1. 2004 Mechanical & Industrial Engineering, University of Toronto
A Device to Model a Human Lung to Determine the Delivery Efficiency of Inhaled Pharmaceutical Aerosols
2004 Mechanical & Industrial Engineering, University of Toronto

2. 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

3. 2004 Mechanical & Industrial Engineering, University of Toronto
Medication Administration
Medications are administrated by:
Oral ingestion
Intravenous Injections
Respiratory system (Pharmaceutical Inhalers)

4. 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

5. Inhalers Pressurized Metered Dose Inhaler (pMDI)
Breath Activated Inhaler
Pressurized Aerosol Inhaler with Spacer
Nebulizer
Dry Powder Inhaler (DPI)

6. 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

7. 2004 Mechanical & Industrial Engineering, University of Toronto
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

8. 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

9. 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

10. Lung Geometry Weibel Model A Number of generations, z Branch diameter
Branch length

11. 2004 Mechanical & Industrial Engineering, University of Toronto
Lung Geometry
Weibels Model
Z (Branching generation)
N (z) (Number of branches) = 2 Z
d (z) (Branch diameter) = do x 2 –z/3
23 generations of bronchiole branching
Average Trachea diameter is 1.8 cm

12. Particle Deposition Methods and Areas of Particle Deposition Impaction
Sedimentation
Diffusion

13. 2004 Mechanical & Industrial Engineering, University of Toronto
Weibels Model

14. 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 = litres/s
Mild Exercise = 1.25 – 1.5 litres/s

15. 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

16. 2004 Mechanical & Industrial Engineering, University of Toronto
Twin Impinger
Tests the lung penetration capability of a pressurized metered dose inhaler (pMDI)

17. Twin Impinger Apparatus

18. Cascade Impactor
Measures the aerodynamic size distribution and mass concentration levels of solid particulates and liquid aerosols

19. Cascade Impactor Apparatus

20. Other Design Concepts Medical Tubing Concept
Positive displacement pump
Standard medical tubing
Standard connectors
Advantage: Ease of separation
Concern: Flow obstruction at junctions

21. Existing Solutions Computer/Mathematical Models
Limited to the accuracy of the governing equations
Requires experimental verification

22. 2004 Mechanical & Industrial Engineering, University of Toronto
Limitations
Twin Impinger
Only 2 compartments
Simplified particle flow path
No flow visualization
Cascade Impactor
No set path to follow

23. 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

24. 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

25. 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

26. Drawing of the Lung AutoCAD Representation 2-D 8 to 9 generations
Approx. 750 branches

27. Drawing of Lung
SolidWorks 2003 Drawing

28. Drawing Procedure a) The sketch is projected to offset plane.
b) The inter-planes are created.
c) Circles are drawn on the midlines.
d) Circles are extruded to planes.

29. Machining of Lung
MasterCAM file conversion

30. Machining of Lung Machining of Bronchial Tree
Completed by Excentrotech Precision Ltd.
G-code generation: MasterCAM
High-speed 5-axis CNC mill
   
   

31. Machining of Lung Machining of Exit Channels
Completed by MIE Machine Shop
G-code generation: MasterCAM
3-axis CNC mill
   
   

32. Final Design
Machined representation of human lung in aluminum

33. 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

34. 2004 Mechanical & Industrial Engineering, University of Toronto
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

35. 2004 Mechanical & Industrial Engineering, University of Toronto
Creating the 3-D Model

36. 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 ( 500 cc )
Pressure ( 750 mmHg )

37. 2004 Mechanical & Industrial Engineering, University of Toronto
Construction Overview
3-D Model Creation Stages
Construction of the wax model
Coating of the model with the flexible elastomer shell
Separation of the model from the cured flexible shell
2004 Mechanical & Industrial Engineering, University of Toronto

38. 2004 Mechanical & Industrial Engineering, University of Toronto
Stage 1 Creating the Wax Model

39. 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

40. 2004 Mechanical & Industrial Engineering, University of Toronto
Completed Wax Model

41. 2004 Mechanical & Industrial Engineering, University of Toronto
Mouth/trachea
induction port
Lung model
Outlet port
Stand
2004 Mechanical & Industrial Engineering, University of Toronto

42. 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

43. Hollow Cast Model