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

Jesse V. Jokerst; Archana Raamanathan; Nicolaos Christodoulides; Pierre N. Floriano; Amanda A. Pollard; Glennon W. Simmons; Jorge Wong; Carole Gage; Wieslaw B. Furmaga; Spencer W. Redding; John T. McDevitt

doi:10.1016/j.bios.2009.05.026

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

Jesse V. Jokerst, Archana Raamanathan, Nicolaos Christodoulides, Pierre N. Floriano, Amanda A. Pollard, Glennon W. Simmons, Jorge Wong, Carole Gage, Wieslaw B. Furmaga, Spencer W. Redding, John T. McDevitt

Research output: Contribution to journal › Article › peer-review

231 Scopus citations

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 R² = 0.94 and R² = 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.

Original language	English (US)
Pages (from-to)	3622-3629
Number of pages	8
Journal	Biosensors and Bioelectronics
Volume	24
Issue number	12
DOIs	https://doi.org/10.1016/j.bios.2009.05.026
State	Published - Aug 15 2009

Keywords

Cancer biomarkers
Lab-on-a-chip
Nano-bio-chip
Point-of-care
Quantum dots
Salivary diagnostics

ASJC Scopus subject areas

Biotechnology
Biophysics
Biomedical Engineering
Electrochemistry

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10.1016/j.bios.2009.05.026

Cite this

Jokerst, J. V., Raamanathan, A., Christodoulides, N., Floriano, P. N., Pollard, A. A., Simmons, G. W., Wong, J., Gage, C., Furmaga, W. B., Redding, S. W., & McDevitt, J. T. (2009). Nano-bio-chips for high performance multiplexed protein detection: Determinations of cancer biomarkers in serum and saliva using quantum dot bioconjugate labels. Biosensors and Bioelectronics, 24(12), 3622-3629. https://doi.org/10.1016/j.bios.2009.05.026

Nano-bio-chips for high performance multiplexed protein detection: Determinations of cancer biomarkers in serum and saliva using quantum dot bioconjugate labels. / Jokerst, Jesse V.; Raamanathan, Archana; Christodoulides, Nicolaos et al.
In: Biosensors and Bioelectronics, Vol. 24, No. 12, 15.08.2009, p. 3622-3629.

Research output: Contribution to journal › Article › peer-review

Jokerst, JV, Raamanathan, A, Christodoulides, N, Floriano, PN, Pollard, AA, Simmons, GW, Wong, J, Gage, C, Furmaga, WB, Redding, SW & McDevitt, JT 2009, 'Nano-bio-chips for high performance multiplexed protein detection: Determinations of cancer biomarkers in serum and saliva using quantum dot bioconjugate labels', Biosensors and Bioelectronics, vol. 24, no. 12, pp. 3622-3629. https://doi.org/10.1016/j.bios.2009.05.026

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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 R2 = 0.94 and R2 = 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.",

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note = "Funding Information: The authors acknowledge funding provided by the National Institutes of Health through the National Institute of Dental and Craniofacial Research (U01 DE017793). The content is solely the responsibility of the authors and does not necessarily represent or reflect views of the NIH or the Federal Government. Support was also provided by a private gift to UTHSCSA. ",

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AU - Christodoulides, Nicolaos

AU - Floriano, Pierre N.

AU - Pollard, Amanda A.

AU - Simmons, Glennon W.

AU - Wong, Jorge

AU - Gage, Carole

AU - Furmaga, Wieslaw B.

AU - Redding, Spencer W.

AU - McDevitt, John T.

N1 - Funding Information: The authors acknowledge funding provided by the National Institutes of Health through the National Institute of Dental and Craniofacial Research (U01 DE017793). The content is solely the responsibility of the authors and does not necessarily represent or reflect views of the NIH or the Federal Government. Support was also provided by a private gift to UTHSCSA.

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N2 - 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 R2 = 0.94 and R2 = 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.

AB - 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 R2 = 0.94 and R2 = 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.

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

Abstract

Keywords

ASJC Scopus subject areas

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