Saliva-based microfluidic point-of-care diagnostic

Abstract

There has been a long-standing interest in point-of-care (POC) diagnostics as a tool to improve patient care because it can provide rapid, actionable results near the patient. Some of the successful examples of POC testing include lateral flow assays, urine dipsticks, and glucometers. Unfortunately, POC analysis is somewhat limited by the ability to manufacture simple devices to selectively measure disease specific biomarkers and the need for invasive biological sampling. Next generation POCs are being developed that make use of microfluidic devices to detect biomarkers in biological fluids in a non-invasive manner, addressing the above-mentioned limitations. Microfluidic devices are desirable because they can provide the ability to perform additional sample processing steps not available in existing commercial diagnostics. As a result, they can provide more sensitive and selective analysis. While most POC methods make use of blood or urine as a sample matrix, there has been a growing push to use saliva as a diagnostic medium. Saliva represents an ideal non-invasive biofluid for detecting biomarkers because it is readily available in large quantities and analyte levels reflect those in blood. However, using saliva in microfluidic devices for POC diagnostics is a relatively new and an emerging field. The overarching aim of this review is to provide an update on recent literature focused on the use of saliva as a biological sample matrix in microfluidic devices. We will first cover the characteristics of saliva as a sample medium and then review microfluidic devices that are developed for the analysis of salivary biomarkers.

Keywords: Diagnostics; Saliva; lab-on-chip; microfluidic.; point-of-care.

Figure 1

A visual abstract outlining the current unmet clinical need in the development of POC microfluidic devices when using saliva as the body fluid.

Figure 2

A schematic representation of biomolecular transport between salivary glands and blood endothelium cells. (1A) Displays the dominant salivary production sites and locations where circulatory molecules enter saliva. (1B) The composition of saliva is then visualized to represent its complex molecular makeup with various biomolecules. . (2) Consists of two images that illustrate the modalities of entry for molecules into saliva: (A) The passive diffusion of small and neutral biomolecules through acinar cells. The ultrafiltration of molecules below 190kDa that passage between the gap junctions between acinar cells. The active transport of large molecules that exceed 190kDa through cell mediated, selective, active mechanisms , . B represents the entry of molecules between the transgingival junction via diffusion. The figure was created using Servier Medical Art templates, licensed under a Creative Commons Attribution 3.0 Unported License; https://smart.servier.com.

Figure 3

Visual illustration of the deviations among commercially available salivary collection devices. The devices depicted are as follows: A: Super•SAL™ Universal Saliva Collection Kit, B: Pedia•SAL™ Infant Salivary Collection, C: UltraSal-2™, D: Oragene DNA | OG-500, E: SimplOFy™, F: Versi•SAL® Saliva Collection Kit.

Figure 4

Pictorial representations of three different microfluidic devices developed for salivary analyte detection. (A) A LFIA for the detection of cocaine with the ability for color intensity analysis through a mobile phone. (B) A µPAD for electrochemical quantification of prostate specific antigen. (C) Another µPAD with the ability for electrochemical detection of Hepatitis B viral DNA detection. Adapted with permission from , , , copyright 2017,2018,2015.