title: Fluidic Logic Used in a Systems Approach to Enable Integrated Single-Cell Functional Analysis.
abstract: The study of single cells has evolved over the past several years to include expression and genomic analysis of an increasing number of single cells. Several studies have demonstrated wide spread variation and heterogeneity within cell populations of similar phenotype. While the characterization of these populations will likely set the foundation for our understanding of genomic- and expression-based diversity, it will not be able to link the functional differences of a single cell to its underlying genomic structure and activity. Currently, it is difficult to perturb single cells in a controlled environment, monitor and measure the response due to perturbation, and link these response measurements to downstream genomic and transcriptomic analysis. In order to address this challenge, we developed a platform to integrate and miniaturize many of the experimental steps required to study single-cell function. The heart of this platform is an elastomer-based integrated fluidic circuit that uses fluidic logic to select and sequester specific single cells based on a phenotypic trait for downstream experimentation. Experiments with sequestered cells that have been performed include on-chip culture, exposure to various stimulants, and post-exposure image-based response analysis, followed by preparation of the mRNA transcriptome for massively parallel sequencing analysis. The flexible system embodies experimental design and execution that enable routine functional studies of single cells.
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Naveen
authors.initials: N
authors.lastname: Ramalingam
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Fowler
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Szpankowski
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Anne A
authors.initials: AA
authors.lastname: Leyrat
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Hukari
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Myo Thu
authors.initials: MT
authors.lastname: Maung
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Wiganda
authors.initials: W
authors.lastname: Yorza
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Norris
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Cesar
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Joe
authors.initials: J
authors.lastname: Shuga
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Gonzales
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Chad D
authors.initials: CD
authors.lastname: Sanada
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Rudy
authors.initials: R
authors.lastname: Yeung
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Win
authors.initials: W
authors.lastname: Hwang
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Axsom
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Naga Sai Gopi Krishna
authors.initials: NS
authors.lastname: Devaraju
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Ninez Delos
authors.initials: ND
authors.lastname: Angeles
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Cassandra
authors.initials: C
authors.lastname: Greene
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Ming-Fang
authors.initials: MF
authors.lastname: Zhou
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Eng-Seng
authors.initials: ES
authors.lastname: Ong
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Chang-Chee
authors.initials: CC
authors.lastname: Poh
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Marcos
authors.initials: M
authors.lastname: Lam
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Henry
authors.initials: H
authors.lastname: Choi
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Zaw
authors.initials: Z
authors.lastname: Htoo
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Leo
authors.initials: L
authors.lastname: Lee
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Chee-Sing
authors.initials: CS
authors.lastname: Chin
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Zhong-Wei
authors.initials: ZW
authors.lastname: Shen
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Chong T
authors.initials: CT
authors.lastname: Lu
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Ilona
authors.initials: I
authors.lastname: Holcomb
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Aik
authors.initials: A
authors.lastname: Ooi
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Craig
authors.initials: C
authors.lastname: Stolarczyk
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Tony
authors.initials: T
authors.lastname: Shuga
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Livak
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Cate
authors.initials: C
authors.lastname: Larsen
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Unger
authors.affiliation: New Technologies Research Department, Fluidigm Corporation , South San Francisco, CA , USA.
authors.forename: Jay A A
authors.initials: JA
authors.lastname: West
keywords: Fluidigm; Polaris; functional studies; mRNA-seq; single-cell