1. ContiPress™
Sense A/S
DTU April 9. 2013
Lars Lading
LL@sense-as.dk

2. Topics
 ContiPress™: The problem and our solution
 Sense history
 How to succeed?
 Some general comments about venture capital and
IPR
 IPR:
• The procedure
• What can you do yourself – and what not?
• About claims, descriptions, figures
• Publications and patents
 Venture Capital:
• Do you really need it?
• Consequences
 Summary
2

3. The Challenge
3

4. Hypertension
 25% of world populations
suffers from hypertension
 33% of these are being
treated
 1 out of 8 deaths are
attributted to hypertension
4

5. Blood Pressure: Continuous measurements
are needed
 A strong need for continuous, non interfering blood pressure
measurements: Ambulatory Blood Pressure Measurements (ABPM)
 No current commercial product satisfies this need
 First product focus is non-interfering 24 hours ABPM
SBPSleep
Dip 1 100%
SBPWake Unhealthy
Pressure
Healthy
Waken Sleep
24 hours
5

6. No interference!
6

7. Recommendations: Hypertension
NICE guideline 34: Hypertension, August 2011
1.2.3 If the clinic blood pressure is 140/90 mmHg
or higher, offer ambulatory blood pressure
monitoring (ABPM) to confirm the diagnosis of
hypertension. [new 2011]
1.2.4 If a person is unable to tolerate ABPM, home
blood pressure monitoring (HBPM) is a
suitable alternative to confirm the diagnosis
of hypertension. [new 2011]
- In line with extensive investigations on the value
of continuous BP measurements
7

8. Cost-effectiveness of Ambulatory BP
Kate Lovibond et al, Cost-effectiveness of options for the
diagnosis of high blood pressure in primary care: a modeling
study. www.thelancet.com published online August 24, 2011
DOI:10.1016/S0140-6736(11)61184-7
“Ambulatory monitoring was the most cost-effective
strategy for the diagnosis of hypertension for men
and women of all ages”
8

10. Solution for
Blood Pressure
10

11. Continuous non-interfering
blood pressure
 Disposable
patch/sensor band
 Miniaturized
electronics for
excitation, collection,
processing, and
storage of data
 Docking station for
data transfer and
charging
 Dedicated software
11

12. Key Features
 Distension
 Stiffness
 No counter pressure
 No wire – or hose – connections to external devices
 Disposable patch: no cross-contamination
 The method is model based!
 Why is this not common practice?
 Because arterial distension is (has been) difficult to
measure and
 Arterial stiffness has been almost impossible to measure
at a single location
12

13. ContiPress consists of four parts
Patch
2
1
3 4
Control panel
Docking station
(Charging/Transfer)

14. Usage
2 4
1
3 5
14

15. Graphical User Interface
15
15

16. Blood Pressure: How?
 Arterial distension (artery expansion
with heart beat) from dynamic tissue
response
 Arterial stiffness from Pulse Wave
velocity
 The nonlinear stress-strain relation
facilitates the mean arterial pressure
from the pulse pressure and distension
Compare with a spring: If the increase in length (distension)
as a result of an unknown force (pressure) is measured then
the force can be calculated if the spring constant (stiffness)
is known 16

17. The Circulatory System:
Pump, vessels, capillaries, organs
From: McDonald’s Blood Flow in Arteries
17

18. The circulatory system
Most important:
 Transport (flow + content) according to needs: awake, work/rest,
sleep
 Can the pump deliver according to needs?
 Can the vascular (arterial) system support flow and pressure?
What affects the functioning of the cardiovascular system?
 Psychological (white coat syndrome)
 Physiological
 Genetics, intake (salt), diseases + + +
What is measured?
 Pressure when flow is blocked (systolic)
 At a single point in time, in doctors office: a psychological and a very
strong physiological impact on the subject (e.g. inflating a cuff during
sleep defeats the purpose)
No current system complies with the need of continuous
and non-interfering blood pressure measurements.
18

19. From ZYGOTE BODY
19

20. Anatomy
MR images
20

21. Arterial stiffness
 Highly nonlinear
(Pressure)
 Central and periphal
stiffnesses are
different
(Diameter)
21

22. Pulse Wave Velocity
 A good indicator of the state of the cardiovascular
system – in particular of arteries
 High velocity large stiffness fragile arteries
 Typically measured over large
stretches, e.g. heart to wrist
 Velocity depends on:
o Stiffness
o Diameter
o Blood density
o Wall thickness
22

23. Pulse reflections are important
 At bifurcations
 At localized depositions
23

24. Field Lines and tissue properties
A simplified cross-section of an organ and the
distribution of field lines
Bioimpedance: See e.g. S. Grimnes and Ø. G. Martinsen,
Bioimpedance and Bioelectricity Basics, AP Oxford 2008
24

25. Electrical Impedance
A macroscopic quantity
25

26. Permittivity and refractive index
 The permittivity relates to a material's ability to
transmit (or "permit") an electric field.
 Complex permittivity
ˆ ´ i
 Refractive index
n r r
26

27. Electrical properties of tissue and blood
 Conductivities and permittivities are generally
different for different types of tissues.
 They vary greatly with excitation frequency.
 Anisotropic.
1.8
1.6
1.4
1.2
Conductivity, muscle [S/m]
1 Conductivity, blood [S/m]
0.8 Conductivity, skin dry
0.6 Conductivity, skin wet
0.4 Conductivity, fat
0.2
0
1.00E+03 1.00E+04 1.00E+05 1.00E+06 1.00E+07 1.00E+08 1.00E+09
27

28. Permittivity
28

29. Impedance of a cross-section
 Finite element calculations
 Equivalent circuits
29

30. Sensor Band
30

31. Pulse Pressure and Waveforms
30 year old healthy 20
young male
10
0
BMI = 24 kg/m2  10
SBP = 126 mmHg  20
BP = 45 mmHg
112 113 114 115 116 117
Sec
62 year old female 40
20
BMI = 23 kg/m2  20
0
SBP = 182 mmHg  40
 60
BP = 85 mmHg 5 6 7 8 9 10
Sec
52 year old male
20
10
BMI = 46 kg /m2  10
0
SBP = 186 mmHg  20
BP = 62 mmHg  30
2 3 4 5 6 7
Sec
From a clinical study at Copenhagen Univ. Hospital:
Tine Willum Hansen et al. 2011 31

32. Sense History
32

33. Sense History
 Established in 2000: A device for monitoring amount
and quality of milk to prematurely born babies during
breast feeding. Technology principles developed, but
potential investors did not beleive in market.
 2005: Similar technology for vascular transport
monitoring: A new technology and a new application:
Too much up-hill
 2006-7: Non-interfering blood pressure
 2008-9: A scheme identified and some very
preliminary measurements (Innovation funding)
 2009: Vækstfonden decides to invest jointly with Seed
Capital
 2010: Personnel hired (now 10 persons)
 2010-now: Product development, key itereations, QA
and regulatory, clinical trials
33

34. Sense IPR
Patent appl. Status Priority Importance Action Freedom to
from to Sense operate
WO Pending 2006 Preventive Rejected; A successful appeal is Large
2007/000164 considered very likely
A2
WO2007 Granted in 2007 Small Maintain in Europe Large, can be
DK00553 Europe affected by
RFID patents
PCT/DK2009/ Pending 2009 Preventive Maintained at least until a Large
000241 Protection preliminary evaluation of 5 has
been given
Not 2010 Substituted Withdrawn before publication in Large
publicized by 5 before order not to become prior art to
being 5
publicized
5 Submitted 2011 Protection Submitted as a method Very large
Feb. 2011 Prevention
6 In 2012 Protection Impedance sensing methods - Large
preparation Prevention additional
34

35. How to
succeed?
35

36. How to succeed?
 There is no safe recipe!
 But a few things may help:
 A need
• Existing
• Potential
 A unique solution (not a ”me too” product)
 Market access
 Financing
 IPR
 Avoid dead ends
 Keep it small – but not too small!
 And luck!
36

37. Device Challenges
 Market needs and trends
 Basic method
 Algorithms
 Electronics
 Patches
 Design (aesthetic) and usability
37

38. 38

39. Organizational Challenges
 Interdisciplinary
 Physics
 Electrical and mechanical
 Medical – needs, clinical methods, anatomy, and physiology
 Engineering competences
 Electronics
 IT
 Materials/mechanics
 Market
 Management
 Financing
 Accounting
 Regulatory
 Partnerships
39

40. IPR
 Time consuming
 Expensive
 Often frustrating
 But mandatory esp. for attracting venture capital
 Make it short!
 Claims and figures are most important
 Description should support claims but also
contain material that prevents other applications
threatening the freedom to operate.
40

41. Financing
 The valley of death
 Venture capital
 Preferable to avoid
 May strengthen milestones and plans
 You loose control
 There may be no other way
 Strategic partners
 May pay for development conditioned by
• Full right to product
• Right to marketing
• Right of first refusal
 Self financing
 Slow growth
 Higher risk
 Potentially much higher return
 Crowd Funding
41

42. External Resources
Medical
 Rigshospitalet (the major university hospital in Denmark)
 Odense Univ. Hospital
 Frederiksberg Hospital
Market
 Lundbeck
Technology
 DELTA, Electronics, Sound, and Optics
 Danish Technological Institute
 Technical Univ. of Denmark
 Univ. of Southern Denmark
 Ambu A/S
IPR and Legal
 Hegner and Partners
 Law Firm Bech-Bruun
A strong international network
42

43. Summary
 Starting a company implies a lot of work, can be
very frustrating
 but few other activities are more challenging
and rewarding
 Market needs
 Idea: a relevant solution, novel, design and
usability
 People: The right competences
 Money: Difficult with – impossible without!
43

44. Hale’s method
for BP
measurements
44