Advancement in biomarker based effective diagnosis of neonatal sepsis

Figures & data

Table 1. Major differences in EOS and LOS.

Parameters	EOS	LOS	Ref
Duration	<72 h after birth	>72 h after birth	[6]
Risk factors	Maternal GBS colonisation, chorioamnionitis, early rupture of membranes, prolonged rupture of membranes, Premature birth, Multiple gestation	Prematurity, low birth weight, ventilator associated pneumonia, prolonged use of antibiotics
Pathogen associated	GBS, Escherichia coli, Streptococcus viridans, Enterococci, Staphylococcus aureus, Pseudomonas aeruginosa	Coagulase-negative Staphylococci, GBS, Staphylococcus aureus, Acinetobacter baumannii, Candida albicans, Klebsiella pneumonia, Escherichia coli, Enterococci, Pseudomonas aeruginosa	[7,8]
Mode of transmission	vaginal environment, infected intra-amniotic fluid, and during delivery through birth canal	unhygienic hospital environment, health professionals, infected nutrient source, infected intravenous catheters, and prone family members	[9]

[Abbreviations - EOS: Early Onset Sepsis, LOS: Late Onset Sepsis, GBS: Group B Streptococcus].

Figure 1. Schematic representation of fabricating electrochemical sensor to detect neonatal sepsis biomarker. [Abbreviations - CV: Cyclic voltammetry, EIS: electrochemical impedance spectroscopy, DPV: differential pulse voltammetry, SWA: square wave voltammetry, CA: chronoamperometry, POC: point of care].

Figure 2. Flow diagram of literature search for neonatal sepsis diagnostic biomarkers.

Figure 3. Schematic representation of different diagnostic biomarker expressions due to bacterial infection in neonatal sepsis. [Abbreviations - SAA: serum amyloid A, CRP: C reactive protein, LBP: Lipopolysaccharide Binding Protein, PCT: procalcitonin, IL: interleukin].

Table 2. The diagnostic parameters of biomarkers for the identification of neonatal sepsis.

S.No	Biomarker	Normal level	Level in NS	Cut off	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)	DA (%)	Advantages	Disadvantages and limitations	Ref
1	CRP (C-Reactive Protein)	0–3 mg/L	12–48 mg/L	6 mg/dl	65.1	95.5	97.5	60.5	–	Advantageous	Poor specificity and sensitivity, false positive reports, short half life, affected by premature membrane rupture, foetal distress, maternal fever, etc.	[31–37]
				3 mg/l	82.5	77.5	88	68.9	–	over blood
				>13.49	80.0	65.7	25.0	95.8	–	culture
				>10 mg/L	76.9	49.2	49.2	76.9	60.0
2	PCT (Procalcitonin)	0.21 ± 0.12 mg/L	56.27 ± 81.89 mg/L	1.2 ng/ml	90.9	88.0	76.0	95.0	–	More specific than CRP, shows high expression for 24 h after birth	Less cost-effective	[38–42]
				–	95.8	87.7	90.1	98.0	–
				0.5 mg/100 ml	74.8	100	100	56.3	–
				<0.05 ng/ml	83.3	100	100	74.9	–
3	SAA (Serum Amyloid A)	3.2 ± 3.4 mg/dl	44.4 ± 57.3 mg/dl	>2.8 µg/ml	86.7	85.0	86.7	85.0	–	elevates early & more sharply than CRP, observed in 8 h after infection & maintains its usage for 96 h	No rise in multiple NS patients, observed in intra-ventricular haemorrhage & asphyxia	[2, 43–45]
				69.28 mg/L	83.0	66.1	–	–	–
4	LBP (Lipopolysaccharide Binding Protein)	2.1–30.6 mg/L	12.4–82.8 mg/L	17.5 mg/L	94.1	77.8	88.9	87.5	–	superior than CRP in neonatal <2 days & better than CRP & IL-6 in neonatal older than 2 days	non specific, can be influenced by hepatic function & nutritional status	[46–48]
				11.4 mg/l	82.0	86.0	65.0	94.0	–
5	IL-6 (Interleukin-6)	0.50–3.5 pg/ml	3.08–54.50 pg/ml	>61.8 pg/ml	80.0	85.0	–	–	–	detectable in serum before rise in CRP	very short half life, false positive reports	[49–53]
				>95.32 pg/ml	54.0	96.0	–	–	–
				>68pg/ml	85.0	80.0	–	–	–
				10–150pg/ml	75–87	50–82	92.0	52.0	–
				24.65 pg/ml	72.0	84.0	95.0	42.0	–
6	IL-8 (Interleukin-8)	0.05–0.87 pg/ml	0.01–1.41 pg/ml	0.65 pg/ml	34.6	86.2	69.2	59.5	60.4	accurate & useful for early NS diagnosis	short half-life, decline rapidly by 4 h after infection	[51,52, 54–56]
				>70.86 pg/ml	78.0	70.0	–	–	–
				>269.51 pg/ml	80.0	50.0	–	–	–
7	CD-64 (Cluster of Differentiation 64)	16.5–95.5 MFI	29–1647 MFI	44.3 MFI	86.7	73.3	72.0	69.2	–	high expression till 24 h, diagnostic accuracy in superior than CRP, require small volume of sample	low specificity & sensitivity, inability to differentiate between systemic infection & intra-abdominal sepsis or inflammation	[49, 56–58]
				2.19–3.62	75–78	59–77	29–54	81–96
8	CD11b (Cluster of Differentiation 11b)	112.18 ± 13.82	284.31 ± 66.36	131.0	85.0	93.3	96.0	76.0	74.2	positive correlation with severity of systemic inflammation	limited sensitivity	[49, 59–61]
				–	50.0	94.0		87.2	–
				290.0	75.0	100.0	69.6 100.0	86.0
9	Neopterin	2.4–38 nmol/L	28–124 nmol/L	32.2 nmol/L	78.9	95.0	93.8	82.6	–	found in different body fluids i.e. serum, urine, cerebro-spinal fluid etc.	non specific	[31, 62–64]
				100.3 nmol/l	100.0	83.3	83.3	89.5	–
				–	78.9	95.0	93.8	82.6	–
				70.5 nmol/L	94.7	88.6	–	–
10	Presepsin	168.9–935.6 pg/ml	1174–4854 pg/ml	767 pg/ml	100.0	86.7	84.4	100.0	88.7	not affected by gender	influence of pathophysiological conditions	[57, 60, 65–68]
		339.5–595 pg/ml	748–2425 pg/ml	686 pg/mL	82.7	95.5	95.4	83.1	–
				1800 µg/l	97.6	95.1	90.2	97.3	–
				>799 pg/dL	93.3	90.0	94.9	87.1	–
				722 pg/ml	100.0	97.5	98.7	100.0	–
				885 ng/L	94.0	100.0	100.0	95.0	–
				788 ng/l	93.0	100.0	100.0	94.0
11	TNF-ɑ (Tumour Necrosis Factor Alpha)	9.3 ± 4.4 pg/ml	161.9 ± 78.4 pg/ml	>36.8 pg/ml	95.0	55.0	–	–	–	detected in blood earlier than CRP, not affected by gestational or postnatal age	rapid change in concentration, half-life of 70 min.	[26, 50, 54]
		0.5–5.2 pg/ml	10–3364 pg/ml	≥7.5 pg/ml	100.0	96.6	96.2	96.5	98.3
12	Progranulin	–	–	> 37.89 ng/ml	94.3	51.6	61.7	91.7	–	no increase in concentrations	non-specific	[69,70]
				1.39 pg/mL	67.1	80.3	76.5	67.6	–	over first days of neonatal life

Table 3. Potential genes and miRNA based biomarkers for the diagnosis of NS.

Gene	Potential function	Potential action in NS	Ref
ITGAM (CD11b)	regulates activation, attachment & movement of leucocyte from blood to injury location	High expression depicts decreased survival	[124]
TLR-8	ability to sense ssRNA from viruses	Cell activation by bacterial infection demonstrated by TLR-8 inhibition
IL1ß	Regulates inflammation, angiogenesis & hematopoisis	Contribute to NS development	[125]
MMP9	Activates inflammation & inhibition, platelet aggregation	Role in NS pathophysiology with increased level	[126]
MPO	Indicates oxidative stress, neutrophil infiltration	Mitochondrial damage, sepsis mediated organ failure	[124]
ELANE	Manages LPS-induced immune response during infection, maturation of neutrophil granulocyte	Expected role in sepsis development
SPI1	Regulation of myeloid lineage specification during hematopoisis	Its activation leads to bone marrow suppression during NS	[127]
C3a/c3aR axis	Mediate immune response, protective role in endotoxin shock	Increased level depicts endotoxemia severity & disease outcome	[124]
miR-23b	Regulator of innate immune response & various inflammatory processes	Investigate disease severity & prognosis, mediate development of myocardial dysfunction in sepsis	[128]
miR-34a-5p	Development of inflammatory & auto-immune diseases, regulates TLR signalling	NF-κB-mediated inflammatory response	[129]
miR-199-3p
miR-16a	Inhibiting cell proliferation & cell cycle progression, activate apoptosis	Increased level results into respiratory discomfort in NS	[130]
miR-451	Role in hematopoitic system differentiation
miR15a/16	Regulation of gene expression at post-transcriptional level	Pathogenesis of NS by targeting BCL11B	[131]

[Abbreviations - ITGAM: Mac-1 integrin alpha chain, TLR-8: Toll-like receptor-8, MMP9: matrix metalloproteinase, MPO: myeloperoxidase, ELANE: elastane neutrophil expressed, SPI1: Salmonella pathogenicity island 1, C3a/c3aR axis: complement component 3a receptor 1 miR: micro RNA].

Table 4. Recent Advances in developing electrochemical biosensor to diagnose neonatal sepsis.

Analyte under detection	Sensing platform	Biorecognition element	LOD	Linear range	Advantages	Ref
CRP	Polycrystalline gold electrode immobilised with PEG	Anti-CRP Ab	176 pM	0.5–50 nm	Reusable, label-free, portability, cheap	[133]
	SPE electrode immobilised on streptavidin functionalised magnetic beads	Anti-CRP Ab	1.5 ng/mL	0.05–1 µg/mL	Small sample volume, rapid	[134]
	SPE electrode coated with Au-Pt bimetallic nanomaterial	CRP imprinted polymer	0.1 nM	0.1–500 nM	User-friendly, rapid	[135]
	SPE electrode electrodeposited with graphene quantum dots	Anti-CRP Ab	0.036 ng/mL	0.5–10 ng/mL	Label-free, disposable, rapid	[136]
	Carbon electrode functionalised with Au nanobeads & COOH modified Au nanoparticles	Anti-CRP Ab	–	1–100 µg/mL	Reusable, portable	[137]
	Carbon electrode based on carbon nano-fibre-chitosan nanocomposite	RNA aptamer probe	0.37 pM	1.0–15.0 pM	Stable, reproducible	[138]
	Polydeep eutectic solvent (PDES) graphene coated with Au nanoparticles	DNA aptamer	0.0003 ng/mL	0.001–50 ng/mL	Label-free, selective	[139]
PCT	Phthalocyanine nanoparticles functionalised MWCNT	Anti-PCT Ab	1.23 pg/mL	0.01–100 ng/mL	No labeliing, no redox mediator	[140]
	Streptavidin functionalised magnetic beads based chip	Anti-PCT Ab	0.02 ng/mL	0.05–100 ng/mL	Rapid, small sample volume, compact	[141]
	GCE modified with graphitic carbon nitride nanosheet	Polypeptide probe	0.11 fg/mL	0.15–11.7 pg/mL	Label-free	[142]
	Polystyrene nanosphere with polyglutamic (PGA) & Rhodamine-6G fluorescent dye on magnetic bead	Anti-PCT Ab	0.022 ng/mL	0.113–0.45 ng/mL	Enzyme-free immunoassay	[143]
	GCE with palladium nanoparticle functionalised MoS2-NiCO heterostructure	Anti-PCT Ab	0.36 pg/mL	0.001–50 ng/mL	Label-free, remarkable reproducibility	[144]
	Fe3S4 with Pd nanoparticles & functionalised pineal mesoporous bioactive glass	Anti-PCT Ab	130 fg/mL	500 fg/mL-50 ng/mL	Sandwich type sensing with signal off mode	[145]
SAA	SPE coated with MWCNT, MnO2NSs & CO3O4 nanoparticles	SAA specific MIP	0.01 pM	0.01 pM-1 µM	Long half-life	[146]
	GCE with PPy-αCOOH-MWCNT-chitosan	Anti-SAA Ab	0.3 pg mL^-1	0.001 to 900 ng mL^−1	Stablitiy	[147]
LPS	Nylon membrane integrated on Au microelectrode with PDMS encapsulant	Anti-LPS Ab	1 µg/mL	1 µg/mL-1000 µg/mL	Multiplexed biosensing	[148]
IL-6	Needle-shaped silicon substrates	Anti-IL-6 Ab	20 pg/mL	20–100 pg/mL	Real time measurement	[149]
	Metal electrode with Dithiobis(succinimidyl propionate)	Anti-IL-6 Ab	0.1 pg/mL	0.01 pg/mL-10 ng/mL	Rapid analysis from a single drop of undiluted plasma sample	[150]
	Molybdenum electrode on Au coated nanoporous polyamie substrate	Anti-IL-6 Ab	1 pg/mL	1–100 pg/mL	Portable	[151]
IL-8	GO modified super-paramagnetic Fe3O4 nanoparticle	IL-8 specific MIP	0.04 pM	0.110 pM	Easy fabrication	[152]
TNF-α	Au electrode with Au nanoparticles, probe & doxorubicin hydrochloride	Aptamer	0.7 pg/mL	1 to 1 × 10^4 pg/mL	Reusable	[153]
Neopterin	Bis-bithiophene derivatized with cytosine & bithiophene derivatized with boronic acid based MIP film	MIP with neopterin as template	22 µM	0.15–2.5 nM	Able to discriminate interferences	[154]
	Poly(ethylene-co-vinyl alcohol) based thin films on ITO glass electrode	MIP with neopterin as template	0.041 pg/mL	35–55 ng/mL	Portable	[155]

[Abbreviations - PEG: Polyethylene glycol, Ab: antibody, SPE: screen printed electrode, Au-Pt: gold-platinum, MWCNT: multi walled carbon nanotubes, GCE: glassy carbon electrode, MoS₂-NiCO: molybdenum disulphide-nickel carbonate, Fe₃S₄: iron sulphide, Pd: palladium, MnO₂NSs: manganese oxide nanospheres, CO₃O₄: cobalt oxide, PPy-αCOOH: carboxy-endcapped polypyrrole, PDMS: Polydimethylsiloxane, GO: graphene oxide, Fe₃O₄: iron oxide, MIP: molecularly imprinted polymers, ITO: indium tin oxide].

Karabulut B, Arcagok BC. New diagnostic possibilities for early onset neonatal sepsis: red cell distribution width to platelet ratio. Fetal Pediatr Pathol. 2020;39(4):297–306.

 PubMed Web of Science ®Google Scholar

Satar M, Arısoy AE, Çelik İH. Turkish neonatal society guideline on neonatal infections-diagnosis and treatment. Turk Pediatri Ars. 2018;53(Suppl 1):S88–S100.

 PubMedGoogle Scholar

Shah BA, Padbury JF. Neonatal sepsis: an old problem with new insights. Virulence. 2014;5(1):170–178.

 PubMed Web of Science ®Google Scholar

Procianoy RS, Silveira RC. The challenges of neonatal sepsis management. J Pediatr (Rio J). 2020;96 Suppl 1(Suppl 1):80–86.

 PubMedGoogle Scholar

Jyoti A, Kumar S, Srivastava VK, et al. Neonatal sepsis at point of care. Clin Chim Acta. 2021;521:45–58.

 PubMed Web of Science ®Google Scholar

Prashant A, Vishwanath P, Kulkarni P, et al. Comparative assessment of cytokines and other inflammatory markers for the early diagnosis of neonatal sepsis–a case control study. PLoS One. 2013;8(7):e68426.

 PubMed Web of Science ®Google Scholar

Boskabadi H, Zakerihamidi M. Evaluate the diagnosis of neonatal sepsis by measuring interleukins: a systematic review. Pediatr Neonatol. 2018;59(4):329–338.

 PubMed Web of Science ®Google Scholar

Sharma A, Thakur A, Bhardwaj C, et al. Potential biomarkers for diagnosing neonatal sepsis. Curr Med Res Pract. 2020;10(1):12–17.

 Google Scholar

Boseila S, Seoud I, Samy G, et al. Serum neopterin level in early onset neonatal sepsis. J Am Sci. 2011;7(7):343–352.

 Google Scholar

El-Madbouly AA, El Sehemawy AA, Eldesoky NA, et al. Utility of presepsin, soluble triggering receptor expressed on myeloid cells-1, and neutrophil CD64 for early detection of neonatal sepsis. Infect Drug Resist. 2019;12:311–319.

 PubMed Web of Science ®Google Scholar

Hashem HE, Ibrahim ZH, Ahmed WO. Diagnostic, prognostic, predictive, and monitoring role of neutrophil CD11b and monocyte CD14 in neonatal sepsis. Dis Markers. 2021;2021:4537760–4537712.

 PubMedGoogle Scholar

Iroh Tam P-Y, Bendel CM. Diagnostics for neonatal sepsis: current approaches and future directions. Pediatr Res. 2017;82(4):574–583.

 PubMed Web of Science ®Google Scholar

Bhowmik A, Samanta M, Hazra A, et al. Study to evaluate the role of TNFa, IL1ß, IL6 in diagnosis and severity assessment of neonatal sepsis among term, appropriate for gestational age newborns. Perinatal J. 2021;29(3):179–185.

 Google Scholar

Kocabaş E, Sarikçioğlu A, Aksaray N, et al. Role of procalcitonin, C-reactive protein, interleukin-6, interleukin-8 and tumor necrosis factor-alpha in the diagnosis of neonatal sepsis. Turk J Pediatr. 2007;49(1):7–20.

 PubMed Web of Science ®Google Scholar

Rao L, Song Z, Yu X, et al. Progranulin as a novel biomarker in diagnosis of early-onset neonatal sepsis. Cytokine. 2020;128:155000.

 PubMed Web of Science ®Google Scholar

Yang K-D, He Y, Xiao S, et al. Identification of progranulin as a novel diagnostic biomarker for early-onset sepsis in neonates. Eur J Clin Microbiol Infect Dis. 2020;39(12):2405–2414.

 PubMed Web of Science ®Google Scholar

Xie K, Kong S, Li F, et al. Bioinformatics-Based study to investigate potential differentially expressed genes and miRNAs in pediatric sepsis. Med Sci Monit. 2020;26:e923881-1.

 Web of Science ®Google Scholar

Khaertynov KS, Boichuk S, Khaiboullina S, et al. Comparative assessment of cytokine pattern in early and late onset of neonatal sepsis. J Immunol Res. 2017;2017:8601063–8601068.

 PubMed Web of Science ®Google Scholar

Cardoso FL, Herz J, Fernandes A, et al. Systemic inflammation in early neonatal mice induces transient and lasting neurodegenerative effects. J Neuroinflamm. 2015;12(1):82.

 PubMedGoogle Scholar

Smith CL, Dickinson P, Forster T, et al. Identification of a human neonatal immune-metabolic network associated with bacterial infection. Nat Commun. 2014;5(1):4649.

 PubMedGoogle Scholar

Fatmi A, Rebiahi SA, Chabni N, et al. miRNA-23b as a biomarker of culture-positive neonatal sepsis. Mol Med. 2020;26(1):1–9.

 Web of Science ®Google Scholar

Abdelaleem OO, Mohammed SR, El Sayed HS, et al. Serum miR-34a-5p and miR-199a-3p as new biomarkers of neonatal sepsis. PLoS One. 2022;17(1):e0262339.

 PubMed Web of Science ®Google Scholar

El-Hefnawy SM, Mostafa RG, Elfeshawy EM, et al. Biochemical and molecular study on serum miRNA-16a and miRNA-451 as neonatal sepsis biomarkers. Biochem Biophys Rep. 2021;25:100915.

 PubMedGoogle Scholar

Huang L, Qiao L, Zhu H, et al. Genomics of neonatal sepsis: has-miR-150 targeting BCL11B functions in disease progression. Ital J Pediatr. 2018;44(1):145.

 PubMedGoogle Scholar

Bryan T, Luo X, Bueno PR, et al. An optimised electrochemical biosensor for the label-free detection of C-reactive protein in blood. Biosens Bioelectron. 2013;39(1):94–98.

 PubMed Web of Science ®Google Scholar

Molinero-Fernández Á, Moreno-Guzmán M, López MÁ, et al. An array-based electrochemical magneto-immunosensor for early neonatal sepsis diagnostic: fast and accurate determination of C-reactive protein in whole blood and plasma samples. Microchem J. 2020;157:104913.

 Web of Science ®Google Scholar

Balayan S, Chauhan N, Chandra R, et al. Electrochemical based C-Reactive protein (CRP) sensing through molecularly imprinted polymer (MIP) pore structure coupled with Bi-Metallic tuned Screen-Printed electrode. Biointerface Res Appl Chem. 2022;6:38.

 Google Scholar

Lakshmanakumar M, Nesakumar N, Sethuraman S, et al. Fabrication of GQD-Electrodeposited Screen-Printed carbon electrodes for the detection of the CRP biomarker. ACS Omega. 2021;6(48):32528–32536.

 PubMed Web of Science ®Google Scholar

Guillem P, Bustos R-H, Garzon V, et al. A low-cost electrochemical biosensor platform for C-reactive protein detection. Sens Bio-Sens Res. 2021;31:100402.

 Google Scholar

Amouzadeh Tabrizi M, Acedo P. Highly sensitive RNA-Based electrochemical aptasensor for the determination of C-Reactive protein using carbon Nanofiber-Chitosan modified Screen-Printed electrode. Nanomaterials. 2022;12(3):415.

 Web of Science ®Google Scholar

Mahyari M, Hooshmand SE, Sepahvand H, et al. Gold nanoparticles anchored onto covalent poly deep eutectic solvent functionalized graphene: an electrochemical aptasensor for the detection of C-reactive protein. Mater Chem Phys. 2021;269:124730.

 Web of Science ®Google Scholar

Yang Z-H, Zhuo Y, Yuan R, et al. Electrochemical activity and electrocatalytic property of cobalt phthalocyanine nanoparticles-based immunosensor for sensitive detection of procalcitonin. Sens Actuators, B. 2016;227:212–219.

 Web of Science ®Google Scholar

Molinero-Fernández Á, López MÁ, Escarpa A. An on-chip microfluidic-based electrochemical magneto-immunoassay for the determination of procalcitonin in plasma obtained from sepsis diagnosed preterm neonates. Analyst. 2020;145(14):5004–5010.

 PubMed Web of Science ®Google Scholar

Liu J, Liu Y, Bao L, et al. Electrochemical sensitive determination of sepsis biomarker procalcitonin at graphitic carbon nitride nanosheets modified electrodes. Available at SSRN 3950172. 2021.

 Google Scholar

Jin Y, Wu J, Hu D, et al. Development of enzyme-free immunosensor based on nanobrush and fluorescence dye for sensitive detection of procalcitonin. Dyes Pigm. 2021;193:109548.

 Web of Science ®Google Scholar

Ding H, Yang L, Jia H, et al. Label-free electrochemical immunosensor with palladium nanoparticles functionalized MoS2/NiCo heterostructures for sensitive procalcitonin detection. Sens Actuators, B. 2020;312:127980.

 Web of Science ®Google Scholar

Qu L, Yang L, Ren Y, et al. A signal-off electrochemical sensing platform based on Fe3S4-Pd and pineal mesoporous bioactive glass for procalcitonin detection. Sens Actuators, B. 2020;320:128324.

 Web of Science ®Google Scholar

Balayan S, Chauhan N, Chandra R, et al. Molecular imprinting based electrochemical biosensor for identification of serum amyloid A (SAA), a neonatal sepsis biomarker. Int J Biol Macromol. 2022;195:589–597.

 PubMed Web of Science ®Google Scholar

Xia C, Li Y, Yuan G, et al. Immunoassay for serum amyloid a using a glassy carbon electrode modified with carboxy-polypyrrole, multiwalled carbon nanotubes, ionic liquid and chitosan. Microchim Acta. 2015;182(7-8):1395–1402.

 Web of Science ®Google Scholar

Panneer Selvam A, Prasad S. Companion and point-of-care sensor system for rapid multiplexed detection of a panel of infectious disease markers. SLAS Technol. 2017;22(3):338–347.

 PubMed Web of Science ®Google Scholar

Russell C, Ward AC, Vezza V, et al. Development of a needle shaped microelectrode for electrochemical detection of the sepsis biomarker interleukin-6 (IL-6) in real time. Biosens Bioelectron. 2019;126:806–814.

 PubMed Web of Science ®Google Scholar

Tanak AS, Muthukumar S, Krishnan S, et al. Multiplexed cytokine detection using electrochemical point-of-care sensing device towards rapid sepsis endotyping. Biosens Bioelectron. 2021;171:112726.

 PubMed Web of Science ®Google Scholar

Kamakoti V, Kinnamon D, Choi KH, et al. Fully electronic urine dipstick probe for combinatorial detection of inflammatory biomarkers. Future Sci OA. 2018;4(5):FSO301.

 PubMed Web of Science ®Google Scholar

Tang P, Zhang H, Huo J, et al. An electrochemical sensor based on iron (II, III)@ graphene oxide@ molecularly imprinted polymer nanoparticles for interleukin-8 detection in saliva. Anal Methods. 2015;7(18):7784–7791.

 Web of Science ®Google Scholar

Li L, Li M, Wang W, et al. High sensitivity determination of TNF-α for early diagnosis of neonatal infections with a novel and reusable electrochemical sensor. Sensors. 2017;17(5):992.

 PubMed Web of Science ®Google Scholar

Sharma PS, Wojnarowicz A, Sosnowska M, et al. Potentiometric chemosensor for neopterin, a cancer biomarker, using an electrochemically synthesized molecularly imprinted polymer as the recognition unit. Biosens Bioelectron. 2016;77:565–572.

 PubMed Web of Science ®Google Scholar

Huang C-Y, Hsieh C-H, Chen Y-L, et al. Portable potentiostatic sensor integrated with neopterin-imprinted poly (ethylene-co-vinyl alcohol)-based electrode. IET Nanobiotechnol. 2011;5(4):126–131.

 PubMed Web of Science ®Google Scholar

Data availability statement

The data that support the findings of this study are openly available in [google scholar, pubmed] at https://www.scopus.com/home.uri, https://scholar.google.com/, https://pubmed.ncbi.nlm.nih.gov/, https://www.researchgate.net/, reference number [1-156].