David M. Cate

Multilayer Paper-Based Device for Colorimetric and Electrochemical Quantification of Metals

The release of metals and metal-containing compounds into the environment is a growing concern in developed and developing countries, as human exposure to metals is associated with adverse health effects in virtually every organ system. Unfortunately, quantifying metals in the environment is expensive; analysis costs using certified laboratories typically exceed

Sensitive electrochemical sensor using a graphene-polyaniline nanocomposite for simultaneous detection of Zn(II), Cd(II), and Pb(II).

100/sample, making the routine analysis of toxic metals cost-prohibitive for applications such as occupational exposure or environmental protection. Here, we report on a simple, inexpensive technology with the potential to render toxic metals detection accessible for both the developing and developed world that combines colorimetric and electrochemical microfluidic paper-based analytical devices (mPAD) in a three-dimensional configuration. Unlike previous mPADs designed for measuring metals, the device reported here separates colorimetric detection on one layer from electrochemical detection on a different layer. Separate detection layers allows different chemistries to be applied to a single sample on the same device. To demonstrate the effectiveness of this approach, colorimetric detection is shown for Ni, Fe, Cu, and Cr and electrochemical detection for Pb and Cd. Detection limits as low as 0.12 μg (Cr) were achieved on the colorimetric layer while detection limits as low as 0.25 ng (Cd and Pb) were achieved on the electrochemical layer. Selectivity for the target analytes was demonstrated for common interferences. As an example of the device utility, particulate metals collected on air sampling filters were analyzed. Levels measured with the mPAD matched known values for the certified reference samples of collected particulate matter.

A microfluidic paper-based analytical device for rapid quantification of particulate chromium.

This work describes the development of an electrochemical sensor for simultaneous detection of Zn(II), Cd(II), and Pb(II) using a graphene-polyaniline (G/PANI) nanocomposite electrode prepared by reverse-phase polymerization in the presence of polyvinylpyrrolidone (PVP). Two substrate materials (plastic film and filter paper) and two nanocomposite deposition methods (drop-casting and electrospraying) were investigated. Square-wave anodic stripping voltammetry currents were higher for plastic vs. paper substrates. Performance of the G/PANI nanocomposites was characterized by scanning electron microscopy (SEM) and cyclic voltammetry. The G/PANI-modified electrode exhibited high electrochemical conductivity, producing a three-fold increase in anodic peak current (vs. the unmodified electrode). The G/PANI-modified electrode also showed evidence of increased surface area under SEM. Square-wave anodic stripping voltammetry was used to measure Zn(II), Cd(II), and Pb(II) in the presence of Bi(III). A linear working range of 1-300 μg L(-1) was established between anodic current and metal ion concentration with detection limits (S/N=3) of 1.0 μg L(-1) for Zn(II), and 0.1 μg L(-1) for both Cd(II) and Pb(II). The G/PANI-modified electrode allowed selective determination of the target metals in the presence of common metal interferences including Mn(II), Cu(II), Fe(III), Fe(II), Co(III), and Ni(II). Repeat assays on the same device demonstrated good reproducibility (%RSD<11) over 10 serial runs. Finally, this system was utilized for determining Zn(II), Cd(II), and Pb(II) in human serum using the standard addition method.

Rapid Detection of Transition Metals in Welding Fumes Using Paper-Based Analytical Devices

Occupational exposure to Cr is concerning because of its myriad of health effects. Assessing chromium exposure is also cost and resource intensive because the analysis typically uses sophisticated instrumental techniques like inductively coupled plasma-mass spectrometry (ICP-MS). Here, we report a novel, simple, inexpensive microfluidic paper-based analytical device (μPAD) for measuring total Cr in airborne particulate matter. In the μPAD, tetravalent cerium (Ce(IV)) was used in a pretreatment zone to oxidize all soluble Cr to Cr(VI). After elution to the detection zone, Cr(VI) reacts with 1,5-diphenylcarbazide (1,5-DPC) forming 1,5-diphenylcarbazone (DPCO) and Cr(III). The resulting Cr(III) forms a distinct purple colored complex with the DPCO. As proof-of-principle, particulate matter (PM) collected on a sample filter was analyzed with the μPAD to quantify the mass of total Cr. A log-linear working range (0.23-3.75 μg; r(2)=0.998) between Cr and color intensity was obtained with a detection limit of 0.12 μg. For validation, a certified reference containing multiple competing metals was analyzed. Quantitative agreement was obtained between known Cr levels in the sample and the Cr measured using the μPAD.

A simple microfluidic electrochemical HPLC detector for quantifying Fenton reactivity from welding fumes

Metals in particulate matter (PM) are considered a driving factor for many pathologies. Despite the hazards associated with particulate metals, personal exposures for at-risk workers are rarely assessed due to the cost and effort associated with monitoring. As a result, routine exposure assessments are performed for only a small fraction of the exposed workforce. The objective of this research was to evaluate a relatively new technology, microfluidic paper-based analytical devices (µPADs), for measuring the metals content in welding fumes. Fumes from three common welding techniques (shielded metal arc, metal inert gas, and tungsten inert gas welding) were sampled in two welding shops. Concentrations of acid-extractable Fe, Cu, Ni, and Cr were measured and independently verified using inductively coupled plasma-optical emission spectroscopy (ICP-OES). Results from the µPAD sensors agreed well with ICP-OES analysis; the two methods gave statistically similar results in >80% of the samples analyzed. Analytical costs for the µPAD technique were ~50 times lower than market-rate costs with ICP-OES. Further, the µPAD method was capable of providing same-day results (as opposed several weeks for ICP laboratory analysis). Results of this work suggest that µPAD sensors are a viable, yet inexpensive alternative to traditional analytic methods for transition metals in welding fume PM. These sensors have potential to enable substantially higher levels of hazard surveillance for a given resource cost, especially in resource-limited environments.

Personal exposure assessment to particulate metals using a paper-based analytical device

Development and characterization of a simple microfluidic electrochemical flow cell that can be coupled with HPLC to enable dual absorbance/electrochemical detection is described. Coupling absorbance and electrochemical detection increases the information that can be gathered from a single injection, but a second (typically expensive) detection system is required. Here, an inexpensive, customizable microfluidic electrochemical detector is coupled in series with a commercial HPLC/UV system. The microfluidic device is made from poly(dimethylsiloxane) and contains carbon paste electrodes. To demonstrate the utility of this dual-detection system, the reaction products of the radical scavenging agent salicylic acid and hydroxyl radical generated by Fenton chemistry were analyzed. The dual-detection system was used to quantify 2,5-dihydroxybenzoic acid, 2,3-dihydroxybenzoic acid, and catechol produced by the addition of H2O2 to filter samples of welding fumes. Measurement recovery was high, with percent recoveries between 97-102%, 92-103%, and 95-103% for 2,5-dihydroxybenzoic acid, 2,3-dihydroxybenzoic acid, and catechol, respectively, for control samples. The methods described in this work are simple, reliable, and can inexpensively couple electrochemical detection to HPLC-UV systems.

Characterizing nonconstant instrumental variance in emerging miniaturized analytical techniques.

The development of a paper-based analytical device (PAD) for assessing personal exposure to particulate metals will be presented. Human exposure to metal aerosols, such as those that occur in the mining, construction, and manufacturing industries, has a significant impact on the health of our workforce, costing an estimated

Recent Developments in Paper-Based Microfluidic Devices

10B in the U.S and causing approximately 425,000 premature deaths world-wide each year. Occupational exposure to particulate metals affects millions of individuals in manufacturing, construction (welding, cutting, blasting), and transportation (combustion, utility maintenance, and repair services) industries. Despite these effects, individual workers are rarely assessed for their exposure to particulate metals, due mainly to the high cost and effort associated with personal exposure measurement. Current exposure assessment methods for particulate metals call for an 8-hour filter sample, after which time, the filter sample is transported to a laboratory and analyzed by inductively-coupled plasma (ICP). The time from sample collection to reporting is typically weeks and costs several hundred dollars per sample. To exacerbate the issue, method detection limits suffer because of sample dilution during digestion. The lack of sensitivity hampers task-based exposure assessment, for which sampling times may be tens of minutes. To address these problems, and as a first step towards using microfluidics for personal exposure assessment, we have developed PADs for measurement of Pb, Cd, Cr, Fe, Ni, and Cu in aerosolized particulate matter.

Simple, distance-based measurement for paper analytical devices

Measurement variance is a crucial aspect of quantitative chemical analysis. Variance directly affects important analytical figures of merit, including detection limit, quantitation limit, and confidence intervals. Most reported analyses for emerging analytical techniques implicitly assume constant variance (homoskedasticity) by using unweighted regression calibrations. Despite the assumption of constant variance, it is known that most instruments exhibit heteroskedasticity, where variance changes with signal intensity. Ignoring nonconstant variance results in suboptimal calibrations, invalid uncertainty estimates, and incorrect detection limits. Three techniques where homoskedasticity is often assumed were covered in this work to evaluate if heteroskedasticity had a significant quantitative impact-naked-eye, distance-based detection using paper-based analytical devices (PADs), cathodic stripping voltammetry (CSV) with disposable carbon-ink electrode devices, and microchip electrophoresis (MCE) with conductivity detection. Despite these techniques representing a wide range of chemistries and precision, heteroskedastic behavior was confirmed for each. The general variance forms were analyzed, and recommendations for accounting for nonconstant variance discussed. Monte Carlo simulations of instrument responses were performed to quantify the benefits of weighted regression, and the sensitivity to uncertainty in the variance function was tested. Results show that heteroskedasticity should be considered during development of new techniques; even moderate uncertainty (30%) in the variance function still results in weighted regression outperforming unweighted regressions. We recommend utilizing the power model of variance because it is easy to apply, requires little additional experimentation, and produces higher-precision results and more reliable uncertainty estimates than assuming homoskedasticity.