# Advances in Electrochemical Biosensors Based on Nanomaterials for Protein Biomarker Detection in Saliva

**Authors:** Tao Dong, Nuno Miguel Matos Pires, Zhaochu Yang, Zhuangde Jiang

PMC · DOI: 10.1002/advs.202205429 · 2022-12-30

## TL;DR

This paper reviews how nanomaterial-based electrochemical biosensors can detect protein biomarkers in saliva for quick disease diagnosis and monitoring.

## Contribution

The paper provides a critical review of recent advances in nanomaterial-enhanced electrochemical biosensors for point-of-care protein detection in saliva.

## Key findings

- Nanomaterials improve the analytical performance of electrochemical biosensors for saliva-based biomarker detection.
- Current sensors need optimization for reliable next-generation sample-in-answer-out systems.
- Electrochemical biosensors are promising for rapid and accurate point-of-care diagnostics.

## Abstract

The focus on precise medicine enhances the need for timely diagnosis and frequent monitoring of chronic diseases. Moreover, the recent pandemic of severe acute respiratory syndrome coronavirus 2 poses a great demand for rapid detection and surveillance of viral infections. The detection of protein biomarkers and antigens in the saliva allows rapid identification of diseases or disease changes in scenarios where and when the test response at the point of care is mandated. While traditional methods of protein testing fail to provide the desired fast results, electrochemical biosensors based on nanomaterials hold perfect characteristics for the detection of biomarkers in point‐of‐care settings. The recent advances in electrochemical sensors for salivary protein detection are critically reviewed in this work, with emphasis on the role of nanomaterials to boost the biosensor analytical performance and increase the reliability of the test in human saliva samples. Furthermore, this work identifies the critical factors for further modernization of the nanomaterial‐based electrochemical sensors, envisaging the development and implementation of next‐generation sample‐in‐answer‐out systems.

This article reviews the recent developments of electrochemical sensors for the detection of disease‐signaling protein biomarkers in saliva bio‐samples. The role of nanomaterials in synergy with bio‐recognition probes and electrochemical sensing techniques for boosting the analytical performance of resultant sensors is described and discussed. Perspectives and views in this field are also given.

## Linked entities

- **Diseases:** severe acute respiratory syndrome coronavirus 2 (MONDO:0100096)

## Full-text entities

- **Genes:** TNNT2 (troponin T2, cardiac type) [NCBI Gene 7139] {aka CMD1D, CMH2, CMPD2, LVNC6, RCM3, TnTC}, KLK3 (kallikrein related peptidase 3) [NCBI Gene 354] {aka APS, KLK2A1, PSA, hK3}, MMP8 (matrix metallopeptidase 8) [NCBI Gene 4317] {aka CLG1, HNC, MMP-8, PMNL-CL}, ACE2 (angiotensin converting enzyme 2) [NCBI Gene 59272] {aka ACEH}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, CSTB (cystatin B) [NCBI Gene 1476] {aka CPI-B, CST6, EPM1, EPM1A, PME, STFB}, TNNI3 (troponin I3, cardiac type) [NCBI Gene 7137] {aka CMD1FF, CMD2A, CMH7, RCM1, TNNC1, cTnI}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, TPI1 (triosephosphate isomerase 1) [NCBI Gene 7167] {aka HEL-S-49, TIM, TPI, TPID}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, ODAM (odontogenic, ameloblast associated) [NCBI Gene 54959] {aka APIN}, CD79A (CD79a molecule) [NCBI Gene 973] {aka IGA, IGAlpha, MB-1, MB1}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, F2 (coagulation factor II, thrombin) [NCBI Gene 2147] {aka PT, RPRGL2, THPH1}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, HP (haptoglobin) [NCBI Gene 3240] {aka HP2ALPHA2, HPA1S}, PARK7 (Parkinsonism associated deglycase) [NCBI Gene 11315] {aka DJ-1, DJ1, GATD2, HEL-S-67p}, NUCB2 (nucleobindin 2) [NCBI Gene 4925] {aka HEL-S-109, NEFA}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, S (surface glycoprotein) [NCBI Gene 43740568] {aka spike glycoprotein}, IL19 (interleukin 19) [NCBI Gene 29949] {aka IL-10C, MDA1, NG.1, ZMDA1}, LGALS3 (galectin 3) [NCBI Gene 3958] {aka CBP35, GAL3, GALBP, GALIG, L31, LGALS2}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, N (nucleocapsid phosphoprotein) [NCBI Gene 43740575]
- **Diseases:** SARS-CoV-2 (MESH:D000086382), lung inflammation (MESH:D011014), oral cancer (MESH:D009062), lung cancer (MESH:D008175), Parkinson s disease (MESH:D010300), heart disease (MESH:D006331), Oropharyngeal cancer (MESH:D009959), asthma (MESH:D001249), viral infections (MESH:D014777), cancer (MESH:D009369), malaria (MESH:D008288), Alzheimer's disease (MESH:D000544), cardiovascular disease (MESH:D002318), acute coronary syndrome (MESH:D054058), Breast cancer (MESH:D001943), Oral squamous cell carcinoma (MESH:D000077195), periodontal disease (MESH:D010510), acute lymphoblastic leukemia (MESH:D054198), Mucositis (MESH:D052016), asthmatic (MESH:D013224), prostate-specific antigen ( (MESH:D011472), systemic inflammatory disorders (MESH:D018746), Myocardial infarction (MESH:D009203), malignant brain tumors 1 (MESH:D001932), Periodontitis (MESH:D010518), lung disease (MESH:D008171), chronic diseases (MESH:D002908), bronchial inflammation (MESH:D007249), Gastric cancer (MESH:D013274), systemic autoimmune disorder (MESH:D020274), epilepsy (MESH:D004827), infected (MESH:D007239), localized and systemic diseases (MESH:D034721), infectious and (MESH:D003141), bowel diseases (MESH:D015212), primary Sjogren s syndrome (MESH:D012859), organ failure (MESH:D009102), Heart failure (MESH:D006333), diseases (MESH:D004194), muscle and joint diseases (MESH:D007592)
- **Chemicals:** zirconia (MESH:C028541), H2O2 (MESH:D006861), Pd NPs (MESH:C057114), CdS (MESH:D002104), CuSO4 (MESH:D019327), Bi2WO6 (MESH:C000626718), S (MESH:D013455), Graphitic carbon nitride (MESH:C000629596), Nitrogen (MESH:D009584), PDMS (MESH:C013830), Ti (MESH:D014025), Analyte (-), methylene blue (MESH:D008751), ITO (MESH:C109984), Yttrium oxide (MESH:C091417), PD (MESH:D010165), dopamine (MESH:D004298), perovskite (MESH:C059910), PVDF (MESH:C024865), starch (MESH:D013213), tungsten trioxide (MESH:C511604), polymer (MESH:D011108), 1-NPP (MESH:C014694), Si3N4 (MESH:C032734), poly(ethylene glycol) (MESH:D011092), peptides (MESH:D010455), glucose (MESH:D005947), Oligonucleotide (MESH:D009841), 1-naphthol (MESH:C029350), SiO2 (MESH:D012822), Ferrocene (MESH:C004998), TiO2 (MESH:C009495), Au (MESH:D006046), ascorbic acid (MESH:D001205), polydopamine (MESH:C568283), MOF (MESH:D000073396), ethylenediamine (MESH:C031234), PEDOT:PSS (MESH:C533756), EDC (MESH:C024565), metal (MESH:D008670), N-hydroxy succinimide (MESH:C001426), GO (MESH:C000628730), uric acid (MESH:D014527), N-hydroxy sulfosuccinimide (MESH:C035761), HCl (MESH:D006851), thiol (MESH:D013438), poly(glycidyl methacrylate) (MESH:C042535), graphene (MESH:D006108), Carbon nanotubes (MESH:D037742), SrTiO3 (MESH:C119252), Na2SO4 (MESH:C012036), MIP (MESH:D000082582), p (MESH:D010758), Si (MESH:D012825), Silver (MESH:D012834), agarose (MESH:D012685), polythiophene (MESH:C066730), TMB (MESH:C021758), Azide (MESH:D001386), EDA (MESH:C564336)
- **Species:** Zika virus (no rank) [taxon 64320], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Homo sapiens (human, species) [taxon 9606], Dengue virus (no rank) [taxon 12637], Middle East respiratory syndrome-related coronavirus (no rank) [taxon 1335626], Human papillomavirus 16 (serotype) [taxon 333760], Severe acute respiratory syndrome-related coronavirus (no rank) [taxon 694009], Human papillomavirus (species) [taxon 10566]

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC9951322/full.md

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Source: https://tomesphere.com/paper/PMC9951322