Pursuing single cells: a story of the future of biology

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Pursuing single cells: a story of the future of biology
Pursuing single cells:
a story of the future of biology
Gajus Worthington
Founder and CEO
Cowen Health Care Conference 2015
Forward looking statements
This presentation contains statements that are forward-looking within the meaning of the Private Securities Litigation
Reform Act of 1995, including statements regarding Fluidigm’s business, objectives, expectations and/or strategies;
expectations for the development and growth of the single-cell biology and production genomics markets; Fluidigm’s
new products and expectations and/or strategies relating to such new products; and current estimates of 2015 total
revenue, GAAP and non-GAAP operating expenses, stock-based compensation expense, interest expense, capital
spending, and currency related impact on 2015 revenue; and the future growth of our business. Statements that are not
purely historical are forward looking statements. These statements may contain words such as "believe,” “may,” “will,”
“estimate,” “continue,” “anticipate,” “intend,” “expect” and similar expressions.
Forward-looking statements are subject to numerous risks and uncertainties that could cause actual results to differ
materially from currently anticipated results, including but not limited to, risks relating to the future financial performance
of Fluidigm’s proteomics and genomics product lines; the possible loss of key employees, customers, or suppliers;
intellectual property risks arising from the recent acquisition, including risks relating to maintaining material in-licensed
intellectual property rights; challenges inherent in developing, manufacturing, launching, marketing, and selling new
products; competition; its sales, marketing and distribution capabilities; its planned sales, marketing, and research and
development activities; reduction in research and development spending or changes in budget priorities by customers;
interruptions or delays in the supply of components or materials for, or manufacturing of, its products; seasonal
variations in customer operations; unanticipated increases in costs or expenses; and risks associated with international
operations. Information on these and additional risks, uncertainties, and other information affecting Fluidigm’s business
and operating results are contained in its Annual Report on Form 10-K for the year ended December 31, 2014 and other
filings with the Securities and Exchange Commission. These forward-looking statements speak only as of the date
hereof. Fluidigm Corporation disclaims any obligation to update these forward-looking statements except as may be
required by law.
***
Fluidigm, the Fluidigm logo, C1, Biomark, EP1, Access Array, CyTOF, Juno, Calisto, Polaris, and Singular are trademarks
or registered trademarks of Fluidigm Corporation.
Number of cells Population averages can mislead
average
Transcripts per cell Real-world example:
splice variants in PBMCs
Single cells
Density
1.0
average
0.5
0
0
Shalek et al, Nature 2013
50
100
Real-world example:
splice variants in PBMCs
10,000 cells
Density
1.0
0.5
0
0
Shalek et al, Nature 2013
50
100
Gene B
Bulk gene expression
Gene A
A, B fully correlated
Gene B
Gene B
Single-cell gene expression
Gene A
Gene A
A, B fully correlated
A, B anticorrelated
Real world example: CD4+ T-cells
Dominguez et al, J Immunological Methods, 2013
“It is not a simple life to be a single cell, although I
have no right to say so, having been a single cell
so long ago myself that I have no memory at all of
that stage in my life.”
Lewis Thomas
Biological relevance
of heterogeneity
7000 single cells analyzed Newell et al., Immunity 36, 142 (2012) Single cell biology impacts
many areas of research
Stem Cell Research Developmental Biology Immunology Cancer Neurobiology Over 200 single cell publications using
Fluidigm technology for single cell biology
Fluidigm’s contribution
through innovation
Biomark
The first genomics system with
the throughput, flexibility and sensitivity
required for single-cell studies
C1
The first system to automate and integrate
cell capture and processing for RNA, DNA
and miRNA analysis
CyTOF2
The only commercial mass cytometer,
enabling high-throughput, highlyparametric single-cell protein
expression profiling
A PCA view of our single-cell
product portfolio
Proteins
CyTOF2
mRNA
Whole Genome
Biomark
C1
Whole Exome
Targeted Seq
miRNA
100
1,000
10K
Single cells per experiment
100K
How deep does the immune system go?
5
1
2
3
4
Enrich
T-cells
mRNA
Prep
mRNA
Seq
T-Cell
Gene
Validation Confirmation
C1
Biomark
CyTOF
How does cancer regenerate?
5
1
2
3
4
Enrich
Cancer
Stem
Cells
mRNA
Prep
mRNA
Seq
CSCs in
CSC
Blood &
Pathway
Validation Biopsy
C1
Biomark
CyTOF
What’s next?
A PCA view of our single-cell
product portfolio
Proteins
CyTOF2
mRNA
Whole Genome
Biomark
C1
Whole Exome
Targeted Seq
miRNA
100
1,000
10K
Single cells per experiment
100K
The need to scale
C1 mRNA Seq HT defines a new benchmark
single-cell transcriptomics
Throughput, workflow and chemistry innovations make large
studies (~10K cells) readily accessible. Available on 1H ‘15
Cell fate and function is mediated by a
complex environment
Moustakas and Heldin , Development 2009;136:3699-­‐3714. The regula:on of TGFβ signal transduc:on.
What about the biological niche?
Polaris: control of the biological niche
with single-cell genomics
Enabling control of the single cell
environment
1
2
3
4
5
4-parameter
single-cell
selection
Culture
Dosing
Single-cell
Library
prep
Expression
Sequence
miRNA
Polaris 1.0
Enabling control of the single cell
environment
1
2
3
4
5
4-parameter
single-cell
selection
Culture
Dosing
Single-cell
Library
prep
Expression
Sequence
miRNA
Cells in parJJon for selecJon X X ü
ü
X Enabling control of the single cell
environment
2
3
4
5
4-parameter
single-cell
selection
Culture
Dosing
Single-cell
Library
prep
Expression
Sequence
miRNA
Polaris Image -­‐ FAM 1
Captured Captured Empty Enabling control of the single cell
environment
1
2
3
4
5
4-parameter
single-cell
selection
Culture
Dosing
Single-cell
Library
prep
Expression
Sequence
miRNA
Enabling control of the single cell
environment
1
2
3
4
5
4-parameter
single-cell
selection
Culture
Dosing
Single-cell
Library
prep
Expression
Sequence
miRNA
Enabling deliberate single cell assembly
and genomics analysis
1
2
3
4
5
4-parameter
single-cell
selection
Multi-cell
binning
Culture &
Dosing
Single-cell
Library
prep
Expression
Sequence
miRNA
Polaris 2.0
With Polaris: Integrate cell selecJon, dose response, Jme course studies and quanJtaJve gene expression preparaJon into a single system. Correlate gene expression with phenotypic informaJon and discover the molecular pathways that regulate cell funcJon. Execute needed funcJonal studies that were previously impossible. Simplify the
complex quest to
understand and
apply biology.

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