Inorganic nanoparticles‐based strategies for the microbial detection in infectious diseases

Infectious diseases pose significant threats to public health and the global economy, necessitating rapid and accurate detection of the causative microorganisms to prevent their transmission. Nanomaterials, with their unique size‐dependent physical and chemical attributes, present innovative solutions for the detection of infectious diseases, thereby playing a crucial role in the development of advanced detection technologies. This review describes the application of inorganic nanomaterials in the detection of infectious diseases, focusing on the potential uses of nanomaterials, including carbon nanoallotropes, quantum dots, gold and silver nanoparticles, magnetic nanoparticles and upconversion nanoparticles.


| Carbon nanoallotropes
Carbon-based nanomaterials, mostly composed of elemental carbon, constitute a significant and varied class of nanomaterials.Their diverse range of physicochemical characteristics renders them versatile for a multitude of applications.These materials are systematically categorized into zero-dimensional (0D), one-dimensional (1D), and two-dimensional (2D) carbon nanomaterials (Figure 1A), notable members of this family include carbon dots (CDs), carbon nanotubes (CNTs), and graphene. 9Various carbon nanoallotropes have been applied in the diagnosis of infectious illnesses (Table 1).

| Carbon dots
Carbon dots are quasi-spherical carbon nanoparticles, typically ranging in diameter from 2-10 nm.They are composed of a mixture of carbon in the turbine layer and graphite with different volume ratios and are distinguished by their high oxygen content.These carbon atoms are primarily hybridized with sp 3 and typically exhibit a non-crystalline structure. 9Despite their mostly non-crystalline structure, CDs exhibit remarkable physical properties due to their ultrasmall size including exceptionally high specific surface area, which enables them to readily associate with a wide array of biological components.
The surface chemistry of CDs is particularly notable for their variety of functional groups, such as carboxylic, amino, sulfur, and epoxy groups.These functionalities can either be introduced during the synthesis of CDs or added post-synthetically by functionalizing CDs with appropriate polymers that carry the desired functional groups. 25This versatility in surface chemistry underpins CDs' relatively strong photoluminescence (PL) properties, which are primarily influenced by factors such as nanoparticle size, excitation wavelength, and surface functionalization.The interaction of CDs with different substances can alter their fluorescence emission, making CDs highly effective in differentiating between various analytes. 26For instance, a novel fluorescence sensor array was designed to integrate CDs with three multifunctional receptors (boric acid, polysaccharides, and vancomycin) and demonstrated the ability to emit distinct fluorescence signals in response to different bacterial species.This approach, enhanced by machine learning (linear discriminant dimensionality reduction algorithm), resulted in a straightforward and rapid differentiation of six bacteria (Figure 1B). 10 In addition to their advantageous optical properties, CDs are recognized for their ease of functionalization, hydrophilicity, stable luminescence, and biocompatibility, making them suitable for a range of applications including use as colorimetric markers in lateral-flow immunochromatographic assays (LFIAs).A notable application by Ju et al. involved the development of an innovative fluorescent lateral-flow assay (LFA) technique for the detection of SARS-CoV-2-specific IgM and immunoglobulin G antibodies.This method employed CDs conjugated to the SARS-CoV-2 spike protein, achieving detection limits as low as 100 pg/mL, showcasing the potential of CDs in sensitive and specific diagnostic applications. 27 2.1.2 | Graphene quantum dots Graphene quantum dots (GQDs) are made from a single graphene layer and cut into tiny disc-like pieces with diameters typically between 2 and 20 nm. Tey are primarily composed of crystallized sp 2 -hybridized carbon atoms.The unique aspect of GQDs lies in their tunable band gaps and photoelectric properties, which can be meticulously adjusted by altering their size, shape, geometry, and edge configurations.Moreover, GQDs exhibited potent strong PL that varies with the changes of bandgap size.9 The margins of GQDs often feature functional groups such as carboxyl, hydroxyl, carbonyl, and epoxide, which, through non-covalent interactions such as hydrogen bonding, electrostatic forces, and π-π stacking, these functional groups facilitate the adsorption of nucleic acid molecules onto the surface of GQDs.15 Researchers have successfully employed GQD-modified glassy carbon electrodes to transport specific DNA sequences as probes to detect Hepatitis B virus (HBV) DNA, showcasing a linear detection range from 10 to 500 nM and a limit of detection (LOD) of 1 nM, demonstrating its high sensitivity (Figure 1C).11 F I G U R E 1 (A) Various forms of carbon nanomaterials.Reproduced under terms of the CC-BY license. 9Copyright 2015, The Authors, published by American Chemical Society.(B) A new fluorescence sensor array with three carbon points was designed.Reproduced with permission.10 Copyright 2019, Elsevier. () A Graphene quantum dots (GQDs) as a label-free electrochemical platform for highly sensitive detection of hepatitis B viral DNA.Reproduced under terms of the CC-BY license.11 Copyright 2018, The Authors, published by Royal Society of Chemistry.(D) A hyaluronic acid-carbon nanotube hybrid film-based label-free electrochemical immunosensor for hepatitis B. Reproduced with permission.12 Copyright 2016, Elsevier.
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-3 of 20 T A B L E 1 Application of carbon nanoallotropes for detection of pathogenic bacteria.

Mechanism of detection
Linear range g/mL 2.4 pg/mL PBS Light-activated CQDs can serve as either electron donor or acceptor.They easily interact with both ambient and surface-modified ligands, facilitating charge or energy transfer processes, making them suitable for application in fluorescence resonance energy transfer (FRET) sensors.Li et al. reported the application of CQDs and gold nanoparticles (AuNPs) as donors and acceptor elements respectively for the rapid quantitative detection of SARS-CoV-2 spike proteins.This selective detection mechanism is predicated on modifying the surfaces of GQDs and AuNPs with SARS-CoV-2 antibodies, leveraging the distance-dependent FRET phenomenon to achieve a low detection limit of 0.05 ng/mL and a linear detection range from 0.1 to 100 ng/mL, demonstrating the technology's potential for sensitive and specific viral detection. 28 2.1.3 | Carbon nanotubes Carbon nanotubes are cylindrical nanostructures composed of seamless layers of carbon atoms arranged in a lattice. Tese structures are categorized into two types according to the number of carbon atom layers present: single-walled CNTs and multi-walled CNTs.The carbon atoms in CNTs are primarily sp 2 hybridized, endowing them with remarkable mechanical strength.9 Due to their outstanding electrical conductivity and the abundance of surface functional groups such as carboxyl and hydroxyl, CNTs find extensive application in the fabrication of electrochemical biosensors.29 One notable application involves an electrochemical immunosensor designed for detecting hepatitis B core protein antibodies by immobilizing hepatitis B surface antigen on CNTs modified with hyaluronic acid.The interaction between the hepatitis B core protein antibodies and the antigen results in a measurable decrease in current, detected through square wave voltammetry, achieving a notably low LOD of 0.034 ng/mL (Figure 1D).12 Beyond biosensing, CNTs are also integral in the development of field-effect transistors (FETs).An FET is a semiconductor-based electronic device that controls current flow by altering the carrier density in the semiconductor.Tran et al. developed a DNA sensor utilizing a CNT-based FET for the detection of influenza A virus DNA, where the probe DNA is physically adsorbed onto the CNT.This configuration allows for current variation upon hybridization with the target DNA, facilitating viral concentration determination. T 2.1.4 | raphene Graphene is an incredibly versatile material and serves as the foundation of natural graphite.The carbon atoms within graphene sheets are predominantly hybridized with sp 2 bonds.9 Graphene features exceptional electrical and thermal conductivity, chemical stability, flexibility, optical transparency extensive surface area of 2630 m 2 /g.Despite of its many advantages, graphene exhibited poor hydrophilicity.This challenge has spurred extensive research aimed at enhancing its water solubility, leading to the creation of various graphene derivatives such as graphene oxide (GO), nitrogen-doped graphene, and reduced graphene oxide (rGO).30 These derivatives maintain graphene's distinctive physicochemical traits while offering an increased presence of hydrophilic and reactive functional groups, making them especially useful in infectious disease detection.24,31 Graphene also plays a crucial role in the development of optical sensors due to its efficient PL quenching properties.A notable application is a GO-based Polymerase Chain Reaction (PCR) system designed for the detection of influenza virus RNA.21 This system employs a fluorescence-labeled (fluorescein amidite (FAM) DNA probe that is complementary to the hemagglutinin gene target influenza strain (H3N2).During the Reverse Transcription-Polymerase Chain Reaction (RT-PCR) process, the Taq polymerase enzyme hydrolyzes the FAM-labeled DNA probe that is bound to the hemagglutinin gene, releasing the FAM fluorophore.When the target influenza virus RNA is present, the released FAM does not attach to the GO, allowing detectable fluorescent signal to be emitted. Coersely, in the absence of the target RNA, the PCR process is halted, and the intact fluorescent DNA probe binds to the GO, effectively quenching the FAM fluorescence.This innovative method achieved a lower detection limit (LOD) of 3.8 pg, outperforming the traditional real-time qRT-PCR technique.21 The high conductivity of graphene is leveraged to develop electrochemical sensors.In a novel approach for the label-free detection of the influenza virus H1N1, a unique microfluidic device integrated with an rGO-based electrochemical immunosensor was developed.23 This design facilitated the enrichment of the H1N1 virus directly on the electrode's surface by establishing a specific linkage between the carboxyl group present on the rGO surface and the amino group of the virus-specific monoclonal antibody.23 Graphene can potentially be used to detect infectious diseases.An FET-based immunoassay was established for the detection of inactivated Ebola virus (EBOV).24 EBOV glycoprotein antibodies were immobilized on rGO-modified FETs.This specific interaction between the antibodies and the inactivated EBOV triggered a notable leftward shift in the Dirac voltage, indicative of binding.Utilizing this method, EBOV detection was accomplished across a broad concentration range, from 2.4 � 10 −12 to 1.2 � 10 −7 g/mL, achieving a remarkable LOD of 2.4 pg/ mL.24 This showcases graphene's potential in developing sensitive diagnostic tools for infectious diseases, highlighting its significant impact on public health and safety.

| Gold nanomaterials
Gold nanomaterials are among the multifunctional nanomaterials for pathogen detection (Table 2).They are chemically stable, and their size ranges from 1 to 800 nm, with diverse morphological shapes, including spheres, rods, and prisms. 46 3.1.1| Gold nanoparticles AuNPs are polycrystalline gold nanostructures, typically exhibiting a quasi-spherical shape and ranging in diameter from 5 to 100 nm.46 These nanostructures are known for their color variance based on size; smaller colloidal gold particles (2-5 nm) appear orange-yellow color, mediumsized particles (10-20 nm) show a burgundy color, and larger colloidal gold particles (30-80 nm) exhibit a purplered hue.AuNPs can be synthesized through various methods, including the citrate reduction method, white phosphorous reduction method, ascorbic acid reduction method, and ethanol ultrasonic reduction method.46 AuNPs are distinguished by their substantial specific surface area and a high density of free electrons, resulting in unique optical, electrical, and catalytic properties and excellent biocompatibility.These features, especially the modifiable surface physicochemical properties of AuNPs, are instrumental in detecting infectious diseases.
Particularly effective in colorimetric assays due to their ultra-high extinction coefficient and the color shifts resulting from aggregation under high salt concentrations, AuNPs have been utilized in developing diagnostic tools, such as a colorimetric test kit for SARS-CoV-2 in saliva, leveraging a DNA aptamer-AuNP system. 47,48NA aptamers, designed specifically to target the SARS-CoV-2 spike protein (S1), were attached to the surface of AuNPs.When the S1 protein was introduced, it competitively removed the DNA aptamer from the surface of the AuNPs.By altering the salt concentration, the aptamer covered AuNPs were induced to cluster, resulting in a shift in color from red to blue.This color change, correlating with absorbance alterations, allowed for the quantification of viral content, achieving a LOD as low as 1.25 nM.
Colloidal AuNPs have commonly been employed as colorimetric markers in LFIAs. 46It demonstrated superior sensitivity and specificity in detecting specific antibodies against herpes simplex virus type 2, outperforming the traditional assays (Figure 2). 49AuNPs also find applications in electrochemical detection due to their excellent conductivity and catalytic performance, enabling the development of assays for detecting DNA sequences of viruses like the human cytomegalovirus (HCMV) through hybridization techniques. 47,50The assay was based on the hybridization of single-stranded target HCMV DNA with an oligonucleotide-modified AuNPs probe, followed by the oxidative solubilization of gold atoms tethered to the hybrid.Detection was achieved through the indirect determination of dissolved Au(III) ions via screen-printed microstrip electrode anodic dissolution voltammetry. 50onsidering that AuNPs have a large spectral overlap with fluorescence emissions, they are also used for FRET applications. 46A FRET system was designed to contain AuNPs and fluorescein (FAM) for HBV DNA sequences. 39 thin layer of cetyltrimethylammonium bromide was wrapped onto the surface of positively charged AuNPs.In the presence of complementary target DNA, a FRET process occurred from FAM to AuNPs, leading to the quenching of FAM fluorescence.Under optimized conditions, FAM fluorescence intensity linearly decreased with increasing complementary DNA concentration from 0.045 to 6.0 nM, with a low LOD of 15 pM (Figure 3A).39 Furthermore, AuNPs are known for their strong SERS signals, biocompatibility, stability, and the versatile surface functionalization capabilities.46 A highly sensitive immunoassay based on SERS spectroscopy was reported for the multiplex detection of viral zoonotic diseases, West Nile virus, and Rift Valley Fever virus.51 For each antigenic target, the researchers used Raman reporter-coated AuNPs and paramagnetic nanoparticles (PMNPs) in conjunction with specific polyclonal antibodies.This approach allowed for the magnetic concentration of Gold nanoparticles)/antigen/PMNP complexes, followed by detection through antibody recognition and Raman spectroscopy with LOD as low as 5 fg/mL (Figure 3B).surface properties similar to those of QDs, including high fluorescence intensity, exceptional photostability, and heightened surface activity.47 Both AuNCs and AuNPs are composed of gold monomers, yet they display distinct characteristics.Specifically, AuNCs possess superior fluorescence properties compared to AuNPs but lack the SPR features found in AuNPs.52 The chemiluminescence of AuNCs has been widely applied in various biological fluids, including plasma, urine, and tissue fluids.Gold nanoclusters can be employed to detect a wide array of substances, including amino acids, dopamine, small molecules, proteins, and nucleic acids.This approach substantially enhances detection sensitivity (minimum LOD) compared with traditional fluorescent labeling methods.Electrochemiluminescence (ECL) generates chemiluminescence through electrochemical processes, where the emitted light is captured by a detector to measure electrochemical luminescence signals.The sensing technique of ECL is predicated on the correlation between the electroluminescence signal and the concentration of the analyte, facilitating accurate and sensitive detection in samples.43 ECL sensors based on AuNCs offer several advantages, including good biocompatibility, low toxicity, and high sensitivity.43 An example of their application includes the detection of human papillomavirus DNA using an AuNC-based ECL sensor (Figure 3C).43

| Gold nanorods
AuNRs are cylindrical rod-shaped particles with uniform diameters ranging from a few to hundreds of nanometers.As non-spherical nanoparticles, the analytical properties of AuNRs, such as the intensity and spectrum position of the SPR band, aggregation stability, electrical conductivity, and redox potential, are largely determined by their physical size. 53In addition, the unique shape of AuNRs introduces two SPR modes along their longitudinal and transverse axes, enabling them to support a broad spectrum of radiation spanning from the visible to the near-infrared regions. 53A biosensor has been developed for detecting HBV, utilizing antibodies affixed to gold electrodes to capture viral antigens.It allows for quantification within a linear range of 0.01 IU/ mL to 1 IU/mL. 54Furthermore, an innovative and sensitive HBV-DNA biosensor has been developed through the surface etching of spiral gold nanorods (HGNRs) at the single-particle level under a dark field microscope.This approach achieves ultra-sensitive detection of HBV-DNA by monitoring changes in scattering intensity resulting from HGNR etching. 55

| Silver nanomaterials
Silver nanoparticles (AgNPs) feature similar chemical properties to AuNPs and are renowned for their exceptional photoelectric propertiess 56 (Table 3).These distinct optical features result from surface equipartition excitonic resonances, caused by the collective oscillation of conduction electrons.These oscillations are induced by several factors, including (1) the acceleration of conduction electrons by the electric field of incident radiation, (2) the presence of restoring forces generated by induced polarization in the nanoparticles and surrounding medium, and (3) electron confinement to sizes smaller than the wavelength of light.These qualities are highly reliant on the size, shape, content, and spatial organization of the nanoparticles. 63ilver nanoparticles are widely used as SERS active substrates owing to their ability to provide a millionfold enhancement in Raman scattering, making them a highly sensitive tool for trace analysis and single-molecule detection.For instance, a rapid SERS-based viral detection platform utilizing AgNPs, enhanced with calcium ions and acetonitrile, was developed to identify emerging viruses swiftly. 57Acetonitrile boosts the SERS signal by intensifying the calcium-induced "hot spots" on AgNPs, significantly stabilizing the nanoparticles, and making viruses emit extremely sensitive SERS signals.This approach successfully distinguished unique SERS signals of SARS-CoV-2, human adenovirus 3, and H1N1 influenza virus at a concentration of 100 copies/test, demonstrating high signal-to-noise ratios and reproducibility.Machine learning techniques were then applied to 1000 spectra from each virus, enabling the qualitative differentiation between the three viral types (Figure 4A). 57reover, AgNPs are known for their high extinction coefficient and pronounced distance-dependent optical properties, making them excellent candidates for colorimetric sensors.Triangular AgNPs of various sizes and colors were designed and synthesized to create TAg-DNA probes, tailored for the detection and identification of four serotypes of dengue fever.These specific colored probes were designed to bind exclusively to the RNA corresponding to a particular dengue fever serotype, showcasing the potential of AgNPs in targeted viral detection (Figure 4B). 61

| Magnetic nanoparticles
Magnetic nanoparticles (MNPs) are nanoscale (1-100 nm) magnetic materials, 64 hat leverage magnetic properties to enrich detection targets 65 (Table 4).Some MNPs feature core-shell structures, and there are two major types of MNPs with core magnetic materials: natural and artificial core MNPs.Natural core MNPs exhibit magnetic properties in living organisms, such as those found in the beaks of pigeons that sense magnetic fields or in magnetotropic bacteria. 77However, the use of natural core MNPs in research is limited owing to uncontrollable magnetic material content, the limited yield of natural magnetic vesicles, and unclear shell composition.Therefore, artificial cores, including iron-containing oxides, metals, and alloys, are more prevalent in current MNP research. 78The shells of MNPs, which are either inorganic silicon or organic polymers, play crucial roles in passivation, preventing core material oxidation or T A B L E 3 Application of silver nanomaterials for detection of pathogenic bacteria.Magnetic nanoparticles have peroxidase catalytic activity that catalyzes the peroxidase substrate and produces a distinct color reaction, allowing them to be used as nanas probes in a variety of applications. 66An MNPbased immunochromatographic strip was developed for detecting EBOV glycoproteins, demonstrated a sensitivity 100 times greater than traditional methods, down to 1 ng/ mL (Figure 5A). 66iant magnetoresistance (GMR) is a property describing the dependence of resistivity on an applied magnetic field, and it mainly occurs in multilayer structures with alternating ferromagnetic and nonmagnetic metal layers.A sensitive method based on GMR biosensors was developed for detecting influenza A virus.Monoclonal antibody against viral nucleoprotein (NP) was combined with MNPs.The presence of the influenza virus caused MNPs to bind to the GMR sensor, leading to a resistance change proportional to the virus concentration.A low LOD (1.5 � 10 2 TCID 50 /mL) was achieved (Figure 5B). 79agnetic tunnel junctions, similar to GMR spin valves but with an insulating layer between adjacent ferromagnetic layers, have been utilized in biosensors.MTJ-based biosensors, integrated with portable, electronic, and microfluidic devices, offer compact platforms for detecting DNA hybridization, facilitating bacterial and viral genotyping (Figure 5C). 70he magnetic properties of MNPs make them suitable for target separation using external magnetic fields, eliminating the need for traditional filters or separation steps.This makes MNP cost-effective, efficient, environmentally friendly, and easy to separate.To specifically identify traces of the hepatitis A virus (HAV), a magnetic resonance light scattering sensor based on molecularly imprinted polymer (MIP) technology was developed. 71Biomimetic polydopamine was synthesized on the surface of Fe 3 O 4 MNPs, and viral magnetic MIP was prepared via surface imprinting.The MIP was further used to capture the virus in water.Resonance light scattering intensity varied with particle size and shape upon viral identification.With an LOD of 6.2 pM, the sensor identified HAV in the linear concentration range of 0.02-1.40nM (Figure 5D). 71uclear magnetic resonance technology has been adapted for MNP applications, establishing a nucleic acid detection platform based on a magnetic barcoding strategy.PCR-amplified mycobacterial genes were specifically captured on microspheres, labeled with magnetic nanoprobes, and detected by Nuclear magnetic resonance.This platform enabled the detection of Mycobacterium tuberculosis within 2.5 h and the identification of drug-resistant strains (Figure 6).

| Upconversion nanoparticles
Following ordinary organic dyes and semiconductor QDs, UCNPs are the third class of fluorescent materials that play an important role in the diagnosis of infectious diseases (Table 5).They boast a multitude of benefits including high light stability, chemical stability, low toxicity, profound light penetration depth, minimal background interference from biological tissues, and negligible damage to those tissues (Figure 7A). 86he mechanisms of UCNPs involve the absorption of two or more low-energy photons followed by the emission of a single high-energy photon in response, a phenomenon termed upconversion luminescence.This process is driven by three primary luminescence mechanisms: excited-state absorption, energy transfer, and photon avalanche (Figure 7B). 87Illuminated by near-infrared light sources, UCNPs effectively reduce background interference from biological tissues, thereby enhancing sensitivity for both in vitro detection and in vivo imaging applications. 88Furthermore, UCNPs may generate light of various wavelengths, which can be used to detect a variety of infectious illness indicators. 89ne notable advantage of UCNPs is their ability to provide a clear numerical cut-off value, which is instrumental in delineating a patient's health status and enhancing sensitivity, particularly in antigen detection.The upconversion nanoparticle reporter technique has been used to detect antiviral antibodies, offering an advantage over conventional fluorescent labeling by eliminating background autofluorescence.Although lateral chromatography (LFA) is a commonly used method for traditional fluorescent labeling, the UCNPbased LFA for anti-HIV antibodies provides a more accurate method than previous traditional fluorescent labeling LFAs.Additionally, this innovative technique holds promise for broadening its application to other infectious diseases, including malaria and hepatitis B (Figure 7C). 81emission spectra, significant effective Stokes shifts, a long fluorescence lifespan, and outstanding multiphoton emission. 90,91QDs can be grouped into different types according to their components and structure.The three main types of QDs include core-type QDs, core-shell QDs, and alloyed QDs. 92Moreover, QDs play a role in infectious disease detection through FRET and LFIA (Table 6).
The optical detection principle of QD materials is mainly based on FRET.Ghasem Rezanejade Bardajeed et al. developed a fluorescent CdTe QD-DNA (QDs-DNA) nanosensor.The sensor, with a traditional "Sandwich" structure, exhibited an LOD of 2.52 � 10 −9 M for the specified target complementary DNA or RNA.Moreover, the nanosensor efficiently identified the SARS-CoV-2 virus. 95uantum dots feature unique characteristics of high stability, a high extinction coefficient, high quantum yield, and a long fluorescence lifetime, making them suitable as colorimetric markers in LFIAs. 92Wang et al. developed a magnetic QD-based dual-mode LFIA biosensor that could concurrently detect SARS-CoV-2 spike (S) and NP antigens.This improved the accuracy and efficiency of SARS-CoV-2 infection detection.The LODs for SARS-CoV-2 S and NP antigens were 1 and 0.5 pg/mL, respectively. 93

| CONCLUSION
Inorganic nanoparticles have garnered significant attention in the field of infectious disease detection owing to their unique features and broad application potential.Their high specific surface area and unique electrical structures enable efficient interactions with biomolecules, facilitating the highly sensitive detection of infectious disease markers.Moreover, the accuracy and reliability of disease detection can be significantly enhanced through the surface modification or functionalization of these nanomaterials.These advancements T A B L E 6 Application of quantum dots (QDs) for detection of pathogenic bacteria.allow for their integration into diverse detection techniques and signal amplification strategies.Additionally, the exceptional chemical and physical robustness of inorganic nanoparticles, combined with their capacity to reduce interference in complex biological samples, contributes to improved detection precision.Consequently, inorganic nanomaterials may pave the way for the development of sophisticated nanosensors for the identification of infectious microbes.Despite the great potential of the application of inorganic nanomaterials in clinical diagnosis, transitioning inorganic nanomaterials from laboratory research to practical clinical applications poses challenges.These include the necessity for rigorous validation studies to establish the reliability and accuracy of nanomaterialbased diagnostic procedures in real-world clinical settings.Achieving high levels of sensitivity and specificity is vital to accurately identify diseases, with the need to address issues of false positives and negatives to ensure reliable and precise disease detection.Additionally, inorganic nanomaterials may induce adverse reactions when in contact with living organisms, necessitating comprehensive biocompatibility and toxicity assessments.Potential solutions to this challenge include optimizing nanomaterial surface modification, developing degradable materials, and implementing effective removal and exclusion procedures.

3. 1 . 2 |of 20 -
Gold nanoclusters    Gold nanoclusters (AuNCs) are formed of several to hundreds of gold atoms and are typically smaller than 2 nm in size.They exhibit quantum-limited effects and 6 DING ET AL.T A B L E 2 Application of gold nanomaterials for detection of pathogenic bacteria.
3 (A) An AuNP and fluorescein FAM-based fluorescence resonance energy transfer (FRET) method for the identification of Hepatitis B virus (HBV) DNA sequences.Reproduced with permission. 39Copyright 2012, Royal Society of Chemistry.(B) A SERS-based immunoassay for the multiplex detection of surface envelope and capsid antigens of the viral zoonotic diseases West Nile Virus and Rift Valley fever virus.Reproduced with permission. 51Copyright 2013, Elsevier.(C) An AunC-based Electrochemiluminescence (ECL) sensor for the detection of HPV DNA.Reproduced with permission. 43Copyright 2021, Elsevier.F I G U R E 2 A colloidal gold nanoparticle based immunoglobulin G (IgG) specific antibody lateral-flow immunochromatographic assay (LFIA) to herpes simplex virus type 2 (HSV-2).

74 T A B L E 4
Application of Magnetic nanoparticles (MNPs) for detection of pathogenic bacteria.

5.2 | Quantum dots
Application of upconverting nanoparticles for detection of pathogenic bacteria.
T A B L E 5