Application of microchip assay system for the measurement of C-reactive protein in human saliva

Nicolaos Christodoulides, Sanghamitra Mohanty, Craig S. Miller, M. Chris Langub, Pierre N. Floriano, Priya Dharshan, Mehnaaz F. Ali, Bruce Bernard, Dwight Romanovicz, Eric Anslyn, Philip C. Fox, John McDevitt

Research output: Contribution to journalArticle

Abstract

In the last decade, saliva has been advocated as a non-invasive alternative to blood as a diagnostic fluid. However, use of saliva has been hindered by the inadequate sensitivity of current methods to detect the lower salivary concentrations of many constituents compared to serum. Furthermore, developments in the areas related to lab-on-a-chip systems for saliva-based point of care diagnostics are complicated by the high viscocity and heterogeneous properties associated with this diagnostic fluid. The biomarker C-reactive protein (CRP) is an acute phase reactant and a well-accepted indicator of inflammation. Numerous clinical studies have established elevated serum CRP as a strong, independent risk factor for the development of cardiovascular disease (CVD). CVD has also been associated with oral infections (i.e. periodontal diseases) and there is evidence that systemic CRP may be a link between the two. Clinical measurements of CRP in serum are currently performed with "high sensitivity" CRP (hsCRP) enzyme-linked immunosorbent assay (ELISA) tests that lack the sensitivity for the detection of this important biomarker in saliva. Because measurement of salivary CRP may represent a novel approach for diagnosing and monitoring chronic inflammatory disease, including CVD and periodontal diseases, the objective of this study was to apply an ultra-sensitive microchip assay system for the measurement of CRP in human saliva. Here, we describe this novel lab-on-a-chip system in its first application for the measurement of CRP in saliva and demonstrate its advantages over the traditional ELISA method. The increased sensitivity of the microchip system (10 pg ml-1 of CRP with 1000-fold dilution of saliva sample) is attributed to its inherent increased signal to noise ratio, resulting from the higher bead surface area available for antigen/antibody interactions and the high stringency washes associated with this approach. Finally, the microchip assay system was utilized in this study to provide direct experimental evidence that chronic periodontal disease may be associated with higher levels of salivary CRP.

Original languageEnglish (US)
Pages (from-to)261-269
Number of pages9
JournalLab on a Chip - Miniaturisation for Chemistry and Biology
Volume5
Issue number3
DOIs
StatePublished - Mar 2005

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Saliva
C-Reactive Protein
Assays
Proteins
Periodontal Diseases
Salivary Proteins and Peptides
Lab-on-a-chip
Immunosorbents
Cardiovascular Diseases
Biomarkers
Chronic Disease
Enzymes
Enzyme-Linked Immunosorbent Assay
Point-of-Care Systems
Fluids
Acute-Phase Proteins
Signal-To-Noise Ratio
Antigens
Serum
Antibodies

ASJC Scopus subject areas

  • Clinical Biochemistry

Cite this

Application of microchip assay system for the measurement of C-reactive protein in human saliva. / Christodoulides, Nicolaos; Mohanty, Sanghamitra; Miller, Craig S.; Langub, M. Chris; Floriano, Pierre N.; Dharshan, Priya; Ali, Mehnaaz F.; Bernard, Bruce; Romanovicz, Dwight; Anslyn, Eric; Fox, Philip C.; McDevitt, John.

In: Lab on a Chip - Miniaturisation for Chemistry and Biology, Vol. 5, No. 3, 03.2005, p. 261-269.

Research output: Contribution to journalArticle

Christodoulides, N, Mohanty, S, Miller, CS, Langub, MC, Floriano, PN, Dharshan, P, Ali, MF, Bernard, B, Romanovicz, D, Anslyn, E, Fox, PC & McDevitt, J 2005, 'Application of microchip assay system for the measurement of C-reactive protein in human saliva', Lab on a Chip - Miniaturisation for Chemistry and Biology, vol. 5, no. 3, pp. 261-269. https://doi.org/10.1039/b414194f
Christodoulides, Nicolaos ; Mohanty, Sanghamitra ; Miller, Craig S. ; Langub, M. Chris ; Floriano, Pierre N. ; Dharshan, Priya ; Ali, Mehnaaz F. ; Bernard, Bruce ; Romanovicz, Dwight ; Anslyn, Eric ; Fox, Philip C. ; McDevitt, John. / Application of microchip assay system for the measurement of C-reactive protein in human saliva. In: Lab on a Chip - Miniaturisation for Chemistry and Biology. 2005 ; Vol. 5, No. 3. pp. 261-269.
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