Editors' ChoiceNanotechnology

Sifting for Diagnostic Gold

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Science Translational Medicine  12 Mar 2014:
Vol. 6, Issue 227, pp. 227ec44
DOI: 10.1126/scitranslmed.3008861

Endogenous serum peptides hold great promise as disease biomarkers; however, detecting low-abundance peptides among more highly abundant and larger proteins is a challenge that prevents clinical application of assays for these markers. Such is the case for the bioactive form of hepcidin (Hep-25), a hormone peptide whose serum concentration is linked to various iron-related diseases, and for which there is no U.S. Food and Drug Administration–approved detection assay. Antibody detection of this protein lacks isoform specificity, and mass spectroscopy–based methods are time-consuming and labor-intensive. Fan and colleagues have developed a nanoporous silica (NPS) thin film that is capable of enriching the key hepcidin isoform, Hep-25, from blood and urine samples and can serve as an important step in the development of a commercially and clinically viable assay for detection of low-abundant biomarker peptides from biological fluids.

Using a triblock copolymer that forms organized mesostructures in the presence of increasing silicate surfactant concentrations, NPS thin films can be further customized for pore size, and their shapes optimized for enrichment of the desired peptides. Comparing human urine and serum samples by means of mass spectroscopy before and after mesoporous chip enrichment, the authors demonstrated that the mesoporous chips were capable of enriching for previously undetectable amounts of Hep-25. Applying this method to clinical samples from healthy volunteers and patients suffering from a variety of inflammatory conditions, the authors were able to identify increased concentrations of Hep-25 in patients suffering from inflammation as well as in post-menopausal women.

This work demonstrates the clinical potential of using label-free nanopore structures in enriching for low-abundance serum peptides. The addition of this enrichment device improves the speed of sample preparation as well as the sensitivity of current detection methods. Integration of this mesoporous chip into a more user-friendly system of detection will further speed acceptance of this device into the clinic. In addition to Hep-25, however, this work should enhance biomarker detection of endogenous peptides for a wide range of diseases.

J. Fan et al., Nanopore film based enrichment and quantification of low abundance hepcidin from human bodily fluids. Nanomed. Nanotechnol. Biol. Med., published online 24 February 2014 (10.1016/j.nano.2014.02.005). [Abstract]

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