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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

2

Presentation Overview

Backgound & introduction to illumina

Technology to acquire a genetic sequence

Impact on medicine

Concluding remarks

3

All Living Organisms Contain DNA

Bacteria

Plants

Humans

Animals

Isolated DNA

4

Genetically we are very close to other life forms:

5

98% similar to Chimpanzees

6

90% similar to Mice

7

85% similar to zebra fish

8

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…

9

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

10

If you were to start reciting out load your

genome sequence, A,C,G,T

before you reached

the end…

11

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!

12

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

13

DNA: Nature’s Nanotechnology

~2 nm

~3.5 B Bases in each of our genomes

0.2 nm

14

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

15

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

16

Our Mission

To improve human health by unlocking the power of the genome

17

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™

18

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

19

What is the Secret Sauce?

Scalable/extensible

technology

Committed and driven

organization

An engaged community

20

Camera Design

Technology Elements

Surface Chemistry

Sequencing Chemistry

Nanofabrication

Flowcell Manufacturing

Optical Design

Fluidic Design

Software

21

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

22

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.

23

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

24

Patterned Flowcells in Action

HiSeq X image of DNA clusters in a patterned flowcell

25

Conceptual challenge

Beating Poisson

Maximizing well occupancy

and monoclonality

Amplification challenge:

• Random arrays are fundamentally monoclonal

• Ordered arrays require one library seed/nanowell

26

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

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

28

Flowcell Bonding Surface chemistry requires nonconventional processing conditions

Interposer

Glass – interposer interface

Chemically

Patterned glass

wafers

Glass – interposer interface

29

Impact Who We Serve

Research

Forensics Agriculture

Complex Disease

Reproductive Health Oncology

Consumer

Genetic Health BioPharm

Infectious Disease

Population Sequencing

30

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

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…

32

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

33

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

Demand for Sequencing is Increasing…

Nature, Vol. 527, 5 November 2015

35

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.

Thank You

37

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

38

Project Firefly

Low capital cost Ultra-high reliability

Extreme ease of use Customer installation

Small footprint

39

Sequencing on CMOS

40

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