Multiplexed Anodic Stripping Voltammetry Detection of Heavy Metals in Water Using Nanocomposites Modified Screen-Printed Electrodes Integrated With a 3D-Printed Flow Cell.

In this study, we present multiplexed anodic stripping voltammetry (ASV) detection of heavy metal ions (HMIs)-As(III), Cd(II), and Pb(II)-using a homemade electrochemical cell consisting of dual working, reference and counter screen-printed electrodes (SPE) on polyimide substrate integrated with a 3D-printed flow cell. Working and counter electrodes were fabricated by the screen-printing of graphite paste while the Ag/AgCl paste was screen-printed as a reference electrode (Ag/AgCl quasi-reference electrode). The working electrodes were modified with (BiO)2CO3-reduced graphene oxide (rGO)-Nafion [(BiO)2CO3-rGO-Nafion] and Fe3O4 magnetic nanoparticles (Fe3O4MNPs) decorated Au nanoparticles (AuNPs)-ionic liquid (IL) (Fe3O4-Au-IL) nanocomposites separately to enhance HMIs sensing. Electrochemical detection was achieved using square wave ASV technique. The desired structure of the flow electrochemical cell was optimized by the computational fluid dynamic (CFD). Different experimental parameters for stripping analysis of HMIs were optimized including deposition time, deposition potential and flow rate. The linear range of calibration curves with the sensing nanocomposites modified SPE for the three metal ions was from 0-50 µg/L. The limits of detection (S/N = 3) were estimated to be 2.4 µg/L for As(III), 1.2 µg/L for Pb(II) and 0.8 µg/L for Cd(II). Furthermore, the homemade flow anodic stripping sensor platform was used to detect HMIs in simulated river water with a 95-101% recovery, indicating high selectivity and accuracy and great potential for applicability even in complex matrices.

Effect of Al2O3 Passive Layer on Stability and Doping of MoS2 Field-Effect Transistor (FET) Biosensors.

Molybdenum disulfide (MoS2) features a band gap of 1.3 eV (indirect) to 1.9 eV (direct). This tunable band gap renders MoS2 a suitable conducting channel for field-effect transistors (FETs). In addition, the highly sensitive surface potential in MoS2 layers allows the feasibility of FET applications in biosensors, where direct immobilization and detection of biological molecules are conducted in wet conditions. In this work, we report, for the first time, the degradation of chemical vapor deposition (CVD) grown MoS2 FET-based sensors in the presence of phosphate buffer and water, which caused false positive response in detection. We conclude the degradation was originated by physical delamination of MoS2 thin films from the SiO2 substrate. The problem was alleviated by coating the sensors with a 30 nm thick aluminum oxide (Al2O3) layer using atomic layer deposition technique (ALD). This passive oxide thin film not only acted as a protecting layer against the device degradation but also induced a strong n-doping onto MoS2, which permitted a facile method of detection in MoS2 FET-based sensors using a low-power mode chemiresistive I-V measurement at zero gate voltage (Vgate = 0 V). Additionally, the oxide layer provided available sites for facile functionalization with bioreceptors. As immunoreaction plays a key role in clinical diagnosis and environmental analysis, our work presented a promising application using such enhanced Al2O3-coated MoS2 chemiresistive biosensors for detection of HIgG with high sensitivity and selectivity. The biosensor was successfully applied to detect HIgG in artificial urine, a complex matrix containing organics and salts.

Nanoengineering Approaches Toward Artificial Nose.

Significant scientific efforts have been made to mimic and potentially supersede the mammalian nose using artificial noses based on arrays of individual cross-sensitive gas sensors over the past couple decades. To this end, thousands of research articles have been published regarding the design of gas sensor arrays to function as artificial noses. Nanoengineered materials possessing high surface area for enhanced reaction kinetics and uniquely tunable optical, electronic, and optoelectronic properties have been extensively used as gas sensing materials in single gas sensors and sensor arrays. Therefore, nanoengineered materials address some of the shortcomings in sensitivity and selectivity inherent in microscale and macroscale materials for chemical sensors. In this article, the fundamental gas sensing mechanisms are briefly reviewed for each material class and sensing modality (electrical, optical, optoelectronic), followed by a survey and review of the various strategies for engineering or functionalizing these nanomaterials to improve their gas sensing selectivity, sensitivity and other measures of gas sensing performance. Specifically, one major focus of this review is on nanoscale materials and nanoengineering approaches for semiconducting metal oxides, transition metal dichalcogenides, carbonaceous nanomaterials, conducting polymers, and others as used in single gas sensors or sensor arrays for electrical sensing modality. Additionally, this review discusses the various nano-enabled techniques and materials of optical gas detection modality, including photonic crystals, surface plasmonic sensing, and nanoscale waveguides. Strategies for improving or tuning the sensitivity and selectivity of materials toward different gases are given priority due to the importance of having cross-sensitivity and selectivity toward various analytes in designing an effective artificial nose. Furthermore, optoelectrical sensing, which has to date not served as a common sensing modality, is also reviewed to highlight potential research directions. We close with some perspective on the future development of artificial noses which utilize optical and electrical sensing modalities, with additional focus on the less researched optoelectronic sensing modality.

Detection of a secreted protein biomarker for citrus Huanglongbing using a single-walled carbon nanotubes-based chemiresistive biosensor.

Citrus greening, or Huanglongbing (HLB), is currently the most devasting disease of citrus, creating unprecedented crisis for the multibillion-dollar global citrus industry. To-date, there is no effective cure and disease management relies on early detection and removal of infected trees. Thus, it is imperative that accurate, timely, and robust disease detection and diagnosis technologies are available to minimize the spread of disease. This study reports a sensitive and selective label-free biosensor that combines the physical and chemical advantages of carbon nanomaterials like single-walled carbon nanotubes (SWNTs) in a field-effect transistor (FET)/chemiresistor architecture with selective antibodies against Sec-delivered effector 1 (SDE1), a secreted protein biomarker, for the detection of HLB. The biosensor detected SDE1 biomarkers for citrus greening in plant tissue extracts with the dynamic range over three orders of magnitude in the low nanomolar to micromolar concentration range and limit of detection of 5 nM. The study also demonstrated the use of the standard additions assay method with the biosensor to attain a 90-percent signal recovery in concentrated plant tissue extract, allowing for quantitative detection without an external calibration. Adopting the novel detection strategy targeting the secreted protein biomarker, SDE1, addresses some of the challenges faced by current methods of nucleic acid-based assays and symptom-based diagnosis, which have been found prone to false negatives and misdiagnoses, respectively.

Graphene nanogap electrodes in electrical biosensing.

Graphene nanogap electrodes are reported here for the first time in an electrical biosensor for the detection of biomolecular interactions. Streptavidin-biotin was chosen as a model system for evaluating the sensor's performance. High-affinity interactions of streptavidin-gold nanoparticles (strep-AuNPs) to the biotin-functionalized nanogap localizes AuNPs, thereby bridging the gap and resulting in changes in device conductance. Biosensing performance was optimized by varying the gap size, AuNP diameter, and streptavidin coverage on AuNPs. The sensitivity and limit of detection (LOD) of streptavidin detection with the optimized parameters were determined to be 0.3 µA/nM and 0.25 pM, respectively. The proposed platform suggests high potential as a portable point-of-use biosensor for the detection of other affinity-based biomolecular interactions, such as antigen-antibody, nucleic acid, or chemo-selective interactions.

A paper-based chemiresistive biosensor employing single-walled carbon nanotubes for low-cost, point-of-care detection.

Paper-based biosensors are promising for low-cost diagnostics. However, its widespread use has been hampered due to a lack of sensitive detection methods that can be easily implemented on paper substrates. On the other hand, single-walled carbon nanotubes (SWNTs) -based chemiresistive biosensors are gaining popularity as label-free, highly sensitive biosensors. However, traditional SWNT-based chemiresistors need to be more affordable for use in resource-limited settings. In this study, we report fabrication, optimization and analytical characterization of a chemiresistive biosensor on paper for label-free immunosensing. We synthesized a water-based ink using pyrene carboxylic acid (PCA) through non-covalent π-π stacking interaction between PCA and SWNTs. The PCA/SWNTs ink concentration can reach ~4 mg mL-1 and was stable at room temperature for one month. We introduced a combination of wax printing and vacuum filtration to fabricate the hydrophilic channels and the well-defined PCA/SWNTs ink deposition on paper in a facile manner requiring no additional masks or stencils. Specific antibodies were then functionalized on the PCA/SWNTs. Quantitative and selective detection of human serum albumin (HSA) is demonstrated with a limit of detection (LOD) of 1 pM. This low LOD is attributed to the porous structure of the paper surface, which can accommodate more SWNTs. Furthermore, the hydroxyl group-containing cellulose fibers help connect the SWNTs into an electrical network. The paper-based chemiresistive biosensor proposed here is easy to fabricate, and designed for rapid, sensitive and selective detection of HSA. This work provides a potential platform for automated, disposable paper-based biosensors with multiplexed detection capability and microfluidic controls.

Affinity sensor for haemoglobin A1c based on single-walled carbon nanotube field-effect transistor and fructosyl amino acid binding protein.

Haemoglobin A1c (HbA1c) is a significant glycaemic marker for diabetes mellitus. The level of HbA1c reflects the mean blood glucose level over the prior 2-3 months and it is useful for the assessment of therapeutic effectiveness and for diagnosis. In this study, we report the label-free affinity sensor for HbA1c based on the chemiresistor-type field-effect transistor, which has a simple sensor configuration. Single-walled carbon nanotubes (SWNTs) were used as the transducing element. The fructosyl amino acid binding protein from Rhizobium radiobacter (SocA), which binds to α-fructosyl amino acid specifically, was used as the biorecognition element for fructosyl valine (FV), the product of the proteolytic hydrolysis of HbA1c. The developed sensor shows the ability to measure as low as 1.2 nM FV, which is 14-fold more sensitive compared to the previously reported fluorescence-based sensor using SocA. This sensor also exhibits high specificity where no significant response is observed from either fructosyl lysine (FK) or glucose, which are potential interferents. FK is the ε-fructosyl amino acid from glycated albumin, another glycated protein, whereas glucose is naturally present at very high concentration in the blood. We propose that the modulation of the surface charges on the SWNTs caused by the conformational change in SocA upon ligand binding leads to the proportionate changes in the number of carriers in the SWNT channel.

A Pathogen Secreted Protein as a Detection Marker for Citrus Huanglongbing.

The citrus industry is facing an unprecedented crisis due to Huanglongbing (HLB, aka citrus greening disease), a bacterial disease associated with the pathogen Candidatus Liberibacter asiaticus (CLas) that affects all commercial varieties. Transmitted by the Asian citrus psyllid (ACP), CLas colonizes citrus phloem, leading to reduced yield and fruit quality, and eventually tree decline and death. Since adequate curative measures are not available, a key step in HLB management is to restrict the spread of the disease by identifying infected trees and removing them in a timely manner. However, uneven distribution of CLas cells in infected trees and the long latency for disease symptom development makes sampling of trees for CLas detection challenging. Here, we report that a CLas secreted protein can be used as a biomarker for detecting HLB infected citrus. Proteins secreted from CLas cells can presumably move along the phloem, beyond the site of ACP inoculation and CLas colonized plant cells, thereby increasing the chance of detecting infected trees. We generated a polyclonal antibody that effectively binds to the secreted protein and developed serological assays that can successfully detect CLas infection. This work demonstrates that antibody-based diagnosis using a CLas secreted protein as the detection marker for infected trees offers a high-throughput and economic approach that complements the approved quantitative polymerase chain reaction-based methods to enhance HLB management programs.

An oligonucleotide-functionalized carbon nanotube chemiresistor for sensitive detection of mercury in saliva.

Divalent mercuric (Hg(2+)) ion and monomethyl mercury (CH3Hg(+)) are two forms of mercury that are known to be highly toxic to humans. In this work, we present a highly selective, sensitive and label-free chemiresistive biosensor for the detection of both, Hg(2+) and CH3Hg(+) ions using DNA-functionalized single-walled carbon nanotubes (SWNTs). The SWNTs were functionalized with the capture oligonucleotide, polyT, using a linker molecule. The polyT was hybridized with polyA to form a polyT:polyA duplex. Upon exposure to mercury ions, the polyT:polyA duplex dehybridizes and a T-Hg(2+)-T duplex is formed. This structure switch leads to the release of polyA from the SWNT surface and correspondingly a change in the resistance of the chemiresistive biosensor is observed, which is used to quantify the mercury ion concentration. The biosensor showed a wide dynamic range of 0.5 to 100 nM for the detection of CH3Hg(+) ions in buffer solution with a sensitivity of 28.34% per log (nM) of CH3Hg(+). Finally, real world application of the biosensor was demonstrated by the detection of Hg(2+) and CH3Hg(+) ions in simulated saliva samples spiked with a known concentration of mercury ions.

Biofunctionalized Nanostructured Zirconia for Biomedical Application: A Smart Approach for Oral Cancer Detection.

Results of the studies are reported relating to application of the silanized nanostructured zirconia, electrophoretically deposited onto indium tin oxide (ITO) coated glass for covalent immobilization of the monoclonal antibodies (anti-CYFRA-21-1). This biosensing platform has been utilized for a simple, efficient, noninvasive, and label-free detection of oral cancer via cyclic voltammetry technique. The results of electrochemical response studies conducted on bovine serum albumin (BSA)/anti-CYFRA-21-1/3-aminopropyl triethoxy silane (APTES)/ZrO2/ITO immunoelectrode reveal that this immunoelectrode can be used to measure CYFRA-21-1 (oral cancer biomarker) concentration in saliva samples, with a high sensitivity of 2.2 mA mL ng-1, a linear detection range of 2-16 ng mL-1, and stability of six weeks. The results of these studies have been validated via enzyme-linked immunosorbent assay.

Affinity chemiresistor sensor for sugars.

In this work, a non-enzymatic chemiresistive sugar sensor has been developed by combining a synthetic receptor with aligned single-walled carbon nanotubes (SWNTs) device. Briefly, boronic acid as a multivalent sugar receptor was immobilized on carbon nanotubes through amide bond formation. The interaction between three common sugars (d-glucose, d-fructose and sucrose) and boronic acid modified SWNTs device was studied. The effect of pH on the receptor-ligand binding was examined and highest response was observed at pH 9. The chemiresistive sensor exhibited specific and reproducible detection with sensitivity over the concentration range of 1-20mM, 1-25 mM, and 1-30 mM for fructose, glucose, and sucrose, respectively. The sensor showed no interference from common electroactive compounds such as citric acid, uric acid, and ascorbic acid. Furthermore, the sensor retained 97.4% of the initial value after five regeneration cycles with an acidic buffer at pH 5, thus ensuring good reusability.