Open access peer-reviewed chapter

Nanomaterials-Based Biosensors against Aspergillus and Aspergillosis: Control and Diagnostic Perspectives

Written By

Xiaodong Guo, Mengke Zhang, Mengzhi Wang, Jiaqi Wang and Marie-Laure Fauconnier

Submitted: 01 May 2023 Reviewed: 02 May 2023 Published: 23 October 2023

DOI: 10.5772/intechopen.111725

From the Edited Volume

Aspergillus and Aspergillosis - Advances in Genomics, Drug Development, Diagnosis and Treatment

Edited by Mehdi Razzaghi-Abyaneh, Mahendra Rai and Masoomeh Shams-Ghahfarokhi

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Abstract

Aspergillosis is the name given to the spectrum of diseases caused by the genus Aspergillus. Research on aspergillosis has shown a progressive expansion over the past decades, largely due to the rise in the number of immunocompromised individuals who are at risk for the infection. Nanotechnology provides innovative tools in the medicine, diagnosis, and treatment. The unique properties of nanomaterials like small size in the nanoscale have attracted researchers to explore their potential, especially in medical diagnostics. Aptamers, considered as chemical antibody, are short, single-stranded oligonucleotide molecules with high affinity and specificity to interact with target molecules even superior to antibody. Accordingly, development of nanomaterials-based biosensors technology such as immunosensors and aptasensors against Aspergillus and Aspergillosis is of great significance and urgency. In this book chapter, we comprehensively introduce and analyze the recent progress of nanomaterials-based biosensors against Aspergillus and Aspergillosis. In addition, we reveal the challenges and provide our opinion in future opportunities for such sensing platform development. Ultimately, conclusion and future prospects are highlighted and summarized.

Keywords

  • nanomaterials
  • biosensor
  • Aspergillus
  • Aspergillosis
  • biomarker

1. Introduction

Biosensors are integrated analytical devices that are capable of transferring the binding events between bioreceptor and target into detectable optical and electric signals. Therefore, bioreceptors, regarded as the recognition elements, play a crucial role for constructing advanced biosensors. Conventional bioreceptors like antibodies have been extensively prepared and developed for immunosensors’ establishment. The barriers such as high cost, complicated procedures, and lack of stability limited the wide applications of such sensing approaches [1, 2, 3]. Fortunately, nucleic acid aptamers are short and single-stranded oligonucleotides, selected and identified by SELEX (Systematic Evolution of Ligands Exponential Enrichment) in vitro selection process [4, 5]. Aptamer, considered as chemical antibody and even superior to antibody, can recognize the target molecule to form unique 3D configuration with high affinity and selectivity [6, 7]. Accordingly, aptasensors have attracted increasing attention in recent years toward a variety of target molecules including proteins, cells, viruses, bacteria, metal ions, as well as the disease biomarkers [8, 9].

It is worth noting that the current biosensors generally suffer from the concerns such as lack of biocompatibility, low stability, as well as the poor detection sensitivity. Various advanced nanomaterials can be integrated into the sensing systems for signal transduction and improved analytical performance [10, 11, 12]. The commonly used nanomaterials for biosensors mainly include fluorophores, quantum dots (QDs), graphene oxide (GO), gold nanoparticles (AuNPs), silver nanoparticles (AgNPs), metal-organic frameworks (MOFs), upconversion nanoparticles (UCNPs), zinc oxide (ZnO) and other semiconducting nanomaterials, and so on [13, 14, 15]. Fascinatingly, bioreceptors can be universally designed and modified with these nanomaterials and are available for optical and electrochemical signal transduction strategies, which further are measured by portable detectors such as fluorimeter, naked eyes, strip readout, as well as electrochemical detectors [16, 17]. For instance, in our recent study, we have introduced a fluorescent aptasensor toward mycotoxin fumonisin B1 (FB1) based on the aptamer recognition. In this effort, GO was embedded for fluorescent quenching and acted as a protectant of the specific aptamer from nuclease cleavage. The target cycling was then triggered for signal amplification and improved detection sensitivity [9].

At the present time, great advances have been achieved for immunosensors and aptasensors in numerous hazard control. Nevertheless, in this book chapter, we only outlined and highlighted the recent progress toward Aspergillus and Aspergillosis (Figure 1). Aspergillus is an extraordinary fungus that occurs naturally all around the world. Sixteen of the 200 known species of Aspergillus are isolated and identified due to their severe hazards to animals and humans. Prolonged exposure to high levels of Aspergillus can induce allergic symptoms, toxic symptoms, and infection. In particular, for instance, Aspergillus fumigatus is the most common and predominate one that can cause invasive aspergillosis (IA) [18, 19]. Conventional approaches for the detection of Aspergillus detection like biopsies of cerebral lesions and extraction of cerebrospinal fluid are usually not appropriate for immunocompromised patients. Therefore, simple, rapid, and accurate analytical techniques for Aspergillus and Aspergillosis diagnosis are of great importance for human health.

Figure 1.

Comprehensive overview of aptamer- and antibody-based biosensors toward Aspergillus and Aspergillosis based on advanced nanomaterials.

Immunosensors and aptasensors have witnessed a remarkable progress over the past decade. To the best of our knowledge, the comprehensive discussion on immunosensors and aptasensors toward Aspergillus and Aspergillosis diagnosis has not yet been reported. Inspired by this status, we proposed an overview of the biosensor construction and their improved performance (Figure 1). Moreover, we highlighted the challenges and new opportunities of advanced biosensors for early diagnosis of Aspergillosis infection.

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2. Recent advances of biosensors

In the past three decades, antibody-based immunoassays have been well established from scientists in medical and biotechnology fields, including biosensing, therapy, environment, and so on, and gradually extend to disease diagnosis for various targets and biomarker identification and determination. Classic immunoassays like ELISA (enzyme-linked immunosorbent assays) and LFIA (lateral flow immunoassay) are frequently realized for screening purposes and commercial application in the market [20, 21, 22]. In particular, ELISA kit, one of the most widely available products, is suitable for qualitative and quantitative assessment of target biomolecule [23]. The ELISA-based rapid screening methods exhibit desirable sensitivity and selectivity, as well as ease of operation [24, 25]. However, high cost in antibody production and antibody stability issue in complicated environment restrict their extended applications [26, 27]. More importantly, antibody preparation against small molecule remains a rigorous challenge since its non-immunogenic and antibody generation are not significant in the process of animal immune [28, 29, 30].

Fortunately, nucleic acid aptamer, considered as “chemical antibody,” is short ssDNA or RNA that shows excellent affinity and specificity against its target biomolecule even superior to antibody. Noteworthy, the aptamer selection is performed in vitro by SELEX technique instead of the complicated animal experiments in vivo [10]. Therefore, compared to antibody, the aptamer possesses obvious advantages like convenient production, low cost, high stability, non-immunogenicity, ease of modification, as well as various targets (proteins, cell, tissue, even small molecules) [31, 32]. Correspondingly, the past decade witnessed a remarkable progress on the development of novel aptasensors against Aspergillus and Aspergillosis and mycotoxin contamination. However, it is worth noting that there were few studies focusing on the comparison of analytical performance between antibody and aptamer. Stimulated by this status, we noticed that previous works on aptasensors demonstrated the more excellent analytical performance than that of immunosensors [33, 34]. Therefore, the discovery of specific aptamer and its further research opened up a new horizon for rapid and accurate determination of various hazards with high sensitivity and selectivity.

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3. Applications of biosensing strategies for Aspergillus

Aspergillus has received global concern due to its hazards on food spoilage and food safety [35]. In particular, Aspergillus flavus contamination can produce aflatoxins and cause Aspergillosis [36]. AflD gene, a potential biomarker for Aspergillus flavus pollution, is a structural gene in aflatoxins gene cluster of Aspergillus species like Aspergillus flavus [37]. Nevertheless, the analytical strategies for Aspergillus control are relatively less reported. Biosensors are thus emerged as advanced techniques for the detection of DNA attributed to their portability, high sensitivity, as well as ease of operation [38]. Sedighi-Khavidak et al. firstly fabricated a novel biosensor toward aflD gene analyses of Aspergillus flavus based on impedimetric electrochemical signal detection and Au NPs [39]. The Au NPs modified with specific DNA probe were immobilized on the glassy carbon electrode. The presence of target DNA induced the formation of double-stranded DNA via hybridization reaction, disrupting the reduction of [Fe(CN)6]3− and enhancing the electrochemical signal (Figure 2A). The electrochemical biosensor exhibited a dynamic response of aflD gene that ranged from 1 nM to 10 μM with an LOD of 0.55 nM. Furthermore, the feasibility of this sensing protocol was confirmed for the detection of aflD gene in real pistachio samples.

Figure 2.

(A) Schematic representation of impedimetric electrochemical DNA sensor for sensitive detection of aflD gene of Aspergillus flavus based on the Au NPs modification on electrode. The illustration was recreated according to ref. [39]. Copyright 2017: Taylor & Francis Group, LLC. (B) Schematic diagram of lateral flow immunoassay for colorimetric and photothermal detection of Aspergillus flavus via the functionalization of Cu-anchored PDA. The illustration was recreated according to ref. [40]. Copyright 2022: Elsevier. (C) Schematic illustration of the colorimetric biosensor toward Aspergillus flavus attributed to the analysis of VOCs by integrating nanocomposites. The illustration was recreated according to ref. [41]. Copyright 2022: Elsevier. (D) Mechanism illustration of a novel whole-cell biosensor for identification and monitoring of VOCs and Aspergillus contamination by integrating machine-learning models. The illustration was recreated according to ref. [42]. Copyright 2023: Elsevier.

Very recently, Liang et al. have synthesized Cu-anchored PDA (polydopamine) nanomaterials, which exhibited photothermal property and catalytic ability for colorimetric signal [40]. In this regard, the nanomaterials were further embedded into LFIA for multimodal sensing of Aspergillus flavus based on a sandwich design (Figure 2B). Consequently, compared to traditional colorimetric method, the novel LFIA platform showed a significantly sensitive detection of Aspergillus flavus with LODs of 0.45 and 0.22 ng/mL, respectively. The feasibility of the sensing strategy was further investigated to monitor Aspergillus flavus in peanut and maize samples. On the other hand, apart from the detection of Aspergillus flavus, volatile organic compounds (VOCs), the representative metabolites of Aspergillus flavus, could be identified and detected for Aspergillus flavus contamination [43]. In order to improve the detection efficiency, Lin et al. incorporated three types of nanomaterials into nanocomposites for colorimetric sensing of VOCs [41]. MOF (metal-organic framework), PSA (poly styrene-co-acrylic acid), and PSN (porous silica nanoparticles) were employed and integrated for improved performance due to their ultra-large surface area, excellent catalytic property, and numerous binding sites (Figure 2C). The developed sensing method showed high sensitivity and stability for the detection of VOCs and great promise for wheat mildew monitoring. From another viewpoint, the identification and detection of VOCs is significantly correlated with food spoilage event [44]. Traditional analytical technologies like gas chromatography-ion mobility spectrometry (GC-IMS) [45] and electronic nose [46] require expensive instruments, professional personnel, and complicated procedures. Fortunately, whole-cell biosensor possesses a great promise for rapid, portable, highly efficient, and sensitive control of VOCs [47]. Herein, Ma et al. developed a novel whole-cell biosensing platform for VOCs finding and Aspergillus infection monitoring by engineering machine learning models [42]. Three VOCs’ markers were identified in peanut by Aspergillus flavus infection and further realized for the validation of various response modes and the construction of biosensor (Figure 2D). Moreover, the proposed biosensor coupled with machine-learning models exhibited excellent prediction accuracy in both infected matrices and pre-mold stages. Hence, this novel biosensing strategy opened a new avenue for Aspergillus infection prediction and food control.

Conventional Aspergillus analytical methods generally involve sampling and culturing of Aspergillus spores for immunoassay signal detection, followed by DNA sequencing and quantitative analysis. These protocols suffer from the drawbacks like high cost, complicated procedures, and time-consuming [48, 49, 50]. To overcome the barrier, advanced nanomaterials-based biosensors are attracting increasing attention for improved performance. For instance, Jin et al. developed a nanoscale immunosensor for real-time monitoring of Aspergillus niger via single-walled carbon nanotube (SWNT) and antigen-antibody recognition (Figure 3A) [51]. Encouragingly, the integrating of carbon nanomaterials significantly increased the antibody immobilization sites for enhanced detection signal and high sensitivity at sub-picomolar levels. On the basis of similar antigen-antibody recognition, Lee et al. proposed an electrochemical immunosensor for selectively quantification of Aspergillus niger via detecting the extracellular proteins (Figure 3B), which relied on the immobilization of the extracellular proteins and its interference of redox cycling in interdigitated electrodes [52]. The utilization of secretion promoter at the sampling stage realized a highly sensitive response by 200-fold improvement for the Aspergillus niger monitoring in their previous study [53], which might attribute to the specific antibody recognition rather than to the amplified oxidation oxygen reduction reaction.

Figure 3.

(A) Schematic illustration of the novel immunosensor for highly sensitive detection of Aspergillus Niger based on the functionalization of single-walled carbon nanotube (SWNT). The illustration was recreated according to ref. [51]. Copyright 2015: Royal Society of Chemistry. (B) Schematic diagram of electrochemical immunosensor for selective quantification of the Aspergillus Niger based on the extracellular proteins monitoring and antibody–antigen reaction. The illustration was recreated according to ref. [52]. Copyright 2021: Elsevier.

More importantly, current diagnosing methods for Aspergillus infection are not appropriate in clinical POC testing. To solve this concern, Yu et al. developed a novel simple and rapid analytical technique for DNA amplification based on loop-mediated isothermal amplification (LAMP) [54]. The LAMP approach was employed to detect the target gene TR34, a biomarker for Aspergillus fumigatus infection in patients. Assisted by the primer design of LAMP, this protocol contributed to rapid and selective identification of TR34, as well as the high detection sensitivity with 10 genomic copies per reaction. It was demonstrated that the TR34-LAMP platform can be considered as a POC diagnosis strategy for the screening of clinical Aspergillus fumigatus infection.

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4. Applications of biosensing strategies for Aspergillosis

4.1 Gliotoxin-related biomarker

Genus Aspergillus is a group of fungi that can induce a majority of Aspergillus infection from allergic reaction to invasive diseases. Invasive aspergillosis (IA), one of the most severe and devastating Aspergillus infections, is defined as a rapid, acute, and life-threatening invasive disease with mortality rate as high as 90%. Of the various Aspergillus (such as Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger), Aspergillus fumigatus is the most common and predominate one that causes IA. Gliotoxin, considered as the most toxic metabolites occurred by Aspergillus fumigatus, poses great hazards to immunosuppressed individuals. Therefore, the development of simple, rapid, sensitive, and point-of-care strategies for gliotoxin control is of high significance and urgency for early diagnosis of IA.

In the direction, assisted by the immobilization-free and GO (graphene oxide)-SELEX technique, Gao et al. proposed the pioneer work for the isolation and selection of the specific aptamer toward gliotoxin (Figure 4A) [55]. After the eighth selection cycle, fortunately, the ssDNA was enriched, and the aptamer APT8 was obtained and sequenced with a dissociated constant (KD) of 376 nM. Then, the APT8 was further truncated into a shorter sequence consisting of only 24 nucleotides according to the mfold structure prediction. More encouragingly, the truncated aptamer APT8T1 was confirmed to recognize the gliotoxin with higher specificity (KD = 196 nM) and could be further designed to APT8T1M with 18-fold improvement of KD value. Accordingly, to validate the feasibility and selectivity of the aptamer, a simple fluorescent aptasensor was established for the detection of gliotoxin based on base pairing between the aptamer and its complementary DNA. The specific recognition of aptamer against gliotoxin caused the release of the aptamer/gliotoxin complex from the microplate and the fluorescent signal enhancement. The fluorescent signal was observed to be in linear relationship with levels of target gliotoxin in the range of 0.1–100 nM. The LOD was estimated to be 0.05 nM, which is significantly lower than the previous instrument methods like HPLC-MS/MS. Moreover, the successful application of the fluorescent aptasensor in human serum and urine samples demonstrated that this developed aptasensing platform offered a promising value in gliotoxin control. Inspired by this pioneer finding, combining the unique superiorities of MXene (Ti3C2) and TDNs (tetrahedral DNA nanostructures), Wang et al. developed a novel electrochemical aptasensor for highly efficient detection of gliotoxin based on nanomaterial functionalization (Figure 4B) [56]. Ti3C2 nanosheets, exhibiting large surface area, were modified with TDNs via the coordination interaction. The prepared nanocomposites allowed outstanding conductivity and molecule recognition toward the target for signal amplification. After the binding events between the aptamer and target, the cDNA was released and bound to the aptamer-modified nanocomposites, leading to the streptavidin-decorated HRP (horseradish peroxidase) catalysis and current signal generation. As a consequence, a dynamic response was achieved between the electrochemical signal and concentrations of gliotoxin ranged from 5 pM to 10 nM with an LOD of 5 pM. Accordingly, the detection sensitivity of this electrochemical aptasensor was improved by an order of magnitude than that of the previous fluorescent detection. Notably, the practicality of this method was excellent for gliotoxin detection in human serum samples. It was demonstrated that, from this viewpoint, advanced aptasensor technology possessed a significant potential against gliotoxin for early diagnosis of IA.

Figure 4.

(A) Working principle of the fluorescent aptasensor against gliotoxin detection for early diagnosis of invasive aspergillosis based on the specific aptamer selection. The illustration was recreated according to ref. [55]. Copyright 2018: American Chemical Society. (B) Schematic representation of electrochemical biosensor for label-free detection of gliotoxin incorporating of tetrahedral DNA nanostructures (TDNs) and MXene nanocomposites. The illustration was recreated according to ref. [56]. Copyright 2019: Elsevier. (C) Schematic diagram of isolation and characterization of the specific aptamer against spores of three representative Aspergillus species. The illustration was recreated according to ref. [57]. Copyright 2021: Royal Society of Chemistry.

On the other hand, considering the obvious superiorities of aptamer-based biosensors, Seo et al. isolated and identified the specific aptamers that can specifically recognize Aspergillus spore by using cell-SELEX technique for the first time [57]. In this effort, the aptamers against three Aspergillus spores including Aspergillus fumigatus, Aspergillus flavus, and Aspergillus niger were selected in the spore-SELEX process (Figure 4C). With 12 rounds of selection, the ssDNA was successfully enriched, and the specific aptamer Asp-3 was achieved and sequenced with dissociated constants (KD) of 80.12, 35.17, and 101.19 nM versus Aspergillus fumigatus, Aspergillus flavus, and Aspergillus niger, respectively. It was worth noting that the above aptamer also exhibited strong affinity to 1,3 β-D-glucans (BDGs) with KD of 79.76–103.7 nM, demonstrating the excellent affinities and recognition potential toward Aspergillus spore surface molecules. However, the representative aptasensors have not been further developed. Hence, how to select and optimize the aptamer for Aspergillus spore control is of vital significance in the future. On the other hand, the biosynthesis of gliotoxin is related to gliP gene, and gliP gene-encoded enzyme further affects the occurrence of gliotoxin. In this direction, gliP gene can be considered as a potential biomarker for Aspergillus control, and it eventually contributed to the early diagnosis of IA. Encouragingly, Bhatnagar et al. fabricated an electrochemical biosensor toward gliP gene detection for the first time [58]. The gliP gene was immobilized onto chitosan-stabilized Au NPs on gold electrode. DNA hybridization reaction induced the formation of double-stranded DNA and its interaction with toluidine blue. The toluidine blue was acted as the electrochemical indicator for signal output. Upon the optimal conditions, the novel biosensor exhibited a dynamic response of the target in the range of 1 × 10−14–1 × 10−2 M with an LOD of 0.32 × 10−14. The proposed biosensor is stable and selective for detection of glip-T, demonstrating that it is useful for Aspergillus analysis and clinical diagnosis.

4.2 Galactomannan-related biomarker

GM (Galactomannan), regarded as a popular biomarker Aspergillus infection, is a heat-stable polysaccharide consisting of a linear mannan core with side chains of galactofuran. GM is metabolized and released in the blood and bronchoalveolar fluid (BALF) and is occurred as soluble antigen mainly in the cell wall of the genera Aspergillus. Ab (antibody)-based immunoassays such as ELISA (enzyme-linked immunosorbent assay), LFIA (lateral flow immunoassay), and immunosensor are the most frequently used protocols for the detection of GM in early infection of IA. Raval et al. firstly proposed an ELISA method to capture and detect GM based on the conjugation of polyclonal antibody to Au NPs [59]. The developed Au NPs immunoassay possessed simple and accurate detection of GM with low LOD at picomolar level (Figure 5A). Based on the similar mechanism, Guo et al. introduced a sandwich chemiluminescence immunoassay toward GM detection incorporated with luminescent nanomaterials (Figure 5B) [60]. In this attempt, the donor consisted of photosensitizer and phthalocyanine, and the acceptor contained the chemiluminescent dye, allowing the luminescent signal output under laser irradiation. The donor and the acceptor formed immunocomplex due to the close proximity less than 200 nm. The developed chemiluminescence ELISA platform displayed a linear response of GM in the range 0.05–100 ng/mL with an LOD of 0.032 ng/mL and was capable of highly efficient GM detection in serum and BALF. Besides, nanomaterials-based miniaturized biosensors possessed outstanding advantages in portable monitoring and high-throughput analytical manner [62, 63, 64]. Therefore, Piguillem et al. prepared the ZnO nanoflowers (ZnONFs), conjugated the nanomaterials to microfluidic channel, and employed the nanocomplex for antibody modification [61]. Correspondingly, a novel immunosensor was established for fluorescent detection of GM via the generation of fluorescent substance resorufin (Figure 5C). The immunoassay principle was designed by HRP-modified antibody for catalysis of 10-acetyl-3,7-dihydroxyphenoxacine oxidation to resorufin. Excitingly, the proposed immunosensor can realize a more sensitive and highly efficient detection of GM by 14-fold improvement in LOD over the commercial ELISA method.

Figure 5.

(A) Schematic diagram of the ELISA-based immunoassay for the detection of galactomannan for early diagnosis of invasive aspergillosis based on the Au NPs conjugation. The illustration was recreated according to ref. [59]. Copyright 2019: Microbiology society. (B) Working principle of the chemiluminescence immunoassay toward galactomannan detection based on the donor and the acceptor. The illustration was recreated according to ref. [60]. Copyright 2022: Elsevier. (C) Schematic illustration of the fluorescence immunosensor to monitor galactomannan based on sandwich format and ZnO nanoflowers (ZnONFs). The illustration was recreated according to ref. [61]. Copyright 2020: Elsevier.

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5. Conclusions and outlook

Over the past decade, immunosensors and aptasensors have been well established for the detection and control of Aspergillus and Aspergillosis. Advanced nanomaterials-integrated approaches possess great potential to improve the performance for early diagnosis of IA. Of them, optical and electrochemical responses (including fluorescent, colorimetric, electrochemical, and electrochemiluminescence systems) are the two major signal transduction mechanisms. Besides, several researches have also focused on the principles toward binding events between the aptamer and target, catalytic transformation of target, truncation of the known aptamer, as well as the selection of new aptamers, and so on. These efforts indicated that advanced biosensors possessed excellent dynamic response and high sensitivity for AFB1 detection, as well as the feasibility and accuracy in Aspergillus detection and Aspergillosis diagnosis. Accordingly, biosensors techniques should have fascinating potential in industrial applications for food safety and risk assessment in the future.

Even though nanomaterials-based biosensors toward Aspergillus and Aspergillosis have witnessed the remarkable achievement, there are still several vital scientific limitations and challenges that required to overcome. (i) Advanced material-integrated biosensors exhibited excellent and improved analytical performance. For instance, as mentioned in this article, combining GO with AuNCs can significantly improve the fluorescent quenching efficiency compared to single GO. Novel luminescent materials such as UCNPs, PLNPs, and AIE probes displayed unique superiorities in terms of photostability, anti-interference, and even label-free detection. Therefore, the exploration of new materials and their synergistic effects are of great significance. (ii) Numerous reports are rarely aimed at developing the novel biosensors for their detection analysis rather than at the mechanism research. It is worth noting that the configuration change, site modification, and binding kinetics are of vital importance to better understand the principles and signal response. (iii) The selectivity assay is not appropriate in some case studies; the structural analogues should be taken into consideration for the interferences. (iv) It can be seen that the novel aptamer and aptasensors were relatively less developed, which is mainly attributed to the barriers in precise selection of aptamers. The stability and folding characteristics may be influenced by the special conditions like temperature, pH, ionic strength, and so on, thereby affecting the detection performance. Thus, how to select and identify high-quality aptamers that can undergo various reaction systems is a pursuing work. (v) Most established aptasensing protocols are limited in the laboratory conditions; in particular, at the present time, no commercial kits integrated by aptamers are available in the market. Enormous endeavors should be exerted to design and develop portable sensors or miniaturized devices in POC testing of Aspergillus and Aspergillosis.

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Acknowledgments

We thank the University of Liège-Gembloux Agro-Bio Tech and more specifically the research platform AgricultureIsLife for the funding of the scientific stay in Belgium that made this paper possible.

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Funding

This work was supported by the National Natural Science Foundation of China (No. 32001682, 21305158), the Special Fund for Agro-scientific Research in the Public Interest (201403071), and the Agricultural Science and Technology Research system of the PR China (ASTIP-IAS12).

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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.

References

  1. 1. Farka Z, Jurik T, Kovář D, Trnkova L, Skládal P. Nanoparticle-based immunochemical biosensors and assays: Recent advances and challenges. Chemical Reviews. 2017;117(15):9973-10042. DOI: 10.1021/acs.chemrev.7b00037
  2. 2. Wu J, Wang X, Wang Q, Lou Z, Li S, Zhu Y, et al. Nanomaterials with enzyme-like characteristics (nanozymes): Next-generation artificial enzymes (II). Chemical Society Reviews. 2019;48(4):1004-1076. DOI: 10.1039/C8CS00457A
  3. 3. Chrouda A, Ayed D, Zinoubi K, Majdoub H, Jaffrezic-Renault N. Highly stable and ultra-sensitive amperometric aptasensor based on pectin stabilized gold nanoparticles on graphene oxide modified GCE for the detection of aflatoxin M1. Food Chemistry Advances. 2022;1:100068. DOI: 10.1016/j.focha.2022.100068
  4. 4. Qi S, Duan N, Khan IM, Dong X, Zhang Y, Wu S, et al. Strategies to manipulate the performance of aptamers in SELEX, post-SELEX and microenvironment. Biotechnology Advances. 2022;55:107902. DOI: 10.1016/j.biotechadv.2021.107902
  5. 5. Meirinho SG, Dias LG, Peres AM, Rodrigues LR. Voltammetric aptasensors for protein disease biomarkers detection: A review. Biotechnology Advances. 2016;34(5):941-953. DOI: 10.1016/j.biotechadv.2016.05.006
  6. 6. Zhang M, Guo X. Gold/platinum bimetallic nanomaterials for immunoassay and immunosensing. Coordination Chemistry Reviews. 2022;465:214578. DOI: 10.1016/j.ccr.2022.214578
  7. 7. Jiang G, Li Y, Liu J, Liu L, Pi F. Progress on aptamer-based SERS sensors for food safety and quality assessment: Methodology, current applications and future trends. Critical Reviews in Food Science and Nutrition. 2022:1-18. DOI: 10.1080/10408398.2022.2108370
  8. 8. Qiao Q, Guo X, Wen F, Chen L, Xu Q, Zheng N, et al. Aptamer-based fluorescence quenching approach for detection of aflatoxin M1 in milk. Frontiers in Chemistry. 2021;9:653869. DOI: 10.3389/fchem.2021.653869
  9. 9. Guo X, Qiao Q, Zhang M, Fauconnier ML. Nuclease triggered “signal-on” and amplified fluorescent sensing of fumonisin B1 incorporating graphene oxide and specific aptamer. International Journal of Molecular Sciences. 2022;23:9024. DOI: 10.3390/ijms23169024
  10. 10. Hou Y, Jia B, Sheng P, Liao X, Shi L, Fang L, et al. Aptasensors for mycotoxins in foods: Recent advances and future trends. Comprehensive Reviews in Food Science and Food Safety. 2022;21(2):2032-2073. DOI: 10.1111/1541-4337.12858
  11. 11. Zhai W, You T, Ouyang X, Wang M. Recent progress in mycotoxins detection based on surface-enhanced Raman spectroscopy. Comprehensive Reviews in Food Science and Food Safety. 2021;20(2):1887-1909. DOI: 10.1111/1541-4337.12686
  12. 12. Park H, Baek S, Sen A, Jung B, Shim J, Park YC, et al. Ultrasensitive and selective field-effect transistor-based biosensor created by rings of MoS2 Nanopores. ACS Nano. 2021;16(2):1826-1835. DOI: 10.1021/acsnano.1c08255
  13. 13. Wei M, Rao H, Niu Z, Xue X, Luo M, Zhang X, et al. Breaking the time and space limitation of point-of-care testing strategies: Photothermometric sensors based on different photothermal agents and materials. Coordination Chemistry Reviews. 2021;447:214149. DOI: 10.1016/j.ccr.2021.214149
  14. 14. Liu Y, Li B, Zhang H, Liu Y, Xie P. Participation of fluorescence technology in the cross-disciplinary detection of microcystins. Coordination Chemistry Reviews. 2022;457:214416. DOI: 10.1016/j.ccr.2022.214416
  15. 15. Li Y, Liu D, Meng S, Zhang J, Li L, You T. Regulation of Ru (bpy)32+ electrochemiluminescence based on distance-dependent electron transfer of ferrocene for dual-signal readout detection of aflatoxin B1 with high sensitivity. Analytical Chemistry. 2022;94(2):1294-1301. DOI: 10.1021/acs.analchem.1c04501
  16. 16. Zhou Y, Yin H, Zhao WW, Ai S. Electrochemical, electrochemil-uminescent and photoelectrochemical bioanalysis of epigenetic modifiers: A comprehensive review. Coordination Chemistry Reviews. 2020;424:213519. DOI: 10.1016/j.ccr.2020.213519
  17. 17. Hu D, Hu Y, Zhan T, Zheng Y, Ran P, Liu X, et al. Coenzyme A-aptamer-facilitated label-free electrochemical stripping strategy for sensitive detection of histone acetyltransferase activity. Biosensors & Bioelectronics. 2020;150:111934. DOI: 10.1016/j.bios.2019.111934
  18. 18. Lian X, Scott-Thomas A, Lewis JG, Bhatia M, MacPherson SA, Zeng Y, et al. Monoclonal antibodies and invasive Aspergillosis: Diagnostic and therapeutic perspectives. International Journal of Molecular Sciences. 2022;23:5563. DOI: 10.3390/ijms23105563
  19. 19. Johnson G, Ferrini A, Dolan SK, Nolan T, Agrawal S, Doyle S, et al. Biomarkers for invasive aspergillosis: The challenges continue. Biomarkers in Medicine. 2014;8(3):429-451. DOI: 10.2217/bmm.13.129
  20. 20. Suri CR, Boro R, Nangia Y, Gandhi S, Sharma P, Wangoo N, et al. Immunoanalytical techniques for analyzing pesticides in the environment. TrAC Trends in Analytical Chemistry. 2009;28(1):29-39. DOI: 10.1016/j.trac.2008.09.017
  21. 21. Venkataramana M, Rashmi R, Uppalapati SR, Chandranayaka S, Balakrishna K, Radhika M, et al. Development of sandwich dot-ELISA for specific detection of Ochratoxin a and its application on to contaminated cereal grains originating from India. Frontiers in Microbiology. 2015;6:511. DOI: 10.3389/fmicb.2015.00511
  22. 22. Jafari M, Rezaei M, Kalantari H, Tabarzad M, Daraei B. Optimization of aflatoxin B1 aptasensing. Journal of Toxicology. 2017;2017:2461354. DOI: 10.1155/2017/2461354
  23. 23. Mozaffari Nejad AS, Sabouri Ghannad M, Kamkar A. Determination of aflatoxin B1 levels in Iranian and Indian spices by ELISA method. Toxin Reviews. 2014;33(4):151-154. DOI: 10.3109/15569543.2014.942319
  24. 24. Sharma P, Gandhi S, Chopra A, Sekar N, Suri CR. Fluoroimmunoassay based on suppression of fluorescence self-quenching for ultra-sensitive detection of herbicide diuron. Analytica Chimica Acta. 2010;676(1-2):87-92. DOI: 10.1016/j.aca.2010.07.042
  25. 25. Tey JN, Gandhi S, Wijaya IPM, Palaniappan A, Wei J, Rodriguez I, et al. Direct detection of heroin metabolites using a competitive immunoassay based on a carbon-nanotube liquid-gated field-effect transistor. Small. 2010;6(9):993-998. DOI: 10.1002/smll.200902139
  26. 26. Shim WB, Kim MJ, Mun H, Kim MG. An aptamer-based dipstick assay for the rapid and simple detection of aflatoxin B1. Biosensors & Bioelectronics. 2014;62:288-294. DOI: 10.1016/j.bios.2014.06.059
  27. 27. Shim WB, Mun H, Joung HA, Ofori JA, Chung DH, Kim MG. Chemiluminescence competitive aptamer assay for the detection of aflatoxin B1 in corn samples. Food Control. 2014;36(1):30-35. DOI: 10.1016/j.foodcont.2013.07.042
  28. 28. Gandhi S, Banga I, Maurya PK, Eremin SA. A gold nanoparticle-single-chain fragment variable antibody as an immunoprobe for rapid detection of morphine by dipstick. RSC Advances. 2018;8(3):1511-1518. DOI: 10.1039/C7RA12810J
  29. 29. Gandhi S, Caplash N, Sharma P, Suri CR. Strip-based immunochromatographic assay using specific egg yolk antibodies for rapid detection of morphine in urine samples. Biosensors & Bioelectronics. 2009;25(2):502-505. DOI: 10.1016/j.bios.2009.07.018
  30. 30. Talan A, Mishra A, Eremin SA, Narang J, Kumar A, Gandhi S. Ultrasensitive electrochemical immuno-sensing platform based on gold nanoparticles triggering chlorpyrifos detection in fruits and vegetables. Biosensors & Bioelectronics. 2018;105:14-21. DOI: 10.1016/j.bios.2018.01.013
  31. 31. Ni SJ, Zhuo ZJ, Pan YF, Yu YY, Li FF, Liu J, et al. Recent progress in aptamer discoveries and modifications for therapeutic applications. ACS Applied Materials & Interfaces. 2021;13:9500-9519. DOI: 10.1021/acsami.0c05750
  32. 32. Zon G. Recent advances in aptamer applications for analytical biochemistry. Analytical Biochemistry. 2022;644:113894. DOI: 10.1016/j.ab.2020.113894
  33. 33. Aswani Kumar YVV, Renuka RM, Achuth J, Venkataramana M, Ushakiranmayi M, Sudhakar P. Development of hybrid IgG-aptamer sandwich immunoassay platform for aflatoxin B1 detection and its evaluation onto various field samples. Frontiers in Pharmacology. 2018;9:271. DOI: 10.3389/fphar.2018.00271
  34. 34. Mukherjee M, Manonmani HK, Bhatt P. Aptamer as capture agent in enzyme-linked apta-sorbent assay (ELASA) for ultrasensitive detection of aflatoxin B1. Toxicon. 2018;156:28-33. DOI: 10.1016/j.toxicon.2018.11.001
  35. 35. Kollia E, Proestos C, Zoumpoulakis P, Markaki P. Inhibitory effect of Cynara cardunculus L. extract on aflatoxin B1 production by aspergillus parasiticus in sesame (Sesamum indicum L). International Journal of Food Properties. 2017;20(6):1270-1279. DOI: 10.1080/10942912.2016.1206928
  36. 36. Sardiñas N, Vázquez C, Gil-Serna J, González-Jaén MT, Patiño B. Specific detection and quantification of aspergillus flavus and aspergillus parasiticus in wheat flour by SYBR® green quantitative PCR. International Journal of Food Microbiology. 2011;145(1):121-125. DOI: 10.1016/j.ijfoodmicro.2010.11.041
  37. 37. Rodrigues P, Soares C, Kozakiewicz Z, Paterson R, Lima N, Venâncio A. Identification and characterization of aspergillus Flavus and aflatoxins. Communicating Current Research and Educational Topics and Trends in Applied Microbiology. 2007;2:527-534
  38. 38. Wang C, Yuan X, Liu X, Gao Q, Qi H, Zhang C. Signal-on Impedimetric electrochemical DNA sensor using Dithiothreitol modified gold nanoparticle tag for highly sensitive DNA detection. Analytica Chimica Acta. 2013;799:36-43. DOI: 10.1016/j.aca.2013.09.024
  39. 39. Sedighi-Khavidak S, Mazloum-Ardakani M, Khorasgani MR, Emtiazi G, Hosseinzadeh L. Detection of aflD gene in contaminated pistachio with aspergillus flavus by DNA based electrochemical biosensor. International Journal of Food Properties. 2017;20(S1):S119-S130. DOI: 10.1080/10942912.2017.1291675
  40. 40. Liang M, Cai X, Gao Y, Yan H, Fu J, Tang X, et al. A versatile nanozyme integrated colorimetric and photothermal lateral flow immunoassay for highly sensitive and reliable aspergillus flavus detection. Biosensors and Biolelectronics. 2022;213:114435. DOI: 10.1016/j.bios.2022.114435
  41. 41. Lin H, Wang F, Lin J, Yang W, Kang W, Jiang H, et al. Detection of wheat toxigenic aspergillus flavus based on nano-composite colorimetric sensing technology. Food Chemistry. 2023;405:134803. DOI: 10.1016/j.foodchem.2022.134803
  42. 42. Ma J, Guan Y, Xing F, Eltzov E, Wang Y, Li X, et al. Accurate and non-destructive monitoring of mold contamination in foodstuffs based on whole-cell biosensor array coupling with machine-learning prediction models. Journal of Hazardous Materials. 2023;449:131030. DOI: 10.1016/j.jhazmat.2023.131030
  43. 43. Lin H, Jiang H, He P, Haruna SA, Chen Q, Xue Z, et al. Non-destructive detection of heavy metals in vegetable oil based on nano-chemoselective response dye combined with near-infrared spectroscopy. Sensors & Actuators, B: Chemical. 2021;335:129716. DOI: 10.1016/j.snb.2021.129716
  44. 44. Tietel Z, Melamed S, Lebiush S, Voet H, Namdar D, Eltzov E, Tsror (Lahkim) L. Characterization of volatile signatures of Pectobacterium and Dickeya spp. As biomarkers for early detection and identification - a major tool in potato blackleg and tuber soft rot management. LWT. 2021;144:111236. DOI:10.1016/j.lwt.2021.111236
  45. 45. Josselin L, De Clerck C, De Boevre M, Moretti A, Jijakli MH, Soyeurt H, Fauconnier ML. Volatile organic compounds emitted by aspergillus flavus strains producing or not aflatoxin B1. Toxins. 2021;13(10):705-724. DOI:10.3390/toxins13100705
  46. 46. Loulier J, Lefort F, Stocki M, Asztemborska M, Szmigielski R, Siwek K, et al. Detection of fungi and oomycetes by volatiles using E-nose and SPME-GC/MS platforms. Molecules. 2020;25(23):5749-5776. DOI: 10.3390/molecules25235749
  47. 47. Liu CJ, Yu H, Zhang BC, Liu SL, Liu CG, Li F, et al. Engineering whole-cell microbial biosensors: Design principles and applications in monitoring and treatment of heavy metals and organic pollutants. Biotechnology Advances. 2022;60:108019. DOI: 10.1016/j.biotechadv.2022.108019
  48. 48. Monaci L, Pilolli R, De Angelis E, Godula M, Visconti A. Multi-allergen detection in food by micro high-performance liquid chromatography coupled to a dual cell linear ion trap mass spectrometry. Journal of Chromatography. A. 2014;1358:136-144. DOI: 10.1016/j.chroma.2014.06.092
  49. 49. Koeberl M, Clarke D, Lopata AL. Next generation of food allergen quantification using mass spectrometric systems. Journal of Proteome Research. 2014;13:3499. DOI: 10.1021/pr500247r
  50. 50. Svobodova M, Mairal T, Nadal P, Bermudo MC, O'Sullivan CK. Ultrasensitive aptamer based detection of β-conglutin food allergen. Food Chemistry. 2014;165:419. DOI: 10.1016/j.foodchem.2014.05.128
  51. 51. Jin JH, Kim J, Jeon T, Shin SK, Sohn JR, Yi H, et al. Real-time selective monitoring of allergenic aspergillus molds using pentameric antibody-immobilized single-walled carbon nanotube-field effect transistors. RSC Advances. 2015;5:15728. DOI: 10.1039/C4RA15815F
  52. 52. Lee J, Kim S, Chung HY, Kang A, Kim S, Hwang H, et al. Electrochemical microgap immunosensors for selective detection of pathogenic aspergillus Niger. Journal of Hazardous Materials. 2021;411:125069. DOI: 10.1016/j.jhazmat.2021.125069
  53. 53. Kwon J, Cho EM, Nandhakumar P, Yang SI, Yang H. Rapid and sensitive detection of aspergillus Niger using a single-mediator system combined with redox cycling. Analytical Chemistry. 2018;90:13491-11349. DOI: 10.1021/acs.analchem.8b03417
  54. 54. Yu LS, Rodriguez-Manzano J, Malpartida-Cardenas K, Sewell T, Bader O, Armstrong-James D, et al. Rapid and sensitive detection of azole-resistant aspergillus fumigatus by tandem repeat loop-mediated isothermal amplification. The Journal of Molecular Diagnostics. 2019;21(2):286-295. DOI: 10.1016/j.jmoldx.2018.10.004
  55. 55. Gao S, Zheng X, Tang Y, Cheng Y, Hu., X., Wu, J. Development of a fluorescently labeled Aptamer structure-switching assay for sensitive and rapid detection of Gliotoxin. Analytical Chemistry. 2019;91(2):1610-1618. DOI: 10.1021/acs.analchem.8b05094
  56. 56. Wang H, Li H, Huang Y, Xiong M, Wang F, Li C. A label-free electrochemical biosensor for highly sensitive detection of gliotoxin based on DNA nanostructure/MXene nanocomplexes. Biosensors & Bioelectronics. 2019;142:111531. DOI: 10.1016/j.bios.2019.111531
  57. 57. Seo JW, Kim JY, Kim DH, Oh JJ, Kim YJ, Kim GH. Selection and characterization of toxic aspergillus spore-specific DNA aptamer using spore-SELEX. RSC Advances. 2021;11:2608-2615. DOI: 10.1039/D0RA09571K
  58. 58. Bhatnagar I, Mahato K, Ealla KKR, Asthana A, Chandra P. Chitosan stabilized gold nanoparticle mediated self-assembled gliP nanobiosensor for diagnosis of invasive Aspergillosis. International Journal of Biological Macromolecules. 2018;110:449-456. DOI: 10.1016/j.ijbiomac.2017.12.084
  59. 59. Raval KM, Ghormade V, Rajamohananet PR, Choudhary H, Rudramurthy SM, Chakrabarti A, et al. Development of a nano-gold immunodiagnostic assay for rapid on-site detection of invasive aspergillosis. Journal of Medical Microbiology. 2019;68(9):1341-1352. DOI: 10.1099/jmm.0.001040
  60. 60. Guo Y, Li J. Sandwich-type homogeneous chemiluminescence immunoassay based on nanoparticle toward detection of aspergillus galactomannan antigen. Talanta. 2022;243:123392. DOI: 10.1016/j.talanta.2022.123392
  61. 61. Piguillem SV, Regiart M, Bertotti M, Raba J, Messina GA, Fernández-Baldoet MA. Microfluidic fluorescence immunosensor using ZnONFs for invasive aspergillosis determination. Microchemical Journal. 2020;159:105371. DOI: 10.1016/j.microc.2020.105371
  62. 62. Wang HS, Wang C, He YK, Xiao FN, Bao WJ, Xia XH, et al. Core–Shell Ag@SiO2 nanoparticles concentrated on a micro/Nanofluidic device for surface Plasmon resonance-enhanced fluorescent detection of highly reactive oxygen species. Analytical Chemistry. 2014;86(6):3013-3019. DOI: 10.1021/ac4037075
  63. 63. Seia MA, Pereira SV, Fontán CA, De Vito IE, Messina GA, Raba J. Laser-induced fluorescence integrated in a microfluidic immunosensor for quantification of human serum IgG antibodies to helicobacter pylori. Sensors & Actuators, B: Chemical. 2012;168:297-302. DOI: 10.1016/j.snb.2012.04.026
  64. 64. Fernández-Baldo MA, Ortega FG, Pereira SV, Bertolino FA, Serrano MJ, Lorente JA, et al. Nanostructured platform integrated into a microfluidic immunosensor coupled to laser-induced fluorescence for the epithelial cancer biomarker determination. Microchemical Journal. 2016;128:18-25. DOI: 10.1016/j.microc.2016.03.012

Written By

Xiaodong Guo, Mengke Zhang, Mengzhi Wang, Jiaqi Wang and Marie-Laure Fauconnier

Submitted: 01 May 2023 Reviewed: 02 May 2023 Published: 23 October 2023