First-Order Individual Gas Sensors as Next Generation Reliable Analytical Instruments.

It is conventionally expected that the performance of existing gas sensors may degrade in the field compared to laboratory conditions because (i) a sensor may lose its accuracy in the presence of chemical interferences and (ii) variations of ambient conditions over time may induce sensor-response fluctuations (i.e., drift). Breaking this status quo in poor sensor performance requires understanding the origins of design principles of existing sensors and bringing new principles to sensor designs. Existing gas sensors are single-output (e.g., resistance, electrical current, light intensity, etc.) sensors, also known as zero-order sensors (Karl Booksh and Bruce R. Kowalski, Analytical Chemistry, DOI: 10.1021/ac00087a718). Any zero-order sensor is undesirably affected by variable chemical background and sensor drift that cannot be distinguished from the response to an analyte. To address these limitations, we are developing multivariable gas sensors with independent responses, which are first-order analytical instruments. Here, we demonstrate self-correction against drift in two types of first-order gas sensors that operate in different portions of the electromagnetic spectrum. Our radiofrequency sensors utilize dielectric excitation of semiconducting metal oxide materials on the shoulder of their dielectric relaxation peak and achieve self-correction of the baseline drift by operation at several frequencies. Our photonic sensors utilize nanostructured sensing materials inspired by Morpho butterflies and achieve self-correction of the baseline drift by operation at several wavelengths. These principles of self-correction for drift effects in first-order sensors open opportunities for diverse emerging monitoring applications that cannot afford frequent periodic maintenance that is typical of traditional analytical instruments.

Digital electrical impedance analysis for single bacterium sensing and antimicrobial susceptibility testing.

Single-molecule and single-cell analysis techniques have opened new opportunities for characterizing and analyzing heterogeneity within biological samples. These detection methods are often referred to as digital assays because the biological sample is partitioned into many small compartments and each compartment contains a discrete number of targets (e.g. cells). Using digital assays, researchers can precisely detect and quantify individual targets, and this capability has made digital techniques the basis for many modern bioanalytical tools (including digital PCR, single cell RNA sequencing, and digital ELISA). However, digital assays are dominated by optical analysis systems that typically utilize microscopy to analyze partitioned samples. The utility of digital assays may be dramatically enhanced by implementing cost-efficient and portable electrical detection capabilities. Herein, we describe a digital electrical impedance sensing platform that enables direct multiplexed measurement of single cell bacterial cells. We outline our solutions to the challenge of multiplexing impedance sensing across many culture compartments and demonstrate the potential for rapidly differentiating antimicrobial resistant versus susceptible strains of bacteria.