1. PRELIMINARY DESIGN
REPORT
Noah Ellis BME
Zach Quicksall BME
Charlie Heinke BME
Christopher Tito EE
Edward Chiang MAE
Aishwarya Vijayan CHE
Coach: Dr. Carlos Rinaldi BME
2. PROJECT SCOPE
Morphogenesis Inc.
Biotechnology company, Tampa
Florida
Goal: Capture circulating tumor cells
(CTCs) for characterization
Personalized cancer therapeutics
How?
Morphogenesis’ patented Polymer
Antibody Cell
Separator (PACS)
Fluid handling system
Modular and Disposable Column
3. Fluid Handling System
Column Design
• Holds Morphogenesis
Beads (Coated with
Antibodies)
• Minimizes Leaking
• Ensures Cell Viability
(Biocompatible
Materials)
Electrical Stimuli
Parallel Plates
• Two Possible Solutions:
• Internal Electrode
(Current)
• External Electrode
(Voltage)
• Goal: capture and recover
high quantities of live
CTCs
PROJECT SCOPE
4. REQUIREMENTS/SPECIFICATIONS
Category Customer need Imp.
PRODUCT
Cost R01- Cost Effective 2
Features R02- Modularity 5
R03-Disposable 4
R04- Uniformity of Electric Stimuli 4
R05-Pressure Sensors 4
R06- Cell Viability 5
Quality R07- Non-specific Binding 5
R08-Biocompatability of Materials 5
Safety R09-Sterility 5
IMPORTANCE RANGE 1 to 5
Provides an overview of the requirements for the project design. The rankings are from 1
to 5 with 1 being the least important and 5 the most important.
5. REQUIREMENTS/SPECIFICATIONS
Specification Unit
S01. Non-cytotoxic materials n/a
S02. Sterilizable components n/a
S03. Column will be coated with protein to prevent binding of
proteins/cells
Cells/mL
S04. Knowledge of cell concentrations before and after experiment Cells/mL
S05. Ease of replacement of column, tubing, and electrodes n/a
S06. Environmental Impact n/a
S07. Cost of replacement Components $
S08. Uniformity of Electric Field V/Amp
Displays the project specifications along with associated units of measure. Specifications
with nonexistent units of measure have not applicable (n/a) under the units column.
6. ANALYSIS OF COMPETITIVE PRODUCTS
Cell Search
Cost of clinical operation per patient = $370
Detects epithelial markers on CTC’s
Use for breast, colon, and prostate cancer
Cell Collector
In vivo collection processes
Uses antibodies bound to a hydrogel on
the gold-coated surface of metallic wires to bind CTC’s
Issues: Cells can be counted, but cannot be processed in large
volumes. You also cannot recover large quantities of viable
cells.
8. CONCEPT GENERATION
Column Design:
• 3D printed
• Material: Polypropylene, MED610
• Constrain Dimensions
• Bead Retention Mechanisms
• Uniform electric field delivery
Rectangular Design:
Bead Holding Mechanisms:
Bead Stopper
Integrated Mesh
Displays 3D Solidworks
model of preliminary
design. Orange highlight is
representative of integrated
mesh.
3D model is
representative of
column design
with bead stopper
mechanism for
microsphere
retention.
Representation of
a honeycomb
mesh design for
microsphere
retention.
9. CONCEPT GENERATION
Substitute Microsphere:
• Size
• Average Diameter: 250µm
• Range of Diameters: 212µm –
250µm
• Cost
• $275 for uniform 250µm diameter
beads (.5g)
• $197 for range 212µm – 250µm
diameter beads(5g)
• Material
• Polypropylene (PP)
• Polystyrene (PS)
• Polymethylmethacrylate (PMMA)
SEM image of microspheres
13. Design Evolution
2 Inch dead space for flow
equilibration
PMMA 212µm - 250µm
diameter microspheres
Honeycomb mesh with
thickness of 0.2In (.5cm)
Press fit column
integration for
prototype
14. Design Evolution
Column Integration with
Removable Cap
Press Fit Opening for
1/8” ID x ¼” OD
Rubber O-Ring or
Silicone Tape Placed
Around Groove
Snap on Groove
Feature for Stability
15. Today
10/12/2015 - 10/14/2015Column Material Selection
10/14/2015 - 10/19/2015Send Design to Fab Lab to Manufacture
10/22/2015 - 10/31/2015Column Testing
10/31/2015Acquire Data
11/1/2015 - 11/6/2015Review Prototype/Make Changes
9/30/2015 - 10/2/2015Bead Size and Material
10/12/2015 - 10/16/2015Purchase Beads
10/17/2015 - 10/31/2015Bead Testing
11/1/2015 - 11/6/2015Review Bead Selection/Make Changes
2015 2015Sep Oct Nov Dec
Official Meeting with Morphogenesis
9/21/2015
Rough Outline of PDR for Rinaldi
9/27/2015
Basic draft of PDR Presentation with Rinaldi
10/2/2015
Complete (close as possible) PDR report
10/16/2015
Morphogenesis Tour (Present PDR)
10/23/2015
Final PDR Report due to Stanfill
10/27/2015
Outline of System Level Design Review
Report due to Rinaldi
11/13/2015
Prototype Inspection Day
11/24/2015
Complete (close as possible) System Level
Design Review Report to Rinaldi and
Morphogenesis
11/30/2015
System Level Design Report due to
Stanfill
12/14/2015
End of Fall Semester
12/18/2015
Column Prototype: (Edward)
Bead Selection: (Noah and Zach)
16. 10/3/2015 - 10/6/2015Focus on Current or Voltage
10/7/2015 - 10/13/2015Run Electrode Simulations
10/13/2015 - 10/14/2015Purchase Electrodes
10/17/2015 - 10/31/2015Electrode Testing
11/1/2015 - 11/6/2015Review Electrode Design/Make Changes
10/9/2015 - 10/12/2015Deicde Tubing
10/12/2015 - 10/16/2015Decide Pressure Sensors
10/12/2015 - 10/16/2015Decide Column Cap Design
10/17/2015 - 10/19/2015Purchase Tubing+Sensors
10/19/2015 - 10/21/20153D-Print Cap
10/21/2015 - 10/31/2015Column Testing
11/1/2015 - 11/6/2015Review FHS/Make Changes
Electrode Design: (Chris)
Optimize Fluid Handling System: (Charlie and Ash)
Today
2015 2015Sep Oct Nov Dec
Official Meeting with Morphogenesis
9/21/2015
Rough Outline of PDR for Rinaldi
9/27/2015
Basic draft of PDR Presentation with Rinaldi
10/2/2015
Complete (close as possible) PDR report
10/16/2015
Morphogenesis Tour (Present PDR)
10/23/2015
Final PDR Report due to Stanfill
10/27/2015
Outline of System Level Design Review
Report due to Rinaldi
11/13/2015
Prototype Inspection Day
11/24/2015
Complete (close as possible) System Level
Design Review Report to Rinaldi and
Morphogenesis
11/30/2015
System Level Design Report due to
Stanfill
12/14/2015
End of Fall Semester
12/18/2015
17. BUSINESS CASE
Cell Seeker is developing a processes that aids in the
eradication of cancer
It can be used for BOTH therapeutics and diagnostics
by capturing clinically relevant quantities of CTCs
Capturing CTCs will expand the field of personalized
cancer therapeutics
Statistics by American Cancer Society:
• Approximately 14.5 million men and women have a
form of cancer in the US
• Current Products marketed at $370 per test.
• Potential Revenue $5.4 billion alone in the US
• Projected revenue globally yields exponential growth
18. ISSUES/RECOMMENDATIONS
No. Description of Risk and Impact Mitigation Strategy Owner Status
0
Risk of leaking within the 3D printed integrated
column
Use secondary sealing processes such as Acetone Vapor Bath,
epoxy resin, etc.
Edward,Ash Open
1 Risk of losing cell viabiltiy from electric stimulus
Further testing (hone in on ideal voltage), worst case switch to
internal electrode design
Chris Open
2 Risk of losing cell viabiltiy from cytotoxic materials
Find another manufacturer as fast as possible, or find other
biocompatable materials.
Noah,Zach,Charlie Open
3
Risk of losing cell viability due to fluid handling
processes and column integration
Further testing and having different tubing mates/materials,
implement new column design
Edward,Ash Open
4
Risk of column clogging within the fluid handling
system
Further Testing (change packing bed distribution) Change
entrance length of column
All Open
5 Non-Specific Binding
Find another manufacturer as fast as possible, or find other
biocompatable materials.
Noah,Zach,Charlie Open
6
Pressure sensing integration into computer control
system
Adding new code to current computer control system,
implementing a new micro controller
All Open
25. FORCE ON MESH ANALYSIS
Column Dimensions:
Height of Column = 13.58 cm
Height of Packed Bed = 8.5 cm
Width = 0.6937 cm
Length = 0.6937 cm
26. FORCE ON MESH ANALYSIS
Dead Space Volume (D.S.V): Determined to be any space within the
column that allows for fluid flow. The dead space taken into account is
any dead space that resides above the integrated mesh.
Weight of Fluid (𝑾 𝒇): Determined to be the weight attributed by the
buffy coat re-suspended within a PBS solution. The fluid was assumed
to be comprised mostly of PBS so the density used for conversions
involving this variable is that of PBS.
Weight of Microspheres (𝑾 𝒎): The microspheres that will be utilized
are made of PMMA and a diameter of 250µm was used or calculations.
The density for PMMA was found to be 1.18 g/𝑐𝑚3
Force due to Pressure Drop (𝑭 𝒑): This is the force attributed to the
pressure drop within the column.
Counter Force (𝑭 𝒄): The counter force is defined as the force that the
mesh must be able to withstand without buckling. To calculate this
force the weight of fluid, weight of microspheres, and force due to
pressure were summed together.
27. FORCE ON MESH ANALYSIS
Constants
Pressure Drop (ΔP) = 10180.91 Pa
Calculated Number of Microspheres = 484848
Density of PMMA (𝜌 𝑃𝑀𝑀𝐴) = 1.18 g/𝑐𝑚3
Density of PBS (𝜌 𝑃𝐵𝑆) = 1050.6 kg/𝑚3
Volume of a sphere =
4
3
π𝑟3
PMMA Microsphere Diameter = 250 µm
28. FORCE ON MESH ANALYSIS
Volume of an individual microsphere =
4
3
π (125 ∗ 10−6 m)3 = 8.181 ∗
10−12 𝑚3
Total Volume of microspheres = (8.181 ∗ 10−12 𝑚3) * (484848) =
3.96 ∗ 10−6 𝑚3
Mass of Microspheres = (3.96 ∗ 10−6 𝑚3) (𝜌 𝑃𝑀𝑀𝐴) = 4.68 g = 0.00468 kg
Weight of Microspheres = (0.00468 g)(9.81 m/𝑠2
) = 0.0459108 N
Dead Space Volume = (0.6937 𝑐𝑚 ∗ 0.6937 𝑐𝑚 ∗ 5.08 𝑐𝑚) + (0.12099
𝑐𝑚3) = 2.5656 𝑐𝑚3
Mass of Fluid = (2.5656 𝑐𝑚3
) (𝜌 𝑃𝐵𝑆) = 0.002695 kg
Weight of Fluid = (0.002695 kg)(9.81m/𝑠2) = 0.026442 N
Force due to Pressure Drop = (ΔP)(A) = (10180.91 N/𝑚2)(4.8122 ∗
10−5 𝑚2) = 0.489926 N
Counter Force = 0.0459108 N + 0.026442 N + 0.489926 N = 0.562279
N
29. FORCE ON MESH ANALYSIS
Interpretation: The mesh must have the structural
integrity to withstand a force of 0.562279 N. The
force acting on the mesh is so small that it can be
assumed that as long as the mesh isn’t paper thin it
should be able to withstand the applied forces.
Mesh
Counter Force (𝑭 𝒄)
Weight of Fluid (𝑾 𝒇), Weight of Microspheres (𝑾 𝒎)
Force due to Pressure Drop (𝑭 𝒑),
