nanotechnology for a genomic revolution€¦ · financials $2.22 b 19 % 2015 revenue revenue growth...
TRANSCRIPT
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© 2016 Illumina, Inc. All rights reserved.
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HiSeq X, Infinium, iScan, iSelect, MiniSeq, MiSeq, MiSeqDx, MiSeq FGx, NeoPrep, NextBio, Nextera, NextSeq, Powered by Illumina, SureMDA, TruGenome, TruSeq, TruSight, Understand Your Genome,
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and other trademarks are the property of their respective owners.
illumina
Nanotechnology for a Genomic Revolution
Shane Bowen, PhD
Director, Scientific Research
Department of Research and Technology Development
International MicroNano Conference
Amsterdam, December 14, 2016
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Presentation Overview
Backgound & introduction to illumina
Technology to acquire a genetic sequence
Impact on medicine
Concluding remarks
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All Living Organisms Contain DNA
Bacteria
Plants
Humans
Animals
Isolated DNA
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Genetically we are very close to other life forms:
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98% similar to Chimpanzees
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90% similar to Mice
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85% similar to zebra fish
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If all of the DNA from all of your cells was stretched out into a single thread, it would extend -
Back and forth from the moon (239,900 miles) about…
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If all of the DNA from all of your cells was stretched out into a single thread, it would extend -
Back and forth from the moon (239,900 miles) about one million times
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If you were to start reciting out load your
genome sequence, A,C,G,T
before you reached
the end…
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If you were to start reciting out load your
genome sequence, A,C,G,T
before you reached
the end…
57 years would
have passed!
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DNA double helix
The four bases:
• Adenine
• Cytosine
• Thymine
• Guanine
Chromosome
Coiled DNA
Understanding Genomics Genomics seeks to understand the structure, function, evolution
and mapping of genomes
DNA provides the “blue-print of life”
All of your DNA is called your genome
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DNA: Nature’s Nanotechnology
~2 nm
~3.5 B Bases in each of our genomes
0.2 nm
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Our Background
FINANCIALS
$2.22B 19% 2015 Revenue Revenue Growth YOY
AWARDS
SMARTEST COMPANY 2014 MIT TECHNOLOGY REVIEW
10 BREAKTHROUGH
TECHNOLOGIES
2013 MIT TECHNOLOGY REVIEW
12 MOST DISRUPTIVE
NAMES IN BUSINESS
2013 FORBES
TOP 10 INNOVATIONS
2015 THE SCIENTIST MAGAZINE
TOP 10 INNOVATIONS
2012 THE SCIENTIST MAGAZINE
FASTEST GROWING
TECH COMPANIES
2010 FORBES
COMPANY
Fall, 1998 FOUNDED
July 27, 2000 IPO
>5,000 EMPLOYEES
San Diego, CA HEADQUARTERS 20
Francis deSouza President and CEO
OFFICES
GLOBALLY
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Global Organization
Tokyo, Osaka (2) Japan
Shanghai China
Eindhoven Netherlands
Beijing China
Cambridge (3) United Kingdom
Singapore (2)
Victoria, BC Canada
San Diego, CA (2) United States (headquarters)
Melbourne Australia
Madison, WI
United States
São Paulo Brazil
San Francisco Bay Area, CA (4) United States
Commercial
Manufacturing/R&D
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Our Mission
To improve human health by unlocking the power of the genome
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Illumina Platforms SEQUENCING SYSTEMS | Sequencing by Synthesis (SBS)
FLEXIBLE POWER
NextSeq™ 500/550
POPULATION POWER
HiSeq X™ Five/Ten
PRODUCTION POWER
HiSeq® 2500/3000/4000
ARRAY SCANNER | Infinium
CUTTING-EDGE ARRAY SCANNER
iScan®
* For in vitro diagnostic use
FOCUSED POWER
MiSeq®, MiSeqDx™*, MiSeqFGx™
MiniSeq™
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The Human Genome Project: Genomic Revolution
1990-2003
13 years
~40 Institutions
8-9X Coverage
$3.8 Billion
Illumina’s HiSeq X Platform
1 instrument, 72 hours,<1 FTE
16 Genomes at 30X coverage
$1000/genome
Approximately the output of the
entire, 13-year HGP in <5 hours
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What is the Secret Sauce?
Scalable/extensible
technology
Committed and driven
organization
An engaged community
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Camera Design
Technology Elements
Surface Chemistry
Sequencing Chemistry
Nanofabrication
Flowcell Manufacturing
Optical Design
Fluidic Design
Software
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Flowcell Architecture
• Three layer construction
• Glass – interposer – Glass
• Laser based bonding process
300um Glass coverslip / window
100um thick interposer
1000um Glass bottom with inlet/outlet vias
Fluidics interface from bottom
Optical Readout from top
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Fundamental Technical Advancement:
Chemical Patterning
Ordered array of clusters resulting from
patterned surface chemistry
Current distribution of clusters
resulting from random seeding of DNA
Nanofabrication process yields a
binary distribution of surface chemistry.
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Fabricating Patterned Flowcells
Photoresist
Substrate
Pattern resist
Pattern transfer
Strip resist
Silanize substrate
Spin coat hydrogel & link
Polish to isolate hydrogel
to nanowells
400 nm CD, 700 nm
pitch nanowell array
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Patterned Flowcells in Action
HiSeq X image of DNA clusters in a patterned flowcell
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Conceptual challenge
Beating Poisson
Maximizing well occupancy
and monoclonality
Amplification challenge:
• Random arrays are fundamentally monoclonal
• Ordered arrays require one library seed/nanowell
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Simultaneous Seeding
And Amplification
Maximizing well occupancy
and monoclonality
Exclusion Amplification
Amplification occurs at a rate >> seeding rate
Templates are excluded from occupied wells
Allows us to work with wells that are larger than the templates
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Benefits of Patterning Tunable Density, Higher Quality, Optimized Utilization of Materials
Pitch (Center to Center)
Defined feature shape
Ordered spacing
Tunable Density
Decrease feature Size
Defined feature shape
Tunable pitch
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Flowcell Bonding Surface chemistry requires nonconventional processing conditions
Interposer
Glass – interposer interface
Chemically
Patterned glass
wafers
Glass – interposer interface
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Impact Who We Serve
Research
Forensics Agriculture
Complex Disease
Reproductive Health Oncology
Consumer
Genetic Health BioPharm
Infectious Disease
Population Sequencing
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Impact What Can We Do by Knowing Your Genome?
Suggest predispositions
and symptoms Guide selection of drug choices
Help inform proactive
health management Provide family planning insight
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Impact What is Sequencing Doing for Medicine?
1. Stops the diagnostic odyssey
Setting the patient up for proper monitoring
2. Community connection
Patient with others fighting the same battle
Clinician network
3. Opens access to resources
Clinical trials
Changes management of treatment
~50% of those sequenced are receiving modified treatments and of those,
~50% are seeing an improvement in their quality of life.
This is only the beginning…
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The Latest in Population-Scale Sequencing Enabled by HiSeq X
™
’ s unmatched speed and throughput
$215M investment;
Calls for new era of
precision medicine
White House Initiative for Precision Medicine
$1B to accelerate 10
years of research to
just 5 years
US Cancer Moonshot Task Force
Sequence 100,000
genomes over 4 years
Genomics England China’s Precision Medicine Initiative
$10B over 15 years;
2 million people
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New Constructs to Accelerate Markets
Cancer Screening
GRAIL www.grailbio.com
Mission Enable the early detection of
cancer in asymptomatic individuals
through a blood screen.
Discover Your DNA Story
Consumer
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Demand for Sequencing is Increasing…
Nature, Vol. 527, 5 November 2015
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Closing Remarks
We have entered into an extremely exciting time for micro-, nano- and bio-
technology:
– Biggest impact is through collaboration across classically orthogonal disciplines.
New methods for manufacturing are enabling high-end functionality at
minimized cost
– Unique, relaxed requirements for bio-tech allow early adoption of these
processes / methods
Engineered materials will be the foundation of our next round of sensors
illumina is committed to driving these technologies forward.
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Thank You
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Price to Sequence a Human Genome
$100M
$10M
$1M
$100,000
$10,000
$1,000
$100
$10
$1,000
2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 201
1
2012 2013 2014 2015 2016
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Project Firefly
Low capital cost Ultra-high reliability
Extreme ease of use Customer installation
Small footprint
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Sequencing on CMOS
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CMOS Sensor with Nanowells
CMOS sensor
Flow channel
Top lid
Photodiode array
Nanowells
Optical Excitation
Passivation layer
Color filter
Silicon
State of the art CMOS imager technology
Nanowells fabricated over each photodiode
Excitation light blocking 1000X industry standard
Surface layer compatibility with SBS
Structural design for best in class inter pixel across talk