Lab‐on‐a‐Chip Methods for Point‐of‐Care Measurements of Salivary Biomarkers of Periodontitis

Abstract

Salivary secretions contain a variety of molecules that reflect important pathophysiological activities. Quantitative changes of specific salivary biomarkers could have significance in the diagnosis and management of both oral and systemic diseases. Modern point-of-care technologies with enhanced detection capabilities are needed to implement a significant advancement in salivary diagnostics. One such promising technology is the recently described lab-on-a-chip (LOC) assay system, in which assays are performed on chemically sensitized beads populated into etched silicon wafers with embedded fluid handling and optical detection capabilities. Using this LOC system, complex assays can be performed with small sample volumes, short analysis times, and markedly reduced reagent costs. This report describes the use of LOC methodologies to assess the levels of interleukin-1beta (IL-1beta), C-reactive protein (CRP), and matrix metalloproteinase-8 (MMP-8) in whole saliva, and the potential use of these biomarkers for diagnosing and categorizing the severity and extent of periodontitis. This study demonstrates that the results achieved by the LOC approach are in agreement with those acquired with standard enzyme-linked immunosorbent assay (ELISA), with significant IL-1beta and MMP-8 elevations in whole saliva of periodontitis patients. Furthermore, because of the superior detection capacities associated with the LOC approach, unlike those with ELISA, significant differences in CRP levels between periodontitis patients and normal subjects are observed. Finally, principal component analysis (PCA) is performed to yield an efficient method to discriminate between periodontally healthy and unhealthy patients, thus increasing the diagnostic value of these biomarkers for periodontitis when examined with the integrated LOC sensor system.

Use of Saliva-Based Nano-Biochip Tests for Acute Myocardial Infarction at the Point of Care: A Feasibility Study

“…Just as in the initial biomarker validation phases, our LOC studies also document measurable signal differences in protein fingerprint patterns of these 2 patient groups. Bead-based immunoassay systems display strong analytical performance characteristics (typical intraassay variance of 4%-8% and interassay variance of 6%-10%) (26,27,31 ). Correlation studies completed with FDAapproved instruments for serum CRP yield R 2 values of 0.98.…”

“…Design, fabrication, and testing methods for LOC structures have been described in detail in previous reports (23,24,26,27,30,31 ). New modifications to procedures and methods for multiplexed AMI diagnosis are described in the Supplemental Data section (see Lab-on-aChip (LOC) Multiplexed Test in Supplemental Materials in the Data Supplement that accompanies the online version of this article at http://www.clinchem.org/content/ vol55/issue8]).…”

“…Through the last decade, our team has made sustained efforts to combine and adapt lab-on-a-chip (LOC), microfluidic, microelectromechanical systems and nano-biochip tools for practical implementation of highly sensitive and accurate miniaturized sensors that are suitable for variety of important applications, including multiplex analysis of minute amounts of bioanalytes in serum and saliva (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32). These integrated test systems can complete all aspects of sample processing and separation and analyte detection and are amenable to POC applications.…”

Programmable Bio-NanoChip Technology for the Diagnosis of Cardiovascular Disease at the Point of Care

“…toward this goal, we have worked to improve the current state of PoC ivd through the development, validation, and implementation of P-BnCs ( Figure 1a). [17][18][19][20][21][22][23][24] the "programmability" feature of the system refers to the capacity of the sensor ensemble to function as a standard platform that can be reprogrammed to serve a new application by inserting a molecular-level code (i.e., the biomarker-specific reagents). the "bio" terminology refers to the capacity to measure and extract the bio-signatures associated with the disease progression.…”

Nanotechnology in dentistry: prevention, diagnosis, and therapy

“…176 It is the ability of the biochip to detect very low concentrations of CRP present in the saliva compared to serum that has enabled the researchers to distinguish between healthy periodontium and chronic gingival inflammation based directly on salivary CRP levels. 177 Moreover, CRP is also classified as a systemic marker of inflammation that has been shown to significantly increase in other conditions, including myocardial infarction, atherosclerosis, and arthritis. [178][179][180] Another device called the integrated microfluidic platform for oral diagnostics was developed to perform immunological assays in less than 10 minutes with low sample volume and concentration requirements to test for periodontal disease.…”