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Hybrid Nanobioengineered Nanomaterial-Based Electrochemical Biosensors: History
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Subjects: Engineering, Chemical | Nanoscience & Nanotechnology | Health Care Sciences & Services
Contributor:
Dayana Soto
,
Jahir Orozco

Nanobioengineered-based hybrid electrochemical biosensors exploit the synergistic properties of hybrid systems that connect biomolecules with nanomaterials to engineer highly sensitive biosensing platforms for the specific electrochemical detection of different target analytes.

  • hybrid
  • nanobiomaterial
  • bioreceptor
  • bioaffinity
  • biocatalytic
  • biosensor
  • cytosensor
  • genosensor
  • immunosensor
  • electrochemical

Graphical abstract

1. Introduction

Nanobioengineered-based hybrid electrochemical biosensors exploit the synergistic properties of hybrid systems that connect biomolecules with nanomaterials to engineer highly sensitive biosensing platforms for the specific electrochemical detection of different target analytes. Nanobioengineered platform-based electrochemical biosensors have been implemented in biomedicine, environmental, food, and security industries, demonstrating their versatility and great potential. Notably, in the biomedical field, modern nanobioengineered biosensing devices are escalating their horizon to face multitudinous medical complications, i.e., providing early, accurate, and specific diagnoses of diseases [1][2][3].
Electrochemical nanobiosensors are devices designed as alternatives to conventional laboratory-based detection techniques for disease diagnosis due to their robustness, small size, user-friendly operation, amenability for miniaturization, and potential for personalized diagnosis [4][5][6]. Electrochemical nanobiosensors comprise electroactive transducer platforms that anchor specific and selective bioreceptors, generating a nanobioconjugate. The nanobioconjugate uses different interactions between enzymes, antibodies, DNA(RNA) strands, cell-organelles, proteins, peptides, glycans, etc., with target analytes to report superficial electrochemical changes [7]. The sensing mechanism involves the target analyte–bioreceptor interaction, generating a stimulus transduced (transformed) into a decipherable signal that correlates to the target analyte’s concentration in a particular sample [8].
Despite the tremendous promise of electrochemical nanobiosensors in biomolecular analysis, they sometimes suffer from poor sensitivity and short shelf life. The limit of detection (LOD) and narrow dynamic range often limit their practical application, hindering their path toward the market [9]. In this context, current investigations in the biosensing field aim to engineer nanomaterials that, coupled with biomolecules and transducer platforms, can give rise to specific and versatile nanobiohybrid-based biosensors to address the commented limitations, paving the way toward real solutions.
In recent years, researchers have dedicated efforts to harnessing the unique atomic and molecular properties of nanobioengineered nanomaterials, including carbon nanomaterials, semiconductor/conductor polymers, metallic nanoparticles, and their nanoconjugates [10][11][12]. Such nanobiostructures may improve the interaction with the bioreceptors, thus dramatically amplifying the resultant signal, lowering the LOD, extending the linear detection range, shortening the testing time, and increasing the long-term stability of the detection systems [13][14][15].
Given such recent developments in nanomaterial engineering, this review reports understandings of advanced nanomaterials, giving an insight into the elucidation of their role in enhancing the analytical performance of electrochemical biosensors, unlike other reports from the literature. In this context, types of hybrid nanomaterials are systematically categorized, discussing their importance in detecting different target analytes of biomedical interest. Special attention is given to electrochemical biosensors incorporating various hybrid nanomaterials, explaining the chemistry of functionalization with biomolecules for assembling the biosensing systems and signal enhancement strategies’ fundaments, differencing elements concerning the state-of-the-art. Finally, a selected representative group of applications of nanomaterials in electrochemical biosensing were discussed to provide a more comprehensive background, including the detection of protein, peptidic, and genetic-disease-related biomarkers; small molecules; and metabolites, among others. It is anticipated that this review will be helpful for newcomers in the field and show them the importance of nanobiohybrid-biosensors in real-time medical diagnostic applications published in the last years.

2. Nanohybrids and Nanocomposites

Nanostructured nanomaterials, both nanohybrids and nanocomposites, have been increasingly exploited in developing electrochemical biosensors [16] and functional interfaces [17][18][19][20][21] with enhanced properties in terms of sensitivity, selectivity, robustness, and simplicity [22].
Nanocomposite materials are prepared by combining two or more different materials with different physicochemical properties, where one of the constituents has dimensions at the nanoscale or, instead, the nanocomposite structure exhibits a nanometric phase separation of the individual components. In preparing nanocomposites, one of the constituent materials acts as a support matrix in which other materials called reinforcement agents are incorporated [23][24]. Nanocomposites present mixed properties based on the original properties of each constituent nanomaterial, not modified during the preparation process [25].
Similarly, a hybrid nanomaterial combines organic and inorganic building blocks [4], which present a continuous interface between the structural components [25], and new, improved physicochemical properties emerge that are distinct from the specific properties of the components alone [26]. Hybrid nanomaterials can function as novel electrode materials, signal amplifiers, and catalysts of the electrochemical reaction of the product generated in situ during the biorecognition event. To date, the most common hybrid nanomaterials applicable to electrochemical biosensing include metallic nanostructures [27][28], silicon nanomaterials [29][30][31][32], carbon nanostructures [17][33][34], and semiconductor polymers [35][36][37][38][39], with great potential for the development of electrochemical nanobiosensors with enhanced performance [40][41][42], as commented. This section will comment on the main examples of the last ten years (Table 1), focused on nanostructured nanomaterials employed in developing nanohybrids for their implementation in electrochemical biosensing.
Table 1. Comparative analytical characteristics of nanomaterial-based electrochemical biosensors focused on the last ten years.

Nanomaterial

Hybrid a

Target b

Analytical Characteristics

Comments

References

Linear Range

LOD

Metallic nanostructures

3D hybrid graphene–GNR.

H2O2

0 to 50 mM

2.9 µM

Metallic nanostructures have high catalytic activity, easy preparation, and relatively low cost. However, this kind of nanomaterial can change its oxidation state due to variations in conditions of the medium, such as pH, ionic strength, and temperature upon time.

[43]

TiO2 nanoparticles encapsulated ZIF-8

Glucose

2 to 10 mM

80 nM

[44]

Nanohybrid of VS2/AuNP and CoFe2O4 nanozyme

Kana

1 pM to 1 μM

0.5 pM

[45]

Ag and hybrid Ag–Fe3O4 metallic nanoparticles.

AA

0.2–60 μM

74 nM

[46]

Silicon nanomaterials

mSiO2@MWCNT.

Thrombin

0.0001 nM and 80 nM

50 fM

These nanomaterials have high mechanical resistance, thermal stability, long functional life, and versatility; nonetheless, they require long synthetic processes, and their application is limited to certain analytes.

[31]

MSF/APTES/AgNP

STR

1 to 6.2 ng/mL

0.33 fg/mL

[47]

Ap–GA–NH2MCM-41–GCE

hemin and Hb

1.0 × 10−19 to 1.0 × 10−6 M

7.5 × 10−20 M and 6.5 × 10−20 M

[48]

AuNPs loaded in functionalized MSNPs

CEA

1.0 × 10−3 to 100 ng/mL

9.8 × 10−4 ng/mL

[49]

Carbon nanostructures

MWCNTs and GQDs.

IL-13Rα2

2.7 to 100 ng/mL

0.8 ng/mL

These nanomaterials enjoy thermal stability, large surface area, and a wide range of nanostructures and functional groups. They are the main nanomaterials used in the preparation of electrochemical biosensors.

[50]

GQDs/AuNPs.

P53

0.000592–1.296 pM

0.065 fM

[51]

CQDs/AuNps

Glucose

0.05 mM to 2.85 mM

17 μM

[52]

CoCu-ZIF@CDs

B16-F10 cells

1 × 102 to 1 × 105 cells/mL

33 cells/mL

[53]

Polymers

(Chi-Py) mixture, AuNPs, and MWCNT

Escherichia coli

3 × 101 to 3 × 107 cfu/mL

~30 CFU/mL

These have high biocompatibility, high affinity, strong adsorption ability, low molecular permeability, physical rigidity, and chemical inertness in biological processes. However, functionalizing their surface is necessary for the anchorage of bioreceptors, and some polymers oxidize due to changes in medium conditions.

[54]

PANI/active carbon and n-TiO2

Glucose

0.02 mM to 6.0 mM

18 μM

[55]

PEG/AuNPs/PANI

alpha-fetoprotein

10−14 to 10−6 mg/mL

0.007 pg/mL

[56]

Other nanostructured nanomaterials

WSe2 and AuNPs

Thrombin

0–1 ng/mL

190 fg/mL

Other hybrid nanostructures have a large specific surface area, excellent electrical conductivity, and electrocatalytic properties.

[57]

MoS2/Ti3C2 nanohybrids

miRNA

1 fM to 0.1 nM

0.43 fM

[58]

AuNPs/Ti3C2 MXene 3D

miRNA155

1.0 fM to 10 nM

0.35 fM

[59]

a GNR, graphene–gold nanorod; AuNPs, gold nanoparticles; Ap, aptamer; GA, glutaraldehyde; GCE, glassy carbon electrode; MSNPs, mesoporous silica nanoparticles; MWCNTs, multiwalled carbon nanotube; MSF, mesoporous silica thin film; APTES, (3-aminopropyl) triethoxysilane; AgNP, silver nanoparticles; CDs, carbon-dots; Chi-Py, pyrrole branched chitosan; PEG, polyethylene glycols; PANI, polyaniline. b AA, ascorbic acid; STR, streptomycin; miRNA; micro-RNA.

3. Conjugation of Nanohybrid Materials with Biomolecules

Biosensors can be label-free and label-based. Briefly, in a label-free mode, the detected signal is generated directly by the interaction of the analyzed (bio)material with the transducer. In contrast, label-based sensing involves chemical or biological compounds that act as labels, generating a detectable signal by analytical techniques such as colorimetry, fluorescence, and electrochemistry [60].

3.1. Bioreceptors

Biological receptors are biomolecules that bind to a specific ligand with a defined structure, commonly through bioaffinity interactions. These biological components are used when assembling nanobiosensors due to their high specificity, differentiating the target molecule from analogous counterparts and even isomers of the same molecule (Figure 1). Different bioreceptors can be anchored at electrochemical transducers to confer specificity to nanobioengineered devices. They can generally be classified into five major categories, i.e., enzymes, antibody/antigens, nucleic acids, cellular structures/cells, and biomimetic entities, as depicted in Figure 1.
Molecules 27 03841 g005 550
Figure 1. Scheme of electrochemical biosensors based on proteins, glycoproteins, antibodies, nucleic acids, aptamers, cells, or microorganisms at an electrode surface decorated with NPs, silicon nanomaterials, CNTs, graphene, QDs, polymers, or other nanomaterials.

4. Functional Groups and Conjugation Chemistry

Assembling nano(bio)sensors involves binding the bioreceptor’s specific and oriented form to the transducer surface [61] by physical or chemical methods. The physical methods include the following: (i) physical adsorption of the bioreceptor on a matrix based on hydrophobic, electrostatic, and van der Waals attractive forces; (ii) enzyme entrapment in a sol–gel, hydrogel, or paste, confined by semipermeable membranes; (iii) encapsulation—confinement of the biomolecule within a solid matrix. The chemical immobilization methods include (i) covalent binding of the bioreceptor to a solid matrix or directly to the surface of the transducer; (ii) crosslinking employing multifunctional, low-molecular-weight reagents based on the formation of strong covalent bonding between the transducer and the biological material using a bifunctional agent; (iii) affinity binding, exploiting specificity of a bioreceptor to its support under different physiological conditions (Figure 2). Conjugation is achieved either by coupling the bioreceptor to the matrix based on affinity interactions or conjugating the bioreceptor to an entity that develops affinity toward the matrix [62].
Molecules 27 03841 g006 550
Figure 2. Conjugation of nano(bio)sensors involves binding the bioreceptor’s specific and oriented form to the transducer surface by physical (A) or chemical methods (B). (A) The physical methods include (I) physical adsorption; (II) enzyme entrapment in a sol–gel, hydrogel, or paste, confined by semipermeable membranes; and (III) encapsulation. (B) The chemical methods include (I) covalent binding, (II) crosslinking, and (III) affinity binding.
The physical methods used in developing nano(bio)sensors are based on weak interactions and, therefore, the most straightforward and affordable. However, they are affected by environmental conditions such as pH, temperature, and ionic strength, generating biomolecule leaching processes during biodetection and storage. For this reason, covalent binding is commonly used as an immobilization alternative. However, this methodology requires modifying the surface of the electrode with a specific functional group that includes carboxylic acid (-COOH), aldehyde (-CHO), amine (-NH2), sulfhydryl (-SH), and azide (-N3) for the anchorage of bioreceptors. Therefore, this methodology requires precise knowledge of the surface chemistry of the electrode surface and the bioreceptor to favor the specific and oriented anchoring of the biomolecules [42].
Modification of the surface of the transducer can be achieved by bifunctional agents such as 4-aminobenzylamine (ABA) [63], 1-pyrenebutanoic acid, acid/basic treatment, or by modification of the electrode surface with affinity agents such as cysteamine [64], cyclodextrin [65], and biotin-avidin [38]. Finally, the modulation of bioreceptor–platform interactions [25] through specific groups on the nanostructured surface and the bioreceptors determines the methodology of immobilization, promotes the bioreceptor orientation, and increases its compatibility with the platform interface, thus influencing the selectivity, specificity, and stability of the resultant nanobioengineered platforms [28][61][65][66]. Therefore, changes in the surface chemistry of the platforms influence the physicochemical and electrochemical properties of the resultant (bio)sensing devices [67][68].
Bioreceptors can be reversibly adsorbed or trapped and retained or embedded on the surface of electrochemical platforms through ionic, electrostatic, hydrogen bonding, hydrophobic, or van der Waals interactions or irreversibly through covalent bonds. The interactions depend not only on the morphology and reactive functional groups on the electrochemical platform but also on the chemical nature, affinity, isoelectric point, and polarity of the solvent as well as the medium conditions for bioreceptor anchoring. As an illustration, the physical adsorption of bioreceptors can show low reproducibility due to the leaching effect during the analysis and little stability in different medium conditions. In contrast, the binding of biomolecules by covalent bonds through activated functional groups, often including carboxylic acid, amino, thiols, and esters, offers high stability despite possible aggregation, polymerization, and random biomolecule orientation [69]. Conjugation of nano(bio)sensors involves binding the bioreceptor’s specific and oriented form to the transducer surface by physical or chemical methods, as depicted in Figure 2.

5. Characterization of Nanobioengineered Platforms

Some of the main techniques to characterize nanoengineered platforms include electrochemical and physiochemical techniques such as CV, EIS, and DPV to characterize electrochemical behavior and electron transfer; Fourier transform infrared spectroscopy (FTIR) to characterize the composition and surface chemistry; scanning electron microscopy (SEM) to characterize morphology and composition; and dynamic light scattering (DLS) to determine the surface properties, summarized in Table 2 [70].
Table 2. Characterization techniques of hybrid nanomaterials, nanobioconjugates and electrochemical biosensors.

Techniques

Physicochemical Characteristics Analyzed

Fourier transform infrared spectroscopy (FTIR).

This technique characterizes the functional groups, surface properties, structure, and conformation of hybrid nanomaterials and nanobioconjugates.

Thermogravimetric analysis (TGA).

Thermogravimetric analysis of nanohybrids determines their thermal stability by estimating organic and inorganic material extent.

Ultraviolet spectroscopy (UV-Vis).

This technique can be used to estimate variables such as Km and Vmax in enzyme nanobioconjugates.

Dynamic light scattering (DLS).

This technique can estimate the hydrodynamic size distribution of nanostructures.

Electrophoretic light scattering.

The stability of nanomaterials is highly dependent on the surface charge, among other factors.

X-ray diffraction (XRD).

These techniques characterize hybrid nanomaterials’ size, shape, and crystalline structure.

X-ray photoelectron spectroscopy (XPS).

Transmission electron microscopy (TEM).

Imaging techniques study size, size distribution, aggregation, dispersion, heterogeneity, morphological characteristics, and compositional analysis of the hybrid nanomaterials and nanobioconjugates.

Scanning electron microscopy (SEM).

Electrochemical techniques.

Electrochemical techniques such as CV and EIS are used to evaluate electron transfer before, during, and after the bioreceptors attach to the surface of hybrid nanomaterials. They are also used to characterize the analytical properties of the resultant biosensors.

6. Examples of Nanobioengineered Platforms for Electrochemical Biosensing in the Last Five Years

The significant advance in developing nanobioengineered platforms for electrochemical biosensing has been remarkable in the last five years. However, new 2D and 3D nanomaterials emerge year by year with various improved properties ranging from quantum tunneling, excellent stability, and high conductivity and versatility, which provide new opportunities to develop electrochemical biosensors with high selectivity and extremely low LODs. Furthermore, the appearance of these novel nanostructured materials has led to the implementation of advanced and ultrasensitive biodetection tools (Table 3).

Biosensor

Application a

Nanobiohybrid: Nanomaterial and Biomolecules b

Characterization c

Analytical Performance

(Linear Range and LOD) d

Reference

Immunosensor

PSA

Antibody/HP5@AuNPs@g-C3N4 bioconjugated with PSA-Ab2

CV, EIS, and DPV

0.0005 to 0.00 ng/mL with LOD of 0.12 pg/mL

[71]

HER2

Ab/g-C3N4/AuNPs/Cu-MOF

CV and EIS

1.00 to 100.00 ng/mL with LOD of 3.00 fg/mL

[72]

AXL

Ab/fGQDs

XRD, FTIR, UV-Vis, TEM, EIS, DPV

1.7 to 1000 pg/mL with LOD of 0.5 pg/mL

[73]

CEA

CdSe-QD-melamine and Ab1-TiO2-AuNP-ITO

DPV

0.005 - 1000 ng/mL with a LOD of 5 pg/mL

[74]

CA19-9

CeO2/FeOx@mC

XPS, TEM, EIS, CV

0.1 mU/mL to 10 U/mL with a LOD of 10 μU/mL

[75]

NMP-22

Co-MOFs/CuAu NWs/Ab

SEM, XPS, CV, and chronoamperometry

0.1 pg/mL to 1 ng/mL with a LOD of 33 fg/mL

[76]

Genosensor

Zika

Anti-Dig-HRP

Chronoamperometry, CV, EIS

5 to 300 pmol/L with LOD of 0.7 pM

[77]

Zika genes

AuNPs/ssDNA

SEM, CV, DPV, and chronoamperometry

10 to 600 fM with LOD of 0.2 fM

[78]

CaMV35S gen

Fe3O4-Au@Ag-sDNA on MWCNT/AuNPs/SH-sDNA

TEM, XRD, UV-Vis, CV, and DPV

1 ×10−16 M to 1 ×10−10 M with LOD of 1.26 × 10−17 M 

[79]

mi-R21

3-(trimethoxysilyl)propyl methacrylate/ITO/PET/Fc-hybrid DNA hydrogel

DPV

10 nM to 50 μM with a LOD of 5 nM

[80]

miRNA-122

rGO/Au/DNA

XRD, TEM, Raman, XPS, CV, and DPV

10 μM to 10 pM with a LOD of 1.73 pM

[81]

OVA

SiO2@Au/dsDNA/CeO2

DPV

1 pg/mL to 1000 ng/mL with a LOD of 0.87 pg/mL

[82]

Enzymatic

Glucose

GOx/n-TiO2/PANI

CV and chronoamperometry

0.02 to 6.0 mM with LOD of 18 μM

[83]

Glucose

Cu-nanoflowers-Gox-HRP/AuNPs-GO-PVA nanofibers

UV-Vis, SEM, TEM, XDR, CV, and chronoamperometry

0.001 to 0.1 mM with a LOD of 0.018 μM

[84]

Organophosphate pesticides

acetylcholinesterase/chitosan-transition metals/graphene/GCE

SEM, TEM, XPS, XRD, CV, DPV and EIS

11.31 μM to 22.6 nM with LOD of 14.45 nM

[85]

β-hydroxybutyric acid

Ti3C2Tx nanosheets conjugated with β-hydroxybutyrate dehydrogenase

SEM, CV, and chronoamperometry

0.36 to 17.9 mM with a LOD of 45 μM

[86]

Based on peptides

norovirus

Cys/peptide/gold layer

CV and EIS

The LOD was 99.8 nM and 7.8 copies/mL for rP2 and human norovirus, respectively.

[87]

PSA

MXene-Au-MB nanohybrid/peptide

DPV

5 pg/mL to 10 ng/mL with a LOD of 0.83 pg/mL

[88]

PKA and CK2

Peptide/MSF/ITO

Chronoamperometry

The LODs were 0.083 and 0.095 U/mL, for PKA and CK2, respectively

[89]

NHE

Cys -PEG-QRRMIEEPA-MB

DPV and SWV

10 and 150 nM with a LOD of 250 pM

[90]

Based on glycoproteins

Toxoplasma gondii

Ab glycosylphosphatidylinositol/SPAuE

CV, EIS

1.0 to 10.0 IU/mL, with a LOD of 0.31 IU/mL

[91]

MIPs/glycoproteins

Fc/MPBA/AuNPs-SiO2 nanobioconjugate

FTIR, CV, EIS, DPV, and chronoamperometry

1 pg/mL to 100 ng/mL and reached a LOD of 0.57 pg/mL

[92]

Based on aptamers

tumor exosomes extracted from lymph node carcinoma of a prostate cells line

MNPs/aptamer-DNA/double-stranded DNA/GCE

DPV

The LOD was 70 particles/μL

[93]

miRNA

DSN/AuNPS/HRP

CV, EIS and chronoamperometry

The LOD was 43.3 aM

[94]

CA125 and living MCF-7 cells

Tb-MOF-on-Fe-MOF

SEM, TEM, XPS, CV, and  EIS

100 μU/mL to 200 U/mL with a LOD of 58 μU/mL towards CA125. Moreover, biosensor detecting MCF-7 cells with a LOD of 19 cells/mL

[95]

CEA and NSE

Paper-electrode functionalized with amino-modified graphene-Thi-AuNPs and PB-PEDOT

DPV

0.01 to 500  ng/mL for CEA and 0.05 - 500  ng/mL for NSE with a LOD of 2 pg/mL for CEA and 10  pg/mL for NSE, respectively

[96]

Other types of biosensors (based on cells or mimicking biosensors)

Impedimetric biosensor/Escherichia coli B.

CNT/PEI-T2 virus/GCE

EIS

103 to 107 CFU/mL with LOD of 1.5 × 103 CFU/mL

[97]

Nonenzymatic biosensor/glucose

GS/GNR/Ni

Chronoamperometry

5 nM to 5 mM with a LOD of 2.5 nM.

[98]

Mimicking biosensor/H2O2 released from H9C2 cardiac cells

AuNFs/Fe3O4@ZIF-8-MoS2

SEM, fluorescence, CV, EIS, and chronoamperometry

5  μM - 120  mM and a LOD of 0.9  μM

[99]

Electrochemical/glucose

CuOx@Co3O4 core-shell nanowires/ZIF-67

SEM, TEM, XRD, XPS, CV, and chronoamperometry

0.1 to 1300.0 μM with a LOD of 36 nM

[100]

Mimicking/L-tyrosinase

UT-g-C3N4/Ag hybrids

TEM, XPS, XRD, AFM, EIS, CV, and DPV

1.00× 10−6 to 1.50 × 10−4 mol/L with a LOD of 1.40 × 10−7 mol/L

[101]

Biomimetic biosensor/glucose

Fe3O4@PNE-GOx

Chronoamperometry

0.24 to 24 mM with a LOD of 6.1 µM

[102]

PAD/creatinine

CuO/IL/ERGO/SPCE

Chronoamperometry

0.01 to 2.0 mM and a LOD of 0.22 μM

[103]

3D paper-based microfluidic electrochemical biosensor/glucose

 

rGO-TEPA/PB

SEM, Raman, CV, and chronoamperometry

0.1 mM - 25 mM with a LOD of 25  μM

[104]

aPSA, prostate-specific antigen; HER2, human epidermal growth factor receptor 2; AXL, tyrosine kinase; CaMV35S, cauliflower mosaic virus 35S; SAMs, self-assembled monolayers; MIPs, molecular imprinted polymers; miRNA, micro-ribonucleic acid; CA19-9, carbohydrate antigen 19-9; CA125, carbohydrate antigen 125; NMP-22, nuclear matrix protein-22; PKA, protein kinase A; CK2, casein kinase II; PAD, paper-based analytical devices; OVA, ovalbumin; CEA, carcinoembryonic antigen; NHE, human neutrophil elastase; NSE, neuron-specific enolase.

bHP5, hydroxylpillar[5]arene; AuNPs, gold nanoparticles; Ab, antibody; Gox, glucose oxidase; PANI, polyaniline; Cys, cysteine; MOFs, metal-organic framework; fGQDs, functionalized graphene quantum dots; anti-Dig-HRP, antibody-digoxigenin-horseradish peroxidase; ssDNA, single-strand DNA; MWCNT, multiwalled carbon nanotube; CNT, carbon nanotube; PEI, polyethyleneimine; GCE, glassy carbon electrode; SPAuE, screen-printed gold electrode; MNPs, metallic nanoparticles; Fc, ferrocene; MPBA, 4-mercaptophenylboronic acid; QD, quantum dots; ITO, indium tin oxide; DSN, duplex-specific nuclease; PET, polyethylene terephthalate; GO, graphene oxide; PVA, poly(vinyl alcohol); GS, graphene sheet; GNR, graphene-gold nanorod; rGO, reduced graphene oxide; UT, ultrathin; PEG, polyethylene glycol; MB, methylene blue; THI, electron-mediating thionin; PB, Prussian blue; PEDOT, poly(3,4-ethylenedioxythiophene), SPCE, screen-printed carbon electrode; MSF, mesoporous silica thin film; PNE, polynorepinephrine; IL, ionic liquid; ERGO, electrochemically reduced graphene.

cCV, cyclic voltammetry; EIS, electrochemical impedance spectroscopy; DPV, differential pulse voltammetry; XRD, X-ray diffraction; XPS, X-ray photoelectron spectroscopy; FTIR, infrared spectroscopy; UV-Vis, ultraviolet visible spectroscopy; SEM, scanning electron microscopy; TEM, transmission electron microscopy; SWV, square wave voltammetry.

dLOD, limit of detection.

  7. Limitations, Opportunities, and Concluding Remarks

Biosensor technology based on nanobiohybrid materials represents a vast field that significantly impacts healthcare, the environment, and food quality control. These functional platforms promote target molecule detection with high specificity and sensitivity, particularly in the biomedical field [105][106][107][108][71][109]. Furthermore, the rational design of the nanobiohybrids has been demonstrated to enhance the response and long-term stability of the resultant devices due to the incorporation of nanomaterials with improved properties that promote a favorable nanoenvironment for bioreceptors anchoring. Besides, the versatility of nanomaterials facilitates the conjugation with molecules by multiple conjugation chemistry, opening options to detect numerous target molecules.

Electrochemical-based nanohybrid biosensors have the potential to solve most of the limitations and concerns of bioanalysis and diagnostic tests while maintaining the required sensitivity, selectivity, and LOD to face real needs. Besides, integrating sample preparation into the device allows the possibility of direct analysis within a sample matrix and offers opportunities for new strategies of long-term analysis in vivo, among many other exciting applications. Electrochemical nanohybrid biosensors are particularly suitable for miniaturization and integration in microfluidic devices, thus reducing the consumption of reagents and samples {Formatting Citation}. Applications include detecting whole cells, cell components, proteins, and small molecules to address diagnostics and food and environmental control tasks online and in real-time, but still require more sophisticated platforms with additional elements, such as sample preparation. Although nanobioengineered biosensors are an affordable analytical strategy relative to gold standard detection methods, the development of large-scale electrochemical nanobiosensors is still challenging because they require state-of-the-art technologies for their production in a reproducible and stable manner, directly influencing the cost of the sensing device [109][110]. This apparent drawback could be overcome by scaling, automation, and mass manufacturing to lower costs through advanced methods in elaborating cost-affordable and disposable electrochemical nanobiosensors based on additive manufacturing, including screen inkjet 3D printing or microfabrication technologies [111][110][112][113].

Overall, this review exemplified nanobiosensors mainly based on screen-printed electrodes modified with nanohybrids conjugated with highly specific bioreceptors for enhanced biosensing. Yet, the richness in the art of biosensors deserves deeper exploration and support of exciting new ideas. Overall, nanobiohybrids are paving the way in the pioneering development of highly sensitive and selective electrochemical nanobiosensors and represent remarkable research advances that are a step forward in increasing the impact of this exciting, cutting-edge technology in the field of biomarker detection of clinical interest [110].

 

This entry is adapted from the peer-reviewed paper 10.3390/molecules27123841

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