Disposable Microchamber with a Microfluidic Paper-Based Lid for Generation and Membrane Separation of SO2 Gas Employing an In Situ Electrochemical Gas Sensor for Quantifying Sulfite in Wine.

This work presents a fully disposable microchamber for gas generation of a sample solution. The microchamber consists of a cylindrical well-reactor and a paper-based microfluidic lid (µFluidic lid), which also serves as the reagent loading and dispensing unit. The base of the reactor consists of a hydrophobic membrane covering an in-house graphene electrochemical gas sensor. Fabrication of the gas sensor and the three-layer µFluidic lid is described. The µFluidic lid is designed to provide a steady addition of the acid reagent into the sample solution instead of liquid drops from a disposable syringe. There are three steps in the procedure: (i) acidification of the sample in the reactor to generate SO2 gas by the slow dispensing of the acid reagent from the µFluidic lid, (ii) diffusion of the liberated SO2 gas through the hydrophobic membrane at the base of the reactor, and (iii) in situ detection of SO2 by cathodic reduction at the graphene electrode. The device was demonstrated for quantitation of the sulfite preservative in wine without heating or stirring. The selectivity of the analysis is ensured by the combination of the gas-diffusion membrane and the selectivity of the electrochemical sensor. The linear working range is 2-60 mg L-1 SO2, with a limit of detection (3SD of intercept/slope) of 1.5 mg L-1 SO2. This in situ method has the shortest analysis time (8 min per sample) among all voltammetric methods that detect SO2(g) via membrane gas diffusion.

Gold leaf electrochemical sensors: applications and nanostructure modification.

This work presents the first planar three-electrode electrochemical sensor comprising local gold leaf as the working electrode and printed, or hand-drawn, counter and reference electrodes, respectively. The gold leaf was mounted on a polyvinyl chloride (PVC) adhesive sheet (15 mm × 30 mm) and covered with a second PVC sheet printed with the counter and reference electrodes. This sheet has a 3 mm circle and a 2 mm × 3 mm rectangle removed to expose the gold electrode area and electrical contacts, respectively. A third shorter insulating layer with a 10 mm circular hole was placed on top to delineate the sensing area of all electrodes. The sensor displayed expected performances in various modes of operation, such as cyclic voltammetry, square wave voltammetry and anodic stripping voltammetry. For the latter mode, the limit of detection of Pb(ii) was 3.2 µg L-1, compliant with regulation for drinking water (10 µg L-1 Pb(ii)). Although designed as a disposable unit, the electrode is effective for up to 200 cycles and applicable for multiple use. The gold leaf was modified by electrodeposition of the gold network and large nano-size gold particles which significantly enhanced the sensitivity of all voltametric sensing, giving lower limits of detection. For stripping voltammetry, the electroplating structure modification improved the simultaneous detection of lead and copper, with the copper response increasing 6-fold. The device has the capability of on-site identification of copper/lead bullets from gunshot residues within 6 min.

Non-Invasive Sweat-Based Tracking of L-Dopa Pharmacokinetic Profiles Following an Oral Tablet Administration.

Levodopa (L-Dopa) is the "gold-standard" medication for symptomatic therapy of Parkinson disease (PD). However, L-Dopa long-term use is associated with the development of motor and non-motor complications, primarily due to its fluctuating plasma levels in combination with the disease progression. Herein, we present the first example of individualized therapeutic drug monitoring for subjects upon intake of standard L-Dopa oral pill, centered on dynamic tracking of the drug concentration in naturally secreted fingertip sweat. The touch-based non-invasive detection method relies on instantaneous collection of fingertip sweat on a highly permeable hydrogel that transports the sweat to a biocatalytic tyrosinase-modified electrode, where sweat L-Dopa is measured by reduction of the dopaquinone enzymatic product. Personalized dose-response relationship is demonstrated within a group of human subjects, along with close pharmacokinetic correlation between the finger touch-based fingertip sweat and capillary blood samples.

A self-powered ingestible wireless biosensing system for real-time in situ monitoring of gastrointestinal tract metabolites.

Information related to the diverse and dynamic metabolite composition of the small intestine is crucial for the diagnosis and treatment of various diseases. However, our current understanding of the physiochemical dynamics of metabolic processes within the small intestine is limited due to the lack of in situ access to the intestinal environment. Here, we report a demonstration of a battery-free ingestible biosensing system for monitoring metabolites in the small intestine. As a proof of concept, we monitor the intestinal glucose dynamics on a porcine model. Battery-free operation is achieved through a self-powered glucose biofuel cell/biosensor integrated into a circuit that performs energy harvesting, biosensing, and wireless telemetry via a power-to-frequency conversion scheme using magnetic human body communication. Such long-term biochemical analysis could potentially provide critical information regarding the complex and dynamic small intestine metabolic profiles.

An epidermal patch for the simultaneous monitoring of haemodynamic and metabolic biomarkers.

Monitoring the effects of daily activities on the physiological responses of the body calls for wearable devices that can simultaneously track metabolic and haemodynamic parameters. Here we describe a non-invasive skin-worn device for the simultaneous monitoring of blood pressure and heart rate via ultrasonic transducers and of multiple biomarkers via electrochemical sensors. We optimized the integrated device so that it provides mechanical resiliency and flexibility while conforming to curved skin surfaces, and to ensure reliable sensing of glucose in interstitial fluid and of lactate, caffeine and alcohol in sweat, without crosstalk between the individual sensors. In human volunteers, the device captured physiological effects of food intake and exercise, in particular the production of glucose after food digestion, the consumption of glucose via glycolysis, and increases in blood pressure and heart rate compensating for oxygen depletion and lactate generation. Continuous and simultaneous acoustic and electrochemical sensing via integrated wearable devices should enrich the understanding of the body's response to daily activities, and could facilitate the early prediction of abnormal physiological changes.

Contactless conductivity sensor employing moist paper as absorbent for in-situ detection of generated carbon dioxide gas.

This work presents an unconventional use of capacitively coupled contactless conductivity detector (C4D) for detection of gas absorption by moist paper with potential application for chemical analysis. To be suitable for measuring conductivity of moist paper absorbent, the C4D sensor was therefore designed in planar configuration. A layer of dry filter paper, only 20 mm × 25 mm in size, was placed on the C4D sensor and the device installed inside a specifically designed vaporization chamber. A vial (16 mm i.d., 8 mm high) containing a 150-µL solution of sodium bicarbonate was placed alongside. The filter paper was loaded with 110 µL of deionized water through an injection hole in the cover lid. A 100-µL aliquot of 2 M hydrochloric acid solution was directly dispensed into the vial through a second hole in the lid to generate CO2 gas from the bicarbonate solution. It was observed that the C4D sensor gave real-time response that corresponded to the absorption of the gas and subsequent production of H+ and HCO3- in the moist paper. The monitored signal reached a constant value at 160 s after the addition of the acid. Chemistry of the absorption process and equivalent circuit for the C4D are proposed. Direct measurement of cement powder was chosen to demonstrate the potential use of this device for quantifying the CaCO3 content of the cement. The calibration curve for 0.5-3 mg CaCO3 was linear for signals recorded at 160 s: Vdc = (0.172 ± 0.005) · (mg CaCO3) + (0.016 ± 0.009), with coefficient of determination of 0.9965. Linear calibrations were also observed when the signals were monitored at various time less than 160 s. The limit of quantitation (3 SD of intercept/slope) was 0.17 mg CaCO3. The method provided acceptable precision with %RSD of 4.6 (2 mg CaCO3, n = 10).

Paper-based colorimetric biosensor of blood alcohol with in-situ headspace separation of ethanol from whole blood.

This work presents a novel development that exploits the concept of in-situ gas-separation together with a specific enzymatic colorimetric detection to produce a portable biosensor called "Blood Alcohol Micro-pad" for direct quantitation of ethanol in whole blood. The thin square device (25 mm × 25 mm × 1.8 mm) comprises two layers of patterned filter paper held together with a double-sided mounting tape with an 8-mm circular hole (the headspace). In operation, the reagent is deposited on one layer and covered with sticky tape. Then 8 µL of a blood sample is dispensed onto the opposite layer and covered with sticky tape. Diffusion of ethanol across the 1.6 mm narrow headspace permits selective detection of ethanol by the enzymatic reagents deposited on the opposite layer. This reagent zone contains alcohol oxidase, horseradish peroxidase and 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt, as the chromogenic reagent. The color intensity, measured from the recorded digital image, resulting from the enzymatic assay of ethanol, correlates with the concentration of blood alcohol. The results obtained with spiked mice and sheep blood samples, using an external calibration in the range of 1-120 mg dL-1ethanol, gave recoveries of 93.2-104.4% (n = 12). The "Blood Alcohol Micro-pad" gave good precision with %RSD <1 (50 mg dL-1 ethanol, n = 10) and limit of quantification (10SD of intercept/slope) of 11.56 mg dL-1. The method was successfully validated against a headspace gas chromatography-mass spectrometric method. It has good potential for development as a simple and convenient blood alcohol sensor for on-site testing.

Simple Flow-Based System with an In-Line Membrane Gas-liquid Separation Unit and a Contactless Conductivity Detector for the Direct Determination of Sulfite in Clear and Turbid Food Samples.

This study presents a simple flow-based system for the determination of the preservative agent sulfite in food and beverages. The standard method of conversion of sulfite ions into SO2 gas by acidification is employed to separate the sulfite from sample matrices. The sample is aspirated into a donor stream of sulfuric acid. A membrane gas-liquid separation unit, also called a 'gas-diffusion (GD)' unit, incorporating a polytetrafluoroethylene (PTFE) hydrophobic membrane allows the generated gas to diffuse into a stream of deionized water in the acceptor line. The dissolution of the SO2 gas leads to a change in the conductivity of water which is monitored by an in-line capacitively coupled contactless conductivity detector (C4D). The conductivity change is proportional to the concentration of sulfite in the sample. In this work, both clear (wine) and turbid (fruit juice and extracts of dried fruit) were selected to demonstrate the versatility of the developed method. The method can tolerate turbidity up to 60 Nephelometric Turbidity Units (NTUs). The linear range is 5-25 mg L-1 SO32- with precision < 2% RSD. The flow system employs a peristaltic pump for propelling all liquid lines. Quantitative results of sulfite were statistically comparable to those obtained from iodimetric titration for the wine samples.

Contactless conductivity detector from printed circuit board for paper-based analytical systems.

This work presents a capacitively coupled contactless conductivity detector (C4D) etched out from a printed circuit board (PCB) as potential sensor for paper-based analytical systems. Two lines of any desirable pattern forming 35-µm thick planar copper electrodes were produced on a PCB plate (40 mm × 60 mm) by photolithography. The final PCB plate was covered with polypropylene film to serve as the insulating layer for the C4D detector. The film also protected the copper electrodes from corrosion. Electrodes made in this planar geometry make the PCB-C4D suitable as sensor for flat devices such as paper-based analytical devices. For this work, plain paper strips were employed as sample reservoir and as fluidic channel without hydrophobic pattern. A dried paper strip was first placed over the sensor, followed by dispensing a fixed volume of the liquid sample onto the paper. Entrapment of the liquid sample in the paper strip leads to reproducible size and position of the detection zone of the sample liquid for the capacitive coupling effect. High precision was obtained with %RSD ≤1% (n = 18) for standard solutions of KCl. Soil suspensions could be analyzed without prior filtration by placing a drop onto the paper strip extending away from the detector zone. The paper strip filtered out soil particles at the surface of the paper. Therefore, only soil filtrate moved towards the detection zone by lateral flow. The C4D detection using paper strip showed high tolerance to soil suspension with turbidity up to 6657 NTU, offering direct analysis of soil salinity. Cleaning with moist tissue paper between samples is adequate even for dirty samples such as soil suspension. We also monitored conductivity of acid-base reaction in the microfluidic paper channels, which was later applied to the quantification of bicarbonate in water and in antacid tablet ("Soda Mint Tablet").

Miniaturized Potentiometric Titration for Improving Portability and Accuracy in the Determination of Total Acid in Squeezed Fruit Juice.

To determine the total acidity in freshly squeezed fruit juice, we miniaturized the potentiometric titrations and achieved better accuracy compared with titrations from a conventional pH probe. The improvement was the result of a higher jump in pH at the endpoint due to a reduction in the dilutions of both the titrand and titrant. A conventional pH probe requires more than 50 mL of titrand, which can lead to a 25000-fold dilution of the titrant when adding the titrant at 2 µL intervals. Conversely, when the volume of the titrand can be reduced to 1 mL, the dilution is only 500-fold, which results in a higher jump in pH at the endpoint. The concentration of the titrant, NaOH, was optimized by titrating sample solutions containing 25 and 50 mM of citric acid. The addition of 5 M NaOH in intervals of 2 µL led to a more accurate endpoint for both 25 and 50 mM citric acid solutions. Miniaturization of the titration process is advantageous in terms of portability, accuracy, and in requiring less consumption of a sample, thereby simplifying the process of repeat measurements that are helpful in evaluating the precision of analytical results. Practical samples of squeezed fruit juices were titrated via three methods that showed no significant differences: classic titrimetry with an indicator, conventional potentiometry, and miniaturized potentiometry. This process would be effective for use in the field and in developing countries. PRACTICAL APPLICATION: The total acidity of fruits and fruit juices is an important indicator of quality and is generally expressed in terms of the citric acid content. However, a standard potentiometric titration requires a large sample volume, which makes it difficult to assess dispersion of the acidity for individual fruits. The results of this study indicate that the use of miniaturized potentiometric titration could benefit food chemistry in many developing countries in addition to opening new fields of food chemistry such as on-site quality control of citrus fruit and evaluation of variations in quality.

Simple and green method for direct quantification of hypochlorite in household bleach with membraneless gas-separation microfluidic paper-based analytical device.

This work presents development of a microfluidic paper-based analytical device (µPAD) for direct determination of hypochlorite in household bleach. The recent design of a membraneless gas-separation microfluidic paper-based analytical device (MBL-GS µPAD) was employed to fabricate the hypochlorite-µPAD. Chlorine gas is generated in the µPAD via acidification of an aliquot of sample loaded on to the donor reservoir located at the bottom layer of the µPAD. The liberated chlorine gas diffuses through the air space to oxidize iodide ion previously impregnated in the acceptor reservoir at the top layer of the µPAD, leading to formation of the brown color of the tri-iodide ions. Digital image of the brown zone was captured at exactly 5 min after loading the acid. Image J program is used for analysis of the image for quantification of the hypochlorite in unit of g Cl2 L-1. It was found that employing a relatively large volume of the air space (ca. 270 µL) direct analysis of the high concentration of hypochlorite in the bleach was achieved without prior dilution. The method thus provides a linear working range of 25-100 g Cl2 L-1, which is suitable for most commercial household products. The calibration line has a coefficient of determination of 0.999. The precision of measurements is 0.96% RSD and 0.30% RSD at 30 g Cl2 L-1 and 80 g Cl2 L-1 (n = 10), respectively. Using the paired t-test (P = 0.05, n = 8), the method agreed well with the iodometric titration method. Our µPAD for hypochlorite is portable and cost-effective. The method is also "green" since there is a significant reduction in use of reagents compared to other conventional methods.