AAS and/or
through a wireless interface of the Robotic AAS. Optionally, the Suction
Control 2130 may be
coupled to an LPC, for example, to adjust the suction applied according to the
particle counts
established by the LPC. Similarly, the Vibratory Motor 2120 may be integrated
with the EFDA
2110 or within the Robotic AAS.
[00164] Now referring to Figure 22 there are depicted perspective and cross-
sectional views
2200A and 2200B of an exemplary exhaust allergen dispenser (EAD) assembly for
an AAS
according to an embodiment of the invention. As depicted the EFDA / EAD
comprises a Top Cap
2210, Canister Body 2220, Bottom Cap 2230 and Exhaust Fitting 2240. The Bottom
Cap 2230 and
Exhaust Fitting 2240 allow the EFDA / EAD to be demountably attached to the
Robotic AAS such
- 45 -
Date Recue/Date Received 2023-07-10
that the canister (Canister Body 2220) can be pre-filled / replaced etc. It
would be evident that the
relative dimensions of these parts may change according to the design of the
robotic AAS and/or
exhaust of the robotic AAS together with the requirements of the testing to be
performed with the
Robotic AAS. For example, the canister may be larger for extended testing
sessions relative to
those for short duration tests.
[00165] As depicted in Figure 21 the Top Cap 2210 of the EFDA / EAD has a mesh
screen.
However, within other embodiments of the invention this may be replaced to
block the release of
allergens for transportation or storage of the EFDA / EAD or during an
acquisition mode of the
robotic AAS to which the EFDA / EAD fits.
[00166] Now referring to Figure 23 there are depicted an exemplary EFDA / EAD
for a AAS
according to an embodiment of the invention in disassembled and assembled
views 2300A and
2300B respectively. Accordingly, there are depicted the Top Cap 2210, Canister
Body 2220,
Bottom Cap 2230 and Exhaust Fitting 2240. Attached to the Top Cap 2210 is
Vibratory Motor
2120. The Vibratory Motor 2120 provides specific vibration of the EFDA /EAD in
conjunction
with or independent of any vibrations arising from the operation of the
robotic AAS. The Vibratory
Motor 2120 enhances distribution of the allergen(s) within the Canister Body
2220.
[00167] Optionally, the Vibratory Motor 2120 may be attached to or integral
with the Canister
Body 2220 rather than attached to or integral with the Top Cap 2210.
[00168] Optionally, the Vibratory Motor 2120 may be attached to or integral
with the Bottom
Cap 2230 rather than attached to or integral with the Top Cap 2210.
[00169] Optionally, a robotic AAS may have two or more EFDA / EAD assemblies
attached to
one or more exhausts of the Robotic AAS.
[00170] Optionally, a robotic AAS may have two or more EFDA / EAD assemblies
attached to
one or more exhausts of the robotic AAS where each EFDA / EAD has the same
allergen.
[00171] Optionally, a robotic AAS may have two or more EFDA / EAD assemblies
attached to
one or more exhausts of the robotic AAS where each EFDA / EAD has a different
allergen.
[00172] Optionally, a robotic AAS may have one or more EFDA / EAD assemblies
attached to
one or more air outlet ports which are separate to exhausts of the robotic AAS
associated with the
Allergen Extractor(s).
- 46 -
Date Recue/Date Received 2023-07-10
[00173] Optionally, the Top Cap 2210 and Bottom Cap 2230 may be simply to
retain the Canister
Body 2220 where the Canister Body 2220 has an upper membrane which allows air
and the
allergen to pass through it and a lower membrane which only allows air to pass
through it.
[00174] Optionally, a robotic AAS with two or more EFDA / EAD assemblies can
provide
programmatic control through multiple activators such that multiple allergens
can be dispensed in
different quantities, different ratios relative to each other, or with
different temporal / spatial
profiles.
[00175] Optionally, a robotic AAS may have dedicated air inlet / outlets in
dispensing only
embodiments of the invention to suck air into the robotic AAS and via one or
more motors with
one or more impellers generate the required airflow to the one or more EFDA /
EAD assemblies.
These air inlets may include HEPA filters or other particulate filters to
limit aerosolization of the
other particulates other than the desired allergen(s).
[00176] Optionally, a robotic AAS may have dedicated outlets in dispensing
only embodiments
of the invention which couple one or more pressurised gas containers, e.g.
canisters, to the one or
more EFDA /EAD assemblies. The pressurised gas may be air, nitrogen or carbon
dioxide for
example. These pressurised gas containers may be coupled to programmable /
computer controlled
valves allowing controlled release, potentially in bursts / modes not
achievable with a motor /
impeller assembly or at higher flow rates / pressures to allow aerosolization
of heavier particles,
liquids etc.
[00177] Optionally, a robotic AAS may employ additional air inlets and/or
pressurised gas in
conjunction with a system such as described with respect to Figure 20 and/or
Figure 6.
[00178] Accordingly, an embodiment of the invention provides a FD-AEC
comprising a portable
pop-up environmental exposure chamber, an allergen dispersal system such as a
robotic AAS as
described with respect to embodiments of the invention, and a developed
methodology that
produces naturalistic and controlled allergen exposure for clinical research.
The allergen dispersal
system uses a robotic AAS with a custom exhaust channel and an external
allergen reservoir
(Figure 21 to Figure 23). Embodiments of the invention have been validated for
cat allergen
aerosolization (primary allergen Fel d 1) using milled cat hair as allergen
source material as
outlined above and dust mites as outlined below.
[00179] The elements comprising the chamber and necessary for its operation
may be provided
as a package to clients. These elements may include, but not be limited to:
- 47 -
Date Recue/Date Received 2023-07-10
= A FD-AEC housing, e.g. tent.
= A low-pile carpet cut to custom size to be fitted on the floor of the FD-
AEC.
= Air sampling pumps, their charging station, tubing, and hanging supports.
= Sampling cartridges, filters, support pads for collecting air allergen
samples.
= Tweezers and petri dishes for loading and storing allergen samples
(filters).
= Robotic AAS with pulse width modulation voltage regulation with custom
exhaust
fitting, charging station and virtual wall barriers.
= Aluminum bumper boards for adding structure to the inner tent corners and
improving
the motion of the robot vacuum.
= Custom allergen canisters (top cap, canister body and bottom cap,
vibration motor
circuit), empty.
= Predetermined amount of prepared allergen (e.g. milled cat hair, dust
mites) sufficient
for planned use.
= Metal mesh sieve for loading allergen onto carpets
= Scale for weighing allergen.
[00180] The exemplary FD-AEC described and depicted in respect of Figure 19 by
virtue of
being approximately 1.8 meters x 1.8 meters x 2 meters (6 feet x 6 feet by 6
feet 6 inches high)
can accommodate 1-3 human subjects at one time. It has a large zipper door,
one-piece envelope
construction, and minimal vents for allergen containment. The door can be
modified to have a
clear window so that subjects can be observed from outside the chamber. Such a
tent is very easy
and quick to set up, typically by a single person in under half an hour. It
requires no tools for set
up and it can be erected in any indoor space that can accommodate its
footprint and where the
ceiling is more than 2 meters (approximately 6.5 feet) high although it may be
employed externally
with additional means to fix the FD-AEC in position, e.g. guy-ropes, ropes,
pegs, straps etc. The
tent can also be easily transported: it can fit into a carrying case that can
be carried by a single
person.
[00181] Once the tent is erected, a custom-fit low pile carpet is installed,
completely covering the
floor area inside of it. A chair is positioned within the tent for every
subject to be tested per
challenge. Air sampling pump(s) with attached cartridges loaded with filters
are suspended from
the tent ceiling for allergen quantification. The robotic AAS charging station
is installed at the
front of the tent and plugged into a power source.
- 48 -
Date Recue/Date Received 2023-07-10
[00182] The robotic AAS described employs pulse width modulation voltage
control to adjust
the air flow. The exhaust fitting channels the vacuum exhaust up into the air
of the chamber. The
exhaust fitting outlet is threaded to allow mounting of the allergen canister,
and was FDM printed
in ABS.
[00183] Allergen (milled cat hair) is loaded into the custom-designed allergen
canister, which is
then screwed onto the exhaust fitting. The allergen canister as described was
designed in three
parts (Top Cap 2210, Canister Body 2220, and Bottom Cap 2230) that screw
together. In assembly
a pair of allergen containment meshes are included, one between the Top Cap
2210 and Canister
Body 2220 with the other between the Canister Body 2220 and Bottom Cap 2230
although it would
be evident that other configurations are possible according to embodiments of
the invention such
as having these integrated with the Top Cap 2210 and Bottom Cap 2230 for
example.
[00184] Within embodiments of the invention a High Density Polyethylene (HDPE)
6 mm (0.25
inch) diamond mesh was used for the prototype and validation testing, but
other meshes could be
used with little to no modification of the methodology. The allergen is loaded
between the meshes,
which are sized such that the allergen material is retained to a degree while
allowing air to pass
through to aerosolize allergen particles over time. The EFDA / EAD may for
example be formed
in Acrylonitrile Butadiene Styrene (ABS) and manufactured using 3D printing.
[00185] An eccentric rotating mass (ERM) Vibration Motor 2120 is mounted onto
the EFDA /
EAD to promote aerosolization by preventing the allergen from becoming clumped
or matted. A
7.2V DC ERM with motor rates to 8250 revolutions per minute was employed in
prototype robotic
AASs although it would be evident that other ERM motors and/or vibration
motors may be
employed. The Vibration Motor 2120 may be powered by a battery pack or battery
of the robotic
AAS.
[00186] The allergen in the canister is aerosolized and dispersed throughout
the FD-AEC when
the robotic AAS is turned on and the robotic AAS exhausts air through the
porous EFDA / EAD
canister containing the allergen. The allergen is dispersed evenly throughout
the FD-AEC over
time, as the robotic AAS moves about the space. The developed methodology
produced an average
Fel d 1 air concentration of 100 ng/m3 over the course of four 2-hour
aerosolization tests in the
prototype FD-AEC as depicted in Figure 24.
[00187] Further experimental results of the exemplary robotic AAS are depicted
in Figures 25 to
28 respectively. Figure 25 depicts particle distributions at different times
during and after
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Date Recue/Date Received 2023-07-10
aerosolization for very small particles (0.1 - 2 jim) and particles larger
than 2 jim using a AAS
according to an embodiment of the invention.
[00188] Figure 26 depicts the total number of particles >2 pm over time for an
exemplary robotic
AAS with and without a fan within the environment according to an embodiment
of the invention
versus a prior art method of dispersion (blanket shaking).
[00189] Figure 27 depicts the total particles versus time during and after
dispersal with a robotic
AAS according to an embodiment of the invention.
[00190] Figure 28 depicts the total number of particles versus time for
different power levels and
with/without extractors within a robotic AAS according to an embodiment of the
invention.
[00191] Whilst embodiments of the invention for the robotic AAS describe self-
contained
devices with batteries it would be evident that within other embodiments of
the invention the
robotic AAS may be connected to a power source via one or more cables or other
means of routing
electrical power within the NEC AEC, FD-AEC etc.
[00192] Accordingly, an embodiment of the invention comprises providing a
robotic AAS
comprising:
= a body housing a motor, an impeller, an exhaust and a controller;
= the motor coupled to the impeller for generating an exhaust air flow;
= the controller coupled to the motor for adjusting a rate of the exhaust
air flow exhausted
through the exhaust; and
= an exhaust allergen dispenser (EAD) assembly, coupled to the exhaust,
containing an
allergen; wherein
= the allergen is distributed within an environment through the allergen in
the EAD
assembly being exhausted from the EAD assembly by the exhaust air flow.
[00193] Accordingly, in an embodiment of the invention the EAD assembly is
demountably
attached to the exhaust of the robotic AAS.
[00194] Accordingly, in an embodiment of the invention the EAD assembly
comprises:
= a top cap for demountable attachment to a first portion of a canister
body;
= the canister body;
= a bottom cap for demountable attachment to a second portion of the
canister body;
= a first mesh screen disposed between the top cap and the first portion of
the canister
body; and
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Date Recue/Date Received 2023-07-10
= a second mesh screen disposed between the bottom cap and the second
portion of the
canister body; and
= the EAD assembly is demountably attached to the exhaust via an exhaust
fitting.
[00195] Accordingly, in an embodiment of the invention the EAD assembly
comprises:
= a top cap for demountable attachment to a first portion of a canister
body;
= the canister body;
= a bottom cap for demountable attachment to a second portion of the
canister body; and
= a vibratory motor coupled to at least one of the top cap, the bottom cap
and the canister
body; and
= the EAD assembly is demountably attached to the exhaust via an exhaust
fitting.
[00196] Accordingly, in an embodiment of the invention the robotic AAS further
comprises:
= one or more allergen extractors within the body coupled to the motor or
another motor
and a means to move the body over a surface the body sits upon; where
= the controller controls the motor or another motor to adjust a suction
applied through an
opening within which the one or allergen extractors are disposed to the
surface;
= the controller controls the motor and another motor to execute a first
stage and a second
stage;
= in the first stage the controller executes a first sequence of motion of
the body whilst
applying suction (acquisition of allergen(s)); and
= in the second stage the controller executes a sequence of motion of the
body whilst
exhausting air through the EAD assembly (dispersal of allergen(s)).
[00197] Within the preceding description with respect to Figure 19 a field
deployable AEC (FD-
AEC) was described and depicted within which robotic AAS according to
embodiments of the
invention may operate to provide a portable AEC. As discussed above the FD-AEC
is intended to
provide a mobile chamber for allergen chamber studies without needing a
dedicated brick-and-
mortar facility, e.g. an NEC such as described and depicted above.
Accordingly, having established
the robotic AAS the inventors established a study to mimic the aerosolized Fel
d 1 conditions
achieved in the validated NEC within the FD-AEC. This representing a third
stage in the
development of what the inventors refer to as the "Mini-Home." In Stage 1 the
robotic AAS was
established which employs a robotic system to move around within the FD-AEC
and blow air
through an EFDA / EAD containing the allergen under assessment, e.g. milled
cat hair within a
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Date Recue/Date Received 2023-07-10
collapsible tent. In Stage 2, validation tests led to a refinement of the
model and adjustments to the
aerosolization settings of the robotic AAS with the EFDA / EAD to achieve
stable allergen levels
(e.g. Fel d 1) over a two hour timeframe within a target range. The third
stage presented described
below and with respect to Figures 29 to 40 was based upon a series of
characterization tests to
identify the effect of certain parameters on allergen levels within the FD-AEC
whilst aerosolizing
milled cat hair.
[00198] The goal of aerosolization in the FD-AEC study with the robotic AAS
being to achieve
comparable air concentrations of Fel d 1 within the FD-AEC as within the NEC,
these NEC levels
being depicted in Figure 13, where these levels should also be sufficient to
induce allergic
symptoms, e.g. in cat-allergic persons, and similar to levels found in homes
with cats. Accordingly,
the target range for Fel d 1 aerosolization was set to 40-100 ng/m3 where the
robotic AAS should
additionally add adjustability and repeatability. Three variables were
assessed for their effects on
the aerosolized allergen levels with a handheld Laser Particle Counter (LPC)
and air sampling
pumps used to measure the particle and allergen levels during each test.
[00199] The three variables tested in this characterization were:
= the amount of cat hair preloaded onto the carpet covering the floor in
the FD-AEC,
= the amount of cat hair loaded into the canister attached to the robotic
AAS exhaust, and
= the robotic AAS Roomba "power scaling" throughout the test. (i.e. the
adjustment of
vacuum suction level with time).
[00200] The inventors also sought to develop models for each parameter showing
how their
variation affects the aerosolized Fel d 1 levels within the FD-AEC allowing
them to progress
forward with improved control over the allergen levels in the room, with
specific tailoring of the
test parameters to achieve the desired Fel d 1 concentration.
[00201]
During Stage 2 settings for the variable aerosolization parameters were
identified
through trial and error to achieve stable and repeatable allergen levels. In
Stage 3 the intention was
to explore the effects of each of these parameters, to identify how strongly
they influence allergen
levels. Within the tests discussed below each parameter was varied around a
respective fixed value,
to measure the resulting changes in allergen levels and sensitivity to that
variable. The three
variables that were varied separately were the preload amount of cat hair on
the carpet of the FD-
AEC, canister amounts of cat hair within the EFDA/EAD, and power scaling
patterns for the
robotic AAS. The specific parameters used for the Stage 2 validation were 3g
of carpet preload,
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Date Recue/Date Received 2023-07-10
0.5 and 1.0 g of cat hair in the first hour (Hr.1) and second hour (Hr.2)
canisters, respectively, and
a combination robotic AAS power scaling. The protocol used to conduct Stage 2
testing described
above was also applied in the characterization tests, maintaining consistency
across all test results.
Each aerosolization parameter is described in detail below, and the chosen
test configurations are
presented in Table 3.
Variable Preload Hr.1 Canister Power Scaling
Variation 1 Og Og [CO ¨ Constant
(Canister Hr.1: 0.5g (Preload: 3g (Preload: 3g
Hr.2: lg Hr.2: lg Hr.1 : 0.5g
Power: Combination) Power: Combination) Hr.2: lg
Test Length: 1 hr)
Variation 2 lg 0.25g Lowered Scaling
(Canister Hr.1: 0.5g (Preload: 3g (Preload: 3g
Hr.2: lg Hr.2: lg Hr.1 : 0.5g
Power: Combination) Power: Combination) Hr.2: lg
Test Length: 2 hrs)
Variation 3 5g lg Combination Scaling
(Canister Hr.1: 0.5g (Preload: 3g (Preload: 3g
Hr.2: lg Hr.2: lg Hr.1 : 0.5g
Power: Combination) Power: Combination) Hr.2: lg
Test Length: 2 hrs)
Table 3: Test Matrix of Parameter Variations Along with Corresponding Fixed
Conditions. The
values of the varying parameters are bolded, with fixed parameters in
parentheses.
[00202] Preload Amount: With the objective of recreating the aerosolization
conditions of the
NEC in the FD-AEC, the application of allergen source material (milled cat
hair) is required to
simulate the "existing" allergen in the NEC. The variable entitled "Preload,"
is this amount of cat
hair that is applied onto the carpet within the FD-AEC prior to the test(s).
It is applied two hours
prior to the test to allow for any particles to settle. The validation tests
were performed using a
preload amount of 3g, which was found, combined with the other fixed
variables, to achieve an
average of 100 ng/m3Fel d 1, which is on the high end of the target range (40-
100 ng/m3). Having
already conducted enough tests with a preload of 3g, the characterization
tests used to evaluate the
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Date Recue/Date Received 2023-07-10
effect of the preload were conducted using Og, lg, and 5g. Two repeat tests
were performed for
each preload amount, with the Hr.1 and Hr.2 canister amounts fixed at 0.5g and
lg of cat hair,
respectively. The robotic AAS power settings were also fixed at the
combination scaling pattern
used during the Stage 2 tests (as specified in Table 4).
t=Omin t=20min t=40min t=60min t=80min t=100min t=120min
ECO ECO 5 ECO 5 ECO 5 ECO 5 - - -
Lowered ECO 5 ECO 7 ECO 10 PER 3.5 PER 3.5 PER 3.5 PER 3.5
Scaling
Combination ECO 5 PER 4 PER 5 PER 6 PER 6 PER 6 PER 6
Scaling
Table 4: Robotic AAS Mode and Setting at each 20 minute Interval for Each
Power Scaling
Pattern (ECO = ECOnomical, PER = Standard PERformance)
[00203] Canister Amount (within EFDA/EAD): Having a reserve of cat hair for
each hour of the
test is necessary for maintaining stable allergen levels throughout the test.
The canister is used to
store an additional reserve of cat hair, and is replaced with a newly loaded
one every hour of
aerosolization based upon the design of the EFDS/EAD. The canister is placed
directly in the path
of an air exhaust of the robotic AAS to supplement anything the robotic AAS is
picking up from
the carpet and aerosolizing in the FD-AEC. The Stage 2 tests confirmed this
method ensures stable
levels throughout the test, and the canister amounts were chosen as 0.5g and
lg in the first hour
(Hr.1) and second hour (Hr.2) canisters, respectively, for 2-hour tests. In
order to determine the
effect that the amount of cat hair loaded in the canisters has on the allergen
levels and identify the
optimal amount, different amounts were tested while all other parameters were
fixed. Here, only
the Hr.1 canister amount was varied and tests performed using Og, 0.25g, and
lg. Two repeat tests
were performed under each configuration, as well as having collected the
particle data and air
samples for later analysis.
[00204] Power Scaling Pattern: The final parameter is the Power Scaling
Pattern. The robotic
ASS allows for adjustment of the overall power level (suction strength) via
pulse width
modulation, in addition to having two different power modes to operate under,
ECOnomical and
Standard PERformance which provide different lifetimes of the battery. The
power level was
defined as adjustable from 1 to 10 via dial on the robotic AAS but it would be
evident that within
other embodiments of the invention the robotic AAS settings may be programmed
into the robotic
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Date Recue/Date Received 2023-07-10
AAS and/or communicated to the robotic AAS via a wireless interface during its
operation. Tests
were designed to run for two hours, matching the duration of the Stage 2
validation tests, using a
combination of ECO and PER modes throughout. The variation in the power
settings causes the
air flow through the exhaust to vary greatly, and each variation that was
tested to explore those
effects. Figure 29 depicts the resulting exhaust velocity at different power
level configurations,
illustrating the variations seen between the power settings. The power scaling
patterns were then
used to ensure stable particle and allergen levels throughout the test. First
curve 2910 depicts the
standard PERformance mode and second curve 2920 the ECOnomical mode.
[00205] The first power scaling pattern was set to operate at ECO mode for the
entire duration of
the test, at level of 5, just above the lowest power level required for the
robotic AAS to function.
This power scaling pattern was explored to understand how to allergen levels
behave at a baseline
setting of the robotic AAS. This allows us to observe the natural tendency of
the particles and
allergen levels when there is no increase in robotic AAS suction (scaling).
The next power scaling
pattern that was tested was also set to ECO mode throughout the test, but at
increasing power
levels, until reaching the lowest Performance mode setting at the end of the
test. The third power
scaling pattern was referred to as a "combination scaling" pattern, where the
robotic AAS is set to
ECO mode, power level 5, then switches to PER mode and gradually increases in
the overall power
level. This power scaling pattern was the final confirmed configuration of the
Stage 2 tests and
was tested again in this characterization stage to ensure repeatability.
[00206] Upon the completion of the characterization tests, the particle data
and Fel d 1 levels
were compiled to analyze all the tests.
[00207] Figures 30 and 31 depict Fel d 1 concentration and particle level
versus time for tests
using varying carpet preload amounts for a robotic AAS within a portable AEC
according to
embodiments of the invention.
[00208] Figures 32 and 33 depict Fel d 1 concentration and particle level
versus time for tests
using varying canister preload amounts for a robotic AAS within a portable AEC
according to
embodiments of the invention.
[00209] Figures 34 and 35 depict Fel d 1 concentration and particle levels
versus time for tests
using varying power scaling patterns for a robotic AAS within a portable AEC
according to
embodiments of the invention.
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Date Recue/Date Received 2023-07-10
[00210] The outcomes of these characterization tests may be used as tools for
establishing the
appropriate parameters for a robotic AAS within an FD-AEC as they illustrate
the overall effect
of each parameter allowing the tests to be configured to achieve certain
allergen levels. By isolating
each parameter, it is also possible to analyze the correlation between the
particle levels and allergen
levels where this data aided in establishing an understanding of how sensitive
the test was to that
specific variable.
[00211] Preload Amount: The carpet preload amount was expected to greatly
influence the
outcome of an aerosolization, and indeed, the results illustrated that
increased amounts of preload
yield higher allergen levels. As previously stated, the preload amounts that
were tested were Og,
lg, 3g (data from stage 2 tests), and 5g. At the start of the tests, the
numbers of aerosolized particles
(shown in Figure 31) differed significantly, according to the preload amount:
from the tests done
with no preload, particle concentrations were about 200,000 particles/m3
during the first 20
minutes of aerosolization, but they progressively increased for increasing
preloads, and were in
the millions (particles/m3) for the tests done with 5g preload. In every test,
stable particle levels
are maintained, confirming that greater amounts of preloaded cat hair will
result in higher particle
levels throughout the aerosolization.
[00212] Generally, particle levels and allergen levels were highly correlated,
and in this case, the
allergen levels had similar findings as the particle levels. Figure 30 shows
that the lowest allergen
levels occurred when there was Og of preload, and the highest recorded levels
occurred during
when there was 5g of preload. Across the time intervals, the Fel d 1 levels
appear stable, except
for both repeats for the test with 5g of preload. While the Fel d 1 levels for
those tests are highly
dissimilar at each time interval, the time-average levels match well for the
repeat tests. While it
does not have significant consequences, there is a missing Fel d 1 result at
the 1=20 min point for
S3T4-II, (human error). Although it is not the focus of these characterization
tests, these variations
in allergen levels were explored in a series of "Time Dependency" tests
conducted alongside this
characterization, to determine whether the sampling location influenced the
measured allergen
levels. The allergen level outliers observed in Test 4 (S3T4-I and S3T4-II
with 5g preload) were
accepted because they have approximately the same Hr.1 average.
[00213] The 1-hour average was calculated for every test and is plotted versus
the carpet preload
amount in grams in Figure 36. This shows that the average Fel d 1 air
concentration increases
monotonically with carpet preload; i.e., that a higher preload will result in
higher allergen levels
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Date Recue/Date Received 2023-07-10
overall. A second order polynomial was fitted to that data, which can be used
to inform preload
criteria for future tests.
[00214] Canister Amount: The amount of cat hair in the canister is intended to
supplement the
amount of allergen being aerosolized in the room, throughout a two-hour test.
The amounts tested
in the EFDA/EAD were Og, 0.25g, 0.5g (data from stage 2 testing) and lg.
Although, for 2-hour
tests, there are 2 EFDAs/EADs that are loaded with cat hair (one operative in
the first hour and
replaced for the second hour), the second EFDA/EAD was found to maintain
stable levels as
needed throughout the second hour, which is why the Hr.1 EFDA/EAD was the only
one to be
varied. This also simplified Stage 3 by limiting the number of tests, as well
as material needed to
conduct them. It would be evident that within other embodiments of the
invention the robotic AAS
may support multiple EFDAs/EADs with multiple exhausts which can be open /
closed to allow
operation of the multiple EFDAs/EADs concurrently or sequentially or in other
combinations.
[00215] The initial hypothesis was that more cat hair in the EFDA/EAD would
increase overall
allergen levels, however, the results of the characterization tests
illustrated the opposite: more cat
hair in the EFDA/EAD restricted overall allergen levels. This resulted in a
dampening
phenomenon. It was clear that with greater amount of hair in the EFDA/EAD,
there were fewer
particles being aerosolized, resulting in lower allergen levels overall.
Figures 32 and 33 illustrate
these findings through the plotted allergen levels and particle data.
[00216] In Figure 32, the highest reported Fel d 1 levels are seen in 53T5,
where the EFDA/EAD
had Og of hair in the EFDA/EAD where the levels also drop significantly by the
end of the hour.
This suggests that these allergen levels are a result of the robotic AAS
instantly aerosolizing the
allergen contents of the preload, proving that without an additional
reservoir, it is difficult to
maintain stable levels. In the same figure, 53T7 reports considerably lower
allergen levels, despite
having lg of cat hair in the EFDA/EAD. With supporting evidence found in the
particle data in
Figure 33, the increased amount of hair (which is more tightly packed into the
EFDA/EAD than
for lower amounts) limits the amount that is aerosolized. It is hypothesized
that the "clumping"
nature of cat hair acts as a natural filter, preventing the release of
allergen-carrying particles. It is
necessary to find an amount that is not depleted immediately, but also does
not act against the
aerosolization process. The amount used in stage 2 testing was found to be
appropriate in its ability
to serve its purpose as an allergen reservoir, without limiting the number of
particles that can be
aerosolized. For the tests using 0.25g of cat hair in the EFDA/EAD, the Fel d
1 levels were very
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Date Recue/Date Received 2023-07-10
similar to those measured using 0.5g (from Stage 2 validation), and the
particle concentrations
were slightly lower. Again, after computing the average allergen levels in the
first hour of the tests,
and plotting them against each variation, an overall decreasing trend was
seen. Figure 37 ultimately
shows that having a greater amount of cat hair in the Hr.1 EFDA/EAD has the
potential to limit
the amount of allergen that is aerosolized, but not having any can risk lower,
unstable allergen
levels throughout a test.
[00217] Power Scaling Pattern: The adjustable power levels and operating modes
on the robotic
AAS are important to the aerosolization process however, their overall effect
on the allergen and
particle levels throughout the test had not previously been quantified. To
measure this, three
different power scaling patterns were tested, as described above (Table 4):
the "ECO" test, the
"lowered scaling" pattern, and the "combination scaling" used in Stage 2
tests. Figures 34 and 35
illustrate the results of the power scaling tests. The findings from these
tests were as expected, and
provide a guide for making any future changes to robotic AAS power settings in
the protocol. At
the lower power levels, lower particle counts were measured throughout the
test, having the
corresponding allergen levels show the same trend. It is important to note
that in all of the tests,
an initial burst of particles occurs at the start of the test, and the
variations associated with this may
partly obscure the overall effect the power scaling has on the allergen levels
when averaged in
time. The real-time particle data (Figure 35) shows the initial bursts in each
test and the behavior
throughout, indicating that a combination scaling pattern is necessary to
maintain stable levels of
particles and Fel d 1 over the duration of a one or two-hour test. The
findings of these
characterization tests supported the use of the combination scaling for the
aerosolization, as it was
shown to be the most stable, while achieving the desired allergen levels for
future tests. Figures 38
and 39 depict the effect of varying the robotic AAS power scaling on average
Fel d 1 levels in the
first hour of testing using a robotic AAS within a portable AEC according to
embodiments of the
invention; The data from the one-hour average Fel d 1 levels confirmed the
efficacy of the
combination scaling pattern however, there were aspects to improve upon to
achieve more even
levels in time.
[00218] It is important to be able to maintain stable allergen levels
throughout the test, and the
best way to do that was determined to be the combination scaling method.
Additional power
increases added in hours of dispersion after the first could further reduce
particle settling and
stabilize allergen levels.
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Date Recue/Date Received 2023-07-10
[00219] Within the preceding description emphasis has been placed on cat
allergens although
embodiments of the invention may be configured for other allergens. In some
instances, a variant
of the EFFA/EAS may be required due to the nature of the allergen being
dispersed. For example,
Figure 40 to 43 depict different views in assembled, part assembled and
disassembled states for an
exhaust fitting / dispersion assembly (EFDA) or exhaust allergen dispenser
(EAD) assembly
according to an embodiment of the invention designed for house dust mite
allergen. House dust
mite allergen source materials are typically very fine powders, with particles
typically smaller than
0.3mm in diameter. Figure 40 depicts front elevation view 4000A and upper left
side perspective
view 4000B of the structural portion of the EFDA/EAD which attaches to the
robotic AAS.
[00220] Figure 41 depicts a cross-sectional view 4100A of the EFDA/EAD which
attaches to the
robotic AAS comprising:
= Dispenser Pipette 4110;
= Inner Holder 4120;
= Outer Holder 4130;
= Robotic AAS mount (AAS Mount) 4140;
= Dispenser Conduit 4150; and
= Exhaust Outlet 4160.
[00221] It would be evident that some parts described as separate elements
within this description
may be combined within other embodiments of the invention such as Dispenser
Conduit 4150 and
Exhaust Outlet 4160 for example. The Dispenser Pipette 4110 is in essence a
capsule / container
for the allergen with an opening at the bottom to control flow of the allergen
where the allergen is
vibrated to "dispense" it through the opening at the bottom of the Dispenser
Pipette 4110.
[00222] Figure 42 depicts the EFDA/EAD attached to the robotic AAS together
with Pin 4210
and Vibratory Motor 4220. The Vibratory Motor 4220 generating vibrations
through an
asymmetric weight for example which are coupled to the Timer Holder 4120 and
Dispenser Pipette
4110. The Outer Holder 4130 being profiled such that the Vibratory Motor 4220
engages against
the Inner Holder 4120. Accordingly, in the example of dust mites, the
vibration induced by the
Vibratory Motor 4220 "shakes" allergen source material within the Dispenser
Pipette 4110, e.g.
dust mites, down to the opening wherein they enter the inner bore of the
Dispenser Conduit 4150
wherein the air flow from the robotic AAS aerosolizes them out through the
Exhaust Outlet 4160
and into the environment surrounding the robotic AAS fitted with the EFDA/EAD.
The Pin 4210
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Date Recue/Date Received 2023-07-10
acts as a mounting point that connects each of the Inner Holder 4120, Outer
Holder 4130 and the
Dispenser Pipette 4110 which provides some degree of freedom so the parts can
vibrate relative to
one another.
[00223] Figure 43 depicts a variant of the EFDA/EAD in exploded form wherein
the Inner Holder
4120 now has a Mounting 4420 for the Vibratory Motor 4220 to fit into and a
Clip 4410 to retain
the Vibratory Motor 4220 within the Mounting 4420. Figures 44 and 45 depict
the EDFA/EAD
assembly according to an embodiment of the invention fitted to a robotic AAS
according to an
embodiment of the invention. Accordingly, in addition to the EFDA/EAD assembly
there are
depicted the battery pack to power the Vibratory Motor 4220, a relay to turn
the Vibratory Motor
4220 on and off, and the dial based control for the robotic AAS suction / air
flow.
[00224] The Dispenser Pipette 4110 provides a container for the allergen prior
to aerosolization
where the dimensions of the lower end of the Dispenser Pipette 4110 are
determined in dependence
upon factors such as allergen dimensions and desired rate of allergen
dispersal for example. The
orifice at the bottom end of the Dispenser Pipette 4110 is sized to be small
enough that allergen
source material, e.g. dust mites, does not pass through the orifice by gravity
alone unless agitation
is applied (for example, by the Vibratory Motor 4220), but with agitation the
allergen source
material flows through the orifice.
[00225] Optionally, the Dispenser Pipette 4110 may be sealed until use.
[00226] Optionally, the Vibratory Motor relay may be coupled to a wireless
interface for remote
actuation.
[00227] Optionally, the Vibratory Motor relay may be coupled to a
microcontroller for
autonomous execution of a predetermined program.
[00228] Optionally, a stopper may be controlled by a relay such that it can be
electronically
removed / inserted to allow/block the allergen going from the Dispenser
Pipette 4110 into the
Dispenser Conduit 4150.
[00229] Optionally, multiple Dispenser Pipettes 4110 may be coupled to one
Dispenser Conduit
4150 with the same or different allergens. Optionally, multiple Dispenser
Pipettes 4110 with Pins
4210 and Vibratory Motors 4220 may be coupled to a common Dispenser Conduit
4150 allowing
one or multiple allergens to be dispersed concurrently, serially, or a
combination thereof.
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Date Recue/Date Received 2023-07-10
[00230] Optionally, the Inner Holder 4120, Dispenser Pipette 4110, and Pin
4210 may be a single
assembly that mount into the Outer Holder 4130 with the Pin 4210 aligning with
slots in the Outer
Holder 4130.
[00231] It would be evident to one of skill in the art that other mechanical
configurations can
provide the desired functionality without departing from the scope of the
invention.
[00232] An exemplary operating procedure for use of an EFDA/EAD such as
depicted in Figures
40 to 45 is presented below. However, an exemplary configuration of a FD-AEC
is presented first.
Within this configuration the robotic AAS operates within an area bounded by
several physical
"stoppers", although it would be evident that within other embodiments of the
invention the area
could instead by bounded by virtual walls defined by a beam the robotic AAS
detects as it crosses
it (e.g. infra-red beam), by triangulation based upon, for example, wireless
beacons placed within
the FD-AED, or by the edges of a raised platform the robotic AAS detects
before crossing.
[00233]
Figures 46 and 47 depict the evolution of normalized particle count with
particle
sizes greater than 1 gm and 5gm respectively from prototype testing of the
aerosolization of house
dust mites using the EFDA/EAD described and depicted with respect to Figures
40 to 43 with the
robotic AAS as depicted in Figures 44 and 45 within a FD-AEC according to an
embodiment of
the invention. The EFDA/EAD being turned on for the first 90 minute (solid
lines) and
subsequently turned off to allow particle setting (dashed lines). The On/Off
cycles for the
vibrations were varied between the tests and a 0.7mm Dispensing Pipette 4110
was employed.
[00234] Figure 48 depicts depict the distribution of Der p 1 allergen levels
as function of time
from samples collected at one side of a FD-AEC according to an embodiment of
the invention
during prototype testing of the aerosolization of house dust mites using the
EFDA/EAD described
and depicted with respect to Figures 40 to 43 with the robotic AAS as depicted
in Figures 44 and
45. The data was extracted from Enzyme-Linked Immunosorbent Assay (ELISA)
results with
some repeat samples.
[00235] FD-AEC Set Up
= Set up the FD-AEC such as for example described above, virtual wall(s)
and patient
chair/table may be configured different such as outlined below.
= Add physical stoppers around the back and the sides leaving 30 cm (1
foot) between the
physical stopper and the back wall of the FD-AEC for the LPC table.
= Set up a small table in the back of the tent for the LPC.
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= Program the portable pumps with the following settings:
o Flow rate: 5000 cc/min;
o 2-minute delay (allowing the user to leave the tent and start the robotic
AAS
manually although in other configurations remote control of the robotic AAS
may
allow this delay to be adjusted or the pumps may be connected to the same
control.;
o 29-min sampling;
o 1-min delay, allowing time to change the cartridges; and
o 30-min sampling.
= Place the pumps, e.g. within a mesh bag hanging from the FD-AEC. Press
the pump
tubes onto the pumps and ensure that the cartridge support is straight.
[00236] EFDA/AED Exhaust Fitting and Allergen Source Preparation
= Prepare and label 6 cartridges using 2 jim glass fibre filters.
= Screw the EDFA/EAD aerosolization Exhaust Outlet 4160 onto the Dispenser
Conduit
4150.
= Screw the partially-assembled EDFA/EAD aerosolization exhaust fitting
onto the
robotic AAS outlet.
= Set up the Inner Holder 4120 with the Vibration Motor 4220 attached and
the Dispenser
Pipette 4110 to be used:
= Treat the Dispenser Pipette 4110 by spraying the inside with anti-static
spray and drying
the inside using a compressed aerosol duster.
= Align the Inner Holder 4120 and Dispenser Pipette 4110 with the Outer
Holder 4130 on
the Dispenser Conduit 4150.
= Insert the Pin 4210 in the bottom pinhole of the Outer Holder 4130.
= Pass the Pin 4130 through the bottom pinhole of the Timer Holder 4120 and
through the
pinholes of the Dispenser Pipette 4110, and out the bottom pinholes on the
other side
of the Timer and Outer Holders 4120 and 4130 respectively.
= Ensure that the vibration motor relay module and associated remote work
properly before
the test:
o Ensure the battery voltage and the voltage from the relay module are
above 4.1 V
using a voltmeter. Replace the batteries if necessary.
o Connect the relay module to the Vibration Motor 4220 via the connector.
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Date Recue/Date Received 2023-07-10
o Turn on the switch of the battery pack.
o Press once on the remote button and make sure the Vibration Motor 4220
rotates
(check the wires for disconnections if not).
o Press once again on the remote button to turn off the motor.
= Weigh out the required EDFA/EAD allergen source material.
o Prepare two weigh boats and a measuring spatula.
o Turn on the balance and ensure that it is leveled.
o Retrieve the EDFA/EAD allergen source material to be used for the test.
o Tare the scale with one empty weigh boat.
o Use the spatula and transfer the allergen (e.g. dust with dust mites)
into the weigh
boat (on the scale) until the desired dust amount is reached according to the
test plan
(during prototype testing, a 1-hour test required about 0.035 g).
[00237] Experiment Set Up
= Take a baseline particle count using the LPC according to the test plan,
with the LPC on
the table at the back of the chamber (e.g. in prototype testing, 3-5 cycles of
3 minutes
each).
= Reprogram LPC for 30 cycles of 3 minutes each (e.g. 20 cycles vacuum on,
10 cycles
vacuum off).
= Add the allergen to the Dispenser Pipette 4110:
o Cut a thin and long piece of tape, and use one end to close off the small
end of the
Dispenser Pipette 4110 (to avoid dust losses before the start of the test)
with the
other end extending out of the Exhaust Outlet 4160. Ensure that the tape is
long
enough so that it can easily be pulled out right before the test begins.
o Make and place a paper cone onto the Dispenser Pipette 4110 and pour dust
into
cone to go into the Dispenser Pipette 4110, making sure that dust does not
stick to
sides of paper cone. Use a metal scoop to scrape the sides of cone as needed.
= Set up the robotic AAS as per operating procedure.
o Set the robotic AAS to ECO mode and a power level of 5:
= Place the robotic AAS into the chamber and onto its home base, being
careful not to
shake the robotic AAS to prevent dust from dispensing from the Dispenser
Pipette 4110
onto the tape. Make sure the vibration motor battery pack is switched off.
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= Remove the red caps from the cartridges and connect them to the pump
tubing. To begin,
connect the cartridge labeled R1 to the tubing nearest the right wall of the
tent (from
the main entrance of the tent facing the LPC table) and Li to the tubing
nearest the left
wall of the tent.
= Carefully remove the tape that is covering the Dispenser Pipette 4110 and
switch the
battery pack on. Ensure that the power level of the robotic AAS is still at 5.
= Start the pumps, LPC, and a stopwatch at the same time
= Quickly leave the tent and zip the entrances closed.
= At 2 minutes, restart the timer and turn on the robotic AAS by pressing
the "Start" on
the control software application for the robotic AAS. This is t = 0. Ensure
that the
robotic AAS is still on ECO mode.
= At t = 1 minute, use the relay remote to activate the vibration circuit
at intervals according
to the test plan. For example, during prototype testing the motor was
activated for 1
second every 3 minutes (see the Cycles Checklist in Appendix 1).
= At t = 30 minutes, change the "Rl" and "Li" cartridges to the "R2" and
"L2" cartridges.
= At t = 60 minutes, change the "R2" and "L2" cartridges to the "Set R" and
"Set L"
settling cartridges. Stop the robotic AAS and take it out of the tent.
= At t = 90 minutes, take out the settling cartridges.
= To measure the remaining amount of EDFA/EAD allergen source material,
place a pre-
weighed, empty rectangular container inside the prototype under the small end
of the
Dispenser Pipette 4110. Start the vibration motor and the timer at the same
time and
record the time it takes for the dust to empty out from the Dispenser Pipette
4110.
= Use the balance to weigh the rectangular container with the remaining
dust and subtract
its empty weight to determine the remaining amount of dust. Record.
= Use the voltmeter to measure and record the remaining voltage on the
battery pack.
= Wipe down any surfaces that may have been in contact with dust with Lysol
wipes.
= Turn on the robotic AAS on Standard Performance (PER) mode and at a power
level of
and run robotic AAS with the filtered bin and extractors installed for 3 runs.
= Use Lysol wipes to wipe down interior tent walls and LPC table.
= Record sampling time and volume from each pump on the testing log.
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= Clear and turn off the pumps.
= Unplug the LPC, turn it off, and place it back into its case to be ready
for data extraction.
= Store the air samples and clean the cartridges.
[00238] Specific details are given in the above description to provide a
thorough understanding
of the embodiments. However, it is understood that the embodiments may be
practiced without
these specific details. For example, circuits may be shown in block diagrams
in order not to obscure
the embodiments in unnecessary detail. In other instances, well-known
circuits, processes,
algorithms, structures, and techniques may be shown without unnecessary detail
in order to avoid
obscuring the embodiments.
[00239] Implementation of the techniques, blocks, steps and means described
above may be done
in various ways. For example, these techniques, blocks, steps and means may be
implemented in
hardware, software, or a combination thereof. For a hardware implementation,
the processing units
may be implemented within one or more application specific integrated circuits
(ASICs), digital
signal processors (DSPs), digital signal processing devices (DSPDs),
programmable logic devices
(PLDs), field programmable gate arrays (FPGAs), processors, controllers, micro-
controllers,
microprocessors, other electronic units designed to perform the functions
described above and/or
a combination thereof.
[00240] Also, it is noted that the embodiments may be described as a process
which is depicted
as a flowchart, a flow diagram, a data flow diagram, a structure diagram, or a
block diagram.
Although a flowchart may describe the operations as a sequential process, many
of the operations
can be performed in parallel or concurrently. In addition, the order of the
operations may be
rearranged. A process is terminated when its operations are completed, but
could have additional
steps not included in the figure. A process may correspond to a method, a
function, a procedure, a
subroutine, a subprogram, etc. When a process corresponds to a function, its
termination
corresponds to a return of the function to the calling function or the main
function.
[00241] Furthermore, embodiments may be implemented by hardware, software,
scripting
languages, firmware, middleware, microcode, hardware description languages
and/or any
combination thereof. When implemented in software, firmware, middleware,
scripting language
and/or microcode, the program code or code segments to perform the necessary
tasks may be stored
in a machine readable medium, such as a storage medium. A code segment or
machine-executable
instruction may represent a procedure, a function, a subprogram, a program, a
routine, a
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Date Recue/Date Received 2023-07-10
subroutine, a module, a software package, a script, a class, or any
combination of instructions, data
structures and/or program statements. A code segment may be coupled to another
code segment
or a hardware circuit by passing and/or receiving information, data,
arguments, parameters and/or
memory content. Information, arguments, parameters, data, etc. may be passed,
forwarded, or
transmitted via any suitable means including memory sharing, message passing,
token passing,
network transmission, etc.
[00242] For a firmware and/or software implementation, the methodologies may
be implemented
with modules (e.g., procedures, functions, and so on) that perform the
functions described herein.
Any machine-readable medium tangibly embodying instructions may be used in
implementing the
methodologies described herein. For example, software codes may be stored in a
memory.
Memory may be implemented within the processor or external to the processor
and may vary in
implementation where the memory is employed in storing software codes for
subsequent execution
to that when the memory is employed in executing the software codes. As used
herein the term
"memory" refers to any type of long term, short term, volatile, nonvolatile,
or other storage
medium and is not to be limited to any particular type of memory or number of
memories, or type
of media upon which memory is stored.
[00243] Moreover, as disclosed herein, the term "storage medium" may represent
one or more
devices for storing data, including read only memory (ROM), random access
memory (RAM),
magnetic RAM, core memory, magnetic disk storage mediums, optical storage
mediums, flash
memory devices and/or other machine readable mediums for storing information.
The term
"machine-readable medium" includes, but is not limited to portable or fixed
storage devices,
optical storage devices, wireless channels and/or various other mediums
capable of storing,
containing or carrying instruction(s) and/or data.
[00244] The methodologies described herein are, in one or more embodiments,
performable by
a machine which includes one or more processors that accept code segments
containing
instructions. For any of the methods described herein, when the instructions
are executed by the
machine, the machine performs the method. Any machine capable of executing a
set of instructions
(sequential or otherwise) that specify actions to be taken by that machine are
included. Thus, a
typical machine may be exemplified by a typical processing system that
includes one or more
processors. Each processor may include one or more of a CPU, a graphics-
processing unit, and a
programmable DSP unit. The processing system further may include a memory
subsystem
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Date Recue/Date Received 2023-07-10
including main RAM and/or a static RAM, and/or ROM. A bus subsystem may be
included for
communicating between the components. If the processing system requires a
display, such a
display may be included, e.g., a liquid crystal display (LCD). If manual data
entry is required, the
processing system also includes an input device such as one or more of an
alphanumeric input unit
such as a keyboard, a pointing control device such as a mouse, and so forth.
[00245] The memory includes machine-readable code segments (e.g. software or
software code)
including instructions for performing, when executed by the processing system,
one of more of the
methods described herein. The software may reside entirely in the memory, or
may also reside,
completely or at least partially, within the RAM and/or within the processor
during execution
thereof by the computer system. Thus, the memory and the processor also
constitute a system
comprising machine-readable code.
[00246] In alternative embodiments, the machine operates as a standalone
device or may be
connected, e.g., networked to other machines, in a networked deployment, the
machine may
operate in the capacity of a server or a client machine in server-client
network environment, or as
a peer machine in a peer-to-peer or distributed network environment. The
machine may be, for
example, a computer, a server, a cluster of servers, a cluster of computers, a
web appliance, a
distributed computing environment, a cloud computing environment, or any
machine capable of
executing a set of instructions (sequential or otherwise) that specify actions
to be taken by that
machine. The term "machine" may also be taken to include any collection of
machines that
individually or jointly execute a set (or multiple sets) of instructions to
perform any one or more
of the methodologies discussed herein.
[00247] The foregoing disclosure of the exemplary embodiments of the present
invention has
been presented for purposes of illustration and description. It is not
intended to be exhaustive or to
limit the invention to the precise forms disclosed. Many variations and
modifications of the
embodiments described herein will be apparent to one of ordinary skill in the
art in light of the
above disclosure. The scope of the invention is to be defined only by the
claims appended hereto,
and by their equivalents.
[00248] Further, in describing representative embodiments of the present
invention, the
specification may have presented the method and/or process of the present
invention as a particular
sequence of steps. However, to the extent that the method or process does not
rely on the particular
order of steps set forth herein, the method or process should not be limited
to the particular
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Date Recue/Date Received 2023-07-10
sequence of steps described. As one of ordinary skill in the art would
appreciate, other sequences
of steps may be possible. Therefore, the particular order of the steps set
forth in the specification
should not be construed as limitations on the claims. In addition, the claims
directed to the method
and/or process of the present invention should not be limited to the
performance of their steps in
the order written, and one skilled in the art can readily appreciate that the
sequences may be varied
and still remain within the spirit and scope of the present invention.
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