How are microfluidics solving major sample preparation issues in diagnostics? How microfluidic technologies are solving the major issues of IVD sample preparation In the 21st century, in-vitro diagnostics (IVD) are playing a role of unprecedented importance. They are used everywhere in the fields of medicine and biology, whether detecting bacteria in food or water, diagnosing a disease or sequencing DNA. However, before the analysis step, biological samples must be prepared in order to get the most reliable results possible. Sample preparation steps will depend on the type of assay, type of sample, and detection method. Today these are the major issues in laboratory analysis. Without automation, these processes are time-consuming and risk human manipulation errors that have a serious impact on analysis quality. Microfluidic technologies are now ready to address these issues. New solutions are starting to improve sample preparation and bring automation while reducing associated costs. After years of lagging behind microfluidic technologies for detection, microfluidics for sample preparation have taken a big step forward in 2015. Numerous products integrating automated sample preparation steps or even fully dedicated to sample preparation have arrived on the market. In the meantime, the market dynamics have never been more positive. Numerous specialized startups have been acquired by large players, while investor confidence is at an all-time high, leading to numerous and impressive fundraising efforts for innovative companies in the field. The market has reached an inflection point thanks to the arrival of solutions relying on mature microfluidic technologies on the market, which will replace existing manual manipulations. An increasing number of players are involved in the field of sample preparation and this positive dynamic will continue in 2016, with many planned product releases, leading to huge year-to-year growth rates. Some segments of the microfluidics for sample preparation market will double from one year to the next. Their contribution will lead this market to reach $353M by 2020 from $98M in 2014. In the report, we will discuss the state of the market, identify the drivers and current and future trends and explain how and why it will evolve over the next few years.

1. March © 2016
From Technologies to Market
Microfluidics for
Single-Cell Sample
Preparation:
Market &Technology
Analysis
Single Molecule & Single Cell Analysis Conference 2016
From Technologies to Market
Sébastien Clerc
Yole Développement
clerc@yole.fr

2. 2
PRESENTATION OUTLOOK
25 + 5 mins
• Yole Développement Introduction
• Sample preparation issues
• Single-cell challenges
• The rise of microfluidics for single-cell
• What’s next?
• Q&A
©2016 | www.yole.fr | Single Molecule & Single Cell Analysis Conference 2016

3. Yole Développement
Market, technology and strategy consulting
©2016 | www.yole.fr | Single Molecule & Single Cell Analysis Conference 2016

4. 4
MEMS &
Sensors
LED
Compound
Semi.
Imaging Photonics
MedTech
Manufacturing
Advanced Packaging
Batteries / Energy
Management
Power
Electronics
FIELDS OF EXPERTISE
Yole Développement’s 30 analysts operate in the following areas
©2016 | www.yole.fr | Single Molecule & Single Cell Analysis Conference 2016

5. 5
OUR GLOBAL ACTIVITY
©2016 | www.yole.fr | Single Molecule & Single Cell Analysis Conference 2016

6. Microfluidics for Single-Cell
sample preparation
©2016 | www.yole.fr | Single Molecule & Single Cell Analysis Conference 2016

7. 8
SAMPLE PREPARATION ISSUES
Single-cell
sample
preparation
issues is one
of the focus
of our latest
report
Molecular
Diagnostics
Single-cell
Next-Generation
Sequencing
©2016 | www.yole.fr | Single Molecule & Single Cell Analysis Conference 2016

8. 9
WHY SINGLE-CELL?
Single cells
behave
differently
than cell
populations
Objective: understanding the molecular mechanisms at the cellular level:
• Immune system response to an infection
• Cell response to a drug
• Genetic changes
• Tumor characteristics
• …
Problem: heterogeneity among cell populations => different behaviors…
©2016 | www.yole.fr | Single Molecule & Single Cell Analysis Conference 2016

9. 10
WHY SINGLE-CELL?
Cell-to-cell variability
Single-cell
analysis
enables the
identification
of cell
heterogeneity
©2016 | www.yole.fr | Single Molecule & Single Cell Analysis Conference 2016
Let’s compare two cell populations…

10. 11
WHY SINGLE-CELL?
Cell-to-cell variability
3
3
4
3
4
3
4
Average = 3.4
©2016 | www.yole.fr | Single Molecule & Single Cell Analysis Conference 2016
Let’s compare two cell populations…
Single-cell
analysis
enables the
identification
of cell
heterogeneity

11. 12
WHY SINGLE-CELL?
Cell-to-cell variability
3
3
4
3
4
3
4
3
3
6
3
3
3
3
Average = 3.4 Average = 3.4
Let’s compare two cell populations…
©2016 | www.yole.fr | Single Molecule & Single Cell Analysis Conference 2016
Single-cell
analysis
enables the
identification
of cell
heterogeneity

12. 13
WHY SINGLE-CELL?
Cell-to-cell variability
3
3
4
3
4
3
4
3
3
6
3
3
3
3
Average = 3.4 Average = 3.4
Conclusion: all cells have a parameter value of 3 or 4…
…Right?
A single-cell analysis would have enabled the detection of the
orange tumor cell, whereas an average measurement within the
population could not.
©2016 | www.yole.fr | Single Molecule & Single Cell Analysis Conference 2016
Let’s compare two cell populations…
Single-cell
analysis
enables the
identification
of cell
heterogeneity

13. 14
WHY SINGLE-CELL?
Through the
identification of
small but critical
changes from one
cell to another,
single-cell analysis
opens new life
science
opportunities
Single-cell genomics
and proteomics
Cancer research
Personalized medicine
©2016 | www.yole.fr | Single Molecule & Single Cell Analysis Conference 2016

14. 15
SINGLE-CELL ISOLATION TECHNOLOGIES
What we call
“classic”
methods
FACS Acoustic tweezers
Optical tweezers
Laser Capture
Microdissection
©2016 | www.yole.fr | Single Molecule & Single Cell Analysis Conference 2016

15. 16
SINGLE-CELL ISOLATION TECHNOLOGIES
Increasing
emergence of
microfluidic
methods
Droplet cell encapsulation
(picture: Dolomite Microfluidics)
Dielectrophoresis cell isolation
by Silicon Biosystems
Microstructure cell trapping
by Fluidigm
Significant advantages of microfluidic technologies:
• Precise environment control (easier to mimic in-vivo conditions)
• Small samples and low reagent volumes
• High-throughput (parallelization)
• Low shear stress
• Low to medium cost per experiment
• Enable automation
• Reduced risk of contamination using disposables
©2016 | www.yole.fr | Single Molecule & Single Cell Analysis Conference 2016

16. 17
THE RISE OF MICROFLUIDICS FOR SINGLE-CELL
The market is booming
We’ve reached
an inflection
point
CAGR 2016 - 2020: 18%
CAGR 2014 - 2016: 97%
©2016 | www.yole.fr | Single Molecule & Single Cell Analysis Conference 2016

17. 18
THE RISE OF MICROFLUIDICS FOR SINGLE-CELL
A very active field
A lot of things
recently
happened or
were announced
©2016 | www.yole.fr | Single Molecule & Single Cell Analysis Conference 2016
WaferGen launched its ICELL8 single-cell system (Sept. 2015)
NanoCellect raised $1.75M to begin production of the WOLF system (Feb.2016)
Fluidigm announces the new Polaris™ system (Feb. 2015)
Bio-Rad and Illumina announce a collaboration to develop a
comprehensive solution for single-cell genomics (Jan. 2016)
Dolomite launched a microfluidic chip for the creation of single-cell libraries (Nov. 2015)
Cytena raised $1.1M (Apr. 2015)
Sphere Fluidics raised $7M for the development of the Cyto-Mine® system (Feb. 2016)
WaferGen raised $17.25M (Oct. 2015)

18. 19
THE RISE OF MICROFLUIDICS FOR SINGLE CELL
Why this sudden explosion?
A long path led
to this market
explosion
Unsatisfying
methods
Growing demand
Years of
R&D work
Technology
is now ready
Investors
confidence
1 2 3
456
Acquisitions
Startups
are created
CollaborationsNew solutions
arrive
©2016 | www.yole.fr | Single Molecule & Single Cell Analysis Conference 2016

19. 20
THE RISE OF MICROFLUIDICS FOR SINGLE-CELL
Microfluidic players (non-exhaustive list)
The competition
is strenghtening
TimeToday
©2016 | www.yole.fr | Single Molecule & Single Cell Analysis Conference 2016

20. 21
CURRENT OR FUTURE MICROFLUIDIC SOLUTIONS FOR SINGLE-CELL SAMPLE PREPARATION
(non exhaustive list)
Fluidigm C1™
Single-Cell Auto
Prep System
(microstructures)
Silicon Biosystems DEParray™
Cartridge (dielectrophoresis)
Sphere Fluidics Cyto-Mine®
(picodroplet technology)
Cytena cy-Clone Single-Cell Printer
Celsee Diagnostics
(formerly DeNovo Sciences)
Celsee PREP400 liquid biopsy sample
preparation platform
NanoCellect WOLF Cell
Sorter and its microfluidic chip
WaferGen ICELL8
Single-Cell System
(nanodispensing)
©2016 | www.yole.fr | Single Molecule & Single Cell Analysis Conference 2016

21. 22
WHAT’S NEXT?
Opportunities for microfluidic players at each level of the supply chain
Microfluidic
players all along
the supply chain
can benefit from
single-cell
developments
©2016 | www.yole.fr | Single Molecule & Single Cell Analysis Conference 2016
Fabs System developers
Downstream
applications providers

22. 23
WHAT’S NEXT?
Technical limitations
Microfluidics
look promising
and rapidly
improve
Droplet technologies
Microstructured traps
High throughput
Low precision (Poisson distribution)
High precision
Low throughput
Precision
Throughput
?
Improvement/combination
of existing?
New technology
development?
©2016 | www.yole.fr | Single Molecule & Single Cell Analysis Conference 2016

23. 24
WHAT’S NEXT?
Evolution of the competitive environment
Who will take
tomorrow’s
largest market
share?
?
2020
©2016 | www.yole.fr | Single Molecule & Single Cell Analysis Conference 2016

24. 25
SUMMARY AND CONCLUSION
• Microfluidic technologies are now ready to address single-cell challenges
• However, significant improvements are still required
• High double-digit growth rate
• Numerous new entrants and new solutions
• New opportunities for the whole microfluidics supply chain
• The cards will be redistributed among the players
©2016 | www.yole.fr | Single Molecule & Single Cell Analysis Conference 2016

25. 26
THANKS FORYOUR ATTENTION!
Please take a look at our websites www.yole.fr and www.i-micronews.com
To get a complete copy of the presentation, please feel free to come to me (Booth #13) for business cards exchange
MicrofluidicTechnologies for Sample Preparation 2015
Released in Nov. 2015 – More info on www.i-micronews.com
Microfluidic Applications 2015
Released in June 2015 – More info on www.i-micronews.com
Some slides from this presentation were extracted from the following reports
©2016 | www.yole.fr | Single Molecule & Single Cell Analysis Conference 2016

26. Yole Développement
Market, technology and strategy consulting
©2016 | www.yole.fr | Single Molecule & Single Cell Analysis Conference 2016

27. 29
4 BUSINESS MODELS
o Consulting and Analysis
• Market data & research, marketing analysis
• Technology analysis
• Strategy consulting
• Reverse engineering & costing
• Patent analysis
www.yole.fr
o Reports
• Market &Technology reports
• Patent Investigation and patent infringement risk
analysis
• Teardowns & Reverse Costing Analysis
• Cost SimulationTool
www.i-Micronews.com/reports
o Financial services
• M&A (buying and selling)
• Due diligence
• Fundraising
• Maturation of companies
• IP portfolio management & optimization
www.yolefinance.com
www.bmorpho.com
o Media
• i-Micronews.com website
• @Micronews e-newsletter
• Communication & webcast services
• Events
www.i-Micronews.com
©2016 | www.yole.fr | Single Molecule & Single Cell Analysis Conference 2016

28. 30
A GROUP OF COMPANIES
Market,
technology and
strategy
consulting
www.yole.fr
M&A operations
Due diligences
www.yolefinance.com
Innovation and business maker
www.bmorpho.com
Manufacturing costs analysis
Teardown and reverse engineering
Cost simulation tools
www.systemplus.fr
IP analysis
Patent assessment
www.knowmade.fr
©2016 | www.yole.fr | Single Molecule & Single Cell Analysis Conference 2016

29. 32
SERVING THE ENTIRE SUPPLY CHAIN
Our analysts
provide
market
analysis,
technology
evaluation,
and business
plan along
the entire
supply chain
Integrators and
end-users
Device
makers
Suppliers: material,
equipment, OSAT,
foundries…
Financial investors,
R&D centers
©2016 | www.yole.fr | Single Molecule & Single Cell Analysis Conference 2016

30. 33
CONTACT INFORMATION
Follow us on
• Consulting and Specific Analysis
• North America: Steve LaFerriere, Director of Northern America Business Development
Email: laferriere@yole.fr
• Japan & Asia:Takashi Onozawa, Representative Director,Yole KK
Email: onozawa@yole.fr
• RoW: Jean-Christophe Eloy, CEO & President,Yole Développement
Email eloy@yole.fr
• Report business
• North America: Steve LaFerriere, Director of Northern America Business Development
Email: laferriere@yole.fr
• Europe: Fayçal El Khamassi, Headquarter Sales Coordination & Customer Service
Email: khamassi@yole.fr
• Japan & Asia:Takashi Onozawa, Representative Director,Yole KK.
Email: onozawa@yole.fr
• Korea: HaileyYang, Business Development Manager, Korean Office
Email: yang@yole.fr
• Taiwan: Mavis Wang, Business Development Director
Email: wang@yole.fr
• Financial services
• Jean-Christophe Eloy, CEO & President
Email: eloy@yole.fr
• General
• Email: info@yole.fr
©2016 | www.yole.fr | Single Molecule & Single Cell Analysis Conference 2016