Nano-bio-chips for high performance multiplexed protein detection: Determinations of cancer biomarkers in serum and saliva using quantum dot bioconjugate labels

• Published in: Biosensors & bioelectronics Vol. 24; no. 12; pp. 3622 - 3629
• Main Authors: Jokerst, Jesse V., Raamanathan, Archana, Christodoulides, Nicolaos, Floriano, Pierre N., Pollard, Amanda A., Simmons, Glennon W., Wong, Jorge, Gage, Carole, Furmaga, Wieslaw B., Redding, Spencer W., McDevitt, John T.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 15-08-2009; Elsevier
• Subjects: Biological and medical sciences; Biomarkers, Tumor - analysis; Biosensing Techniques - instrumentation; Biotechnology; Blood Chemical Analysis - instrumentation; Cancer biomarkers; Equipment Design; Equipment Failure Analysis; Fundamental and applied biological sciences. Psychology; Humans; Lab-on-a-chip; Nano-bio-chip; Nanotechnology - instrumentation; Neoplasm Proteins - analysis; Neoplasms - diagnosis; Neoplasms - metabolism; Point-of-care; Protein Array Analysis - instrumentation; Quantum Dots; Saliva - chemistry; Salivary diagnostics; Spectrometry, Fluorescence - instrumentation; Staining and Labeling - methods; Cancer biomarkers; Lab-on-a-chip; Salivary diagnostics; Point-of-care; Quantum dots; Nano-bio-chip; Quantum dot; Biological marker; System on a chip; Malignant tumor; Protein; Serum; Diagnosis; Detection; Saliva; Cancer
• ISSN: 0956-5663; 1873-4235
• DOI: 10.1016/j.bios.2009.05.026

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.