Integrated barcode chips for rapid, multiplexed analysis of proteins in microliter quantities of blood
Abstract
As the tissue that contains the largest representation of the human proteome [1], blood is the most important fluid for clinical diagnostics [2, 3, 4]. However, although changes of plasma protein profiles reflect physiological or pathological conditions associated with many human diseases, only a handful of plasma proteins are routinely used in clinical tests. Reasons for this include the intrinsic complexity of the plasma proteome [1], the heterogeneity of human diseases and the rapid degradation of proteins in sampled blood [5]. We report an integrated microfluidic system, the integrated blood barcode chip that can sensitively sample a large panel of protein biomarkers over broad concentration ranges and within 10 min of sample collection. It enables on-chip blood separation and rapid measurement of a panel of plasma proteins from quantities of whole blood as small as those obtained by a finger prick. Our device holds potential for inexpensive, noninvasive and informative clinical diagnoses, particularly in point-of-care settings.
Additional Information
© 2008 Nature Publishing Group. Received 21 July; accepted 21 October; published online 16 November 2008; doi:10.1038/nbt.1507. The authors thank Larry Nagahara and Chris McLeland at the National Cancer Institute (NCI) for providing standard hCG serum samples and requesting the independent hCG measurement. We also thank Bruz Marzolf at the Institute for Systems Biology (Seattle) for printing DNA microarrays, and the UCLA nanolab for photomask fabrication. This work was funded by the National Cancer Institute grant no. 5U54 CA119347 (J.R.H., P.I.) and by the Institute for Collaborative Biotechnologies through grant DAAD19-03-D-0004 from the US Army Research Office. Author contributions: R.F. developed and validated the DEAL barcode assay, measured cancer patient serum samples and analyzed all data. O.V. and B.K.H.Y. developed the blood separation chip. O.V., A.S. and L.Q. performed finger-prick blood test. R.F., O.V., A.S., H.A., G.A.K., C.-C.L. and J.G. participated in the synthesis and validation of reagents and the patterning of DNA barcode microarrays. L.H. and J.R.H. designed and directed the project. Full methods and other supporting data are available in Supplementary Methods and Supplementary Data online. Note: Supplementary information is available on the Nature Biotechnology website. Declaration: J.R.H. and L.H. are co-founders of Integrated Diagnostics, a company that has acquired the rights to license certain of the technologies described in this paper.Attached Files
Accepted Version - nihms-75277.pdf
Supplemental Material - FANnb08movie.wmv
Supplemental Material - FANnb08suppfigs.pdf
Files
Additional details
- PMCID
- PMC2775523
- Eprint ID
- 12844
- DOI
- 10.1038/nbt.1507
- Resolver ID
- CaltechAUTHORS:FANnb08
- 5U54 CA119347
- National Cancer Institute
- DAAD19-03-D-0004
- Army Research Office (ARO)
- Created
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2009-01-15Created from EPrint's datestamp field
- Updated
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2021-11-08Created from EPrint's last_modified field