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.

Laser-etched grooves for rapid fluid delivery for a paper-based chemiresistive biosensor.

Paper-based microfluidic devices are an attractive option for developing low-cost, point-of-care diagnostic tools. To incorporate more complex assays into paper, these devices must become more sophisticated, through the sequential delivery of different liquids or reagents without user intervention. Many flow control strategies focus on slowing the fluid down. However, this can lead to increased assay times and sample loss due to evaporation. We report the use of a CO2 laser to create etched grooves on paper to accelerate wicking speeds in paper-based microfluidic devices. We explored different laser settings to determine the optimal configuration. Our findings showed that simply cutting a slit into the paper created the fastest wicking channels. The slit acted as a macro capillary, allowing fluid to bypass the paper and speed it up. Further studies determined an ideal groove pitch of 0.75 mm (spacing in between grooves) for a paper channel. Additional experiments documented how sealing grooved channels with different adhesives can influence wicking. Overall, sealing the channels with tape made them wick faster. However, sealing methods such as lamination had a negative effect on wicking. Laser-etched grooves were successfully used to design a fluid-handling architecture for a chemiresistive paper-based biosensor. The grooves facilitated rapid, sequential delivery of sample and wash buffer. Human serum albumin spiked in phosphate buffer, artificial urine, and artificial saliva was successfully detected at as low as 15 pM. Etching grooves in paper is a simple process that requires no additional materials or chemicals, allowing single-step fabrication of paper-based microfluidic channels.

Recent developments in flow modeling and fluid control for paper-based microfluidic biosensors.

Over the last 10 years, researchers have shown that paper is a promising substrate for affordable biosensors. The field of paper-microfluidics has evolved rapidly in that time, with simple colorimetric assays giving way to more complex electrochemical devices that can handle multiple samples at a given time. As paper devices become more complex, the ability to precisely control different fluids simultaneously becomes a challenge. Specifically, automated flow control is a necessary attribute to make paper-based devices more useable in resource-limited settings. Flow control strategies on paper are typically developed experimentally through trial-and-error, with little focus on theory. This is because flow behavior in paper is not well understood and sometimes difficult to predict precisely. Additionally, popular theoretical models are too simplistic, making them unsuitable for complex device designs and application conditions. A better understanding of flow theory would allow devices conceived straight from theoretical models. This could save time and resources by reducing experimental work. In this review, we provide an overview of different theoretical models used to characterize imbibition in paper substrates and document the latest flow control strategies that have been applied to automated fluid control on paper. Additionally, we look at current efforts to commercialize paper-based devices along with challenges facing this industry.

An origami electrical biosensor for multiplexed analyte detection in body fluids.

We developed an affordable, highly sensitive, and specific paper-based microfluidic platform for fast multiplexed detections of important biomarkers in various body fluids, including urine, saliva, serum, and whole blood. The sensor array consisted of five individual sensing channels with various functionalities that only required a micro liter-sized sample, which was equally split into aliquots by the built-in paper microfluidics. We achieved the individual functionalizations of various bioreceptors by employing the use of wax barriers and 'paper bridges' in an easy and low-cost manner. Pyrene carboxylic acid-modified single-walled carbon nanotubes (PCA/SWNTs) were deposited by quantitative inkjet printing with an optimal 3-dimensional semiconductor density on a paper substrate. Multiple antibodies were immobilized onto the SWNTs surface for highly sensitive and specific field-effect transistor (FET)/chemiresistor (CR) biosensors. We explored the optimal sensing conditions for the paper-based CR biosensor to achieve high sensitivities and specificities towards the target biomarker proteins (human serum albumin (HSA) and human immunoglobulin G (HIgG)) and achieved an ultralow detectable concentration of HSA and HIgG at 1.5 pM. Besides, origami folding was employed to simplify the fabrication process further. The sensing platform described in this work was cost-effective, semi-automated, and user-friendly. It demonstrated the capability of having multiple sensing functions in one paper-based microfluidic sensing platform. It envisioned the potential of a point-of-care device with full-analysis for practical diagnostics in an ASSURED (Affordable, Sensitive, Specific, User-friendly, Rapid and robust, Equipment-free and Deliverable to end-users) fashion for a quick test of targets of interest.

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.