Editors' ChoiceMicrofluidic Technology

Molecular Snapshot

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Science Translational Medicine  15 Sep 2010:
Vol. 2, Issue 49, pp. 49ec144
DOI: 10.1126/scitranslmed.3001682

As first responders of the immune system, neutrophils play a key role in protecting against infections and modulating inflammatory responses. Gene regulation and signal activation within neutrophils therefore may provide valuable information regarding disease states characterized by inflammation. However, the isolation of neutrophils from peripheral blood samples has proven to be a technically challenging and time-consuming process. This problem prompted Kotz et al. to develop a more efficient procedure for the preparation of neutrophils for molecular profiling.

Building on microfluidic tools previously created for the isolation of cellular subsets from peripheral blood samples of people with HIV or metastatic cancer, the researchers designed a new device that captures neutrophils with high purity by means of cell-surface receptor recognition. The captured cells were then lysed in situ on the device in order to extract RNA and peptide samples for genomic and proteomic analyses. Neutrophils that had been activated with artificial stimuli were captured by the microfluidic cassette and readily distinguished from unstimulated neutrophils upon RNA and protein expression profiling. Lastly, to demonstrate the clinical utility of this technology, Kotz et al. implemented their protocol in a multicenter study designed to investigate genomic alterations after severe traumatic injury. Among samples from 26 trauma subjects and 10 healthy volunteers, the researchers were able to identify genes that were differentially expressed during the initial 4-week period after injury.

Using microfluidic technology, Kotz et al. have designed a device capable of isolating neutrophils from a small volume of whole blood for genome-wide microarray and mass spectrometry–based proteomic analyses. The resultant genomic and proteomic samples were of sufficiently high quality to discern the subtle differences in neutrophil activation states. This approach may be clinically applicable for diagnosis and therapeutic monitoring of conditions characterized by inflammation and may also be easily adaptable for molecular profiling of other cell types.

K. T. Kotz et al., Clinical microfluidics for neutrophil genomics and proteomics. Nat. Med. 16, 1042–1047 (2010). [Abstract]

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