Use of Biosensors within the Oral Environment for Systemic Health Monitoring—A Systematic Review
Abstract
:1. Introduction
2. Materials and Methods
- Inclusion criteria:
- Clinical or laboratory studies, including case reports, researching intraoral applications biosensors for systemic health monitoring.
- Published between 1 January 2015 to 28 October 2023, including e-publications ahead of print.
- Full text available and published in English or with English translation.
- Exclusion criteria:
- Technologies with non-intraoral sensors or point-of-care applications.
- Articles focusing on oral diseases, vital signs, or microorganisms.
- Sensors that detect pressure, energy absorption, or thermal measurements.
- Editorial, reviews, opinion articles, or animal studies.
3. Results
3.1. Biomarkers
3.2. Intraoral Devices
Author, Year | Device | Biomarker | Clinical Relevance | Type of Study | Sensor Technology Sensing Mode¦ Element ¦ Electrodes ¦ Insulation ¦ Additional Details | Data Transceiver | Sensing Medium | Analysis Response Time | Sensing Current /Voltage | Linear Range /mM | Sensitivity | |||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Garcia-Carmona, 2019 [15] | Pacifier | Glucose | Diabetes | In Vitro and In Vivo | Amperometric | No data | Artificial Saliva Unstimulated Human Saliva (1 healthy and 2 patients with type 1 diabetes aged 25–60 years old) | 300 s | Constant Potential −0.20 V | 0.01 to 1.4 | Sensitivity: 0.69 µA/mMmm Correlation Coefficient: 0.994 | |||
Enzymatic (glucose oxidase) | ||||||||||||||
3 electrodes (1 reference—Ag|AgCl ink, 1 working and 1 counter—both Prussian-blue–carbon) | ||||||||||||||
Insulator—N/A | ||||||||||||||
Immobilised—chitosan Silicone nipple with unidirectional inlet for saliva collection | ||||||||||||||
Sangsawang, 2021 [16] | Mouthguard | Thiocyanate | Cancer Cardiovascular disease Smoking Tobacco | In Vitro | Potentiostatic | Potentiostat | Artificial Saliva Phosphate Buffer Solution (both modified with K3[Fe9CN)6] dissolved in KCL) | 15 s | Step potential 0.01 V | 0.1 to11 | Correlation Coefficient: 0.998 | |||
Ion-Selective Electrodes | ||||||||||||||
3 electrodes (1 reference—Ag|AgCl, 1 working—carbon ink and 1 counter) | ||||||||||||||
Insulator—N/A | ||||||||||||||
Immobilised—chitosan | ||||||||||||||
Arakawa, 2016 [18] | Mouthguard | Glucose | Diabetes | In Vitro | Amperostatic | Wireless Transmitter with integrated Potentiostat | Artificial Saliva (modified with variable glucose concentrations) | 60 s for baseline and 3 min for glucose readings | Constant potential −0.12 V | 0.005 to 1 | Sensitivity: 0.08 µA/mM−1mm−2 Correlation Coefficient: 0.999 for Optimised Sensor | |||
Enzymatic (glucose oxidase) | ||||||||||||||
2 electrodes (1 working—Platinum, 1 reference—Ag|AgCl) | ||||||||||||||
Insulator—N/A | ||||||||||||||
Insulator—polydimethylsiloxane (PDMS) | ||||||||||||||
Arakawa, 2020 [19] | Mouthguard | Glucose | Diabetes | In Vitro and In Vivo | Amperostatic | Bluetooth Low Energy Telemeter | Unstimulated Human Saliva Unstimulated Human Saliva (modified with variable glucose concentrations) Artificial Saliva | 20 min | No data | No data | Correlation Coefficient: 0.999 Artificial Saliva No data for other sensing mediums | |||
Enzymatic (glucose oxidase) | ||||||||||||||
3 electrodes (1 reference and 1 counter—both Ag|AgCl ink, 1 working—Platinum) | ||||||||||||||
Insulator—cellulose acetate | ||||||||||||||
Immobilised—crosslinking UV radiation | ||||||||||||||
Lee, 2018 [20] | Retainer | Sodium | Hypertension Kidney Failure Cardiovascular Disease Cancer Osteoporosis | In Vitro and In Vivo | Sensor Mode—Unclear | Bluetooth Low Energy and Monopole Antenna | Human Saliva (modified with different sodium concentrations, sips of salty water, and various food—veggie juice, chicken noodle soup, and potato chip) | No data | No data | No data | No data | |||
Ion-Selective Electrodes | ||||||||||||||
Electrodes—unclear | ||||||||||||||
Insulator—polyamide dielectric layer | ||||||||||||||
Additional Information—N/A | ||||||||||||||
Lim, 2022 [21] | Pacifier | Sodium Potassium | Hypertension Heart Failure Stroke | In Vitro and In Vivo | Amperometric | Wireless Bluetooth | Sodium and Potassium Solutions Neonate Saliva | 30 min | No data | Sodium: 5.7 to 9.1 Potassium: 4.2 to 5.2 | No data | |||
Ion-Selective Electrode | ||||||||||||||
3 Electrodes (2 working—1 sodium ion selective electrode and 1 potassium ion selective electrode, 1 reference electrode) | ||||||||||||||
Insulator—N/A | ||||||||||||||
Additional Information—N/A | ||||||||||||||
Koukouviti, 2023 [22] | Wooden Tongue Depressor | Nitrite Glucose | Periodontitis Diabetes | In Vitro | Amperometric | No data | Artificial Saliva (modified with glucose and nitrite) | 5 s | Detection is performed at +0.8 V for nitrate and +0.5 V for H2O2 | No data—authors report the range is within human saliva range | Correlation Coefficient: 0.997 Glucose 0.998 Nitrite | |||
Enzymatic Glucose Oxidase (glucose) or Oxidation (nitrite) | ||||||||||||||
4 electrodes (2 working, 1 reference, and 1 counter) | ||||||||||||||
Insulator layer—Nafion film | ||||||||||||||
Electrode separated by water-resistant permanent marker | ||||||||||||||
Kim, 2014 [23] | Mouthguard | Lactate | Athletic Performance | In Vitro | Amperometric | No data | Unstimulated human saliva Modified with increasing lactate 0.1–1 mM, uric acid and ascorbic acid | 7 s | 0.042 V for 60 s | Salivary lactate levels peak at 1.6 ± 0.4 | Correlation Coefficient: 0.994 Phosphate Buffer Solution 0.9988 Saliva | |||
Enzymatic (lactate oxidase) | ||||||||||||||
3 electrodes (1 reference—Ag|AgCl conductive ink, 1 working and 1 auxiliary—both Prussian-blue–graphite ink) | ||||||||||||||
Insulator layer—dielectric paste | ||||||||||||||
Immobilised—poly(o-phenylenediamine) (PPR) film | ||||||||||||||
Sha, 2019 [24] | Dental Floss | Glucose | Diabetes | In Vitro | Amperometric | Potentiostat connected via leads | Buffer Solution (modified with H2O2 and glucose) | H2O2 2 min Glucose 3 min | 0.6 V | 0.048 to 12.5 | Sensitivity: 0.0660 µA/mM−1mm−2 Correlation Coefficient: 0.9899 H2O2 0.9928 Glucose | |||
Enzymatic (glucose oxidase) | ||||||||||||||
2 electrodes (1 working—carbon graphite ink and 1 reference—Ag|AgCl ink) | ||||||||||||||
Insulator—N/A | ||||||||||||||
Immobilised—2% dilute glutaraldehyde and Nafion | ||||||||||||||
Liu, 2023 [25] | Toothbrush | Glucose | Diabetes | In Vitro | Amperometric | Potentiostat connected via copper wires | Phosphate buffer solution (modified with variable glucose and H2O2 concentrations) | 1 min H2O2 3 min Glucose | Constant potential of 0.6 V | 0.12 to 13.1 H2O2 0.18 to 5.22 Glucose | Sensitivity: 0.0817 µA/mM−1mm−2 Correlation Coefficient: 0.9924 H2O2 0.9775 Glucose | |||
Enzymatic (glucose oxidase) | ||||||||||||||
2 and 3 electrode models (1 working—Prussian-blue–graphite ink, 1 reference—Ag|AgCl reference, ±1 counter -graphite) | ||||||||||||||
Insulator—N/A | ||||||||||||||
Immobilised—storing in fridge Glue walls on toothbrush to create a saliva reservoir | ||||||||||||||
Kim, 2015 [27] | Mouthguard | Uric Acid | Hyperuricaemia Gout Lesch Hylan Syndrome Renal Syndrome Increase Type 2 Diabetes Mellitus Risk Stress | In Vitro And In Vivo | Amperometric | Wireless Bluetooth Low Energy | Artificial Saliva Unstimulated Human Saliva 2 Human Participants (1 healthy and 1 hyperuricemia) Hyperuricemia with high BUA * level patient managed with Allopurinol over 4 days | No data | −0.3 V for 60 s | No data | Sensitivity: 2.45 µA/mM Correlation Coefficient: Artificial Saliva 0.998 Human Saliva 0.999 | |||
Enzymatic (Uricase) | ||||||||||||||
3 electrodes (1 reference—Ag|AgCl conductive ink, 1 working and 1 counter—both Prussian-blue-graphite ink) | ||||||||||||||
Insulator layer—dielectric paste | ||||||||||||||
Immobilised—polymerised o-phenylenediamine (PPD) |
3.3. Sensor Technology
3.3.1. Electrode Technology
3.3.2. Selectivity, Interference, and In Vivo Confounds of Biosensor Metabolites
3.3.3. Sensitivity
3.3.4. Stability
3.3.5. Saliva Viscosity
3.4. Research Quality
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Biomarker | Enzyme | Reaction | |
---|---|---|---|
Glucose | Glucose Oxidase (GOD) | glucose + O2——GOD → gluconolactone + H2O2 H2O2 → 2H+ + O2 + 2e− | (1) (2) |
Lactate | Lactate Oxidase | L-lactate + O2——L-Lactate oxidase → pyruvate + H2O2 H2O2 → 2H+ + O2 + 2e− | (1) (2) |
Uric Acid | Uricase | uric acid + O2 + 2H2O——Uricase → allantioin + CO2 + H2O2 H2O2 → 2H+ + O2 + 2e− | (1) (2) |
Koukouviti et al., 2023 [22] | Kim et al., 2014 [23] | Kim et al., 2015 [28] | Sha et al., 2019 [24] | Liu et al., 2023 [25] | Garcia-Carmona et al., 2019 [15] | Sangsawang et al., 2021 [16] | Arakawa et al., 2020 [19] | Arakawa et al., 2016 [18] | Lee et al., 2018 [20] | Lim et al., 2022 [21] | |
---|---|---|---|---|---|---|---|---|---|---|---|
Theoretical or conceptual underpinning the research | 2 | 2 | 2 | 2 | 3 | 2 | 2 | 2 | 2 | 1 | 2 |
Statement of research aim/s | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
Clear description of research setting and target population | N/A | N/A | 0 | N/A | N/A | 3 | N/A | 0 | N/A | 0 | 3 |
Study design is appropriate to address the stated research aims | 2 | 2 | 1 | 2 | 1 | 1 | 2 | 2 | 1 | 1 | 2 |
Appropriate sampling to address the research aim/s | N/A | N/A | 0 | N/A | N/A | N/A | 0 | N/A | 0 | 0 | |
Rationale for choice of data collection tools | 1 | 1 | 2 | 1 | 1 | 1 | 1 | 2 | 1 | 1 | 2 |
The format and content of data collection tool is appropriate to address the stated research aim/s | 2 | 22 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 |
Description of data collection procedure | 1 | 1 | 2 | 1 | 2 | 2 | 2 | 2 | 1 | 2 | 2 |
Recruitment data provided | N/A | N/A | 1 | N/A | N/A | 1 | N/A | 0 | N/A | 0 | 0 |
Justification for analytic method selected | 1 | 1 | 2 | 1 | 1 | 1 | 2 | 2 | 1 | 2 | 2 |
The method of analysis was appropriate to answer the research aim/s | 1 | 1 | 2 | 2 | 2 | 1 | 2 | 2 | 2 | 2 | 2 |
Evidence that the research stakeholders have been considered in research design or conduct | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
Strengths and limitations critically discussed | 0 | 1 | 1 | 1 | 1 | 1 | 2 | 1 | 1 | 0 | 1 |
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© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Archer, N.; Ladan, S.; Lancashire, H.T.; Petridis, H. Use of Biosensors within the Oral Environment for Systemic Health Monitoring—A Systematic Review. Oral 2024, 4, 148-162. https://doi.org/10.3390/oral4020012
Archer N, Ladan S, Lancashire HT, Petridis H. Use of Biosensors within the Oral Environment for Systemic Health Monitoring—A Systematic Review. Oral. 2024; 4(2):148-162. https://doi.org/10.3390/oral4020012
Chicago/Turabian StyleArcher, Natalie, Sa’ada Ladan, Henry T. Lancashire, and Haralampos Petridis. 2024. "Use of Biosensors within the Oral Environment for Systemic Health Monitoring—A Systematic Review" Oral 4, no. 2: 148-162. https://doi.org/10.3390/oral4020012