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
1002] 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.
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[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.
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;
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[0022] Figure 11 depicts particle concentrations versus time for a robotic AAS
according to
embodiments of the invention with and without an allergen extractor;
[0023] Figure 12 depicts a test average (Fel 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 (Fel 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 (Fel 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 m;
[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 (El-DA) 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;
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[0033] Figure 24 depicts average (Fel d 1) within a field deployable AEC
employing a robotic
AAS according to an embodiment of the invention;
[0034] Figure 25 depicts particle distributions at different times during and
after aerosolization
for very small particles (0.1 - 2 pm) and particles larger than 2 pm using a
robotic AAS
according to an embodiment of the invention;
[0035] Figure 26 depicts the total number of particles >2 1.tm 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;
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[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;
[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 pm and 511m 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
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"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 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.
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[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,
TFEE 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, Bluetooth', Wi-Fi, Ultra-Wideband and WiMAXim.
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 802.1 lb, 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,
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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, 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, 1-LDs, 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
[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
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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 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
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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 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, WV, and PPT, for example,
as well as others, see for example
http://en.wikipedia.org/wilci/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
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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/1-ED 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, 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
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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 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 Al 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.
- 13 -
Date Recue/Date Received 2021-06-28
[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.
[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
- 14 -
Date Recue/Date Received 2021-06-28
which being coupled to Network 100 via router 105. Second VVi-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 FE,Ds 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 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.
- 15 -
Date Recue/Date Received 2021-06-28
[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 1-EDS; 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 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 WEE 802.11, IEEE
802.15, 'FEE
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
- 16 -
Date Recue/Date Received 2021-06-28
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 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.
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Date Recue/Date Received 2021-06-28
[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
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
- 18 -
Date Recue/Date Received 2021-06-28
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.
[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
(ST) module 244 and a Real Time Streaming Protocol (RTSP) module 246. Protocol
stack 224
- 19 -
Date Recue/Date Received 2021-06-28
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, IF 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
in addition to the depicted IEEE 802.11 interface which may be selected from
the group
comprising TREE 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,
- 20 -
Date Recue/Date Received 2021-06-28
IEEE 802.16, IEEE 802.20, UMTS, GSM 850, GSM 900, GSM 1800, GSM 1900, GPRS,
l'I'U-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 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
- 21 -
Date Recue/Date Received 2021-06-28
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 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)
- 22 -
Date Recue/Date Received 2021-06-28
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.
[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.
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Date Recue/Date Received 2021-06-28
[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 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
- 24 -
Date Recue/Date Received 2021-06-28
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 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
(EHDA), 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.
- 25 -
Date Recue/Date Received 2021-06-28
[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 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
- 26 -
Date Recue/Date Received 2021-06-28
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 pm 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'
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.
- 27 -
Date Recue/Date Received 2021-06-28
[00118] Once validated in the smaller of the two chambers (3 subject
capacity), the
aerosolization 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 mg 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 infoim 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
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.
- 28 -
Date Recue/Date Received 2021-06-28
[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/ (Qpso x ts) (1)
=
I [left, centre, right] (2) xi
[left, left-centre, right-centre, right]
(3)
where M is the number of locations (3 - small room, 4 - large room)
[10, 30, 50, 70, 90, 110]
t= ¨ (4)
¨ [15, 45, 75, 105]
j=1...N, where N is 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) = m1(xi,ti)1(Qpunip x ts) (6)
(Fel d1)ti = ¨mi (7)
N
(Fel d1)xt = ¨NE j=i Fel dl(xi,ti) (8)
(Fel dl) = ¨ E = "(Fel d1)t. (9)
NJ I
- 29 -
Date Recue/Date Received 2021-06-28
[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 pm)
(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 pm) (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 pm; whereas in terms of volume contribution, the volume moment
mean
diameter D(4,3) was 4.34 gm.
[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 pm 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.
- 30 -
Date Recue/Date Received 2021-06-28
[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 p.m
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 pm) 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. 13x106 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 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
-31 -
Date Recue/Date Received 2021-06-28
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 pm. 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 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
- 32 -
Date Recue/Date Received 2021-06-28
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 pm)
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 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 pm 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 pm and 2 gm pore size glass fiber filters and Fel
d 1 was assessed by
- 33 -
Date Recue/Date Received 2021-06-28
ELISA. No significant difference was found in the allergen concentration
between the 1 pm and
2 m 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 103
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, 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
- 34 -
Date Recue/Date Received 2021-06-28
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 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
- 35 -
Date Recue/Date Received 2021-06-28
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 Fe! 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 Fe! 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 Fe!
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;
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Date Recue/Date Received 2021-06-28
= 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 ID-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):
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Date Recue/Date Received 2021-06-28
o Tie a mesh bag to the tent ceiling crossbar.
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.
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Date Recue/Date Received 2021-06-28
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 2 m
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.
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= 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 compartment, then
gently
remove the extractors.
o Verify that the bins have been emptied and the robotic AASs are clean:
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Date Recue/Date Received 2021-06-28
= 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 compartments 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
aerosolization.
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.
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Date Recue/Date Received 2021-06-28
= 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 1-'D-AEC validation testing repeats).
= Make sure the pumps are turned on and ready to start.
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Date Recue/Date Received 2021-06-28
= 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:
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Date Recue/Date Received 2021-06-28
o 0-20 mm: eco 5
o 20-40 mm: performance 4
o 40-60 mm: 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 mm (performance 6
for
FD-AEC validation testing repeats).
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Date Recue/Date Received 2021-06-28
= 10-15 seconds before t =60 mm, 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.
100158] 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.
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Date Recue/Date Received 2021-06-28
= 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 before replacing the mesh grid inside the bin. Wipe the bottom
extractor
compartment 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 (EI-1)A),
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 EI-DA 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 EI-DA / EAD
comprises a Top
- 46 -
Date Recue/Date Received 2021-06-28
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 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).
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Date Recue/Date Received 2021-06-28
[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:
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Date Recue/Date Received 2021-06-28
= A FD-AEC housing, e.g. tent.
= A low-pile carpet cut to custom size to be fitted on the floor of the 14D-
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 ED-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.
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[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.
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[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
aerosolization for very small particles (0.1 - 2 gm) and particles larger than
2 pm using a AAS
according to an embodiment of the invention.
[00188] Figure 26 depicts the total number of particles >2 gm 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;
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Date Recue/Date Received 2021-06-28
= a first mesh screen disposed between the top cap and the first portion of
the canister
body; and
= 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
- 52 -
Date Recue/Date Received 2021-06-28
robotic AAS was established which employs a robotic system to move around
within the Ell-
AEC and blow air through an EFDA / EAD containing the allergen under
assessment, e.g. milled
cat hair within a 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.
- 53 -
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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, 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 ECO ¨ 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.!: 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.!: 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
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Date Recue/Date Received 2021-06-28
preload amount of 3g, which was found, combined with the other fixed
variables, to achieve an
average of 100 ng/m3 Fel 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 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
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Date Recue/Date Received 2021-06-28
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 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.
- 56 -
Date Recue/Date Received 2021-06-28
[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.
[00210] The outcomes of these characterization tests may be used as tools for
establishing the
appropriate parameters for a robotic AAS within an ID-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, 1 g, 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 t=20 min
point for S3T4-1I, (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
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Date Recue/Date Received 2021-06-28
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 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
1g. 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.! 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 EIDAs/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 Fe! 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 1 g of cat hair in the EFDA/EAD. With supporting
evidence found in the
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Date Recue/Date Received 2021-06-28
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 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
- 59 -
Date Recue/Date Received 2021-06-28
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.
[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 E141-A/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.
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Date Recue/Date Received 2021-06-28
[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 Inner 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 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.
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Date Recue/Date Received 2021-06-28
[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.
[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 1-D-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 pm and 5pm 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.
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[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
EIDA/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 1-13-AEC for the LPC table.
= Set up a small table in the back of the tent for the LPC.
= 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-mM delay, allowing time to change the cartridges; and
o 30-mM 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 m 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:
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Date Recue/Date Received 2021-06-28
= 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 Inner Holder 4120 and
through the
pinholes of the Dispenser Pipette 4110, and out the bottom pinholes on the
other side
of the Inner 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.
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).
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Date Recue/Date Received 2021-06-28
= 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.
= 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 "R 1" 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.
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= 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.
= 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.
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[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 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.
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[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 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
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Date Recue/Date Received 2021-06-28
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 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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