Nanomaterial application in bio/sensors for the detection of infectious diseases.

Infectious diseases are a potential risk for public health and the global economy. Fast and accurate detection of the pathogens that cause these infections is important to avoid the transmission of the diseases. Conventional methods for the detection of these microorganisms are time-consuming, costly, and not applicable for on-site monitoring. Biosensors can provide a fast, reliable, and point of care diagnostic. Nanomaterials, due to their outstanding electrical, chemical, and optical features, have become key players in the area of biosensors. This review will cover different nanomaterials that employed in electrochemical, optical, and instrumental biosensors for infectious disease diagnosis and how these contributed to enhancing the sensitivity and rapidity of the various sensing platforms. Examples of nanomaterial synthesis methods as well as a comprehensive description of their properties are explained. Moreover, when available, comparative data, in the presence and absence of the nanomaterials, have been reported to further highlight how the usage of nanomaterials enhances the performances of the sensor.

Introduction

Infectious or transmissible diseases are those diseases that can be transmitted by bacteria, viruses, fungus, and parasites [1]. According to the World Health Organization reports consumption of unsafe foods, that are polluted with harmful bacteria, viruses, parasites, or chemical substances leads to 200 types of sickness including cancers, sepias, homoerotic diarrhea, etc. [2]. Moreover, diarrhea-associated infections related to the intake of contaminated food or water are the third cause of mortality in developing countries, and around a million people's death is reported for this every year [[2], [3], [4]].

Facing threats like Ebola, dengue, Zika, severe acute respiratory syndromes (SARS-Cov-2), Middle East respiratory syndrome (MERS), and severe known as well as unknown pathogens endanger human health and, in a large view, economic welfares [5]. Bacteria such as Escherichia coli O157: H7, Salmonella enterica serovar Typhimurium, Klebsiella pneumonia, Listeria monocytogenes, Enterococcus faecalis, Campylobacter, Acinetobacter baumannii and Viruses like influenza virus H5N1, H N , HIV, HPV, and enterovirus 71 cause enormous hospitalizations and death all over the world. Therefore, the development of new, fast, and reliable approaches to detect these sources of infection are crucial to prevent the epidemic of these diseases [6,7].

Nanomaterials with specific electrical, optical, magnetic, chemical and mechanical properties have been found effective application in many areas including biosensors or chemical sensors, diagnostics methods, drug delivery, energy harvesting, and tissue engineering [8]. This unquestionably owes to the intrinsic high surface area to volume ratio of these materials that can present more recognition sites and quicker signal transduction procedure [9]. Nanomaterials according to the European commission's recommendation 2011, “is a natural, incidental or manufactured material containing particles, in an unbound state or as an aggregate or as an agglomerate and where, for 50% or more of the particles in the number size distribution, one or more external dimensions is in the size range 1 nm–100 nm” [10]. They can be categorized into four groups based on the material using in their fabrication 1) carbon-based nanomaterials that are carbons with different morphology such as hollow tubes, ellipsoids or spheres e.g. Graphene, Graphene oxide, Carbon nanotubes (CNTs), Fullerenes (C60), Carbon black and carbon nano onion. 2) Inorganic-based nanomaterials, these groups involve metal (Au, Ag, Pt, Ni, Cu), metal oxide nanoparticles (ZnO, TiO2, MnO2, Fe2O3, Al2O3), SiO2, semiconductors such as silicon and ceramics, and inorganic semiconductor nanocrystals which also called quantum dots (CdS, ZnO, CdS). 3) Organic-based nanomaterials, these groups are nanomaterial from organic material such as (dendrimers, micelles, liposomes, and polymer NPs). 4) Composite-based nanomaterials, that are multi-phase nanoparticle and nanostructured materials with one phase on the nanoscale size which can combine either with other nanoparticles or bulk-type materials (e.g., hybrid nanofibers) or more complicated structures, such as metal-organic frameworks (MOF). The composites may be any combinations of carbon-based, metal-based, or organic-based nanostructured materials with any form of metal, ceramic, or polymer bulk materials [11,12]. In the present review, we will focus on electrochemical and optical sensors for infectious diseases which used nanomaterials like metallic nanoparticle (Ag, Au), magnetic nanoparticle, bimetallic nanoparticle, silica nanoparticle, graphene family, carbon nanotube, carbon dot, quantum dots, and upconversion nanoparticles.

Nanomaterial

Magnetic nanoparticle (MNP)

Magnetic nanoparticles are well known for special magnetic properties like superparamagnetism and high magnetic susceptibility [13]. These nanoparticles have found extensive applications due to their unique advantages including low production cost, large surface area, high mass transference, direct capture, easy separation, improving the washing steps, and minimizing the matrix effect. Besides their application in sample enrichment, they have been shown to enhance sensor sensitivity, increase the signal-to-noise ratio, and decrease the time of analysis [14,15]. The role of the MNPs is dependent on their sizes that can be influenced by the preparation method [16]. MNPs with a size of less than 30 nm possess superparamagnetic properties making these good candidates for enrichment applications because of an immediate response to the applied magnetic field [17]. Different types of Magnetic nanoparticles like iron oxides (Fe2O3 and Fe3O4); ferrites of manganese, cobalt, nickel, and magnesium; multifunctional composite MNPs, such as Fe3O4-Ag, Fe 3O4-Au, Fe3O4-SiO2 are reported. Among them, Fe3O4 is the preferred magnetic nanoparticle in biosensor development because of its superparamagnetic property, biocompatibility with antibodies and enzymes, and ease of preparation [14]. Among the demonstrated manufacturing methods, like thermal decomposition, microemulsion, electrochemical, solvothermal, sol-gel, sonochemical, and co-precipitation for synthesis Fe3O4 nanoparticle; co-precipitation is the most used technique in the synthesis Fe3O4 [17]. More details about different synthesis method of iron oxide nanoparticles and surface modification [[17], [18], [19]] properties of iron oxide nanoparticles [17], magnetic CoFe2O4 [20] magnetic nanoparticle [21] are available in these references.

Gold nanomaterials

Gold nanomaterials with a wide variety of shapes, such as rods, spheres, cubes, wires, and cages, are among the most popular nanomaterials for sensor applications [22]. Their intrinsic properties, such as good biocompatibility, large surface area, ease of synthesis and modification, and high chemical and thermal stability make Au nanomaterial ideal choice as substrates and transducers for sensors. The optical properties of these materials depend on their size and shape which can be controlled/tuned during the synthesis process. Besides, the surface of gold nanomaterial can be modified by electrostatic, hydrophobic, and covalent bonding; for example, the strong bond between gold atoms and nitrogen or sulfur, enable efficient attachment of molecules via the well-established thiol or amine chemistry [9].

Gold nanoparticle (AuNPs)

Gold nanoparticles (AuNPs) are polycrystalline Au nanostructure with a quasi-spherical shape and typically 5–100 nm diameter size. In electrochemical sensors, AuNPs, have found application due to their ability to improve the charge transfer processes [23] and the electrode's conductivity [24]. AuNPs are extensively applied as a colorimetric indicator, because of their surface plasmon resonance property [25,26]. Along with their optical and electrochemical properties, AuNPs are very attractive in biosensing since their high surface area offer unprecedented opportunities for high loading of biomolecules such as antibodies, enzymes, and aptamers; moreover, gold nanoparticles have been shown to maintain high bioactivity of immobilized biomolecules [23]. Chemical reduction or ligand passivation methods and their variants are popular approaches for manufacturing AuNPs. Peng et al. discussed various methods for the synthesis of gold nanomaterial family [9].

Gold nanorods (AuNRs)

Anisotropic Nanorods are cylindrical rod-shaped particles with uniform diameters ranging from a few nanometers to hundreds of nanometers, with aspect ratios (length to width) larger than 1 but typically smaller than 10 [27]. The main features of AuNRs are depending properties like intensities and spectral positions of SPR-bands, aggregative stability, electroconductivity, and redox potential by physical size [28]. One of the peculiarities of the AuNRs is those to present two distinct surface plasmon resonances; one along with the longitudinal ax and one on the transversal ax. The longitudinal plasmon resonance generates radiation in a wide range from visible to near-infrared regions depending on the AuNRs aspect ratio and their size which is a distinguishable feature of nanorods when compared to nanoparticles [28,29]. Among the different approaches proposed to producing AuNRs, seed-mediated growth is the most commonly used because of a simple procedure, adjustable aspect ratio, great uniformity, and adaptability for post-modification [9,30]. There are promising reviews about the synthesis and properties of gold nanorods [30] gold nanorods and their nanocomposites synthesis and recent applications in Analytical chemistry [28].

Gold nanocluster (AuNCs)

AuNCs are molecular like arrangements consisting of several hundred Au atoms with an average size of 2 nm. They are located between Au atoms and AuNPs and can be fabricated by atoms to clusters and nanoparticles to clusters approaches. Atoms to cluster approach based on template-based synthesis and ligand-protected methods. While, nanoparticles to clusters methods are etching surface atoms of gold nanoparticles by appropriate ligand, or solvents [31]. AuNCs are characterized by photoluminescence [32]and high catalytic properties [33]; on the other end, AuNCs do not present the surface plasmon resonance properties characteristic of the AuNPs and AuNRs [9]. Zhang et al. discussed synthesis methods and biomedical and biosensing applications of Au nanoclusters in a recent review [34].

Silver nanoparticles (AgNPs)

Silver nanoparticles (AgNPs) present unique plasmonic properties that can be influenced by different parameters, such as size, shape, uniformity, composition, dispersion, etc. [35]. Moreover, these nanomaterials have prominent benefits including low cost, simple preparation, high extinction coefficients, and sharp extinction band [36]. AgNPs can be produced, similarly to their counterparts AuNPs, by chemical reduction using reducing agents like NaBH4, tri-sodium citrate, thiosulfate, and polyethylene glycol. Polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA), and CTAB are often used to stabilize particles and avoid sedimentation and agglomeration of nanoparticles [37].

Bimetallic nanoparticles

Bimetallic nanoparticles are consist of two different metal NPs and can have various morphologies and structures. They can be classified based on structures into mixed and segregated structures. Mixed forms subdivide into alloy and intermetallic. In alloyed nanoparticles nanocrystals of two metals are randomly mixed; however, in intermetallic structures, the two metals are mixed in an ordered way. The segregated structures are categorized as subcluster, core-shell, multishell core-shell structures, and multiple core structures. A subcluster is a separate distribution of two metals with a shared interference. Core-shell structures are composed of a metal core surrounded by a shell of the second metal. Multishell core-shell structures are an alternative arrangement of metals forming a shape like onion rings. Multiple core materials are multiple small cores coated by a single shell. Various types of bimetallic nanoparticles are platinum, nickel, iron, palladium, and gold-based bimetallic nanoparticles [38]. Due to the collaborative effect of two different metals, bimetallic nanoparticles display novel features such as tunable surface plasmon band and optical properties and improved stability and dispersibility that make them attractive materials in electrochemical and optical sensors [39,40]. They can prepare with chemical, physical, and biological methods [41]. Some interesting reviews for synthesis, properties, and application of bimetallic nanoparticle [39,42], noble metal bimetallic nanoparticle [43] are provided in the former references.

Quantum dots (QDs)

Quantum dots (QDs) is a family of nanomaterials with outstanding optical properties like narrow emission, wide absorption spectra, size-controlled emission from visible to the infrared range (400–4000 nm), good photostability, and high quantum yields. Generally, these are composed of atoms from IIB-VI, III–V, or IV-VI groups of the periodic table that have 1–10 nm size dimensions which is smaller than the exciton Bohr radius [[44], [45], [46]]; their nanocrystal (dots) nature defines the quantum controlled mechanics of their optical properties. Capping agents on the surface of QD including alcohols, primary amines, carboxylic acid thiols, and long-chain organophosphorates play a pivotal role in the application of these materials. Ligands facilitate modification of the surface with biomolecules and responsible for colloidal stability, solubility, particle size distribution as well as growth or agglomeration [47,48].

Graphene group

Graphene is one of the carbon allotropes with a plane two-dimensional nanostructure. This possesses excellent optical and electronic properties, converting it into a fast-growing material for designing optical and electrochemical sensors [49,50]. There are different graphene-based nanomaterials, pristine graphene, graphene oxide (GO), and reduced graphene oxide (rGO). GO was regarded as a result of chemical exfoliation and oxidizing of layered crystalline graphite [51]. rGO is the product of GO reduction via physical, chemical, or electrochemical methods. These differ from each other in terms of, composition, purity, lateral dimensions, oxygen content, surface chemistry, and electric properties [52,53]. GO is strongly hydrophilic with oxygenated functional groups that facilitate chemical functionalization of it. The presence of versatile functional groups such as OH, COOH, and CHO allows interaction with biomolecules to improve the selectivity of the biosensors [54] but reduce the electrical conductivity due to its insulating nature for electrochemical application [55]. rGO demonstrated an improvement in electrical conductivity and remaining oxygen groups, converted it to a useful material in developing biosensors. Graphene and graphene derivatives can be coupled with different materials, such as metal oxides, metal nanoparticle, and organic polymers obtaining in this way diverse nanocomposites with tailored properties [56,57]. Interesting reviews about graphene-based electrochemical biosensors that discussed different types and synthesis methods [55] and reduced graphene for electroanalytical sensing platforms [58] are available in the former papers.

Carbon nanotube (CNTs)

Carbon nanotubes (CNTs), including single-wall and multiwall carbon nanotubes (SWCNTs and MWCNTs, respectively) [59] have attracted great attention in sensors due to their high surface area, high electrical conductivity, high thermal conductivity, and great mechanical strength. CNTs also possess specific inherent optical properties as, for example, potent resonance Raman scattering and Near-Infrared photoluminescence [60]. CNT can produce by three main synthesis methods including chemical vapor deposition, electric arc method, and laser deposition method [61].

Carbon dot or carbon particles (CD)

Carbon dots (CDs), as a new type of fluorescent carbon-based nanomaterial, have promising properties to design the fluorescent sensor to conventional fluorescent probes like superior optical properties, strong absorption, bright photoluminescence, excellent light stability, resistance to light bleaching, low toxicity, environmental-friendly, good biocompatibility, and facile synthesis [62,63]. CDs are zero-dimensional carbon-dominated nanomaterial, with a size of less than 20 nm which consisted of sp2/sp3carbon skeleton and abundant functional groups/polymer chains [62]. Functional groups are OH, COOH, and NH2 [64,65]. Although there is considerable debate about the classification of CDs, they can be categorized into carbon quantum dots (CQDs) graphene quantum dots (GQDs), carbon nanodots (CNDs), and polymer dots (PDs) [62]. Two main synthesis routes, the top-down include arc discharge, laser ablation, electrochemical synthesis, nanometer etching, hydrothermal/solvothermal/special oxidation cleavage, and the bottom-up method involves combustion, pyrolysis, hydrothermal, solvothermal, and microwave assistant pyrolysis have been reported for the preparation of carbon dots [62,63,66].

Upconversion nanoparticles (UCNPs)

Upconversion nanoparticles (UCNPs) with near-infrared (NIR) excitation characteristics have received considerable attention in bio-imaging (e.g. nanoprobe) [67]. The most used of UCNP-based nanoparticles are in fluorescence resonance energy transfer, FRET sensor. The UCNP's fluorescence were quenched or recovered after the additions of analytes via modulating the absorption of energy acceptors or the distance between donors and acceptors [68].UCNP are a special class of nanomaterial doped with lanthanide ions; these consist of three components, a sensitizer (Yb3+) for absorbing energy from a laser source, an emitter that works as a luminescence hearts of UNCPs (Tm3+, Er+3, Ho+3), and a host matrix. The host matrix has a substantial influence on optical features, fluorescence efficiency, and chemical properties. Fluorides due to their high chemical stability, low photon energy, are well-suited hosts for UCNPs. Synthetic procedures like co-precipitation, thermal decomposition, hydro/solvothermal synthesis, and sonochemical methods have been reported in the manufacturing of UCNPs [67]. These nanoparticles are characterized by low toxicity, sharp emission band, long fluorescence lifetime, less light scattering, high photostability, tunable multicolor emission, high light penetration depth, and larger anti-stocks shifts, when compared with more conventional fluorochromes, making them particularly useful for biosensor applications [68,69].

Silica nanoparticles

Numerous silica nanoparticles (SiNPs) and hybrid silica nanoparticles with solid or porous structures can be prepared via diverse methods such as hydrothermal, sol-gel, and reverse emulsion [70]. Silica nanoparticles can be further modified with organic dye which leads to rich color particles [71]. SiNPs are characterized by high stability, biocompatibility, chemical inertness, large surface area, transparency, and easy functionalization using silane chemistry [72,73]. Besides, silica can be used as a protective and stabilizing layer of magnetic nanoparticles or noble metal particles. Silica covering of gold particles is usually carried out with the Stӧber method allowed thickness control with adjusting reaction time and reagent concentration [73]. A schematic of nanoparticles which are described in this section and the applied biosensors is illustrated in Fig. 1 .

Fig. 1

Schematic of different nanomaterials and biosensors used in detection infectious disease.

Biosensors for infectious disease based on nanomaterials

Electrochemical biosensors

Electrochemical detection methods are widely used because of their easy procedure, high sensitivity, and ready to scale down for portable applications [74,75]. Also, screen printed technology facilitates the large scale fabrication of portable, low-cost analytical systems that can operate with small sample volume [76]. Nanomaterials have found extensive application in electrochemical sensors ranging from analyte separation/concentration (e.g. magnetic particle [[77], [78], [79], [80], [81], [82], [83], [84], [85], [86], [87], [88], [89], [90]]) to the catalyst of redox reactions [23,[90], [91], [92], [93], [94], [95], [96], [97], [98], [99], [100], [101], [102]], enhancer of electrodes’ surface conductivity [24,103], to grafting elements for efficient loading of biomolecules [79,93,104], as well as excellent sensitivity that achieve with QDs [[105], [106], [107], [108]].

Magnetic beads are commonly used in rapid assays to capture the targets from crude samples before detection [15]. The use of these not only allows to pre-concentrate the analyte (e.g. biomarkers) but also to reduce interferences that lead to an increase in the sensitivity and specificity of the sensors. Importantly superparamagnetic properties of magnetic nanoparticles allow their re-dispersion, with limited/no agglomeration, in the absence of the magnetic field. The surface of MNPs can be easily engineered, using specific coating providing in this way an appropriate functional group for the immobilization of biomolecules; furthermore, it has been shown that immobilization of biomolecules reduces their biodegradation when in contact with complex environmental or biological systems [78,90].

Electrochemical immunosensors have been effectively used for the detection of pathogens [78,90,91] due to simple handling methods, high sensitivity, and good applicability in real samples. Moreover, the sandwich assay enables the construction of a more specific and sensitive immunosensor in comparison to direct detection [23].

Fei et al. reported on the preparation of Fe3O4/SiO2/AuNPs and their application in electrochemical immunosensing. Fe3O4-NPs were prepared using the co-precipitation method; these, following capping with SiO2 and pre-functionalization with 3-Mercapto-propyltriethoxysilane (MPTES), were coated by AuNPs that served as anchoring element for S. pullorum and S. gallinarum antibodies. S. pullorum and S. gallinarum in the sample were captured by the Fe3O4/SiO2/AuNPs and separated from the samples by applying an external magnetic field. Au-Nps/Fe3O4NPs with carrying bacteria, re-dispersed in buffer solution contained horseradish peroxidase (HRP) labeled anti-S. pullorum and S. gallinarum to form a sandwich complex. The sandwich complex was dropped on 4-channel screen-printed carbon electrode already modified with electrodeposited AuNPs and supplied with a magnet, followed by the addition of thionine and hydrogen peroxide. To detect S. pullorum and S. gallinarum the reduction peak current change of the CV before and after reaction of HRP with hydrogen peroxide was recorded. The antibody immobilized efficiently on the Fe3O4/SiO2/AuNPs surface and 93.95% of the electrode signal was maintained after 30 days of storage indicated the ability of Fe3O4/SiO2/AuNPs to retain the bioactivity of the adsorbed antibody [90]. The schematic of this procedure is depicted in Fig. 2 A. Wang et al. [80]developed a portable electrochemical system, based on a personal glucose meter (PGM), for detecting E. Coli O157: H7 and S. aureus. In the reported work glucoamylase-quaternized magnetic nanoparticles (QMNP) were used to capture and detect bacteria, via a competitive mechanism. Following the capture of bacteria, via electrostatic interaction, on the positively charged QMNPs nanoparticles, Glucoamylase was released to the solution; this was then used to catalyze the hydrolysis of amylose, added in the solution into glucose which was then detected by PGM. QMNPs also prevented the growth of the bacteria which led to killing and monitoring pathogens at the same time [80]. Luo et al. used PGM to develop a rapid, portable, and sensitive immunosensor for S. pullorum and S.gallinarum. In this work capture of pathogens, performed using MNP-antibody, was followed by the introduction of an enzymatic label (antibody- SiNps-glucose oxidase (GOx). The so generated sandwich system, following magnetic capture and cleaning, was dispersed in a glucose solution. Glucose concentration monitoring before and after hydrolysis of glucose by GOx revealed that the reduction in glucose concentration was proportional to the logarithm concentration of bacteria. The immune nanoparticles used in this work were shown to retain their activity after storage at 4 °C for at least 90 days [109].

Fig. 2

A) Schematic diagram of the synthesis process of the Fe3O4/SiO2 nanoparticle, immobilization antibody, capturing S. pullorum and S. gallinarum from sample, sandwich complex dropped on AuNPs/4-SPCE electrode with permission ref [90], B) Presentation of the assay with enzymatic amplification colorimetric detection and nanoparticle-based amplification and electrochemical detection with permission ref [15] C) Biosensor with npcRNA for simultaneous detection of three pathogens with permission of ref [105] D) Ratiometric photoelectrochemical aptasensor with permission [119].

Oxidoreductase Enzymes, like Horseradish peroxidase (HRP), are generally used in immunoassays to improve signal and reduce noise. Nanoparticles with peroxidase-like activity (e.g. Au@Pt bimetallic nanoparticle) are an attractive alternative to enzymes in immune assays resulting in more stable and cost-effective sensors [79,92]. For example, Zhu and coworkers fabricated two sandwich-type immunosensor with Fe3O4@SiO2-Ab1/E.coliO157: H7/rGO-NR-Au@Pt-Ab2s for Escherichia Coli O157: H7 detection [78,79]. One of the immunosensor utilized HRP [78] while the second one used Au@Pt nanoparticles instead of the enzyme [79]. The non-enzymatic system could reach a LOD of 4.5 × 102 CFU mL −1 and a linear range of 4 × 103 to 4 × 108 CFU mL−1; while the enzyme-based system was linear in 4 × 102 to 4 × 108 CFU mL−1 concentration range with a LOD of 91 CFU mL−1. Besides, 91.0% of the initial response was retained after 5-weeks’ storage of the Non-enzymatic electrode. Mo et al. also demonstrated the ability of non-enzymatic labels, reduced graphene oxide –natural red -Au@Pt, to retain their activity (85.46% of the initial signal) even after ten weeks of storage [92].

Gold nanomaterials have been widely used in electrochemical sensors due to biological compatibility, electrical conductivity, the high surface-to-volume ratio [22]. Moreover, gold nanomaterials can effectively couple with other nano/materials to produce various Au-based nanocomposites biosensor like poly(diallyldimethylammonium chloride)-functionalized graphene oxide and AuNps [98] chitosan/MWCNT/Polypyrrole/AuNPs [24] rGO/AuNR/poly thionine [110] to develop new electrochemical sensors with improving sensitivity, selectivity, and stability.

Xiang et al. developed a sandwich electrochemical immunosensor for the detection of Salmonella based on AuNPs dispersed in oxidized chitosan film on a glassy carbon electrode surface. In the reported work the presence of AuNPs in the film provided a more conducive platform for the immobilization of antibody, improved the catalytic activity of film for H2O2 reduction and the immobilized HRP-antibody structure preserve high catalytic activity on the biocompatible substrate. The developed sensor presented good selectivity and reproducibility with higher sensitivity when compared to the sensor based on pure chitosan film [111]. Lin et al. compared two impedimetric biosensors, based on self-assembled thiolated protein G, which was used for oriented immobilization of goat anti - E. coliO157: H7 IgG using a bare gold electrode and gold nanoparticles modified electrode. Thiolated protein G was applied on the gold electrode surface while for the AuNP modified electrode, the gold electrode surface was first modified with a layer of 1, 6-Hexanedithiol, then colloidal AuNPs and thiolated protein G were applied on the surface. The AuNPs modified electrode was shown to have 2.2 times larger active area and a LOD 48 CFUmL−1 for detection E. Coli O157: H7 which is 3 times lower than those recorded for the bare gold electrode [94]. Lin et al. reported on a regenerable and sensitive impedimetric immunosensor for the detection of type 5 adenovirus; the sensor was based on a multi-layered architecture assembled onto the surface of an Au electrode. The Au electrode was coated with AuNPs, grafted onto the sensor surface via 1, 6 hexane dithiol layers. 11-mercaptoundecanoic acid was then self-assembled on the sensor surface to attach monoclonal anti-adenovirus-5 antibodies. Regenerating the surface was carried out by applying a constant negative potential that could clean the gold electrode surface completely and enable the reuse of the electrode [95]. Ariffin and co-workers reported on ultrasensitive E. coli DNA biosensor based on a screen-printed carbon paste electrode modified with colloidal AuNPs and aminated hollow silica spheres (HSiSs) respectively. HSiSs was non-conductive and AuNps promote the electron transfer from the intercalated DNA hybridization redox label to the SPE surface. HSiSs was treated with glutaraldehyde before attachment of aminated DNA. The sensor was able to detect target DNA in the 1.0 × 10−12 μM −1.0 × 10−2 μM concentration range, with a low LOD of 8. 17 × 10−14 μM via the DPV method; these performances were ascribed to the high loading of DNA probes taking place on the inner and outer surface of hollow silica, and to the conductivity increasing effect of AuNPs [96]. Bonnet and co-workers reported on a nanoparticle sandwich immunoassay based on the boron-doped diamond electrode for E.coli detection in platelet lysate. The system was based on solid-phase oligodeoxyribonucleotide (ODN) synthesis on nano-sized silica particles which was immobilized on micrometric silica beads. The nano-micro structures retained on the DNA synthesis column and ODN could synthesize on the silica nanoparticles with OH group via phosphoramidite chemistry. Then ODN-functionalized nanoparticles hybridized with methylene blue DNA probes. The methylene blue -ODN-functionalized nanoparticles were released from micrometric silica beads and used in the detection procedure. Capturing bacteria from the platelet lysate with antibody functionalized magnetic beads, followed by the formation of a sandwich complex by the second antibody with the streptavidin group. Then above mentioned methylene blue-ODN-functionalized silica nanoparticles, carried out the biotin group, coupled with sandwich structure via biotin/streptavidin chemistry. In the last step, the magnetic beads were suspended in RNase free water and the methylene blues labeled oligonucleotides were released. The boron-doped diamond electrode surface was grafted with a 4-aminobenzyl amine to produce a cationic surface. Then released methylene blue-labeled oligonucleotides were deposited on the surface while negative potential applied for electrostatic attachment. The square wave method was applied to detect the different concentrations of E.coli. The proposed system could achieve detection of 10–100 CFU mL−1 E.coli in platelet concentrates; this was 3 orders of magnitude more sensitive than the assay without nanoparticles. Moreover, the electrochemical system could provide 10 times superior LOD than that ELISA method with the same magnetic sandwich complex ELISA method which used HRP as a biocatalyst for TMB reduction [15]. The schematic of this assay is presented in Fig. 2B. DNA sensor for the invA gene of Salmonella was developed based on the combination of AgNCs (as a label) and cysteine-rich DNA reporting probes. Hybridization of target DNA and reporting DNA probes with the capture probe immobilized on AuNPs modified GCE electrodes resulted, following growth of the AgNCs (at the cystine groups of the reporting probes), in a clear DPV signal (oxidation of Ag). The sensor was demonstrated to have a linear response to DNA target concentration in a wide range between 1 fM and 0.1 nM with a LOD 0.162 fM [97]. Fei et al. reported on an immunoassay for the detection of S. pullorum and based on the combination of magnetic concentration and NP signal generation; more specifically AuNPs were used as redox labels in replacement of more conventional enzymatic labels. Fe3O4/SiO2/antibody1 captured S.pullorum from sample solution. After magnetic separation, the formed complex was incubated with/Ab2/AuNPs/rGO to produce a sandwich structure. The sandwich structure was dropped on the 4-SPCE electrode surface while applying magnet below the electrode. To generate an electrochemical signal AuNPs were per-oxidation, by applying a constant potential followed by a DPV scan to reduce the in-situ generated AuCl− 4 to Au0. The recorded DPV signal correlated with the log CFU concentration of the bacteria and the system showed a LOD of 89CFU mL−1 [77]. Nanocomposite of poly (diallyldimethylammonium chloride) graphene oxide (GO-PDDA) and AuNPs was reported in the manufacturing of an immunosensor for the detection of E.coli DH5 α in the dairy product. The nanocomposite was shown to provides a superior microenvironment for the immobilization of the antibody and 51.7% and 82.9% signal enhancement was achieved in comparison to sensor containing only GO or AuNPs. The sensor was shown to present a LOD 35 CFU mL−1 [98]. Valipour and Roushani investigated the application of AgNPs and thiol graphene quantum dot (AgNPs/GQD-SH) in the development of an immunosensor for the detection of hepatitis C virus core antigen. In the proposed sensor, the glassy carbon surface was first modified with the GQD-SH solution, and then AgNps were attached via thiol groups of the GQD-SH/GCE surface. The antibody was immobilized on AgNps by chemisorption between AgNps and an amino group of anti-HCV core antigen. The electrochemical response was generated by the DPV monitoring of a redox probe (riboflavin). DPV currents decreased with the increase of the concentration of the antigen; The system was show to allow to detect 3 × 10−12 g L−1 of the hepatitis C virus core antigen with a broad linear range of 5 × 10−11-6 × 10−5 g L−1 [112].

Pandey et al. proposed the use of a gold electrode decorated by reduced graphene oxide wrapped copper oxide and cysteine, in the development of E. coli O157: H7 immunosensor. Cysteine was used for the attachment of nanocomposite to the gold surface through the SH group and also as a green route for synthesis rGO. Antibody covalently bond via N-(3-dimethylaminopropyl)-N′-ethyl carbodiimide hydrochloride (EDC)/N-hydroxysuccinimide (NHS) coupling reagent through the carboxylic acid functional group of rGO. The presence of the Cu in the composite was shown to improve the LOD and sensitivity (slope of the calibration curve) of the sensor due to inducing stronger interactions between GO and Cysteine [113].

Bhardwaj et al. fabricated a paper-based electrochemical immunosensor that used carbon paste as a working electrode for the detection of S. aureus. EDC/NHS chemistry was utilized to activate carboxylic acid groups on the SWCNT surface and immobilization of the antibody, then SWCNT-antibody solution-dropped on the carbon paste surface. The DPV response of the sensor was shown to increase with the increase of the concentration of the bacteria; accordingly, to the authors, these results could be associated with three mechanisms: a) deficiency in antibody monolayer coverage as a result of bacteria binding, b) extracellular electron transfer of bacteria with redox mediator in solution and Ab-SWCNT, c) the presence of sodium ion on the bacteria cell wall [114]. Carboxylate graphene nanoflakes, prepared from MWCNT with wet chemical methods, were electrophoretically deposited on ITO coated glass substrate, and the so prepared surface used for the manufacturing a DNA sensor for the detection of a nucleic acid of Escherichia coli O157: H7. The developed genosensor presented higher sensitivity, ca. 2 order of magnitude when compared with resembling rGO counterpart sensor [115]. A dual aptamer sandwich complex consisting of a primary biotinylated aptamer (immobilized onto streptavidin magnetic bead) and a secondary aptamer conjugated with AgNPs was reported for the detection of S.aureus. The formed MB-Apt1/S.aureus/Apt2-AgNPs sandwich was collected and transferred in HNO3 solution (0.1 M) were AgNPs were dissolved to Ag+. The reduction of the formed Ag+ was used as the analytical response of the sensor. Ag reduction signal was shown to be linear concerning S.aureus log concentration (10–106 CFU mL −1); the sensor was reported to present a LOD of 1 CFU mL −1 [116].

A Nanoporous gold structure was manufactured on a glassy carbon electrode by the combination of electrodeposition of Au-Cu alloy and selective dealloying of Cu from the previous deposited film. The so prepared nanostructured surface was used, following attachment of thiolated S. Typhimurium aptamer on the surface, for the development of an impedimetric bacteria biosensor. The proposed sensor was shown to present significant improvement, when compared to the planer Au electrode, in aptamer loading and surface stability. The aforementioned aptasensor was shown to present a low detection limit and excellent selectivity toward other bacteria and was demonstrated in the detection of S. Typhimurium in egg and rotten egg samples [99]. QDs embedded metal-organic framework (ZIF-8) particle were designed as signal-amplifying tags for the ultrasensitive and specific detection of 1 E. Coli O157: H7. (CdS/ZIF-8) particles were modified with polyethyleneimine to introduce amino groups on their surfaces, before reaction with glutaraldehyde for immobilization E. coli O157: H7 antibody (CdS@ZIF-8/PEI/Ab). Glassy carbon electrode which was modified with p-aminobenzoic acid utilized to immobilize antibodies via EDC/NHS chemistry. The prepared electrode was incubated with bacteria and CdS@ZIF-8/PEI/Ab to form a sandwich complex on the electrode surface. Electrochemical detection of pathogens was made possible by the releasing of the Cd (II) ions from the CdS/ZIF-8 in HCl solution followed by their quantification via DPV. A LOD of 3 CFU mL−1 and a wide linear range 10–108 CFU mL−1 were reported; the sensor was also shown to be ca. 16 times more sensitive than the sensor using the CdS QD due to the large number of QD encapsulated in the MOF structure [117].

Vijian et al. reported on the multiplex detection of Vibrio cholera, Salmonella sp., and Shigella sp; in the reported work QDs (PbS, CdS, or ZnS) modified specific reporting probes were used to provide specificity to the sensor (QD-RP). Two hybridization strategies, the step-by-step and premix sandwich hybridization methods were applied for single and multiple pathogen detections. Premix sandwich hybridization methods had better results. For this strategy denaturing the PCR product of Non-protein coding RNAs (npcRNA) with different concentrations of three pathogens, were incubated with QD-RP conjugates. Then, Non-protein coding RNAs (npcRNA) QD-RP, one for each targeted DNA, were applied on SPE modified with a capture probe, followed by, QDs dissolution (using HNO3) and voltammetric detection, via SWV, of released Zn2+. Cd2+and Pb2+ions. Voltammetric detection of the heavy metal ions was made possible by the in-situ formation of a bismuth-film electrode. The prepared sensor presented the excellent LOD values of 22 aM (Salmonella sp.), 34aM (Salmonella sp.) and 42aM (Shigella sp) for single pathogen detection, and 51aM (Salmonella sp.), 53aM (Salmonella sp.), and 38aM (Shigella sp) for multiplex pathogen respectively [105]. The schematic of this procedure is illustrated in Fig. 2C.

Electrochemiluminescence aptasensor for the detection of E.coli using AgBr nanoparticles/3D nitrogen-doped GO hydrogel (AgBr/3DNGH) nanocomposite as the catalyst to enhance the electrochemiluminescence (ECL) of luminol was reported by Hao et al. Luminol was mixed with the AgBr/3DNGH before apply on the glassy carbon surface. The glassy carbon surface is then modified with a chitosan layer and aminated aptamer respectively. After capturing E.coli to the surface, ECL intensity was shown to decrease linearly in the 0.5–500 CFU mL−1 dynamic ranges; the sensor showed a LOD of 0.17 CFU mL−1. The introduction of nitrogen in the GO structure was shown to improve the catalytic ability of the AgBr/3DGH composite; furthermore, the combination of AgBr and 3DNGH presented significantly improved catalytic performances when compared to the single material system [118].

A glassy carbon electrode was modified with electrodeposited Graphene oxide and decorated with CdTeQDs551-capture DNAHBV and CdTeQDs607-capture DNAHCV was used for the detection of HBV and HCV virus, followed by hybridization with the target probe. In the proposed biosensor AuNP-modified reporting probes, specific for the viruses were used as signal generation element. Virus detection was based on the ability of the AuNPs present in the specific reporting probes to quench the electrochemiluminescence of the CdTe QDs in an unreacted capture probe. The unreacted capture probe decreased with increasing concentration of target probe so the ECL signal was raised with increasing concentration of target probe in the range 0.0005–0.5 nmol L−1 and 0.001–1.0 nmol L−1 with LOD of 0.082 and 0.34 pmol L−1 for Hepatitis B and Hepatitis C virus respectively [106]. Hua and co-workers developed a sensitive potentiometric resolved ratiometric photoelectrochemical aptasensor based on three-dimensional graphene hydrogel-loaded with carbon quantum dot (C-dots/3DGH) and graphene-like carbon nitride sheet (g-C3N4); the proposed sensor presented superior photoelectrochemical ability. Appling different bias voltage, the cathodic and anodic current produced, respectively, C-dots/3DGH and g-C3N4 could be detected and differentiated; the proposed dual signal system allowed not only to detect selectively an analyte but also to take into account possible influence of the environment on the sensor response. To demonstrate this, the authors reported on an E.coli aptasensor in which the aptamer was immobilized on the C-dots/3DGH surface. In the presence of E.coli if on one end the cathodic current, associated with the C-dots/3DGH, was reduced due to the blocking effect of aptamer and target on the other end no effect on the anodic current was recorded; subsequently variation in the anodic current was used to estimate environmental change. The quantitative measurement of the target pathogen was carried out by calculating the ratio of cathodic current to anodic current. The aptasensor showed a linear range of (2.9 CFU mL−1to 2.9 × 106 CFU mL−1with an excellent LOD of 0.66 CFU mL−1 [119]. The schematic of this procedure is shown in Fig. 2D

Simple and facile detection of S.Typhimurium and E.coli was demonstrated by the use of hollow electrocatalyst Au-Ag nanoshells that enabled the in situ generations of the readable electrochemical signal; S.Typhimurium and E.coli were mixed with PVP-coated Au-Ag nanoshells and incubated for short time. To generate an electrochemical signal the mixture was dropped to SPCE. Au-Ag nanoshells were deposited, by applying a constant potential followed by a DPV scan to oxide the residual Ag atoms to Ag+ in PBS solution. The proposed electrode was demonstrated to be able to measure 102 CFU mL−1 of bacteria without using specific biomolecule [120]. More examples of the electrochemical bio/sensors are presented in Table 1 .

Table 1

Electrochemical biosensors List of Abbreviation, Amperometry (AM), Antibody (Ab), (Aptamer (Ap), Au Nanoparticle citrate synthesis(AuNPsC), Biomolecule(Bio), Cyclic voltammetry (CV), Differential pulse voltammetry (DPV), Differential pulse anodic stripping voltammetry (DPASV), Electrochemiluminesense (ECL), Electrochemical Impedance Spectroscopy (EIS), Electropolymerized Au nanoparticle(AuNPsE), Horseradish peroxidase (HRP), Linear sweep voltammetry (LSV), Potentiometry (PT), Personal glucose meter(PGM), poly(diallyldimethylammonium chloride (PDDA), Square wave voltammetry (SWV), Square wave voltammetry anodic stripping voltammetry (SWVAW) [[189], [190], [191], [192], [193], [194], [195], [196], [197], [198], [199], [200], [201], [202], [203], [204], [205], [206], [207], [208], [209], [210], [211], [212], [213], [214], [215], [216], [217], [218], [219], [220], [221], [222], [223], [224], [225], [226], [227], [228], [229], [230], [231], [232], [233], [234], [235], [236], [237], [238], [239], [240], [241], [242], [243], [244], [245], [246], [247]].

Colorimetric biosensors

Colorimetry is a well-established method with widespread use in sensor development; this transduction method presents few advantages as low cost, simple/no instrumentation, and ease of fabrication. Naked-eye detection is a fascinating branch of colorimetric methods that enables qualitative detection of analytes; on the other end, the use of spectrophotometric reading allows quantitative measurements [121].

Enzyme induced disaggregation of black magnetic nanobeads (MB) network, based on peptidic crosslinking, was explored by the Zourob team, in the development of optical sensing of several pathogens. MB networks were placed on gold substrates, located on a paper surface, and kept in position with a magnet. Upon addition of bacterial extract, that contains proteases to the sensing surface, disaggregation of the MB network, due to the peptide digestion, take place exposing in this way the underneath Au. The percentage of the observable area was shown to be proportional to the bacteria protease concentration. The proposed sensors could achieve LOD of 7, 12, 49, 2.17 × 102 CFUmL−1 for Methicillin-Resistant S.aureus, E.coli O157: H7, Porphyromonas gingivalis, Listeria monocytogenes respectively [[122], [123], [124], [125]]. The schematic of this procedure is presented in Fig. 3 A. Nanoliposomes contain cysteine were demonstrated in the development of optical ELISA tests for the detection of Salmonella, Listeria, E. coli O157, and rabbit IgG antibody. In the proposed strategies the nanoliposomes were used as a label in the sandwich assay. Optical detection was made possible by the ability of the cysteine, released following rupture of the nanoliposome, to aggregate AuNPs with a subsequent blue shift of the AuNPs plasmonic. The purposed sensor showed 6 orders of magnitude enhancements for IgG detection, down to aM levels, in comparison to the conventional ELISA method which used HRP as a biocatalyst for TMB reduction [126]. The schematic of this assay was illustrated in Fig. 3B.

Fig. 3

A) Schematic of pyrolytic biosensor schema with permission ref [125]. B) Liposome enhanced plasmonic immunosensor with permission ref [126], C) Quantitative Immunoassay Based on SiO2@PAA@CAT-Catalyzed growth of AuNPs with permission ref [127].

Silica nanoparticle with poly(acrylic acid) brushes worked as a carrier for high loading of catalase enzyme; the enzyme loaded particles were used as a label in ELISA for sensitive visual detection of L.monocytogenes (10 CFUmL−1). The proposed assay was based on the differences in AuNPs formation when different concentrations of the reducing agent (hydrogen peroxide) were present in the reaction chamber. In the absence of target analyte the fast reduction of gold ions by hydrogen peroxide, both added in the ELISA well, quasi-spherical non-aggregated gold nanoparticles with red color were formed. By contrast in the presence of analyte the catalase enzymes, loaded on the silica labels, were then able to degrade the hydrogen peroxide giving rise to an aggregated nanoparticle with characteristic blue color. High loading of the enzyme increased LOD 2 and 5 orders of magnitude in comparison with catalase plasmonic ELISA (without silica nanoparticle) and HRP based ELISA methods [127]. The schematic of this assay is depicted in Fig. 3C.

Gold nanomaterials are among the most used material in colorimetric detection. The different detection approached based on Au nanomaterials can be classified into three “groups”: (i) approaches based on aggregation/disaggregation, (ii) approaches based on catalytic properties of the Au nanomaterials, and (iii) growth of hybrid nanomaterials [9]. AuNPs modified with a thiolated Hepatitis C Virus (HCV) specific probe was used to detect unamplified HCV RNA. In the proposed assay probe modified AuNPs were incubated with unamplified HCV RNA at 95 °C for a fixed time; two positively charged gold nanoparticles (cysteamine and CTAB) capped used to promote aggregation of the above-mentioned AuNPs. When no complementary target was present in the solution aggregation of the AuNPs, due to electrostatic interaction was recorded (red to blue color change); on the other end in the presence of HCV RNA the solution remained red. Cysteamine capped AuNps provided sharper color. The biosensor showed a LOD of 4.57 IUμL−1 [128]. AuNPs were also used to transduce the interaction of antibiotics with the bacterial outer membrane; this was shown to enable the sensitive detection of bacteria down to 10CFU mL−1. More specifically in their proof of concept work, Singh et al. used Colistin, a cationic antibiotic, as a bacteria recognition element and as an AuNPs aggregation inducing element [129].

Visual detection can be enhanced by the catalytic activity of nanomaterials to a chromogenic substrate like 3,3,ʹ5,5ʹ-tetramethylbenzidine (TMB) [[130], [131], [132]]. Peroxidase activity of nanomaterial has been also exploited in colorimetric sensing. For example, a sandwich-type biosensor based on apt-MNP and IgY- BSA-MnO2 nanoparticles was reported for the detection of L. monocytogenes. The MnO2 in the label was then used to oxidize TMB to TMB2+; oxidizedTMB2+ reacted with AuNRs resulting in a gradual degradation of the AuNRs with associated variation in their aspect ratio. The shift of longitudinal localized surface plasmon was shown to correlate linearly with the log concentration of L. monocytogenes in the 10–106 CFU mL−1concentration range [133]. Wu et al. developed a colorimetric sandwich-type aptasensor in which ZnFe2O4/reduced GO nanocomposite was used to catalyze the oxidation of the TMB by consuming H2O2 that resulted in the formation of a blue color product which is then measured by micro-reader; detection of Salmonella enterica serovar down to 11 CFUmL−1was demonstrated [134]. In another study, the nanocomposite of AuNPs and CNT was shown to have higher catalytic activity in comparison to AuNPs and CNT alone toward the oxidation of TMB by H2O2. The proposed nanocomposites were utilized in an immunosensor for the sensitive detection of influenza A H3N2 virus down to 10 PFU mL−1 [135].

Magnetic nanoparticles covered with platinum (Pt/MNC) were exploited as a dual functional element in an E.coli O157: H7 immunoassay; these were used to (i) carry the biorecognition element, half-fragment of monoclonal E.coli O157: H7 antibody, and as (ii) catalyst for the oxidation of TMB. Nanoparticles were added to milk solution containing E.coli O157: H7 followed by incubation for short time and separated with a permanent magnet. A precision pipette was used to collect the solution containing both nanoparticle and poly (ethylene glycol) in a pipette tip respectively. Poly (ethylene glycol) medium caused separation Pt/MNC- E.coli O157: H7 nanoparticle from Free Pt/MNC nanoparticle. 10 CFU mL−1 E.coli O157: H7 could detect by color change (oxidation TMB with nanoparticle) [136]. More colorimetric biosensors are presented in Table 2 . Lateral flow and the immunochromatographic assays will discuss in a separate part in section 3.6.

Table 2

Colorimetric biosensors, List of Abbreviation Colorimetry (CO) [[248], [249], [250], [251], [252], [253], [254], [255], [256], [257], [258], [259], [260], [261], [262], [263], [264], [265], [266], [267], [268], [269], [270], [271], [272], [273], [274], [275], [276]].

Fluorescence biosensors

Fluorescence-based sensors have attracted great interest in presenting high sensitivity, low detection limit, rapid response, low signal-to-noise ratio, simple instrumentation, and cost-effectiveness. A variety of fluorescence nano-materials such as metal nanoparticles, quantum dots (QDs), carbon dots (CDs), graphene oxide, dye-doped silica nanobeads, nanotubes, and upconversion nanoparticle have been explored in sensing application [137]. Signal generation in fluorescence sensing has been carried out following a variety of strategies including fluorescence quenching (“turn-off”), fluorescence enhancement (“turn-on”), ratiometric(calculating intensity ratio of two or more fluorescence signal), fluorescence resonance energy transfer (FRET), photoinduced electron transfer (PET) and metal enhanced fluorescence(MEF) [138].

Specific separation and detection of E. coli O157: H7 was reported with the use of a magnetic immunoassay and QDs labeling. The capture of the bacteria was performed in a double layer quartz channel using the immune magnetic nanoparticle trapped on the channel wall by a high gradient magnetic field. Following labeling with QD, the formed sandwich complex was collected from the channel and the fluorescence intensity of the sample measured. This was shown to relate linearly with log concentration of bacteria in the range 8.9 × 100–8.9 × 105 CFUmL−1 [139]. The schematic of this procedure is illustrated in Fig. 4 A. Aptamer coated magnetic particles labeled with QD modified complementary DNA were used in a competitive assay for the detection of S.Typhimurium. In the presence of the target bacteria, the aptamer-DNA label duplex was cleaved due to the aptamer-target interaction resulting in free CdTe QD labeled DNA in solution. After magnetic separation, the QDs signal in solution was recorded and demonstrated to be linearly related to 10–1010 CFU mL−1 of log pathogen concentration [140]. Application of QD and upconversion nanoparticle (UCNP) modified, respectively, with S.Typhimurim and S.aureus aptamers allowed the simultaneous detection of these two food pathogens. After attachment of the two luminescent nanoparticles to the magnetic bead contains a partially complementary DNA sequence, the fluorescence emission spectra obtained at 500 nm for QD and 800 nm for UCNP was recorded; the addition of the target pathogens to the solution containing the sensing complex resulted in the loss of fluorescence labels with a subsequent decrease in the overall signal intensity of the magnetic beads (recorded after magnetic separation). The reduced signal correlated to the log concertation of the bacteria in the 50–106 CFU mL−1 interval [141]. Liu and coworkers extracted V. parahaemolyticus-specific egg yolk antibody and used these to decorate AuNPs. Interaction of CdSe/ZnS QD which was decorated with 3-mercaptopropionic acid (carrying carboxylic acid group) and AuNPs, modulated by COOH groups in the QDs and Au0 atom in AgNps lead to fluorescence quenching of QD. A small amount of free AuNps was also added that enable a higher rate of quenching. In the presence of V. parahaemolyticus due to the interaction of bacteria and antibody, IgY-AuNPs aggregated freeing in this way the QDs and increasing the fluorescence response of them. The system was applied to the sensitive detection V. parahaemolyticus in food samples [142]. Composite of AuNPs, gallic acid-iron oxide nanoparticle, and graphene, modified with hemagglutinin (HA) antibody, was employed as an integrated magnetic and plasmonic surface for the capturing and detection of the influenza virus. The addition of QDs, also decorated with hemagglutinin (HA) antibody, caused the formation of a sandwich complex and the fluorescence of QD increased linearly with virus concentration. The detection limits of 7.27 × 10−12 g L−1 and 6.07 × 10−9 g L−1 were obtained in deionized water and Human serum respectively [143]. Quaternary alloyed CdZnSeTes QDs which can emit in the NIR range is an attractive option for the construction of low detection limit biosensor due to the low photonic-absorption of biological molecule in this area. 2 copies mL−1 of Influenza virus H1N1 RNA were detected with molecular beacons (MB) modified with the aforementioned QDs by fluorescence enhancement signal transduction mechanism. In the absence of the target sequence, QDs and MB in close proximity resulted in an efficient quenching of their IR signal. Hybridization of target viral RNA with the loop sequence of the MB probe formed DNA/RNA heteroduplex which enhanced the fluorescence of QD by inducing the separation of the two particles [144]. The schematic of this procedure is illustrated in Fig. 4.B. A FRET aptasensor consisting of AuNPs modified with aptamer (acceptor) and UCNPs conjugated with complementary DNA (donor) was designed for the ultrasensitive detection of Escherichia coli ATCC 8739, in food sample and water, down to 5 CFU mL−1. Attachment of bacteria to aptamer led to the separation of the UCNP-CDNA from the AuNPs- Aptamer resulting in the loss of the FRET effect with subsequent recovery of the fluorescence signal of the donor [145]. Hollow silica nanospheres (HSNs) encapsulated with fluorescein and covered with polymer layers of poly (acrylic acid) and poly (dimethyldiallylammonium chloride) were synthesized and used in the development of a label in a sandwich magnetic immunoassay, following modification with Ab2 antibodies, for the detection of E.coli. Fe3O4@SiO2@PAA-Ab1 were used for the capture of the bacteria and the separation of the formed sandwich. Signal was generated, following the collection of the formed sandwich, by dissolution, with sodium hydroxide, of the HSNs label, and release of the internal fluorescein. The fluorescence intensity of the released fluorescein is related to the E. coli O157: H7 concentration down to 4 CFUmL−1 [146]. FRET aptasensor based on AuNCs-Vancomycin and aptamer modified AuNPs as the energy donor and acceptor was developed for the sensitive detection of S.aureus. In the presence of S.aureus fluorescence intensity change (ΔF = F0-F) increased linearly with concentration 20-108 of S.aureus [147]. Two main bacteria responsible for sepsis (S. aureus, E. coli) were separated and detected in mouse rat blood. In the presented work, Fe3O4 nanoparticles modified with chlorin e6 and S.aureus and E.coli aptamers were designed for the early and sensitive (10 CFUml−1) detection of the two pathogens by fluorescence microscope. Moreover, chlorin e6, photosensitizers, applied and extracorporeal blood disinfection in mouse rats' blood was achieved with photodynamic therapy [148]. The schematic of this procedure is illustrated in Fig. 4C. A fluorometric aptasensor was fabricated by employing aptamer modified carbon nanoparticle and GO as fluorescent and quencher respectively for the sensitive detection of P. aeruginosa. In the presence of bacteria, the fluorescence signal was increased due to binding aptamer and bacteria that caused distance between the aptamer-carbon nanoparticle and Go, the recorded signal related linearly to 101-107 CFUmL−1 concentration of bacteria with a LOD of 9 CFUmL−1 [149]. An Aptasensor consisting of MNP-Aptamer and UNCP-CDNA was developed to detect, low concentration (58 CFUmL−1), E.coli in pork meat sample. MNP-Aptamer and UNCP-CDNA mixed and incubated for short time. Then, the addition of E.coli release UNCP- CDNA particle due to the specific interaction of aptamer and target. Following the separation of E.coli-MNP-aptamer complex by the magnet, the fluorescence signal of the solution was recorded which was increased by increasing concentration of bacteria [150]. More fluorescence biosensors are demonstrated in table 3

Fig. 4

A)The illustration of double channel coated by immunomagnetic bead and QDs with permission ref [139], B) The Schematic of NIR alloyed QD-MB designed biosensor with the permission of ref [144] C) The pattern of the Fe3O4-Ce6-Apt system for early sepsis diagnosis [148].

Table 3

Fluorometric biosensors Abbreviation Fluorescence (FL), Fluorescence energy transfer resonance (FRET) Emission (em), Reverse assay strategy (RAS) [[277], [278], [279], [280], [281], [282], [283], [284], [285], [286], [287], [288], [289], [290], [291], [292], [293], [294], [295], [296], [297], [298], [299], [300], [301], [302], [303], [304], [305], [306], [307], [308], [309], [310], [311], [312]].

Chemiluminechence and photoluminescence biosensors

Chemiluminescence (CL) takes advantage of the conversion of chemical energy into light. As a result, this method does not require sample radiation reducing in this way interfering phenomena such as light scattering, source instability, providing in this way high signal to noise ratio and high sensitivity; moreover, the readout instruments are less complicated than other optical systems [151,152].

Hao et al. reported on the steady-state Chemiluminescence aptasensor, based on the rolling circle amplification (RCA) method, for the sensitive detection of S.Typhimurium. In the proposed strategy target bacteria are captured using MNP immobilized aptamer; captured S.Typhimurium can then interact with the RCA product to form a sandwich complex. Finally, the formed sandwich was labeled using a Co+2 enhanced N- (aminobutyl)-N-(ethylisoluminol) (ABEI) functional flowerlike gold nanoparticles (AuNFs)-cDNA. Chemiluminescence signal was then generated by the addition of P-Indophenol and H2O2 applied to form ABEI- AuNFs-PIP-H2O2 Chemiluminescence system. The proposed sensor was shown to respond linearly in the concentration range between 3.2 and 3.2 × 106 CFU mL−1 [153]. The schematic of the presented assay was shown in Fig. 5 . More examples of Chemiluminechence and photoluminescence methods are presented in Table 4 .

Fig. 5

The pattern of chemiluminescence biosensor A) Aptamer attachment and bacteria capturing B) Rolling circle amplification and Co2+enhanced signal probes with permission ref [153].

Table 4

Chemiluminescence and photoluminescence biosensors, Abbriviation chemiluminesence (CL) [[313], [314], [315]].

Surface-enhanced Raman scattering (SERS) biosensors

Surface-enhanced Raman scattering is a powerful sensing tool; this presents several advantages including high sensitivity, reduced analysis time, portability as well as the ability for multiplex detection. SERS technology takes advantage of the enhancement of the Raman spectroscopy signal when performed at the surface of noble metal nanomaterials; signal enhancements of several orders of magnitude (107-1014) were reported using this method. SERS is a fascinating method for the identification (fingerprinting) and detection of microorganisms because of its non-destructive nature. Nanomaterials like noble metal colloids, nanospheres, core-shell, gold-coated magnetic nanoparticle, nano aggregates, and bimetallic nanomaterial have been reported as promising materials for SERS detections using both labels (indirect) and label-free (direct) approaches. Labels (SERS reporters) are specific organic molecules like, Rhodamine B, 4-Nitrothiophenol 4-mercaptopurine (4-MPY), 4-amino thiophenol (4-ATP), 4-mercaptobenzoic acid and5,5-dithiobis-2-nitrobenzoic acid (DTNB) that are characterized by well-known Raman signals. Plasmonic nanoparticles decorated with Raman reporter molecules and biorecognition elements have been used to design SERS biosensors [154,155].

In a study reported by Wang et al. [156], positively charged polyethyleneimine was self-assembled on Fe2O4 magnetic nanoparticle; the surface of the MNP was modified, taking advantage of electrostatic interaction, with Au seeds that were then chemically grown to generate rough core/shell (Au/MNPs) label. To enable the selective capture of S.aureus, Au/MNPs were modified by the S. aureus antibody. On the other side, Au nanorods -DTNB modified with antibodies were used to complete the sandwich assay. SERS intensity at Raman peak of 1331 cm−1showed a linear relationship with the logarithmic concentration of the bacteria in the range of 101- 105cells mL−1 [156]. Concanavalin A (Con A) is a lectin that presents the ability to specifically interact with the terminal α -d –mannosyl and α - d -glucosyl groups present on the surface of all bacteria. Kearns et al. reported on a SERS assay based on the use of Ag-MNPs core-shell system modified with Con A. The reported core-shell system enabled the capture and collection of bacteria from samples. With the help of three different SERS reporters, the authors demonstrated the multiplex detection of S. Typhimurium, methicillin-resistant S. aureus, and E.coli down to 10 CFUmL−1 [157]. Zhou et al. carried out extensive studies on the design and fabrication of multifunctional nano-gapped nanoparticles (NNPs). In their works polydopamine (PDA) coating was used to deposit, in a controlled way (e.g. using PDA of different thicknesses), Au shells on a variety of core nanomaterials as spherical AuNPs, anisotropic Au nanorods (AuNRs), metal-organic frameworks (MOFs), and magnetic polymer nanoparticles (MAgNPs). The produced nanogap structures were reported as a carrier for Rhodamine-B or 4-nitrophenol Raman tags in bacteria sandwich assays; magnetic nanoparticle coated with PDA and 2 layers of 15 nm Au nanoshell and modified with 4- nitrophenol (Raman tag) enabled the sensitive detection of E.coli O157: H7 down to concentration 100 CFU mL−1. In the same work, the authors showed that the Raman signal could be significantly enhanced (ca. 5 folds) by the increase in the number of nanoshell layers (2 vs 1). The schematic of preparation nanogap structures is illustrated in Fig. 6 A [158]. Thiol-poly adenine or Thiol-poly thymine was immobilized on the AuNps surface. Then, terminal deoxynucleotidyl transferase which was mediated incorporation of the chain of identical nucleotides utilized to synthesize nucleotide with different lengths due to change of elongation time (0 min −16 h). The prepared nanoconjugate worked as a nano seed to synthesis a gold layer to immobilize the antibody on it. Among different nanogap structures, the optimum one (16 h) with poly adenine was selected for the rest of the investigations. The so prepared particles were used as a Raman reporter in a bacteria immune assay that was shown to enable the detection of 2 CFU mL−1 of E.coli [159]. The schematic of the proposed immunosensor was illustrated in Fig. 6B. AuNPs decorated with 4, 4′-dipyridyl, and coated with silica layers were shown to allow bacterial detection in complex systems being stable for up to 50 h and not being prone to aggregation. The SERS immunosensor based on such nanoparticles was shown to detect 10 CFU mL−1 of E.coli [160]. Label-free detection of S.aureus was performed by the use of specific aptamers and by in situ synthesis, using the aptamer as a template, on AgNPs. The SERS spectra of S.aureus-aptamer/AgNPs were shown to be significantly higher than those recorded in the absence of the aptamer. The system was reported to have a low LOD of 1.5 CFU mL−1 [161]. Ag coated magnetic nanoparticle (AgMNPs) and AuNR –DTNB@Ag-DTNB (DioPNP) as SERS tags were reported in single-cell detection of S.aureus. These were modified with aptamer 1 and 2, respectively, to form a dual sandwich structure; the Raman signal of DioPNPs was shown to be 10 times stronger than those of the AuNR−DTNB due to double-layer DTNB [162]. The schematic of preparation nanoparticle and bacteria detection was shown in Fig. 6C. Dual enhancement SERS aptasensor was developed by Pang et al. and applied to the detection of S.aureus; Fe3O4@Au –Aptamer nanoparticles were used for the specific recognition/capture of the target bacteria with SERS signal, due to the captured target, generated at the Au layer. The second element of the assay was AuNPs modified with-4 mercaptobenzoic acid (Raman label) and vancomycin (for bacteria capturing). The proposed biosensor was shown to allow detection of the pathogen in a wide range of concentrations (10-107 CFUmL−1) with a LOD of 3CFUmL−1 [163]. Ma et al. developed a sensitive aptasensor with the aid of pointy-like AuNPs that have unique field enhancement especially at the tip of the branches. The pointy-like AuNPs were used, following functionalization with 4- mercaptobezoeic acid and thiolated aptamer, as SERS label in ELISA plate-based aptamer assay. ELISA plates were modified with biotinylated aptamer used to capture S.Typhimurium. The proposed detection approach was shown to detect down to 10 CFU mL −1 of S.Typhimurium [164]. Duan et al. reported on an aptasensor for the detection of S.Typhimurium; this was based on the use of an Au@Ag core-shell nanoparticle modified with aptamer 1 as a signal enhancer and of aptamer2-X-rhodamine as SERS label. The fabricated biosensor enables sensitive detection of S.Typhimurim down to 15 CFUmL−1 [165]. More example of SERS bio/sensor are summerized in Table 5 .

Fig. 6

A) Schematic of the synthesis nanogapped nanoparticles based on the polydopamine coating, B) Schematic of the synthetic sequence in producing hT-DENPs for recognition of E. coli O157: H7 C) Synthesis of silver-coated magnetic nanoparticles and their conjugation with aptamer 1, synthesis of core−shell plasmonic nanoparticles (AuNR− DTNB @Ag− DTNB) and their conjugation with aptamer 2 Operating principle for S. aureus detection.

Table 5

Surface-enhanced Raman scattering (SERS) biosensors, Abbreviation Loop-mediated isothermal amplification (LAMP), Membrane filter-assisted (MFA), Recombinase polymerase amplification (RPA) [[316], [317], [318], [319], [320], [321], [322], [323], [324], [325], [326], [327], [328], [329], [330], [331], [332], [333], [334], [335], [336], [337], [338], [339], [340]].

Lateral flow-based biosensors

Lateral-flow immunoassay (LFIA) also known as lateral-flow immunochromatographic (LF- ICA) tests are simple, rapid, and portable systems which enable qualitative, non-invasive point of care detection (POC) with wider applications in medical diagnostic [166]. Conventional LFA system suffers from low sensitivity; nevertheless, in recent times several approaches for the improvement of LFA have reported including gold enhancement, enzyme labeling, increased loading of antibody, and use of various nanomaterials like QD, UCNP, peroxidase-like nanoparticle, and graphene oxide. Besides coupling LFIA systems with instrumental reading (fluorescence, colorimetric, SERS, and magnetic focus) enabled to obtain more reliable and quantitative data [167,168].

An innovative approach, combining gold-coated Fe3O4 magnetic nanoparticle (Au/MNCs) and lateral flow filters, was shown to allow the detection of 103 CFUmL−1 Salmonella from milk samples. In the proposed assay Salmonella was captured in milk samples using antibody fragment modified Au/MNCs; the formed complex following separation was resuspended in a buffer solution. The assay was then performed by immersing one end of the lateral stripe in the solution; if on one end the free Au/MNCs were able to move in the LFI strip and accumulating in the test line, the Salmonella-Au/MNCs were remained in the solution because of their big size; pressing of the nitrocellulose membrane was key factor in the success of the proposed assay. The colour of the test line decreased with increasing pathogen concentration because of a decrease in free Au/MNCs nanoparticle [169]. The same author also developed a similar strategy for the visual detection of E.coli O157: H7 (10 3 CFU mL−1) [170]. Cho et al. developed the lateral-flow immunochromatographic LF-ICA system based on AuNP-biotin and streptavidin -HRP complex. A mixture of tetramethylbenzidine and H2O2, applied in the cross-flow direction of the antigen-antibodies complex, was used as a reagent for the generation of the colorimetric signal; the proposed assay allowed the naked eyes detection of Cronobacter sakazakii down to 102 CFU mL−1 [171]. The size and uniformity in the shape of AuNPs were shown to influence the sensitivity of LFIA. Cui and co-workers investigated the effect of size and uniformity of AuNPs and pre-incubation of AuNPs/antibody/E. coli O157: H7 on the visual and instrumental reading of a colorimetric test strip. The authors synthesized AuNPs with size 20, 28, 35, 43, 54 nm; AuNPs of 35 nm showed the best results. If on one end smaller nanoparticles, due to their smaller steric hindrance, interacted more effectively with bacteria, larger ones offered better optical signal, and the 35 nm nanoparticles had plasmonic resonance wavelength 525 which was the same as the wavelength light of light source in the reader. Nanoparticles with lower polydispersity indices (PDI) provide a superior limit of detection [172]. Yen et al. synthesized AgNPs with different size and colour modified with dengue virus (DENV) NS1 protein, Yellow Fever Virus (YFV) NS1 protein, and Zaire strain Ebola virus glycoprotein (ZEBOV) for single and multiplex detection of these viruses. The visual detection of the three viruses demonstrates to be possible down to 150 ngmL−1 [173]. Different AgNPs with the prepared stripe is depicted in Fig. 7 A. Jin et al. investigated 15 different AuNps decorated polystyrene microparticle (Au-Ps) with different sizes (0.1.0.3,0.46) μm and Au coverage (5, 10, 25, 50, 75%) to find the nanoparticle with the highest sensitivity for visual detection of E.coli O157: H7. The optical density of the different nanoparticles was used as the physical parameter to discriminate between the manufactured particles and to select the best one. According to the optical density values, the UV–vis spectrums, and the TEM images, (50Au-0.46 PS) was expected to provide the better result nevertheless average grayscale analysis by image J software showed that lower LOD could be achieved with the (10Au-0.46 PS) nanoparticle. The same authors also studied the effect of signal enhancement by reduction of HAuCl4 with hydroxylamine; this enhancement step lowered the LOD down to 100 CFUmL−1and average 1.44 folds improvement for each concentration [174]. Eu (III) doped polystyrene nanoparticles were demonstrated in immunochromatographic assay for detection of E .Coli O157: H7. EuNP-6 carbon chain (CC), EuNP-200CC, EuNP-1000CC and EuNP-streptavidin were compared; EuNP-Streptavidin, due to their better ability to load antibodies, showed better sensitivity and wider linear range [175]. Ren et al. reported on the combination of Fe3O4/Au core-shell and HRP signal enhancement for the detection of pathogens. The use of the described system, in combination with an external magnet to slow down the movement of the labeled target which enabled the interaction of pathogens and antibody more readily, allowed detection limits of 25CFUmL−1 E. coli O157: H7 or S. Typhimurium [176]. A fluorescence lateral flow immunosensor was designed by taking advantage of the quenching properties of GO (acceptor) and the fluorescence ability of QDs (donor). In the proposed assay the test line contained CdSe@ZnS QDs/anti-E. coli O157:H7 antibody while the control line only had bare QDs. In the absence of target bacteria, addition of GO resulted in the quenching of the fluorescence of the QDs in both the test and the control lines. By contrast, capturing of E. coli O157: H7 with antibody, increase the distance between QD and GO, therefore reducing the ability of GO to quench the QDs; the intensity of the residual fluorescence was shown to be proportional to the pathogen concentration in the range 50–105 CFU mL−1 with LOD 57 CFU mL−1 [177]. The schematic of the assay was showed in Fig. 7B. Surface positive nitrogen-rich carbon nanoparticle (pNC), prepared from urea by calcination and etching reaction, were shown to have a good ability to adsorb/capturing bacteria. In the proposed LFIA monoclonal antibodies present on the test line were used to capture the complex made between the pNC and the bacteria; the intensity of back color of the test line was shown to relate to the concentration of S. enteritidis in the 102–108 CFU mL−1 interval [178]. Plasmonic LFIA with improved performances based on the AuNPs aggregation induced by polyethyleneimine (BPEI) released from liposome was reported by Ren et al. for the sensitive detection of E. coli O157: H7. Targeted bacteria were incubated with AuNPs modified with an antibody; following a certain time BPEI-loaded liposomes were added to the solution. The obtained mixture was added to the strip followed by the addition of free-AuNPs. The added nanoparticles were then captured at the test line by the BPEI present on the surface of the bacteria/AuNPs complex resulting in the generation of a colorimetric signal due to the aggregation effect. The proposed immunosensor could detect 100 CFUmL−1 of E. coli O157: H7 [179].

Fig. 7

A) AgNPs for multiplexed detection, B) Multiplex detection of dengue, yellow fever, and Ebola viruses with permission ref [173] C) Fluorescent lateral flow immunoassay ref [177]. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

The peroxidase activities of some nanomaterials lead to select them as a prominent candidate for use in LFIA with improved sensitivity. For example, the peroxidases activity of Pt-AuNPs modified with antibody were explored to generate, upon reaction with TMB, a colored band in correspondence of the test line. The proposed assay enabled the detection of 102 CFUmL−1 E. coli O157: H7 [180]. Mesoporous core-shell Pd@Pt with the help of TMB and H2O2 was used for the simultaneous detection of S.enteritidis and E. coli O157: H7 with LFIA and smartphone detection down to 20 and 34 CFUmL−1 of S.enteritidis and E. coli O157: H7 while the detection limit of the system for both pathogens was 106 CFUmL−1 in the absence of TMB and H2O2 system. AuNR@Pt with peroxidase activity toward TMB and H2O2 and also SERS properties with 4-mercaptobezoic acid Raman reporter were explored for dual recognition, LFIA and SERS methods; the two methods allowed, respectively, the detection of C. jejuni in the 102–106 and 102–5 × 106 CFU mL −1 concentration ranges [181]. Use of Fe3O4 MNP as a nano-enzyme probe was reported by Han et al. for the LIFIA detection of the glycoprotein of the Ebola virus. The ability of the MNPs to catalyze the conversion of 3,3′-Diaminobenzidine (DAB) in the presence of H2O2 allowed the detection of the glycoprotein at 1 ng mL−1 concentration which is 100 times lower than that achievable with the standard strip method (1 ng mL−1) [182]. Bimetallic Pd-Pt nanoparticles were also explored as nano-enzyme for the conversion of TMB and H2O2 in LFIA for the detection of E.coli O157: H7; the proposed assay showed LOD of 102 CFUmL−1 [183]. Fe3O4/Au- polyethyleneimine nanoparticles-casein-antibody complex were applied to capture E. coli, followed by cleavage of casein by rennet enzyme to release E.coli. Released bacteria were loaded on strip modified with DTNB labeled AuNPs and AuNPs modified with the antibody on the conjugate pad and test line respectively. The intensity of the test line was recorded which was increased with concentration 101–107 CFU mL−1 E. coli with LOD 0.52 CFU mL−1 [184]. Luo et al. compared 4 different nanoparticles including AuNPs, QD, Fluorescent nanoparticles (FNP), and Eu(III) chelate nanoparticles for application in the immunochromatographic assay for the detection of E.coli O157: H7. The EuNP showed the highest fluorescence intensity, larger Stokes shift, and sharpest emission profile, therefore the EuNP showed the highest sensitivity and fluorescent nanoparticles and EuNP provided the wider linear range. It needs to be noted that fluorescent nanoparticles were shown to require less antibody per strip [185]. Aptamer mediated strand displacement approach was reported for the sensitive detection of E. coli O157: H7. In the reported assay a reporting aptamer and a capture probe, modified with biotin, were used. Target bacteria were incubated with the two aptamers and extracted using streptavidin magnetic beads. After the separation of the magnetic complex, the reporting aptamer was amplified with the isothermal strand displacement amplification method and detected with LFIA. This method enabled visual detection of 10 CFUmL−1 E. coli O157: H7 [186]. Mesoporous silica nanoparticles, embedded with TMB and covered with amin-aptamer gate sequence, were employed for the sensitive detection of L. monocytogenes. The addition of bacteria caused the release of TBM due to their specific interaction with the aptamers. Released TMB interact with HRP enzymes trapped in the test line to produce the visible blue color. The aptasensor could obtain LOD of 53 cells in 1 mL sample [187]. AuNPs modified with 4-mercaptobenzoic acid (as a Raman tag), Ag layer, streptavidin and BSA were used as a label for the detection of L.monocytogenes and S. enterica DNA sequences. In the proposed assay the targeted DNA sequences were amplified, before their LFIA detection, using recombinase polymerase amplification method. The proposed assay allowed the visual and SERS detection of the targeted sequences with LOD of 27 and 19 CFUmL−1. Visual qualitative detection was made possible via the aggregation of the nanoparticle in the two test lines containing specific capturing probes while the SERS signal of test lines was measured for quantitative detection of bacteria. SERS signal was shown to be linear with target concentration in the 1.9 × 101–1.9 × 106 and 2.7 × 101–2.7 × 106 interval for L.monocytogenes and S. enterica respectively [188]. More examples of lateral flow based biosensor are available in Table 6 .

Table 6

Lateral flow-based biosensor detection Lateral flow immunoassay (LFIA) immunochromatographic immunoassay (ICA) Fluorescence Lateral flow immunoassay (FLFIA), Immunomagneticseparation (IMS), Polymerase chain reaction (PCR), Strand displacement amplification (SDA) [[341], [342], [343], [344], [345], [346], [347], [348], [349], [350], [351], [352], [353], [354], [355], [356], [357], [358], [359], [360], [361], [362], [363], [364], [365], [366], [367], [368], [369], [370], [371], [372], [373], [374]].

Conclusion and future prospective

In this review, various nanomaterials and their application in different detection systems for infectious agents covered. Nanomaterials as magnetic nanoparticles alone and in combination with Ag or Au coatings, bimetallic nanoparticles, peroxidase-like nanomaterials, and newly designed nanomaterials have been described and their widespread application in electrochemical and optical biosensing discussed. Applications as separation materials, materials for improving conductivity, and elements for biomolecules grafting have been described. Besides, their application in colorimetric, fluorometric, and SERS detection methods was also reported. Finally, we demonstrated the advantage of the usage of these materials to enhance the sensitivity of the lateral flow strip test. Although some authors illustrated comparative data to highlight the benefits of the usage of nanomaterials, there is still the need for more investigation to understand the real effect and advantages of exploiting nanomaterials in various sensing applications. In the future, we expect novel functional biomimetic and bimetallic nanomaterial or bionanocomposite with fascinating features will be introduced. Moreover, innovative designs strategies with the help of biochemical pathways to shorten the analysis time, to obtain the results of the molecular techniques such as PCR and LAMP and to produce efficient and rapid POC devices to be used in the field will report. Nanoenzye material may replace natural recognition receptors to produce more durable biosensors. One of the biggest challenge for the nanomaterials are their work in various real-samples matrices such as blood, serum, urine or stool in biomedical or various food matrices or for example sewage water in case of environmental samples. Therefore we expect a lot of attention will be directed towards the development of more efficient nanomaterials characteristics with minimum non-specific binding and low false positive signals. We also expect much attention will be paid in the future towards the development of multifunctional nanomaterials where it integrates for example specific analyte fishing or preconcentration tool as well as sensing platform. Despite the numerous proposed biosensors, there is still a crucial need for developing new biosensors for on-site monitoring of infectious diseases to prevent epidemic and economic loss.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.