The document discusses the use of micropost substrates for mechanosensitive cell-based assays that link cell mechanics to gene expression. It explores the impact of mechanical interactions with the environment on cell behavior, particularly in cancer research, and offers various assay options for studying cell migration and mechanical profiles. Additionally, it highlights the advantages of using patient-derived cells for drug discovery and mechanobiology research.

1. Tiny Forces – Huge Impact
Founders
Dr. Goedecke
Dipl. Ing. (FH) Streichan
All About Microposts
Substrates for Mechanosensitive Cell-based Assays

2. Cell Mechanics Linked to Gene Expression!
 Mechanic phenomena exist on all system levels
 Effect visible in tissue/2D-cell culture
 Cell shape dependent on environment
◦ Neighbouring cells
◦ Extra-cellulare matrix (ECM) proteins
 Mechanic interaction with environment
 Influence on gen expression
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nucleus
cell skeleton
ECM
environment

3. 30. May 2015
Assay Workflow
2. Take Microscopic Images
0
20
40
60
80
100
0 1 2 3 4 5
Force [nN]
1.05 nN/um
2.87 nN/um
1. Seed Cells on Substrate
3. Analyse Images
0
1
2
3
4
5
6
HuO9 M132
Avg. Force/post [nN]
4. Summarize Data
Micropost array

4. Different Assay Options
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Migration
Images fixed cell Video footage
Live cell imaging
Video footage
Live cell imaging
Individual
mechano profiles
Twitching

5. Cell Migration
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24h observation video of human
bone cancer cells migrating - 1200x faster
25 m

6. Another Live-cell Assay
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Migration
Images fixed cell Video footage
Live cell imaging
Video footage
Live cell imaging
Individual
mechano profiles
Twitching

7. Twitching Assays
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Human induced pluripotent stem cells – 3.3x faster
Spontaneously twitching

8. Yet Another Assay Option
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Migration
Images fixed cell Video footage
Live cell imaging
Video footage
Live cell imaging
Individual
mechano profiles
Twitching

9. Mechanobiological Differences in
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0
5
10
15
20
25
30
35
40
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
Number of covered Microposts
HuO9
M132
0
1
2
3
4
5
6
HuO9 M132
Avg. Force/post [nN]
HuO9 = parental cell line – cells are stronger and more spread out (n=302)
M132 = metastatic cell line – cells are weaker and smaller (n=302)
Human Bone Cancer Cells

10. Research Targets
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HuO9 bone cancer cell
25 m
Typical effects on mechano profiles
 Change in genotype by
◦ Knock-in, knock-out of genes
◦ Viral infection
 Add of pharmaceutical active compounds
 Change in extra cellular matrix composition
 Environment stiffness or topography

11. Why Cell Mechanics? Why Microposts?
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Advantages
 Single clinical tissue biopsy provides sufficient cells for a large number of
tests
 Enables screening of a wide range of candidate molecules with patient
derived cells in early phases of the drug discovery/development
 Novel level of information for researchers already using tissue-
mechanics testing methods (e.g. wire-myography)
 Enables automated testing of mechanical cells responses (migration,
contraction)
 Easy to integrate

12. Examples of Micropost Assays
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Test Medical Condition Properties of Interest
Wound healing Open wound Sealing process and
potential influences
Pharmacological
active compounds
Cancer development/
primary tumors
Cell size and cyto skeleton
condition
Mutiple sclerosis Re-myelinisation of
glia-cells
Effects of
mutations
Cardiotrophic myopathy/
DiabetisType II
Cell contraction (frequency
and amplitude)
Controlled cell
differentiation
Production of cells for
regenerative medicine
Constant influence of stem
cells for „maturing“

13. Product Status
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 Sensor matrix
◦ Ø=6.4 m, h=18 m, gap = 6.6 m
◦ Material = silicone rubber ~ 50kPa
◦ Surface coating
 Application protocol
 Mechano-profiling software
 Bone cancer cell assay
 Happily returning customers
200 m

14. Mechanobiology – The Race is on!
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Comparison ofTechnology Development: Numbers from Web of Science
0
50
100
150
200
250
300
Number of publications
Year of publication
Gen AND sequen*
Substrate AND elasticity OR
stiffness AND cell
1990 1991 1992 1993 1994 1995 1996 1997 1998 1999
2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
Search:

15. Implementation Step-by-Step
TwinSlide Multi-well Plate Cell Force Kit
Cancer models
Cardio – Vascular
Diseases models
Lung disease
(COPD, Asthma)
Basic
Research
Pharmaceutical
R&D
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Identification &
Validation
Qualification Standardisation

16. ETH Founders Team Entrepreneurs
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Dr Nils Goedecke – CEO & CSO
Dipl. Biophysics, Berlin DE
PhD Analytical Chemistry, London UK
Post-doc MIT – Cambridge, MA US
Sen. Researcher ETH-Zurich, CH
Sen. Researcher UZH Uniklinik Balgrist, CH
Ralf Streichan – CTO & CFO
Dipl. Ing. Microsystems Tech., Berlin DE
Researcher /Engineer ETH Zurich, CH
Process Engineer printed circuit board (PCB)
manufacturing for medical implants, CH

17. Thank you for your time and interest.
Please contact us for further information.
MicroDuits GmbH
Stampfenbachstr. 52
CH - 8006 Zuerich
info@microduits.com
www.MicroDuits.com
30. May 2015