Toward Paper-Based Sensors: Turning Electrical Signals into an Optical Readout System.

Paper-based sensors are gaining increasing attention for their potential applications in resource-limited settings and for point-of-care analysis. However, chemical analysis of paper-based electronic sensors is frequently interpreted using complex software and electronic displays which compromise the advantages of using paper. In this work, we present two semiquantitative paper-based readout systems that can visually measure a change in resistance of a resistive-based sensor. The readout systems use electrochromic Prussian blue/polyaniline as an electrochromic indicator on a resistive gold nanoparticle film that is fabricated on paper. When the readout system is integrated with a resistive sensor in an electrical circuit, and a voltage is applied, the voltage drop along the readout system varies depending on the sensor's resistance. Due to the voltage gradient formed along the gold nanoparticle film, the overlaying Prussian blue/polyaniline will change color at voltages greater than its reduction voltage (green/blue for oxidized state and transparent for reduced state). Thus, the changes in resistances of a sensor can be semiquantified through color visualization by either measuring the length of the transparent film (analog readout system) or by counting the number of transparent segments (digital readout system). The work presented herein can potentially serve as an alternative paper-based display system for resistive sensors in instances where cost and weight is a premium.

High-throughput fabrication and screening improves gold nanoparticle chemiresistor sensor performance.

Chemiresistor sensor arrays are a promising technology to replace current laboratory-based analysis instrumentation, with the advantage of facile integration into portable, low-cost devices for in-field use. To increase the performance of chemiresistor sensor arrays a high-throughput fabrication and screening methodology was developed to assess different organothiol-functionalized gold nanoparticle chemiresistors. This high-throughput fabrication and testing methodology was implemented to screen a library consisting of 132 different organothiol compounds as capping agents for functionalized gold nanoparticle chemiresistor sensors. The methodology utilized an automated liquid handling workstation for the in situ functionalization of gold nanoparticle films and subsequent automated analyte testing of sensor arrays using a flow-injection analysis system. To test the methodology we focused on the discrimination and quantitation of benzene, toluene, ethylbenzene, p-xylene, and naphthalene (BTEXN) mixtures in water at low microgram per liter concentration levels. The high-throughput methodology identified a sensor array configuration consisting of a subset of organothiol-functionalized chemiresistors which in combination with random forests analysis was able to predict individual analyte concentrations with overall root-mean-square errors ranging between 8-17 µg/L for mixtures of BTEXN in water at the 100 µg/L concentration. The ability to use a simple sensor array system to quantitate BTEXN mixtures in water at the low µg/L concentration range has direct and significant implications to future environmental monitoring and reporting strategies. In addition, these results demonstrate the advantages of high-throughput screening to improve the performance of gold nanoparticle based chemiresistors for both new and existing applications.

Recent advances in paper-based sensors.

Paper-based sensors are a new alternative technology for fabricating simple, low-cost, portable and disposable analytical devices for many application areas including clinical diagnosis, food quality control and environmental monitoring. The unique properties of paper which allow passive liquid transport and compatibility with chemicals/biochemicals are the main advantages of using paper as a sensing platform. Depending on the main goal to be achieved in paper-based sensors, the fabrication methods and the analysis techniques can be tuned to fulfill the needs of the end-user. Current paper-based sensors are focused on microfluidic delivery of solution to the detection site whereas more advanced designs involve complex 3-D geometries based on the same microfluidic principles. Although paper-based sensors are very promising, they still suffer from certain limitations such as accuracy and sensitivity. However, it is anticipated that in the future, with advances in fabrication and analytical techniques, that there will be more new and innovative developments in paper-based sensors. These sensors could better meet the current objectives of a viable low-cost and portable device in addition to offering high sensitivity and selectivity, and multiple analyte discrimination. This paper is a review of recent advances in paper-based sensors and covers the following topics: existing fabrication techniques, analytical methods and application areas. Finally, the present challenges and future outlooks are discussed.

Gold nanoparticle chemiresistors operating in biological fluids.

Functionalised gold nanoparticle (Au(NP)) chemiresistors are investigated for direct sensing of small organic molecules in biological fluids. The principle reason that Au(NP) chemiresistors, and many other sensing devices, have limited operation in biological fluids is due to protein and lipid fouling deactivating the sensing mechanism. In order to extend the capability of such chemiresistor sensors to operate directly in biofluids, it is essential to minimise undesirable matrix effects due to protein and lipidic components. Ultrafiltration membranes were investigated as semi-permeable size-selective barriers to prevent large biomolecule interactions with Au(NP) chemiresistors operating in protein-loaded biofluids. All of the ultrafiltration membranes protected the Au(NP) chemiresistors from fouling by the globular biomolecules, with the 10 kDa molecular weight cut-off size being optimum for operation in biofluids. Titrations of toluene in different protein-loaded fluids indicated that small molecule detection was possible. A sensor array consisting of six different thiolate-functionalised Au(NP) chemiresistors protected with a size-selective ultrafiltration membrane successfully identified, and discriminated the spoilage of pasteurised bovine milk. This proof-of-principle study demonstrates the on-chip protein separation and small metabolite detection capability, illustrating the potential for this technology in the field of microbial metabolomics. Overall, these results demonstrate that a sensor array can be protected from protein fouling with the use of a membrane, significantly increasing the possible application areas of Au(NP) chemiresistors ranging from the food industry to health services.

Dynamic response of gold nanoparticle chemiresistors to organic analytes in aqueous solution.

We investigate the response dynamics of 1-hexanethiol-functionalized gold nanoparticle chemiresistors exposed to the analyte octane in aqueous solution. The dynamic response is studied as a function of the analyte-water flow velocity, the thickness of the gold nanoparticle film and the analyte concentration. A theoretical model for analyte limited mass-transport is used to model the analyte diffusion into the film, the partitioning of the analyte into the 1-hexanethiol capping layers and the subsequent swelling of the film. The degree of swelling is then used to calculate the increase of the electron tunnel resistance between adjacent nanoparticles which determines the resistance change of the film. In particular, the effect of the nonlinear relationship between resistance and swelling on the dynamic response is investigated at high analyte concentration. Good agreement between experiment and the theoretical model is achieved.

Gold nanoparticle chemiresistor sensor array that differentiates between hydrocarbon fuels dissolved in artificial seawater.

Gold nanoparticle films (Au(NPF)) functionalized with a range of hydrophobic and hydrophilic thiols were assembled in chemiresistor sensor arrays that were used to differentiate between complex mixtures of analytes in the aqueous phase. A chemiresistor array sampled a simple system of linear alcohols (methanol, ethanol, propan-1-ol, and butan-1-ol) dissolved in water over a range of concentrations. Discriminant analysis confirmed that the response patterns of the array could be used to successfully distinguish between the different alcohol solutions at concentrations above 20 mM for all of the alcohols except methanol, which was distinguished at concentrations above 200 mM. Alcohol solutions more dilute than these concentrations had response patterns that were not consistently recognizable and failed cross validation testing. This defined the approximate limit of discrimination for the system, which was close to the limits of detection for the majority of the individual sensors. Another Au(NPF) chemiresistor array was exposed to, and successfully identified crude oil, diesel, and three varieties of gasoline dissolved in artificial seawater at a fixed concentration. This work is a demonstration that the pattern of responses from an array of differently functionalized Au(NPF) sensors can be used to distinguish analytes in the aqueous phase.

Inkjet-printed gold nanoparticle chemiresistors: influence of film morphology and ionic strength on the detection of organics dissolved in aqueous solution.

The influence of film morphology on the performance of inkjet-printed gold nanoparticle chemiresistors has been investigated. Nanoparticles deposited from a single-solvent system resulted in a "coffee ring"-like structure with most of the materials deposited at the edge. It was shown that the uniformity of the film could be improved if the nanoparticles were deposited from a mixture of solvents comprising N-methyl-2-pyrrolidone and water. Electrical conductivity measurements showed that both "coffee ring" and "flat" films were qualitatively similar suggesting that the films have similar nanoscale structures. To form the functional chemiresistor device, the 4-(dimethylamino)pyridine coating on the nanoparticle was exchanged with 1-hexanethiol to provide a hydrophobic sensing layer. The performance of 1-hexanethiol coated gold nanoparticle chemiresistors to small organic molecules, toluene, dichloromethane and ethanol dissolved in 1 M KCl in regard to changes in impedance and response times was unaffected by the film morphology. For larger hydrocarbons such as octane, the rate of uptake of the analyte into the film was significantly faster when the flatter nanoparticle film was used as opposed to the "coffee ring" film which has a thicker edge. Furthermore, the presence of potassium and chloride ions in the solution media does not significantly affect the impedance of the nanoparticle film at 1 Hz (<2% variation in film impedance over more than four orders of magnitude change in ionic strength). However, the ionic strength of the media affected the partitioning of the analyte into the hydrophobic nanoparticle film. The response of the sensor was found to increase with an increased salt concentration due to a salting-out of the analyte from the solution.

Gold nanoparticle chemiresistor sensors: direct sensing of organics in aqueous electrolyte solution.

A novel chemiresistor sensor for detection of organic analytes in high-conductivity aqueous electrolyte solution is reported. The chemiresistor sensor is based on thin films of gold nanoparticles capped with a 1-hexanethiol monolayer that is inkjet printed onto a microelectrode. In order for a change in nanoparticle film resistance to be measured, the electronic conduction must preferentially occur through the nanoparticle film rather than through the high-conductivity electrolyte solution. This was achieved by miniaturizing the chemiresistor device such that the double layer capacitance of the electrodes in contact with the electrolyte solution gives rise to a significantly larger impedance compared to the nanoparticle film resistance. This system was shown to be sensitive to simple organics dissolved in an aqueous electrolyte solution. The organic analytes, dissolved in the aqueous solution, partition into the hydrophobic nanoparticle film causing the nanoparticle film to swell, resulting in an increase in the low-frequency impedance of the sensor. An increase in the impedance, at 1 Hz, of the gold nanoparticle chemiresistor on exposure to toluene, dichloromethane, and ethanol dissolved in 1 M KCl solution was demonstrated with detection limits of 0.1, 10, and 3000 ppm, respectively. Titration curves over 3 orders of magnitude could be obtained for analytes such as toluene.