title: Nano-bio-chips for high performance multiplexed protein detection: determinations of cancer biomarkers in serum and saliva using quantum dot bioconjugate labels.
abstract: The integration of semiconductor nanoparticle quantum dots (QDs) into a modular, microfluidic biosensor for the multiplexed quantitation of three important cancer markers, carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), and Her-2/Neu (C-erbB-2) was achieved. The functionality of the integrated sample processing, analyte capture and detection modalities was demonstrated using both serum and whole saliva specimens. Here, nano-bio-chips that employed a fluorescence transduction signal with QD-labeled detecting antibody were used in combination with antigen capture by a microporous agarose bead array supported within a microfluidics ensemble so as to complete the sandwich-type immunoassay. The utilization of QD probes in this miniaturized biosensor format resulted in signal amplification 30 times relative to that of standard molecular fluorophores as well as affording a reduction in observed limits of detection by nearly 2 orders of magnitude (0.02 ng/mL CEA; 0.11 pM CEA) relative to enzyme-linked immunosorbent assay (ELISA). Assay validation studies indicate that measurements by the nano-bio-chip system correlate to standard methods at R(2)=0.94 and R(2)=0.95 for saliva and serum, respectively. This integrated nano-bio-chip assay system, in tandem with next-generation fluorophores, promises to be a sensitive, multiplexed tool for important diagnostic and prognostic applications.
authors: Department of Chemistry and Biochemistry, University of Texas at Austin, 1 University Station A5300, Austin, TX 78712, USA.
authors: Jesse V
authors: JV
authors: Jokerst
authors: Archana
authors: A
authors: Raamanathan
authors: Nicolaos
authors: N
authors: Christodoulides
authors: Pierre N
authors: PN
authors: Floriano
authors: Amanda A
authors: AA
authors: Pollard
authors: Glennon W
authors: GW
authors: Simmons
authors: Jorge
authors: J
authors: Wong
authors: Carole
authors: C
authors: Gage
authors: Wieslaw B
authors: WB
authors: Furmaga
authors: Spencer W
authors: SW
authors: Redding
authors: John T
authors: JT
authors: McDevitt
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D015374:Biosensing Techniques / Q000295:instrumentation; D001774:Blood Chemical Analysis / Q000295:instrumentation*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D006801:Humans; D036103:Nanotechnology / Q000295:instrumentation*; D009363:Neoplasm Proteins / Q000032:analysis*; D009369:Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D040081:Protein Array Analysis / Q000295:instrumentation*; D045663:Quantum Dots; D012463:Saliva / Q000737:chemistry*; D013050:Spectrometry, Fluorescence / Q000295:instrumentation; D013194:Staining and Labeling / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins