This document describes a novel stem cell delivery device called Soterias Medical. It discusses the growing stem cell therapy market and need for a device that can deliver stem cells to target dermal regions in a controlled manner with minimal risk. The document outlines the design of Soterias Medical, including a base station to control injection settings and a handheld device. It discusses testing conducted on the prototype to evaluate factors like thaw time, cell viability after injection, and human factors. The document also covers accomplishments, next steps, and financial projections for the startup company.

1. Soterias Medical
SOTERIAS MEDICAL
A Novel Stem Cell Delivery Device
Michael Clark, Prateek Gowda, Angelica Herrera, Seung Jung,
Michael Mow, Arianne Papa, Annabeth Rodriguez, Jose Solis
Project Advisors: Luis Garza, M.D., Ph.D (Johns Hopkins Hospital)
Sewon Kang, M.D. (Johns Hopkins Hospital)
Robert Allen, Ph.D. (Johns Hopkins University)
Johns Hopkins University

2. STEM CELL MARKET
SOTERIAS MEDICAL
● Global stem cell market is
growing at 13.6% from $5.6
billion in 2013
● Currently, 4681 clinical trials on
stem cell therapies in the US
(3000 in Phase I or II)
● Skin Stem Cell Therapies

3. STANDARD OF CARE
SOTERIAS MEDICAL

4. STANDARD OF CARE
SOTERIAS MEDICAL
Traditional Needle Injection
● No consistency in
▪ Thaw rate
▪ Injection volume
▪ Injection rate
▪ Positional control
● Risk of infection
These factors lead to a reduction in cell viability.

5. CLINICAL NEED
SOTERIAS MEDICAL
There is a need for a device that allows
physicians to deliver stem cells to target
dermal regions at adjustable volumes with
minimal risk of infection or viability loss.

6. SOTERIAS MEDICAL
Factor Standard of Care Replicel Soterias Medical
Controlled Injection Rate ☓ ✓ ✓
Minimal Risk of Infection ☓ ☓ ✓
Built-in Thawing Capability ☓ ☓ ✓
Adjustable Volume ✓ ✓ ✓
Consistent Angle of Injection ☓ ✓ ✓
PRODUCT COMPARISON

7. PRIOR DESIGNS
SOTERIAS MEDICAL

8. CURRENT DESIGN
SOTERIAS MEDICAL

9. DERMAL INJECTOR PROCEDURE
SOTERIAS MEDICAL

10. BASE STATION
SOTERIAS MEDICAL
Features
● Docking station for
device when not in use
● Charging station
● LCD screen
● Adjust injection settings
○ Cell thawing
○ Injection rate
○ Injection volume

11. Features
● Controlled feedback
system heats pads to
37°C
● Consistent and quick
thaw time ensures cell
viability
● Eliminates need for water
bath in procedure room
HEATING ELEMENT
SOTERIAS MEDICAL

12. Features
● Larger injection volume
results in fewer number of
injections.
● Closed-loop system
reduces contamination.
● Luer lock connections.
● Microliter precision from
tubing
CLOSED - LOOP SYSTEM
SOTERIAS MEDICAL

13. Features
● Peristaltic Pump
● Motor
● Arduino
○ Motor Control
○ Temperature negative
feedback loop
● Raspberry Pi
○ Program the device
○ User-friendly interface
for physicians
ELECTRONICS
SOTERIAS MEDICAL

14. Features
● Septum improves device
safety
● Angle guards provide
positional control
● Easy setup and safe
removal of disposables.
OTHER FEATURES
SOTERIAS MEDICAL

15. TESTING AND EVALUATION
SOTERIAS MEDICAL
Factor Test Satisfactory Result
Thaw Time Thaw dead cell slurry -196℃ → 37℃, < 2-3 minutes
for 1.0 mL
Cell Viability Ex vivo: Injection Rates and
Diameters
In vivo: Clinical Trial
<40% Reduction in Viability
Injection Volume Determine density of dead cell
slurry, measure mass of
injected volume
Accuracy of ±1 μL
Human Factors Qualitative Feedback No more difficult than current
standard of care

16. 1. Mouse spleen cells to
mimic fibroblasts
a. Used Countess
Automated Cell Counter.
a. Unable to differentiate
between RBCs and
mouse spleen cells
a. Needed ACK RBC lysis
buffer
TESTING RESULTS

17. TESTING RESULTS
SOTERIAS MEDICAL
2. Sole fibroblasts from Dr.
Garza’s lab
a. Inconsistent cell density
when pipetting onto
hemocytometer slides
a. All cells appeared viable
immediately after injection

18. TESTING RESULTS
SOTERIAS MEDICAL
3. L929 mouse fibroblasts from
Dr. Logsdon
a. 60,000/mL cell density too low
to see increased shearing
forces
a. All cells appeared viable
immediately after injection
a. Trypan blue had debris making
images unclear.

19. TESTING RESULTS
SOTERIAS MEDICAL
4. Thermocouple Negative
Feedback Loop
a. Stabilize temperature at
37.0°C with ±0.5°C variation
a. Reduced error with more
frequent temperature checks

20. PROTOTYPE BUDGET ANALYSIS
SOTERIAS MEDICAL
Handheld Component Cost for Device
Plastic PLA Shell $0.16
Buttons $0.16
LEDs $1.32
Pins, Springs, Hinges $13.34
Pump Components $26.55
Heating Components $67.57
Total $109.10
Base Station Component Cost for Device
Plastic PLA Shell $0.18
Buttons $0.90
Power Cord, Contact Leads $9.65
LCD Screen $35.00
Total $45.73
Disposable Component Cost
23 Gauge Needle $0.18
Tubing, Luer Lock $1.42
Cryogenic Bag $31.00
Total $33.25

21. ACCOMPLISHMENTS & AWARDS
SOTERIAS MEDICAL
ACCOMPLISHMENTS
Base station
Prototype angle guards
Pumping mechanism
Heating mechanism
Cell testing
Heating testing
Closed-loop system
Handheld shape design
AWARDS
First Place, Carnegie Mellon University McGinnis
Venture Competition
Finalists, TigerLaunch
Finalists, The Big Sell
Finalists, Towson Incubator
Finalists, Carnegie Mellon Venture Competition
Semifinalists, ASME iShow
Semifinalists, JHU Business Plan
Semifinalists, Tulane Business Model
✓
✓
✓
✓
✓
✓
✓
✓

22. SOTERIAS MEDICAL
SHORT TERM
Visualize Injection Progress
Angle Guards
Shorter Needles
Reduce Size with a New Pump Design
Cartridge
User Interface development
Testing
Power Contacts
LONG TERM
Explore FDA Pathways
Provisional Patent
Intellectual Property
Business Plan Competitions
Partnering
Team Expansion
Exit Strategy
NEXT STEPS

23. Dr. Robert Allen Dr. Elizabeth Logsdon Dr. Warren Grayson Dr. Zijun Zhang
ACKNOWLEDGEMENTS
SOTERIAS MEDICAL
Dr. Luis Garza
Dr. Youseph YazdiDr. Soumyadipta
Acharya
Dr. Hai-Quan Mao
Mihika ReddyAaron ChangNathaniel Leon
Dr. Sewon Kang
Amadeus Zhu Tabetha Ratliff

24. Appendix Index
● Markup Price
● 5 Year Startup Expenses
● Marketing
● Distribution
● Sales Channels
● Client Base
● 10 Year Financial Breakdown
● Cryomaterials
● Cryobags
● Cryotubes
● Cell Viability Post Injection
● Peristaltic Pumps
● Tubing Dead Space
● Needle Dimensions: Length
● Needle Dimensions: Angle
● Dermal Fibroblast Size
● Anatomy of the Dermis
● Epidermal Thickness I
● Epidermal Thickness II
● Replicel RCI-01, RCI-02
● Testing:
○ Injection Volume
○ Human Factors
○ Thaw Time
○ Injection Depth
○ Cell Viability
○ Patient Discomfort
○ Delivery Time
● Detailed Injection Procedure
● Closed-Loop System Details
● Electrical Components
● Motor
● Springs, Clips, Hinges
● Heating
● Pump

25. MARKUP PRICE
SOTERIAS MEDICAL
Markup Price
Device $199.99
Disposables $ 59.99
Manufacturing Cost
Device $154.83
Disposables $ 33.25
Total: $188.08

26. 5 Year Startup Expenses
SOTERIAS MEDICAL

27. MARKETING
SOTERIAS MEDICAL
Market through interactions with hospital sales representatives
Foster awareness through scientific community
Advertised at medical conferences and online
Estimated 9,600 dermatologists and 7,800 dermatology practices in the U.S.
More than 91.5 million people qualify for treatment

28. Secondary Target:
Universities and other
research institutions.
DISTRIBUTION
SOTERIAS MEDICAL
Primary Target:
U.S. hospitals/clinics with a
commitment to the cutting edge
of medical technology.

29. SALES CHANNELS
SOTERIAS MEDICAL
PHASE I - DIRECT
● Seek out leaders in stem cell research
● Target physicians most likely to adopt
novel devices
● Hire and utilize in-house marketing
experts
● Engage customers with face-to-face
encounters
PHASE II - INDIRECT
● Market the device to medical supply
distributors to drive continuing sales
● Pitch the device nationwide to hospitals
and hospital representatives
● Engage private practices throughout the
country
● Others approach our company

30. CLIENT BASE
SOTERIAS MEDICAL
Trusting relationship
Customer loyalty
Customer trust
Improved outcomes
Success of product
Technical assistance

31. 10 Year Financial Breakdown
SOTERIAS MEDICAL

32. Cryomaterials
● Cryogenic materials have special
properties that make them particularly
hazardous to use in the solid, liquid or
gaseous states.
● Cryogenic materials are characterized by
severe low temperature (-60℃ to -270℃).
● Most cryogenic liquids are odorless and
tasteless when vaporized; however, when
exposed to the atmosphere they create a
highly visible dense fog that dissipates
with warming.
● Cryogenic temperatures are achieved by
liquefaction of gases, most commonly
helium, hydrogen, nitrogen, argon, oxygen
or methane.

33. Cryobags
● Designed to process, grow, and
store cells and tissues from -196°C
to over 200°C
● Bags come in various sizes
(Freeze volume range: ~10-200mL)
● Made of two materials
o Ethyl Vinyl Acetate (EVA)
o Fluorinated Ethylene Propylene
(FEP)
● Four known suppliers:
o Charter Medical
o Instant Systems
o OriGen Biomedical
o Quest Biomedical

34. Cryotubes
● Designed for storing biological
material at temperatures as
low as -196°C
● Tubes come in various sizes
(Freeze Volume Range: ~0.5-
5mL)
● Major Suppliers:
○ Sigma-Aldrich
○ Corning
○ ThermoScientific

35. Cell Viability Post-Injection

36. Peristaltic Pumps
Pros Cons
Sterile pathway Tubing Dead Space
Good for shear-sensitive materials Pulsating output at low flow rates
Very fine volume/rate control Need to “calibrate”

37. Tubing Dead Space
Source: http://www.had2know.com/technology/curved-pipe-volume.html
● Tube volume - including the exact
volume of any bends - can be
mathematically determined
● Rough estimate based on the fill
volume of appropriate lengths of tubes
were obtained
o 76uL

38. Needle Dimensions: Tube
Source: Sigma Aldrich

39. Needle Dimensions: Angle
Source: Sigma Aldrich
≈9°
≈23°
≈37°
α
O.D.
O.D./sin(α)

40. Dermal Fibroblast Size
About 20μm diameter

41. Anatomy of the Dermis

42. Epidermal Thickness
Up to 370μm thickness (fingertip)

43. Epidermal Thickness
About 84μm average thickness
2003

44. Total Skin Thickness

45. Replicel

46. Testing: Injection Volume
● Objective: Device should be able
to deliver desired volume (5μL -
1000μL, 5μL increments) with
accuracy of ± 1μL
● Detailed Experiment:
o Pseudo-calibrate pipette using
deionized water
o Determine dead-cell slurry density
o Determine injection volume
accuracy using skin sample

47. Testing: Human Factors
● Objective: Device should not be any
more difficult than current standard of
care
● Detailed Experiment:
o Present prototype to physician
o Observe handling of device and record any
comments or questions he/she brings up
o Instruct physician on proper use of device
o Observe handling issues and/or cumbersome
features
o Acquire feedback on: ambidexterity,
complexity, size, steadiness, weight

48. Testing: Thaw Time
● Objective: Device should thaw solution at the
same rate as a 37°C water bath or human hand
● Detailed Experiment:
o Cryobag/cryovial is frozen in liquid nitrogen
o Samples are removed from liquid nitrogen and thawed
via 3 different methods:
▪ 37°C water bath
▪ Hand heat
▪ Injector device heating element
o Amount of time for entire solution to liquefy will be
measured

49. Testing: Injection Depth
● Objective: Deliver stem cells at a specific vertical depth at a ±
10% depth accuracy
● Detailed Experiment:
o Ex Vivo:
▪ Device is set to predetermined depth and volume
▪ Dead stem cells dyed with trypan blue and loaded into device
▪ After injection, stem cells will be sent for histology
▪ Images quantified by measuring distance from top of epidermis
to top and bottom of cell bolus
o In Vivo:
▪ Device is set to predetermined depth and volume
▪ Stem cells will be injected into patient
▪ OCT/ultrasound imaging will be used to image testing site of
patient immediately after injection and after a set time to allow
for diffusion
▪ Images quantified by measuring distance from top of epidermis
to top and bottom of cell bolus and area of cell bolus

50. Testing: Cell Viability
● Objective: Loss in viability due to injection should be no greater than current
standard of care, preferably < 40% reduction in viability
● Detailed Experiment:
o Ex Vivo
▪ Harvest cells from mouse spleen
▪ Load cells into device with cryosolution
▪ Inject cells onto a petri dish using device as well as a needle and
syringe using different rates of injection and needle diameters
▪ Cells will be then stained using live/dead assay
▪ Stained cells on petri dish can then be counted under a light
microscope using a cell counting software to determine cell viability
o In Vivo
▪ Two 700 µL injections will be performed on lower back of patient:
one with device, one using needle and syringe
▪ Three months later, cell viability will be qualitatively evaluated
▪ Cell viability for each injection technique will be evaluated using
difference in area of growth and OCT/ultrasound/staining methods

51. Testing: Cell Viability
Control: 100 uL Pipette 100 uL Needle and Syringe 100 uL Pump

52. Testing: Patient Discomfort
● Objective: Device should not pose
discomfort greater than that of the
current standard of care
● Detailed Experiment:
o Inject saline solution at desired depth
and volume for normal procedure into
fully informed volunteer human test
subject using prototype
o Inject into upper buttocks of test subject
o Record duration of procedure
o Survey test subjects on degree of pain

53. Testing: Delivery Time
● Objective: Device should be able to thaw
1 mL solution in approx. 2 minutes and
deliver the amount in approx. 1 minute
● Detailed Experiment:
o Thaw solution in cryostore bag
o Load bag into prototype
o Adjust volume and depth dials to desired
values
o Inject cells using prototype into upper buttocks
of patient
o Record total time and any complications

54. Detailed Procedure
1. Lab technician freezes cells in cryobag at -196℃. This is all performed in a hood.
2. “Runner” brings cells from freezer to clinic where procedure will take place while cells are on dry ice.
3. Physician receives cells, feeds cryobag, tubing, and needle into device while sitting in base station.
a. Clip into device
b. Clip tube in
c. Feed tube through pump
d. Clip needle
4. Close device
5. Turn on/program base station (desired injection rate, volume, thawing temperature)
6. Let cells thaw. Device will stop heating when bag is thawed and “beep.”
7. Remove from base station.
8. Pick angle guard/install on tip of device. (optional)
9. Remove cap from needle
10. Remove dead space in tubing by pushing button on device to eject air.
11. Prep for injection
12. Inject
13. Open device, remove everything via bag
14. Place device back in base station

55. Closed - Loop System
Cryobag
● Holds 7-12mL volume
● 3.0 cm x 6.3 cm
Luer Lock
● Male Luer with Spin Lock to Barb
● Fits 1/32 inch ID Tubing
Tubing
● High-Purity Silicone Rubber for
Peristaltic Pump
● OD: 3/32" ID: 1/32"
● 1/32" Wall Thickness
● Sub-microliter precision
Needle
● 23 gauge

56. Electrical Components
The device utilizes an Arduino Micro Board in
the handheld injector and a Raspberry Pi in the
base station
Arduino Micro Functions:
● Motor Control
● Temperature Feedback on Heating
System
● Injection Command
● Internal Power Supply 12V
Raspberry Pi Functions:
● User-friendly color touch screen
● Serves as interactive medium for
dermatologist to set injection volume,
speed and cell temperature

57. Motor Specifications
12V 1/64 Geared Stepper Motor
1024 Step / Revolution Resolution
100 N/mm Holding Torque
Weight: 37g
Diameter: 28mm
Height: 20mm
Provides high resolution and controlled
movement without the need of an encoder

58. Springs, Hinges, and Clips
Springs
- Located behind heating pads.
- Controls the force of contact
between device and cyro-bag.
Hinges
- Located on the side of the device.
- Integrated with design.
Tube Clip
- Located towards the head of the
device.
- 3D printed onto device.
- Holds tubing in place during
injection.

59. Heating
Heating pads
- 2 5V pads
- Squeeze bag together using springs to
heat evenly
Relay
- Electrical component used to switch pads
on/off when the temp. reaches 37℃
Arduino Uno
- Used to receive feedback from heating
pads and control relay
Thermocouple
- Temperature probe that measures temp.
of bag/pads during thawing
Power
- 9V DC power supply from wall plug

60. Pump Specifications
3 cylinder peristaltic pump
Currently PLA but will eventually
be made out of aluminum or
stainless steel for durability.
Setup provides 1uL precision.