A Device to Model a Human Lung to
Determine the Delivery Efficiency of Inhaled
Pharmaceutical Aerosols
2004 Mechanical & Industrial Engineering, University of Toronto
 Overview
 Background
 Existing Models
 Developed Models
Flexible Lung Model
Rigid Lung Model
 Testing Methodology
 Model Assessment and Conclusion
2004 Mechanical & Industrial Engineering, University of Toronto
Medication Administration
Medications are administrated by:
 Oral ingestion
 Intravenous Injections
 Respiratory system (Pharmaceutical Inhalers)
2004 Mechanical & Industrial Engineering, University of Toronto
Pharmaceutical Inhalers
Advantages
 Quick absorption into the blood stream
 Less medicine for similar therapeutic result
Projection
 50% of medication through inhalers
Problem
 Less than 20% of inhaled dosage reaches the
lower respiratory system
Need
 More efficient pharmaceutical inhalers
 Means of testing pharmaceutical inhalers
2004 Mechanical & Industrial Engineering, University of Toronto
 Inhalers
Pressurized
Metered
Dose Inhaler
(pMDI)
Breath
Activated
Inhaler
Pressurized
Aerosol
Inhaler with
Spacer
Nebulizer
Dry Powder
Inhaler (DPI)
 Test Inhaler
 ADVAIR pMDI 120 dose (125 mcg)
 Treats the two main components of asthma, airway constriction
and inflammation
 Each dose contains 25 mcg salmeterol xinafoate and 125 mcg
fluticasone propionate
 Inhalers doped with Rose Bengal Dye for visualization
purposes
 Spectrophotometer
Allows for precise measurements of flow concentration in
all regions of the lung model
Consists of:
 A source that generates electromagnetic radiation
 A dispersion device that selects a particular
wavelength from the broad band radiation of the
source
 A sample area
 A detector to measure the intensity of radiation
2004 Mechanical & Industrial Engineering, University of Toronto
Available Solutions
 Computer / Mathematical Models
 Physical Models
 Twin Impinger
 Cascade Impactor
 Limitations
 Our Goal:
Devise a physical lung model, superior to the existing
models, to test pharmaceutical inhalers
2004 Mechanical & Industrial Engineering, University of Toronto
Lung Properties
Human Respiratory System
Mouth/Nose  Trachea  Bronchioles  Alveoli
Alveoli
2004 Mechanical & Industrial Engineering, University of Toronto
Lung Geometry
• Weibel Model A
– Number of generations, z
– Branch diameter
z
 1
d ( z )  d 0 3  , where  d 0  d trachea
 2
– Branch length
Lung Geometry

Weibels Model
Z (Branching generation)
N (z) (Number of branches) =
2Z
d (z) (Branch diameter)
do x 2 –z/3
=

23 generations of bronchiole branching

Average Trachea diameter is 1.8 cm
2004 Mechanical & Industrial Engineering, University of Toronto
Particle Deposition
• Methods and Areas of Particle Deposition
– Impaction
– Sedimentation
– Diffusion
Weibel Model
Weibels Model
Generation
trachea
bronchi
bronchioles
terminal
bronchioles
0
1
2
3
4
5
BIOENG 589
Length
(cm)
12.0
4.8
1.9
0.8
1.3
1.07
Number
1
2
4
8
16
32
Total
area
2.54
2.33
2.13
2.00
2.48
3.11
0.06
0.17
6 x 104
180.0
0.05
10
5 x 105
103
0.04
0.05
8 x 106
104
From Levitzky, Fig 1-5
16
17
respiratory
18
bronchioles
19
20
alveolar
21
ducts
22
alveolar sacs 23
Diameter
(cm)
1.8
1.22
0.83
0.56
0.45
0.35
University of Washington
2004 Mechanical & Industrial Engineering, University of Toronto
Physical Lung Properties
 Average volume of inhaled air is 500cc
 Average pressure difference is 2mm Hg
 Approximation of airflow within the human lung:
 Quiet breathing
= 0.4
litres/s
 Mild Exercise
= 1.25 – 1.5
litres/s
2004 Mechanical & Industrial Engineering, University of Toronto
 Existing Models
Computer / Mathematical Models
 Not very accurate, based only on mathematical
equations
 No physical data to support the models
 Do not account for the randomness of particle flow and
deposition inside a complex organ like the human lung
Physical Models
 Twin Impinger
 Cascade Impactor
2004 Mechanical & Industrial Engineering, University of Toronto
 Twin Impinger
 Tests the lung penetration
capability of a pressurized
metered dose inhaler
(pMDI)
2004 Mechanical & Industrial Engineering, University of Toronto
 Twin Impinger Apparatus
 Cascade Impactor
 Measures the aerodynamic size distribution and mass
concentration levels of solid particulates and liquid
aerosols
 Cascade Impactor Apparatus
Other Design Concepts
• Medical Tubing Concept
–
–
–
Positive displacement pump
Standard medical tubing
Standard connectors
• Advantage: Ease of separation
• Concern: Flow obstruction at junctions
Existing Solutions
• Computer/Mathematical Models
– Limited to the accuracy of the governing equations
– Requires experimental verification
 Limitations
Twin Impinger
 Only 2 compartments
 Simplified particle flow path
 No flow visualization
Cascade Impactor
 No set path to follow
 No flow visualization
2004 Mechanical & Industrial Engineering, University of Toronto
MUSSL Lung Model Based on
Direct Flow Visualization
• A transparent lung model
• Use particle deposition tracing
– Ink Visualization
– X-ray Scintigraphy using Radiolabeled particles
– Planar Laser Imaging
Design Concepts
• Expanding-Contracting Lung Design
–
Machined representation of lung covered with
silicon membrane
– Expanded by external breathing bag
– Difficult to control expansion and contraction
Detailed Design Description
•
•
•
•
•
•
•
Drawing of lung
Machining of lung
Mouth-trachea induction port
Ventilator/breathing apparatus
Tracer dye labeled aerosol
Filtration and resistance devices
Testing and Apparatus Setup
Drawing of the Lung
• AutoCAD Representation
– 2-D
– 8 to 9 generations
– Approx. 750 branches
Drawing of Lung
• SolidWorks 2003 Drawing
Drawing Procedure
a) The sketch is projected to offset plane.
c) Circles are drawn on the midlines.
b) The inter-planes are created.
d) Circles are extruded to planes.
Machining of Lung
• MasterCAM file conversion
Machining of Lung
• Machining of Bronchial Tree
– Completed by Excentrotech Precision Ltd.
– G-code generation: MasterCAM
– High-speed 5-axis CNC mill
Machining of Lung
• Machining of Exit Channels
– Completed by MIE Machine Shop
– G-code generation: MasterCAM
– 3-axis CNC mill
Final Design
• Machined representation of human lung in
aluminum
Mouth-Trachea Induction Port
• Simulates the filtering effects and geometric
properties of the mouth and throat
• Schematics provided by Nuclear Medicine
Department at McMaster University
Mouth and trachea induction port
development and assembly
 Counter bored for the insertion of the adapter
 Adapter to provide un obstructed/continuous flow
 Not a permanent fit allows switch to the clear mouth/trachea
port
2004 Mechanical & Industrial Engineering, University of Toronto
 Creating the 3-D Model
2004 Mechanical & Industrial Engineering, University of Toronto
 Design Requirements
• Model must transparent to allow for easy flow
visualization to take place
• Model must be able to mimic basic mechanical
proprieties of an average human lung
» Air Volume
» Pressure
( 500 cc )
( 750 mmHg )
2004 Mechanical & Industrial Engineering, University of Toronto
 Construction Overview
3-D Model Creation Stages
1. Construction of the wax model
2. Coating of the model with the flexible
elastomer shell
3. Separation of the model from the cured
flexible shell
2004 Mechanical & Industrial Engineering, University of Toronto
Stage 1
Creating the Wax Model
2004 Mechanical & Industrial Engineering, University of Toronto
Second Attempt:
Heating of the Mold
Plate was heated
above melting
temperature of the
wax
Allowed for uniform
cooling of wax
2004 Mechanical & Industrial Engineering, University of Toronto
Completed Wax Model
2004 Mechanical & Industrial Engineering, University of Toronto
Mouth/trachea
induction port
Lung model
Outlet port
Stand
2004 Mechanical & Industrial Engineering, University of Toronto
Hollow, flexible cast of a
human lung
According to a procedure developed at North
Carolina State University
–
Silicon or latex hollow cast could be used as a
breathing model
Hollow Cast Model