Strong enhancement of gold nanoparticle chemiresistor response to low-partitioning organic analytes induced by pre-exposure to high partitioning organics.

Exposing a thiol-functionalised gold nanoparticle film chemiresistor to methanol in aqueous solution results in only a small electric current response as the thiol ligand/water partition coefficient of methanol is small, leading to only minor swelling of the chemiresistor film. Nevertheless, the current response to methanol can be enhanced if the chemiresistor becomes pre-exposed to a molecule with a large ligand/water partition coefficient P (e.g. octane with Po = 104.3). The large response enhancement is achieved because methanol, when added to an aqueous solution of octane, lowers the large initial partition coefficient of octane. Octane exiting the thiol ligands then leads to strong film shrinkage resulting in a relative current change much greater than the one otherwise induced by methanol alone. This was theoretically modelled for octane and heptane (Ph = 103.6). A strong response enhancement to methanol (>20 times) was observed experimentally by exposure to 2 ppm octane compared to direct testing of methanol in aqueous solution. Besides octane and heptane, molecules with P > 107 (e.g. permethrin) can theoretically be used to provide enhancement factors of several orders of magnitude. For practical reasons, heptane and octane saturate more quickly, thus enabling more rapid detection of methanol than higher P organic molecules.

Ionic Liquid-Modified Disposable Electrochemical Sensor Strip for Analysis of Fentanyl.

The increasing prevalence of fentanyl and its analogues as contaminating materials in illicit drug products presents a major hazard to first responder and law enforcement communities. Electrochemical techniques have the potential to provide critical information to these personnel via rapid, facile field detection of these materials. Here we demonstrate the use of cyclic square wave voltammetry (CSWV) with screen-printed carbon electrodes (SPCE), modified with the room temperature ionic liquid (RTIL) 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide [C4C1pyrr][NTf2], toward such rapid "on-the-spot" fentanyl detection. This CSWV-based disposable sensor strip system provides an information-rich electrochemical fingerprint of fentanyl, composed of an initial oxidation event at +0.556 V (vs Ag/AgCl) and a reversible reduction and oxidation reaction at -0.235 and -0.227 V, respectively. The combined current and potential characteristics of these anodic and cathodic fentanyl peaks, generated using two CSWV cycles, thus lead to a distinct electrochemical signature. This CSWV profile facilitates rapid (1 min) identification of the target opioid at micromolar concentrations in the presence of other cutting agents commonly found in illicit drug formulations. The new protocol thus holds considerable promise for rapid decentralized fentanyl detection at the "point of need".

Wearable Bioelectronics: Enzyme-Based Body-Worn Electronic Devices.

In this Account, we detail recent progress in wearable bioelectronic devices and discuss the future challenges and prospects of on-body noninvasive bioelectronic systems. Bioelectronics is a fast-growing interdisciplinary research field that involves interfacing biomaterials with electronics, covering an array of biodevices, encompassing biofuel cells, biosensors, ingestibles, and implantables. In particular, enzyme-based bioelectronics, built on diverse biocatalytic reactions, offers distinct advantages and represents a centerpiece of wearable biodevices. Such wearable bioelectronic devices predominately rely on oxidoreductase enzymes and have already demonstrated considerable promise for on-body applications ranging from highly selective noninvasive biomarker monitoring to epidermal energy harvesting. These systems can thus greatly increase the analytical capability of wearable devices from the ubiquitous monitoring of mobility and vital signs, toward the noninvasive analysis of important chemical biomarkers. Wearable enzyme electrodes offer exciting opportunities to a variety of areas, spanning from healthcare, sport, to the environment or defense. These include real-time noninvasive detection of biomarkers in biofluids (such as sweat, saliva, interstitial fluid and tears), and the monitoring of environmental pollutants and security threats in the immediate surrounding of the wearer. Furthermore, the interface of enzymes with conducting flexible electrode materials can be exploited for developing biofuel cells, which rely on the bioelectrocatalytic oxidation of biological fuels, such as lactate or glucose, for energy harvesting applications. Crucial for such successful application of enzymatic bioelectronics is deep knowledge of enzyme electron-transfer kinetics, enzyme stability, and enzyme immobilization strategies. Such understanding is critical for establishing efficient electrical contacting between the redox enzymes and the conducting electrode supports, which is of fundamental interest for the development of robust and efficient bioelectronic platforms. Furthermore, stretchable and flexible bioelectronic platforms, with mechanical properties similar to those of biological tissues, are essential for handling the rigors of on-body operation. As such, special attention must be given to changes in the behavior of enzymes due to the uncontrolled conditions of on-body operation (including diverse outdoor activities and different biofluids), for maintaining the attractive performance that these bioelectronics devices display in controlled laboratory settings. Therefore, a focus of this Account is on interfacing biocatalytic layers onto wearable electronic devices for creating efficient and stable on-body electrochemical biosensors and biofuel cells. With proper attention to key challenges and by leveraging the advantages of biocatalysis, electrochemistry, and flexible electronics, wearable bioelectronic devices could have a tremendous impact on diverse biomedical, fitness, and defense fields.

Wearable electrochemical glove-based sensor for rapid and on-site detection of fentanyl.

Rapid, on-site detection of fentanyl is of critical importance, as it is an extremely potent synthetic opioid that is prone to abuse. Here we describe a wearable glove-based sensor that can detect fentanyl electrochemically on the fingertips towards decentralized testing for opioids. The glove-based sensor consists of flexible screen-printed carbon electrodes modified with a mixture of multiwalled carbon nanotubes and a room temperature ionic liquid, 4-(3-butyl-1-imidazolio)-1-butanesulfonate). The sensor shows direct oxidation of fentanyl in both liquid and powder forms with a detection limit of 10 µM using square-wave voltammetry. The "Lab-on-a-Glove" sensors, combined with a portable electrochemical analyzer, provide wireless transmission of the measured data to a smartphone or tablet for further analysis. The integrated sampling and sensing methodology on the thumb and index fingers, respectively, enables rapid screening of fentanyl in the presence of a mixture of cutting agents and offers considerable promise for timely point-of-need screening for first responders. Such a glove-based "swipe, scan, sense, and alert" strategy brings chemical analytics directly to the user's fingertips and opens new possibilities for detecting substances of abuse in emergency situations.

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.

Simultaneous detection of salivary Δ9-tetrahydrocannabinol and alcohol using a Wearable Electrochemical Ring Sensor.

Driving under the influence of cannabis and alcohol represents a major safety concern due to the synergistic or additive effect of these substances of abuse. Hence, rapid road-site testing of these substances is highly desired to reduce risks of fatal accidents. Here we describe a wearable electrochemical sensing device for the simultaneous direct, decentralized, detection of salivary THC and alcohol. The new ring-based sensing platform contains a voltammetric THC sensor and an amperometric alcohol biosensor on the ring cap, along with the wireless electronics embedded within the ring case. Rapid replacement of the disposable sensing-electrode ring cap following each saliva assay is accomplished by aligning spring-loaded pins, mounted on the electronic board (PCB), with the current collectors of the sensing electrodes. The printed dual-analyte sensor ring cover is based on a MWCNT/carbon electrode for the THC detection along with a Prussian-blue transducer, coated with alcohol oxidase/chitosan reagent layer, for the biosensing of alcohol. THC and alcohol can thus be detected simultaneously in the same diluted saliva sample within 3 min, with no cross talk and no interferences from the saliva matrix. The new wearable ring sensor platform should enable law enforcement personnel to screen drivers in a single traffic stop and offers considerable promise for addressing growing concerns of drug-impaired driving.

Wearable Flexible and Stretchable Glove Biosensor for On-Site Detection of Organophosphorus Chemical Threats.

A flexible glove-based electrochemical biosensor with highly stretchable printed electrode system has been developed as a wearable point-of-use screening tool for defense and food security applications. This disposable-mechanically robust "lab-on-a-glove" integrates a stretchable printable enzyme-based biosensing system and active surface for swipe sampling on different fingers, and is coupled with a compact electronic interface for electrochemical detection and real-time wireless data transmission to a smartphone device. Stress-enduring inks are used to print the electrode system and the long serpentine connections to the wireless electronic interface. Dynamic mechanical deformation, bending, and stretching studies illustrate the resilience and compliance of the printed traces against extreme mechanical deformations expected for such on-glove sampling/sensing operation. An organophosphorus hydrolase (OPH)-based biosensor system on the index finger enables rapid on-site detection of organophosphate (OP) nerve-agent compounds on suspicious surfaces and agricultural products following their swipe collection on the thumb finger. The new wireless glove-based biosensor system offers considerable promise for field screening of OP nerve-agents and pesticides in defense and food-safety applications, with significant speed and cost advantages. Such "lab-on-a-glove" demonstration opens the area of flexible wearable sensors to future on-the-hand multiplexed chemical detection in diverse fields.

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.

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.

Multifunctional water-soluble molecular capsules based on p-phosphonic acid calix[5]arene.

p-Phosphonic acid calix[5]arene forms molecular capsules in water based on two of the molecules, which can be loaded with carboplatin using intense shearing, and attached to single wall carbon nano-tubes. Spin coating of the capsules onto a substrate affords 2 nm fibres of stacked calixarenes, with the self-assembly understood using molecular modelling.

Nanofibers of fullerene C60 through interplay of ball-and-socket supermolecules.

Mixing solutions of p-tBu-calix[5]arene and C(60) in toluene results in a 1:1 complex (C(60)) intersection(p-tBu-calix[5]arene), which precipitates as nanofibers. The principle structural unit is based on a host-guest ball-and-socket nanostructure of the two components, with an extended structure comprising zigzag/helical arrays of fullerenes (powder X-ray diffraction data coupled with molecular modeling). Under argon at temperatures above 309 degrees C, the fibers undergo selective volatilization of the calixarenes to afford C(60)-core nanostructures encapsulated in a graphitic material sheath, which exhibits a dramatic increase in surface area. Above 650 degrees C the material exhibits an ohmic conductance response, due to the encapsulation process.