Salivary diagnostics: opportunities and challenges

Abstract

Saliva contains a diverse array of biomarkers indicative of various diseases. Saliva testing has been a major advancement towards non-invasive point-of-care diagnosis with clinical significance. However, there are challenges associated with salivary diagnosis from sample treatment and standardization. This review highlights the biomarkers in saliva and their role in identifying relevant diseases. It provides an overview and discussion about the current practice of saliva collection and processing, and advancements in saliva detection systems from in vitro methods to wearable oral devices. The review also addresses challenges in saliva diagnostics and proposes solutions, aiming to offer a comprehensive understanding and practical guidance for improving saliva-based detection in clinical diagnosis. Saliva diagnosis provides a rapid, effective, and safe alternative to traditional blood and urine tests for screening large populations and enhancing infectious disease diagnosis and surveillance. It meets the needs of various fields such as disease management, drug screening, and personalized healthcare with advances in saliva detection systems offering high sensitivity, fast response times, portability, and automation. Standardization of saliva collection, treatment, biomarker discovery, and detection between different laboratories needs to be implemented to obtain reliable salivary diagnosis in clinical practice.

Keywords: Salivary diagnostics; biomarkers; non-invasive detection; point-of-care testing; result standardization.

Figure 1

Schematic drawing highlighting the review content.

Figure 2

Saliva sampling methods. (a) Stimulated collection of saliva from the parotid gland using sialographic cannulas. (b) Stimulated/unstimulated collection of saliva from parotid gland using Lashley cup. (c) Lashley cup structure. (d) Stimulated saliva produced by chewing gum. (e) Unstimulated collection of saliva from the parotid gland. (f) Unstimulated submandibular and sublingual saliva collection.

Figure 3

Schematic diagram of saliva processing. Among different saliva processing methods, green indicates processing applicable objects; red indicates processing inapplicable objects.

Figure 4

Summary of in vitro saliva detection devices. (a) A laser-treated wooden tongue depressor is transformed into an electrochemical multiplex biosensing device for oral fluid analysis. Reproduced with permission . Copyright 2023, American Chemical Society. (b) An electrochemical aptasensor for simultaneous detection of glucose and insulin on a portable biochip with smartphone signal readout. Reproduced with permission . Copyright 2022, ELSEVIER. (c) μPADs on centrifugal microfluidic discs for the quantification of the N protein of pseudovirus in saliva. Reproduced with permission . Copyright 2022, American Chemical Society. (d) A disposable paper glucose sensor printed with conductive polymer, uses a glucose oxidase enzyme and electron mediator for biorecognition. Reproduced with permission . Copyright 2018, Nature. (e) SARS-CoV-2 infection detection in saliva using microfluidic electrochemical analysis of 3CLpro enzymatic activity. Reproduced with permission . Copyright 2022, Nature. (f) A microfluidic chip detects active SARS-CoV-2 virus from saliva for rapid and accurate infection identifications. Reproduced with permission . Copyright 2022, Science.

Figure 5

Summary of oral wearable monitoring devices. (a) Mouthguard glucose sensor and its reaction with the open-loop injection system and phantom jaw. Reproduced with permission . Copyright 2016, ELSEVIER. (b) Pacifier Biosensor and schematic amperometry response of glucose monitoring. Reproduced with permission . Copyright 2019, American Chemical Society. (c) The intraoral sodium intake sensor enables real-time responses to various diets in vivo by a human subject. Reproduced with permission . Copyright 2018, PNAS. (d) Monitoring fluctuations in the local oral microenvironment pH using wearable devices to detect caries lesions Reproduced with permission. Copyright 2022, Nature. (e) A wearable cellulose acetate-coated mouthguard biosensor for in vivo salivary glucose measurement. Reproduced with permission . Copyright 2020, American Chemical Society. (f) A mouthguard biosensor for uric acid that has built-in wireless electronics. Reproduced with permission . Copyright 2015, ELSEVIER.