Fabrication of a 3D Printed Porous Junction for Ag|AgCl|gel-KCl Reference Electrode

Fused filament fabrication (FFF) is a 3D printing method that is attracting increased interest in the development of miniaturized electrochemical sensor systems due to its versatility, low cost, reproducibility, and capability for rapid prototyping. A key component of miniaturized electrochemical systems is the reference electrode (RE). However, reports of the fabrication of a true 3D-printed RE that exhibits stability to variations in the sample matrix remain limited. In this work, we report the development and characterization of a 3D-printed Ag|AgCl|gel-KCl reference electrode (3D-RE). The RE was constructed using a Ag|AgCl wire and agar-KCl layer housed in a watertight 3D-printed acrylonitrile butadiene styrene (ABS) casing. The novel feature of our electrode is a 3D-printed porous junction that protects the gel electrolyte layer from chloride ion leakage and test sample contamination while maintaining electrical contact with the sample solution. By tuning the 3D printing filament extrusion ratio (k), the porosity of the junction was adjusted to balance the reference electrode potential stability and impedance. The resulting 3D-RE demonstrated a stable potential, with a potential drift of 4.55 ± 0.46 mV over a 12-h period of continuous immersion in 0.1 M KCl, and a low impedance of 0.50 ± 0.11 kΩ. The 3D-RE was also insensitive to variations in the sample matrix and maintained a stable potential for at least 30 days under proper storage in 3 M KCl. We demonstrate the application of this 3D-RE in cyclic voltammetry and in pH sensing coupled with electrodeposited iridium oxide on a gold electrode. Our method offers a viable strategy for 3D printing a customizable true reference electrode that can be readily fabricated on demand and integrated into 3D-printed miniaturized electrochemical sensor systems

Information Theoretic Analysis of Potentiometric Sensor Array Configurations

Abstract: The simultaneous quantitative determination of multiple ions in complex media can be achieved with the use of potentiometric sensor arrays, or “electronic tongues.” Potentiometric sensor arrays are composed of multiple cross-sensitive sensors whose responses are analyzed with multivariate chemometric methods to extract the desired quantitative information. One of the most important considerations for designing an array for a given analytical task is the array configuration, or the number and types of sensors incorporated into the array. However, there are currently no theoretical approaches for the a priori design of a potentiometric sensor array, so arrays are currently designed via experimental trial-and-error. In this work, we propose the application of an information theoretic approach as a means to theoretically evaluate the analytical capability of a potentiometric sensor array configuration for a given analytical task. Using a Fisher Information criterion derived for potentiometric sensors, we explored potentiometric sensor array designs with simulated potentiometric sensors, and compared these designs with conventional, empirically-based designs from the literature. Finally, we compute the theoretical performances of various sensor array configurations using the Fisher Information criterion and compare our predictions to the experimental performances from the literature. Our results suggest that Fisher Information can be applied as a theoretical metric to screen for promising array configurations prior to experimental trial-and-error

Design of Potentiometric Sensor Arrays Using Fisher Information and Genetic Algorithm

Potentiometric sensor arrays, or electronic tongues, are based on combining cross-sensitive electrodes with multivariate chemometric methods for the simultaneous quantitative determination of analytes in complex liquid media. While cross-sensitivity is recognized as a key feature of electronic tongues, there are currently no a priori theoretical approaches to evaluate which combination of cross-sensitive potentiometric sensors can form an effective array for quantitative multi-ion analysis prior to experimental trial-and-error. In this work, we report the derivation of a Fisher Information-based objective function and its implementation with genetic algorithm for a priori sensor selection in potentiometric sensor arrays. As an illustration of the utility of our method, we demonstrate the design of a potentiometric sensor array for the quantitative determination of Na + , K + , Mg 2+ , and Ca 2+ in blood serum through the screening of a library of more than 300 ion-selective electrode membranes. The results of our analysis suggest that array configurations which are predicted to minimize error can have complex patterns of analyte cross-sensitivities. These alternative array configurations can be difficult to deduce intuitively or to discover by experimental trial-and-error. Simulated sensor array responses modeled by artificial neural networks demonstrate the utility of our our method to rank the performances of sensor array configurations

Radial multi-stationary phase thin-layer chromatography for the field-ready fingerprinting of herbal materials

The growing international demand for herbal-based products has prompted the need for more stringent quality control methods to detect substandard and adulterated herbal plant materials. However, most prescreening methods, such as thin-layer chromatography (TLC), remain inaccessible to herbal producers in resource-limited settings. Here, we report a proof-of-concept demonstration of a multi-stationary phase thin-layer chromatography (MSP-TLC) method for the preliminary on-site identification and evaluation of herbal materials. Our method is based on a unique TLC plate design that features multiple phenyl- and octyl-modified silica gel stationary phases configured as radial sectors. The modified stationary phase patterns were fabricated by screen-printing organosilane solutions onto commercial silica gel TLC plates. Radial elution with an ethanol–water mobile phase from the center of the MSP-TLC plate generates multiple chromatographic profiles simultaneously for a single sample extract. To facilitate the interpretation of the multiple TLC profiles, the MSP-TLC system was coupled with image analysis and chemometric pattern recognition to classify a sample as “within-specifications” or “off-specifications” for a given herbal plant species. Application of the system to Blumea balsamifera and Vitex negundo demonstrated sensitivity and specificity rates that range from 73.1 to 95.1% compared to the respective standard Pharmacopeia TLC methods. The presented method holds considerable promise as a cost-effective, user-friendly on-site prescreening tool for herbal materials in resource-limited settings

Fully integrated 3D-printed electrochemical cell with a modified inkjet-printed Ag electrode for voltammetric nitrate analysis

To address the need for low-cost analytical tools for on-site aquaculture water quality monitoring, miniaturized electrochemical sensor systems can be readily fabricated using additive manufacturing technologies such as 3D printing and inkjet printing. In this work, we report the design and fabrication of an additively manufactured electrochemical platform featuring a reusable 3D-printed electrochemical cell with integrated reference and counter electrodes, and a replaceable inkjet-printed Ag (IJP-Ag) working electrode. The electrochemical cell was 3D-printed with acrylonitrile butadiene styrene (ABS) filament and features a 3D-printed ABS-carbon counter electrode and a Ag|AgCl|gel-KCl reference electrode with a 3D-printed porous junction directly integrated along the sides of the sample compartment. The application of the integrated cell is demonstrated with the analysis of nitrate ions on the IJP-Ag electrode, which was modified with electrodeposited nanostructured Ag to enhance sensitivity to nitrate reduction. Linear sweep voltammetry (LSV) was successfully applied to detect nitrate with a LOD of 1.40 ppm and a sensitivity of 0.2086 μA ppm−1 in a background of artificial brackish aquaculture water (pH 8.0). The sensor response showed intra- and inter-electrode reproducibility and no significant interferences to most of the commonly encountered cations and anions in brackish water. The electrochemical sensor system was also applied to nitrate determination in real aquaculture water samples and demonstrated no significant differences with the results obtained using the standard spectrophotometric method at a 95% confidence level. Our results show how additive manufacturing is a promising approach to readily fabricate fit-for-purpose, low-cost miniaturized electrochemical sensor systems for point-of-use applications

In situ electrochemical regeneration of nanogap hotspots for continuously reusable ultrathin SERS sensors

Abstract Surface-enhanced Raman spectroscopy (SERS) harnesses the confinement of light into metallic nanoscale hotspots to achieve highly sensitive label-free molecular detection that can be applied for a broad range of sensing applications. However, challenges related to irreversible analyte binding, substrate reproducibility, fouling, and degradation hinder its widespread adoption. Here we show how in-situ electrochemical regeneration can rapidly and precisely reform the nanogap hotspots to enable the continuous reuse of gold nanoparticle monolayers for SERS. Applying an oxidising potential of +1.5 V (vs Ag/AgCl) for 10 s strips a broad range of adsorbates from the nanogaps and forms a metastable oxide layer of few-monolayer thickness. Subsequent application of a reducing potential of −0.80 V for 5 s in the presence of a nanogap-stabilising molecular scaffold, cucurbit[5]uril, reproducibly regenerates the optimal plasmonic properties with SERS enhancement factors ≈106. The regeneration of the nanogap hotspots allows these SERS substrates to be reused over multiple cycles, demonstrating ≈5% relative standard deviation over at least 30 cycles of analyte detection and regeneration. Such continuous and reliable SERS-based flow analysis accesses diverse applications from environmental monitoring to medical diagnostics

Smartphone-based image analysis and chemometric recognition of the thin-layer chromatographic fingerprints of herbal materials

Thin-layer chromatography (TLC) is commonly used as a screening method to verify the identity and quality of dried herbal medicinal plant material. While TLC is relatively simple, the method still requires technical experience and relies on the subjective classification of sample TLC profiles as “within-specifications” or “off-specifications.” In this work, we report the development of an objective TLC-based system for the identification and quality assessment of herbal medicinal materials. Our proposed system is a miniaturized Pharmacopeia-based TLC method coupled with a smartphone app that allows for an objective interpretation of TLC profiles via multivariate image analysis and chemometric fingerprinting. An image of the TLC profile is captured using a smartphone camera interfaced with a 3D-printed photo-box, and the analysis is automated using a framework of pre-uploaded algorithms hosted on a cloud server. The TLC profile image is converted to an unfolded red, green, and blue (RGB) channel intensity profile, and classified as “within-specifications” or “off-specifications” using aggregated Soft Independent Modeling of Class Analogy (SIMCA) models. We present the application of our system to two herbal medicinal plants, Blumea balsamifera and Vitex negundo. The proposed system demonstrates 90.2% sensitivity and 86.2% specificity for B. balsamifera classification, and 81.4% sensitivity and 92.0% specificity for V. negundo classification when compared to the respective laboratory-based Pharmacopeia TLC protocols for the ability to distinguish authentic samples from non-authentic and degraded samples. The system developed in this work is a cost-effective, rapid method that can serve as a herbal material quality assessment tool in resource-limited settings

In situ electrochemical regeneration of nanogap hotspots for continuously reusable ultrathin SERS sensors.

Surface-enhanced Raman spectroscopy (SERS) harnesses the confinement of light into metallic nanoscale hotspots to achieve highly sensitive label-free molecular detection that can be applied for a broad range of sensing applications. However, challenges related to irreversible analyte binding, substrate reproducibility, fouling, and degradation hinder its widespread adoption. Here we show how in-situ electrochemical regeneration can rapidly and precisely reform the nanogap hotspots to enable the continuous reuse of gold nanoparticle monolayers for SERS. Applying an oxidising potential of +1.5 V (vs Ag/AgCl) for 10 s strips a broad range of adsorbates from the nanogaps and forms a metastable oxide layer of few-monolayer thickness. Subsequent application of a reducing potential of -0.80 V for 5 s in the presence of a nanogap-stabilising molecular scaffold, cucurbit[5]uril, reproducibly regenerates the optimal plasmonic properties with SERS enhancement factors ≈106. The regeneration of the nanogap hotspots allows these SERS substrates to be reused over multiple cycles, demonstrating ≈5% relative standard deviation over at least 30 cycles of analyte detection and regeneration. Such continuous and reliable SERS-based flow analysis accesses diverse applications from environmental monitoring to medical diagnostics

In situ electrochemical regeneration of nanogap hotspots for continuously reusable ultrathin SERS sensors

Acknowledgements: The authors greatly appreciate helpful comments from many colleagues including Oren Scherman, Luis Liz-Marzán, and Duncan Graham. The authors acknowledge financial support from the European Research Council (ERC) under Horizon 2020 research and innovation programme PICOFORCE (Grant Agreement No. 883703), and POSEIDON (Grant Agreement No. 861950) and from the EPSRC (Cambridge NanoDTC EP/L015978/1, EP/L027151/1, EP/X037770/1). S.M.S.-T. is supported by the University of Cambridge Harding Distinguished Postgraduate Scholars Programme. S.M.S.-T., D.-B.G., and N.S. acknowledge support from EPSRC Grant EP/L015889/1 for the EPSRC Centre for Doctoral Training in Sensor Technologies and Applications, and from AstraZeneca (MedImmune Ltd). M.N. is supported by a Gates Cambridge fellowship (OPP1144). B.d.N. acknowledges support from the Royal Society (URF/R1/211162).Funder: University of Cambridge Harding Distinguished Postgraduate Scholars ProgrammeAbstractSurface-enhanced Raman spectroscopy (SERS) harnesses the confinement of light into metallic nanoscale hotspots to achieve highly sensitive label-free molecular detection that can be applied for a broad range of sensing applications. However, challenges related to irreversible analyte binding, substrate reproducibility, fouling, and degradation hinder its widespread adoption. Here we show how in-situ electrochemical regeneration can rapidly and precisely reform the nanogap hotspots to enable the continuous reuse of gold nanoparticle monolayers for SERS. Applying an oxidising potential of +1.5 V (vs Ag/AgCl) for 10 s strips a broad range of adsorbates from the nanogaps and forms a metastable oxide layer of few-monolayer thickness. Subsequent application of a reducing potential of −0.80 V for 5 s in the presence of a nanogap-stabilising molecular scaffold, cucurbit[5]uril, reproducibly regenerates the optimal plasmonic properties with SERS enhancement factors ≈106. The regeneration of the nanogap hotspots allows these SERS substrates to be reused over multiple cycles, demonstrating ≈5% relative standard deviation over at least 30 cycles of analyte detection and regeneration. Such continuous and reliable SERS-based flow analysis accesses diverse applications from environmental monitoring to medical diagnostics.</jats:p