Ion permselectivity can lead to accumulation in zero-dimensional nanopores, producing a significant increase in ion concentration, an effect which may be combined with unscreened ion migration to improve sensitivity in electrochemical measurements, as demonstrated by the enormous current amplification (∼2000-fold) previously observed in nanopore electrode arrays (NEA) in the absence of supporting electrolyte. Ionic strength is a key experimental factor that governs the magnitude of the additional current amplification (AFad) beyond simple redox cycling through both ion accumulation and ion migration effects. Separate contributions from ion accumulation and ion migration to the overall AFad were identified by studying NEAs with varying geometries, with larger AFad values being achieved in NEAs with smaller pores. In addition, larger AFad values were observed for Ru(NH3)6(3/2+) than for ferrocenium/ferrocene (Fc(+)/Fc) in aqueous solution, indicating that coupling efficiency in redox cycling can significantly affect AFad. While charged species are required to observe migration effects or ion accumulation, poising the top electrode at an oxidizing potential converts neutral species to cations, which can then exhibit current amplification similar to starting with the cation. The electrical double layer effect was also demonstrated for Fc/Fc(+) in acetonitrile and 1,2-dichloroethane, producing AFad up to 100× at low ionic strength. The pronounced AFad effects demonstrate the advantage of coupling redox cycling with ion accumulation and migration effects for ultrasensitive electrochemical measurements.

Illicit drug use causes over half a million deaths worldwide every year. Drugs of abuse are commonly smuggled through customs and border checkpoints and, increasingly, through parcel delivery services. Improved methods for detection of trace drug residues from surfaces are needed. Such methods should be robust, fieldable, sensitive, and capable of detecting a wide range of drugs. In this work, commercially produced paper with a pressure-sensitive adhesive coating was utilized for the collection and analysis of trace drug residues by paper spray mass spectrometry (MS). This modified substrate was used to combine sample collection of drug residues from surfaces with rapid detection using a single paper spray ticket. The all-in-one ticket was used to probe different surfaces commonly encountered in forensic work including clothing, cardboard, glass, concrete, asphalt, and aluminum. A total of 10 drugs (acetyl fentanyl, fentanyl, clonazolam, cocaine, heroin, ketamine, methamphetamine, methylone, U-47700, and XLR-11) were evaluated and found to be detectable in the picogram range using a benchtop mass spectrometer and in the low nanogram range using a portable ion trap MS. The novel approach demonstrates a simple yet effective sampling strategy, allowing for rapid identification from difficult surfaces via paper spray mass spectrometry.

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The effects of molecular confinement and crowding on enzyme kinetics were studied at length scales and under conditions similar to those found in biological cells. These experiments were carried out using a nanofluidic network of channels constituting a nanofluidic gradient mixer, providing the basis for measuring multiple experimental conditions simultaneously. The 100 nm × 40 μm nanochannels were wet etched directly into borosilicate glass, then annealed and characterized with fluorescein emission prior to kinetic measurements. The nanofluidic gradient mixer was then used to measure the kinetics of the conversion of the horseradish peroxidase (HRP)-catalyzed conversion of non-fluorescent Amplex Red (AR) to the fluorescent product resorufin in the presence of hydrogen peroxide (H2O2). The design of the gradient mixer allows reaction kinetics to be studied under multiple (five) unique solution compositions in a single experiment. To characterize the efficiency of the device the effects of confinement on HRP-catalyzed AR conversion kinetics were studied by varying the starting ratio of AR : H2O2. Equimolar concentrations of Amplex Red and H2O2 yielded the highest reaction rates followed by 2 : 1, 1 : 2, 5 : 1, and finally 1 : 5 [AR] : [H2O2]. Under all conditions, initial reaction velocities were decreased by excess H2O2. Crowding effects on kinetics were studied by increasing solution viscosity in the nanochannels in the range 1.0-1.6 cP with sucrose. Increasing the solution viscosities in these confined geometries decreases the initial reaction velocity at the highest concentration from 3.79 μM min(-1) at 1.00 cP to 0.192 μM min(-1) at 1.59 cP. Variations in reaction velocity are interpreted in the context of models for HRP catalysis and for molecular crowding.

Rationale Paper spray mass spectrometry (PS‐MS) was used to analyze and quantify ampicillin, a hydrophilic compound and frequently utilized antibiotic. Hydrophilic molecules are difficult to analyze via PS‐MS due to their strong binding affinity to paper substrates and low ionization efficiency, among other reasons. Methods Solvent and paper parameters were optimized to increase the extraction of ampicillin from the paper substrate. After optimizing these key parameters, a Resolution IV 1/16 fractional factorial design with two center points was employed to screen eight different design parameters simultaneously. Results Pore size, sample volume, and solvent volume were the most significant factors affecting average peak area under the curve (AUC) and the signal‐to‐blank (S/B) ratio for the 1 μg/mL ampicillin calibrant. After optimizing the key parameters, a linear calibration curve with a range of 0.2 μg/mL to 100 μg/mL was generated (R2 = 0.98) and the limit of detection (LOD) and lower limit of quantification (LLOQ) were calculated to be 0.07 μg/mL and 0.25 μg/mL, respectively. Conclusions The statistical optimization procedure undertaken here increased the mass spectral signal intensity by more than a factor of 40. This statistical method of screening followed by optimization experiments proved faster and more efficient, and produced more drastic improvements than typical one‐factor‐at‐a‐time experiments.