key: cord-0975400-ipxunbz7
authors: Rahman, Asifur; Kang, Seju; Wang, Wei; Garg, Aditya; Maile-Moskowitz, Ayella; Vikesland, Peter J.
title: Nanobiotechnology enabled approaches for wastewater based epidemiology
date: 2021-07-28
journal: Trends Analyt Chem
DOI: 10.1016/j.trac.2021.116400
sha: 8186ccf66dcd7be0da8ae4a5b7ced617c98ed4bf
doc_id: 975400
cord_uid: ipxunbz7

The impacts of the ongoing coronavirus pandemic highlight the importance of environmental monitoring to inform public health safety. Wastewater based epidemiology (WBE) has drawn interest as a tool for analysis of biomarkers in wastewater networks. Wide scale implementation of WBE requires a variety of field deployable analytical tools for real-time monitoring. Nanobiotechnology enabled sensing platforms offer potential as biosensors capable of highly efficient and sensitive detection of target analytes. This review provides an overview of the design and working principles of nanobiotechnology enabled biosensors and recent progress on the use of biosensors in detection of biomarkers. In addition, applications of biosensors for analysis of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus are highlighted as they relate to the potential expanded use of biosensors for WBE-based monitoring. Finally, we discuss the opportunities and challenges in future applications of biosensors in WBE for effective monitoring and investigation of public health threats.

Early detection and assessment of the threat of pollutants in drinking water and wastewater 43 systems are immensely important from the standpoint of public health and safety. The application 44 of environmental sensing for real-time monitoring of changes in biomarkers (e.g., chemicals, 45 pathogens, metabolites, etc.) can help in the implementation of countermeasures and mitigate the 46 risk of public health outbreaks. Wastewater has been examined as a potential discharge source of 47 illicit drugs to elucidate collective drug usage levels within a community since the early 2000s [1]. 48 The idea of obtaining population information from biomarkers curated from concentrations found 49 in wastewater has grown into the field of wastewater-based epidemiology (WBE). WBE has 50 expanded from primarily looking at drug use in a community to many other aspects surrounding 51 community health, including heavy metal exposure, infectious diseases, and the prevalence of 52 antibiotic resistance genes (ARGs) [2] . Most recently WBE has been used by research groups 53 across the world to track patterns and outbreaks of COVID-19 as a tool against the pandemic [3] . 54 The use of appropriate analytical tools is necessary for the precise quantification of 55 biomarkers in wastewater at environmentally relevant concentrations. As WBE continues to 56 develop as a field, so does the challenge of detecting biomarkers with both high sensitivity and 57 low detection limits. Nanobiotechnology enabled biosensors are sensing platforms that can be 58 modified with target specific recognition elements (e.g., antibodies, proteins, enzymes, etc.) that 59 have biochemical affinity towards target analytes (e.g., chemicals, pathogens, DNA/RNA, etc.) 60 [4]. These interactions between the target and the probe molecules can modify the unique optical, 61 electrical, magnetic, and other properties of the system which can be used for analyte detection 62 and quantification [4] . Advantages, such as low-cost, straightforward application and rapid 63 detection of nanobiotechnology enabled sensing platforms can potentially be used to develop Table 1 . implemented after considering potential biomarkers as target analytes for detection and 96 quantification ( Fig. 1) The design of sensors, at the basic level, involves (i) the use of a material 97 or combinations of materials with unique properties to make nanocomposites, or 98 The robust applicability of biomolecular analyses is appealing for WBE. Nucleic acids 116 extracted from wastewater can provide information on biological identity and function, which can 117 then be used to investigate the prevalence, the spread, and the scale of infectious agents in the 118 sewer catchment. This information can be used as an early warning system for recurrent large- The PCR platform has been successfully used for wastewater surveillance of SARS-CoV- LAMP is a simple, rapid, and sensitive biomolecular platform for the detection of nucleic 155 acids. LAMP uses four (or six) different primers that bind to six (or eight) distinct regions of a 156 target DNA fragment for subsequent gene replication using Bst polymerase. LAMP has been Recently, direct detection of SARS-CoV-2 RNA in wastewater was achieved using RT-qLAMP 168 [29]. The results showed that even in a region with a low number of confirmed cases (e.g., 1-10 169 per 100,000 people), positive detection was confirmed using RT-qLAMP. This result demonstrates 170 that LAMP-based detection can directly detect SARS-CoV-2 in wastewater while avoiding viral 171 concentration and RNA extraction steps. The CRISPR-associated (CRISPR-Cas) system has adaptive immunity against invading 201 nucleic acids. CRISPR-Cas system enzymes (e.g., Cas9, Cas12, Cas13) have been used as CoV-2 in water at 5.5 × 10 4 TCID50/mL level [40] . A portable handheld Raman system was used 243 to detect influenza A virus using 10 µL of sample in water applied to Ag nanorod substrates [41]. Microfluidics, which integrates all analytical procedures on a chip, offers numerous 278 advantages, such as low sample consumption, precise control, fast response, and high efficiency.

Continuous flow platforms and segmented flow platforms are the two most common categories of 280 SERS microfluidic sensors. One type of continuous flow platform is a built-in nanostructured 281 microfluidic device, which consists of an inlet, an outlet, and pre-created nanoarrays within the 282 microchannels. After the analytes are injected into the channels, the highly-designed plasmonic 283 nanostructures specifically bind to the target analytes for SERS detection. This setup has been 284 applied successfully as an effective disease-monitoring system (Fig. 3C,3D) [47]. Another detection of SARS-CoV-2 viral RNA with a detection limit of 6.9 copies/µL (Fig. 4B) [56] . These Rapid, highly sensitive, low cost and real-time detection; Simple and portable instrumentation; Electrical signals unaffected by factors such as sample turbidity or interference from fluorescing compounds.

Low stability and reproducibility in physiological environments; Reduced sensitivity and specificity due to non-specific adsorption of interfering species.

Detection at environmentally relevant concentrations; Easy lab on a chip integration due to low power requirements; Portable instrumentation and compatibility with microfabrication technology for on-site analysis; Real-time detection with simple operation.

Operation in complex media (e.g., wastewater, biofluids) has several challenges including nonspecific adsorption of interfering molecules, Debye screening effect in FET nanosensors, and stability of electrochemical signals under changing physiological conditions.

[51], [52], [53], [63] Combined approaches (SEC sensing) Highly sensitive and selective due to simultaneous acquisition of complementary electrochemical and spectroscopic data; Improved spectroscopic modality (e.g., SERS).

Requires advanced understanding of SEC mechanisms for accurate data interpretation; Incident light beam can affect the electrochemical results.

Single molecule detection capability; Overlapping signals of interfering molecules can be resolved using complementary data allowing detection in complex media (e.g., wastewater, biofluids).

Reproducibility of devices (e.g., EC-SERS substrates); Complex data interpretation and analysis; Improvement and miniaturization of instrumentation for on-site analysis

Synthetic organic dyes as contaminants of the 464 aquatic environment and their implications for ecosystems: a review

A review of the fate of micropollutants in 467 wastewater treatment plants

Antibiotic resistance genes identified 470 in wastewater treatment plant systems-a review

Removal of antibiotic residues, antibiotic 473 resistant bacteria and antibiotic resistance genes in municipal wastewater by membrane 474 bioreactor systems

Seasonal and spatial dynamics of enteric viruses in wastewater and in riverine and estuarine 478 receiving waters

Human enteric bacteria and viruses in five wastewater treatment 481 plants in the Eastern Cape, South Africa

Microplastics in freshwater systems: A review on occurrence, 484 environmental effects, and methods for microplastics detection

The occurrence, characteristics, transformation 487 and control of aromatic disinfection by-products: A review

CRISPR-Cas12-based detection of SARS-CoV-2

SERS detection of multiple 556 antimicrobial-resistant pathogens using nanosensors

Plasmonic and Electrostatic Interactions Enable Uniformly Enhanced Liquid Bacterial 560

Rapid and Sensitive 563 Detection of Respiratory Virus Molecular Signatures Using a Silver Nanorod Array SERS 564

SERS-Based Aptasensor for Rapid Quantitative Detection of SARS

The use of a handheld Raman system 569 for virus detection

A critical review of flexible and porous SERS sensors for 571 analytical chemistry at the point-of-sample

Optical Detection of CoV-SARS-2 Viral Proteins to Sub-Picomolar 575

SERS imaging-based blood plasma

Magnetic SERS 585 strip for sensitive and simultaneous detection of respiratory viruses

A 588 rapid and label-free platform for virus capture and identification from clinical samples

Mixing in microfluidic devices and enhancement methods

Raman scattering based microfluidics for single-cell analysis

Detection 596 of Hepatitis B virus antigen from human blood: SERS immunoassay in a microfluidic system

Electrically transduced sensors based on 599 nanomaterials

Electrochemical sensors and biosensors based 604 on nanomaterials and nanostructures

SARS-CoV-2) in human nasopharyngeal swab specimens using 608 field-effect transistor-based biosensor

SARS-CoV-2 using antisense oligonucleotides directed electrochemical biosensor chip

Recent advances in biomolecular vibrational 617 spectroelectrochemistry

Electrochemical surface-enhanced Raman spectroscopy 620 of nanostructures

High selective spectroelectrochemical biosensor for HCV-RNA 623 detection based on a specific peptide nucleic acid

Influenza 626 virus immunosensor with an electro-active optical waveguide under potential modulation

CoV-2 pandemic: a review of molecular diagnostic tools including sample collection and 630 commercial response with associated advantages and limitations

Grand Challenges in Nanomaterial-Based Electrochemical Sensors

At first, the potential biomarker of interest is selected for detection. Next comes 654 the sensor design step. The design of biosensor involves the selection of core materials, target 655 specific recognition elements and one or more signal transduction methods. The nucleic acid based 656 diagnostic tools can be applied for both indirect sensing using a separate instrument (e.g., 657 amplification of target genes for subsequent detection), or direct sensing by incorporating the tools 658 into the sensor platform. Finally, sensor is deployed using an implementation technique

(A) The workflow of extraction and detection of the genomic population biomarker

wastewater using LAMP and lateral flow device

The illustration of the highly scalable detection of SARS-CoV-2 in the swab samples 669 using Illumina sequencing of combinatorial RT-LAMP-PCR barcoded amplicons (Reprinted with 670 permission from [31]); (C) Four-channel multiplexed CRISPR-Cas system for detection of nucleic 671 acids with orthogonal CRISPR enzymes: PsmCas13b, LwaCas13a, CcaCas13b, and AsCas12a for 672 dsDNA target

A) Detection of bacteria using a liquid SERS platform

Illustration showing the detection of the protein biomarker, neuron specific enolase 679 (NSE) in blood plasma using a paper based lateral flow strip (PLFS) immunoassay (Reprinted with 680 permission from [45]); (C) a microfluidic platform for the capture of avian influenza A viruses 681 from clinical samples and rapid label-free SERS identification

The captured viruses on the chip are (i) immunostained, then (ii) propagated via cell 683 culture and are finally (iii) genome sequenced for identification of subtypes (Reprinted with 684 permission from [47]); (E) Application of a SERS based lateral flow immunoassay (LFIA) for 685 detection of Influenza A H1N1 virus and human adenovirus

A) The illustration of the detection of SARS-CoV-2 via FET nanobiosensors with 692 graphene transducers modified with an antibody specific for the SARS-CoV-2 spike protein 693

The illustration of the rapid detection of SARS-CoV-694 2 viral RNA using an electrochemical sensor made of graphene and gold nanoparticles modified 695 with antisense oligonucleotides