Clinical microfluidics for neutrophil genomics and proteomics

被引:129
作者
Kotz, Kenneth T. [1 ]
Xiao, Wenzong [1 ,2 ]
Miller-Graziano, Carol [3 ]
Qian, Wei-Jun [4 ,5 ]
Russom, Aman [1 ]
Warner, Elizabeth A. [6 ]
Moldawer, Lyle L. [6 ]
De, Asit [3 ]
Bankey, Paul E. [3 ]
Petritis, Brianne O. [4 ,5 ]
Camp, David G., II [4 ,5 ]
Rosenbach, Alan E. [1 ]
Goverman, Jeremy [1 ]
Fagan, Shawn P. [1 ]
Brownstein, Bernard H. [7 ]
Irimia, Daniel [1 ]
Xu, Weihong [2 ]
Wilhelmy, Julie [2 ]
Mindrinos, Michael N. [2 ]
Smith, Richard D. [4 ,5 ]
Davis, Ronald W. [2 ]
Tompkins, Ronald G. [1 ]
Toner, Mehmet [1 ]
机构
[1] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Shriners Hosp Children,Dept Surg, Boston, MA 02115 USA
[2] Stanford Genome Technol Ctr, Palo Alto, CA USA
[3] Univ Rochester, Sch Med, Dept Surg, Rochester, NY USA
[4] Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99352 USA
[5] Pacific NW Natl Lab, Environm Mol Sci Lab, Richland, WA 99352 USA
[6] Univ Florida, Coll Med, Dept Surg, Gainesville, FL USA
[7] Washington Univ, Dept Radiat Oncol, St Louis, MO USA
基金
美国国家卫生研究院;
关键词
T-CELL; EXPRESSION; LIPOPOLYSACCHARIDE; MASS; ACTIVATION; BLOOD; CHALLENGES; APOPTOSIS; SUBSETS; PATHWAY;
D O I
10.1038/nm.2205
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Neutrophils have key roles in modulating the immune response. We present a robust methodology for rapidly isolating neutrophils directly from whole blood with 'on-chip' processing for mRNA and protein isolation for genomics and proteomics. We validate this device with an ex vivo stimulation experiment and by comparison with standard bulk isolation methodologies. Last, we implement this tool as part of a near-patient blood processing system within a multi-center clinical study of the immune response to severe trauma and burn injury. The preliminary results from a small cohort of subjects in our study and healthy controls show a unique time-dependent gene expression pattern clearly demonstrating the ability of this tool to discriminate temporal transcriptional events of neutrophils within a clinical setting.
引用
收藏
页码:1042 / U142
页数:7
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