Durable nonenzymatic electrochemical sensing using silver decorated multi-walled carbon nanotubes for uric acid detection.

In this study, we demonstrate a facile, durable, and inexpensive technique of producing silver nanoparticles-decorated multi-walled carbon nanotubes (MWCNT/AgNP) on the easy-to-use screen-printed carbon electrodes (SPCE) for non-enzymatic detection of uric acid (UA) in an electrochemical sensor. The developed sensors show great durability for three months in storage, and high specificity performance for preclinical study using spiked UA in a synthetic urine sample. A simple route for this hybrid nanocomposite was proposed through an oxidation-reduction with reflux (ORR) process. A significant increase in the electroactive surface area of SPCE was achieved by modifying it with MWCNT/AgNP. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), Fourier-transform infrared (FT-IR) spectroscopy, Raman spectroscopy, and X-ray diffraction (XRD) analysis confirmed this synthesis. The nanocomposite nanostructure electrodes achieved an outstanding UA detection with a sensitivity of 0.1021 µA/µM and a wide dynamic range of 10-1000 µM. In PBS, the measurements achieved a detection limit of 84.04 nM while in pure synthetic urine; it was 6.074 µM. The constructed sensor exhibits excellent stability and durability for several months, and great specificity against interfering compounds, including dopamine (DA), urea, and glucose. Overall, the present outcomes denote the potential of MWCNT/AgNP-decorated SPCE for early uric acid diagnostics tools in health monitoring.

Labeling on a Chip of Cellular Fibronectin and Matrix Metallopeptidase-9 in Human Serum.

We present a microfluidic chip for protein labeling in the human serum-based matrix. Serum is a complex sample matrix that contains a variety of proteins, and a matrix is used in many clinical tests. In this study, the device performance was tested using commercial serum samples from healthy donors spiked with the following target proteins: cellular fibronectin (c-Fn) and matrix metallopeptidase 9 (MMP9). The microfluidic molds were fabricated using micro milling on acrylic and using stereolithography (SLA) three-dimensional (3D) printing for an alternative method and comparison. A simple quality control was performed for both fabrication mold methods to inspect the channel height of the chip that plays a critical role in the labeling process. The fabricated microfluidic chip shows a good reproducibility and repeatability of the performance for the optimized channel height of 150 µm. The spiked proteins of c-Fn and MMP9 in the human serum-based matrix, were successfully labeled by the functionalized magnetic nanoparticles (MNPs). The biomarker labeling occurring in the serum was compared using a simple matrix sample: phosphate buffer. The measured signals obtained by using a magnetoresistive (MR) biochip platform showed that the labeling using the proposed microfluidic chip is in good agreement for both matrixes, i.e., the analytical performance (sensitivity) obtained with the serum, near the relevant cutoff values, is within the uncertainty of the measurements obtained with a simple and more controlled matrix: phosphate buffer. This finding is promising for stroke patient stratification where these biomarkers are found at high concentrations in the serum.

Facile and controllable synthesis of monodisperse gold nanoparticle bipyramid for electrochemical dopamine sensor.

We demonstrated potential features of gold nanoparticle bipyramid (AuNB) for an electrochemical biosensor. The facile synthesis method and controllable shape and size of the AuNB are achieved through the optimization of cetyltrimethylammonium chloride (CTAC) surfactant over citric acid (CA) ratio determining the control of typically spherical Au seed size and its transition into a penta-twinned crystal structure. We observe that the optimized ratio of CTAC and CA facilitates flocculation control in which Au seeds with size as tiny as ∼14.8 nm could be attained and finally transformed into AuNB structures with an average length of ∼55 nm with high reproducibility. To improve the electrochemical sensing performance of a screen-printed carbon electrode, surface modification with AuNB via distinctive linking procedures effectively enhanced the electroactive surface area by 40%. Carried out for the detection of dopamine, a neurotransmitter frequently linked to the risk of Parkinson's, Alzheimer's, and Huntington's diseases, the AuNB decorated-carbon electrode shows outstanding electrocatalytic activity that improves sensing performance, including high sensitivity, low detection limit, wide dynamic range, high selectivity against different analytes, such as ascorbic acid, uric acid and urea, and excellent reproducibility.

Versatile and Low-Cost Fabrication of Modular Lock-and-Key Microfluidics for Integrated Connector Mixer Using a Stereolithography 3D Printing.

We present a low-cost and simple method to fabricate a novel lock-and-key mixer microfluidics using an economic stereolithography (SLA) three-dimensional (3D) printer, which costs less than USD 400 for the investment. The proposed study is promising for a high throughput fabrication module, typically limited by conventional microfluidics fabrications, such as photolithography and polymer-casting methods. We demonstrate the novel modular lock-and-key mixer for the connector and its chamber modules with optimized parameters, such as exposure condition and printing orientation. In addition, the optimization of post-processing was performed to investigate the reliability of the fabricated hollow structures, which are fundamental to creating a fluidic channel or chamber. We found out that by using an inexpensive 3D printer, the fabricated resolution can be pushed down to 850 µm and 550 µm size for squared- and circled-shapes, respectively, by the gradual hollow structure, applying vertical printing orientation. These strategies opened up the possibility of developing straightforward microfluidics platforms that could replace conventional microfluidics mold fabrication methods, such as photolithography and milling, which are costly and time consuming. Considerably cheap commercial resin and its tiny volume employed for a single printing procedure significantly cut down the estimated fabrication cost to less than 50 cents USD/module. The simulation study unravels the prominent properties of the fabricated devices for biological fluid mixers, such as PBS, urine and plasma blood. This study is eminently prospective toward microfluidics application in clinical biosensing, where disposable, low-cost, high-throughput, and reproducible chips are highly required.

A pump-free microfluidic device for fast magnetic labeling of ischemic stroke biomarkers.

This research proposes a low-cost and simple operation microfluidic chip to enhance the magnetic labeling efficiency of two ischemic stroke biomarkers: cellular fibronectin (c-Fn) and matrix metallopeptidase 9 (MMP9). This fully portable and pump-free microfluidic chip is operated based on capillary attractions without any external power source and battery. It uses an integrated cellulose sponge to absorb the samples. At the same time, a magnetic field is aligned to hold the target labeled by the magnetic nanoparticles (MNPs) in the pre-concentrated chamber. By using this approach, the specific targets are labeled from the beginning of the sampling process without preliminary sample purification. The proposed study enhanced the labeling efficiency from 1 h to 15 min. The dynamic interactions occur in the serpentine channel, while the crescent formation of MNPs in the pre-concentrated chamber, acting as a magnetic filter, improves the biomarker-MNP interaction. The labeling optimization by the proposed device influences the dynamic range by optimizing the MNP ratio to fit the linear range across the clinical cutoff value. The limits of detection (LODs) of 2.8 ng/mL and 54.6 ng/mL of c-Fn measurement were achieved for undiluted and four times dilutions of MNP, respectively. While for MMP9, the LODs were 11.5 ng/mL for undiluted functionalized MNP and 132 ng/mL for four times dilutions of functionalized MNP. The results highlight the potential use of this device for clinical sample preparation and specific magnetic target labeling. When combined with a detection system, it could also be used as an integrated component of a point-of-care platform.

Gold nanoparticle-assisted plasmonic enhancement for DNA detection on a graphene-based portable surface plasmon resonance sensor.

The impact of different gold nanoparticle (GNP) structures on plasmonic enhancement for DNA detection is investigated on a few-layer graphene (FLG) surface plasmon resonance (SPR) sensor. Two distinct structures of gold nano-urchins (GNu) and gold nanorods (GNr) were used to bind the uniquely designed single-stranded probe DNA (ssDNA) of Mycobacterium tuberculosis complex DNA. The two types of GNP-ssDNA mixture were adsorbed onto the FLG-coated SPR sensor through the π-π stacking force between the ssDNA and the graphene layer. In the presence of complementary single-stranded DNA, the hybridization process took place and gradually removed the probes from the graphene surface. From SPR sensor preparation, the annealing process of the Au layer of the SPR sensor effectively enhanced the FLG coverage leading to a higher load of the probe DNA onto the sensing interface. The FLG was shown to be effective in providing a larger surface area for biomolecular capture due to its roughness. Carried out in the DNA hybridization study with the SPR sensor, GNu, with its rough and spiky structures, significantly reinforced the overall DNA hybridization signal compared with GNr with smooth superficies, especially in capturing the probe DNA. The DNA hybridization detection assisted by GNu reached the femtomolar range limit of detection. An optical simulation validated the extreme plasmonic field enhancement at the tip of the GNu spicules. The overall integrated approach of the graphene-based SPR sensor and GNu-assisted DNA detection provided the proof-of-concept for the possibility of tuberculosis disease screening using a low-cost and portable system to be potentially applied in remote or third-world countries.

Facile Bacterial Cellulose Nanofibrillation for the Development of a Plasmonic Paper Sensor.

In this present work, a plasmonic sensor is developed through an extremely cheap cellulose-based source, widely known as a food product, nata de coco (NDC). Capturing its interesting features, such as innate surface roughness from naturally grown cellulose during its fermentation period, the engineering and modulation of NDC fibril size and properties were attempted through a high-pressure homogenization (HPH) treatment to obtain highly dense nanofibrils. After the transformation into a thin, paper-sheet form through a casting process, the homogenized bacterial cellulose (HBC) resulting from HPH was compared with the normally agitated bacterial cellulose (BC) pulp and decorated with silver nanoparticles (AgNPs) to produce plasmonic papers, for further application as surface-enhanced Raman scattering (SERS) substrate. As demonstrated in the measurement of Rhodamine 6G (R6G) molecule, the plasmonic HBC paper sheet provided more prominent SERS signals than the plasmonic BC due to its high surface roughness and improved textural properties from the nanofibrillation process favoring better adsorption of AgNPs and effective SERS hotspots generation. The plasmonic HBC obtained a 2 order higher estimated SERS enhancement factor over the plasmonic BC with a limit of detection of approximately 92 fM. Results denote that the proposed approach provides a new, green-synthesis route toward the exploration of biodegradable sources integrated into an inexpensive and simple nanostructuring process for the production of flexible, paper-based, plasmonic sensors.

Plasmonic nanomaterial structuring for SERS enhancement.

Unique structures of a gold island over nanospheres (AuIoN) featuring a three-dimensional (3D) nanostructure on a highly ordered two-dimensional (2D) array of nanospherical particles with different adhesion layers were fabricated as surface-enhanced Raman scattering (SERS) substrates. Ultra-thin Au was thermally evaporated onto PS nanospheres while aluminum oxide (Al2O3) was applied as an Au adhesion layer. The outcomes demonstrate that the higher metallic particle density and surface roughness supplied by the Al2O3 provided larger interatomic bonding than a conventional adhesion layer, the highly-dispersive Cr. Nanosphere lithography (NSL) to deposit templating particles as small as ∼100 nm successfully created a simple initial roughening process which in turn boosted the localized surface plasmon resonance (LSPR) efficiency. So far, PS template deposition of a size less than 200 nm has been challenging, but here, through the use of a simple solvent ratio adjustment on drop-casting NSL, the novelty of natural lithography with downscaled properties as an alternative to the complexity of photolithography which is mostly conducted in the strict ambience of a clean room, is presented. SERS activity was primarily attributed to the synergistic effect of collective LSPRs from the AuIoN structure reinforcing the electromagnetic field, particularly in the crevices of two neighboring AuIoNs, as simulated by FDTD (Finite-Difference Time-Domain) computation. An AuIoN fabricated by the integration of Al2O3 with thinner Au particles showed the optimum SERS activities with an improved enhancement factor of 1.51 × 106. Overall, a non-lithographic technique in tuning SERS hotspots and favorable characteristics of Al2O3 for ultra-thin Au adhesion support, which can potentially be used in the fabrication of various devices, was demonstrated.

Surface Plasmon Resonance Optical Sensor: A Review on Light Source Technology.

The notion of surface plasmon resonance (SPR) sensor research emerged more than eight decades ago from the first observed phenomena in 1902 until the first introduced principles for gas sensing and biosensing in 1983. The sensing platform has been hand-in-hand with the plethora of sensing technology advancement including nanostructuring, optical technology, fluidic technology, and light source technology, which contribute to substantial progress in SPR sensor evolution. Nevertheless, the commercial products of SPR sensors in the market still require high-cost investment, component, and operation, leading to unaffordability for their implementation in a low-cost point of care (PoC) or laboratories. In this article, we present a comprehensive review of SPR sensor development including the state of the art from a perspective of light source technology trends. Based on our review, the trend of SPR sensor configurations, as well as its methodology and optical designs are strongly influenced by the development of light source technology as a critical component. These simultaneously offer new underlying principles of SPR sensor towards miniaturization, portability, and disposability features. The low-cost solid-state light source technology, such as laser diode, light-emitting diode (LED), organic light emitting diode (OLED) and smartphone display have been reported as proof of concept for the future of low-cost SPR sensor platforms. Finally, this review provides a comprehensive overview, particularly for SPR sensor designers, including emerging engineers or experts in this field.

Rapid detection and quantification of Enterovirus 71 by a portable surface plasmon resonance biosensor.

This study presents the first report on a label-free detection and rapid quantification method for human enterovirus 71 (EV71) using a portable surface plasmon resonance (SPR) system. The SPR sensor instrument was configured to run on low power in a miniaturized platform to improve the device portability for a wider application both in laboratories and in the field. A color tunable organic light emitting diode in red spectrum was attached on a trapezoidal prism for the disposable light source module. The SPR signal processing using integration area under the reflectivity curve is applied for optimum signal to noise ratio (SNR) enhancement. The major capsid protein VP1 of EV71 was selected as the biomarker target in the detection study. The experimental time required for the EV71 quantification was reduced from 6 days using the conventional viral plaque assay to several minutes using the proposed method. The study results establish a detection limit of approximately 67 virus particles per milliliter (vp/ml) of EV71 in a Dulbecco's modified Eagle's medium. The VP1 detection in the portable SPR biosensor had a detection limit of approximately 4.8pg/ml in the PBS buffer. Therefore, the proposed direct EV71 viral particle quantification method can be rapidly performed in real time, with high sensitivity and less labor and without assays or fluorescence.