Superlative and Selective Sensing of Serotonin in Undiluted Human Serum Using Novel Polystyrene Sulfonate Conductive Polymer.

In the past 5 years, real-time health monitoring has become ubiquitous with the development of watches and rings that can measure and report on the physiological state. As an extension, real-time biomarker sensors, such as the continuous glucose monitor, are becoming popular for both health and performance monitoring. However, few real-time sensors for biomarkers have been made commercially available; this is primarily due to problems with cost, stability, sensitivity, selectivity, and reproducibility of biosensors. Therefore, simple, robust sensors are needed to expand the number of analytes that can be detected in emerging and existing wearable platforms. To address this need, we present a simple but novel sensing material. In short, we have modified the already popular PEDOT/PSS conductive polymer by completely removing the PEDOT component and thus have fabricated a polystyrene sulfonate (PSS) sensor electrodeposited on a glassy carbon (GC) base (GC-PSS). We demonstrate that coupling the GC-PSS sensor with differential pulse voltammetry creates a sensor capable of the selective and sensitive detection of serotonin. Notably, the GC-PSS sensor has a sensitivity of 179 µA µM-1 cm-2 which is 36x that of unmodified GC and an interferent-free detection limit of 10 nM, which is below the concentrations typically found in saliva, urine, and plasma. Notably, the redox potential of serotonin interfacing with the GC-PSS sensor is at -0.188 V versus Ag/AgCl, which is significantly distanced from peaks produced by common interferants found in biofluids, including serum. Therefore, this paper reports a novel, simple sensor and polymeric interface that is compatible with emerging wearable sensor platforms.

Peptide-Functionalized Carbon Nanotube Chemiresistors: The Effect of Nanotube Density on Gas Sensing.

Biorecognition element (BRE)-based carbon nanotube (CNT) chemiresistors have tremendous potential to serve as highly sensitive, selective, and power-efficient volatile organic compound (VOC) sensors. While many research groups have studied BRE-functionalized CNTs in material science and device development, little attention has been paid to optimizing CNT density to improve chemiresistor performance. To probe the effect of CNT density on VOC detection, we present the chemiresistor-based sensing results from two peptide-based CNT devices counting more than 60 different individual measurements. We find that a lower CNT density shows a significantly higher noise level and device-to-device variation while exhibiting mildly better sensitivity. Further investigation with SEM images suggests that moderately high CNT density with a stable connection of the nanotube network is desirable to achieve the best signal-to-noise ratio. Our results show an essential design guideline for tuning the nanotube density to provide sensitive and stable chemiresistors.

Rapid and Simple Buffer Exchange Using Cation-Exchange Chromatography to Improve Point-of-Care Detection of Pharmacological Agents.

The current COVID-19 pandemic has highlighted the power, speed, and simplicity of point-of-care (POC) diagnostics. POC diagnostics are available for a wide range of targets, including both drugs of abuse as well as performance-enhancing drugs. For pharmacological monitoring, minimally invasive fluids such as urine and saliva are commonly sampled. However, false positives or negatives caused by interfering agents excreted in these matrices may confound results. For example, false positives have, in most cases, prevented the use of POC diagnostics for pharmacological agent detection; the consequence is that centralized labs are instead tasked to perform these screenings, resulting in significant delays between sampling and testing. Thus, a rapid, simple, and inexpensive methodology for sample purification is required for the POC to reach a field-deployable tool for the pharmacological human health and performance assessments. Buffer exchange is a simple, rapid approach to remove interfering agents, but has traditionally been difficult to perform on small pharmacological molecules. Therefore, in this communication, we use salbutamol, a performance-enhancing drug, as a case example to demonstrate the efficacy of ion-exchange chromatography as a technique to perform buffer exchange for charged pharmacological agents. This manuscript demonstrates the efficacy of this technique leveraging a commercial spin column to remove interfering agents found in simulant urines, such as proteins, creatinine, and urea, while retaining salbutamol. The utility and efficacy of the method was then confirmed in actual saliva samples. The eluent was then collected and run on the lateral flow assays (LFAs), improving the reported limit of detection by over 5× (new lower limit of detection of 10 ppb compared to reported 60 ppb by the manufacturer) while simultaneously removing noise due to background interfering agents.

Detection of Asthma Inhaler Use via Terahertz Spectroscopy.

Inhaled medications are commonplace for administering bronchodilators, anticholinergics, and corticosteroids. While they have a defined legitimate use, they are also used in sporting events as performance-enhancing drugs. These performance enhancers can be acquired via both legal (i.e., at a pharmacy through over-the-counter medications or through a prescription) and illicit (i.e., black market and foreign pharmacies) means, thus making monitoring procurement impossible. While urine tests can detect these pharmacological agents hours after they have been inhaled, there is a significant lag time before they are observed in urine. Direct detection of these inhaled agents is complicated and requires a multiplexed approach due to the sheer number of inhaled pharmacological agents. Therefore, detection of propellants, which carry the drug into the lungs, provides a simpler path forward toward detection of broad pharmacological agents. In this paper, we demonstrate the first use of terahertz spectroscopy (THz) to detect inhaled medications in human subjects. Notably, we were able to detect and quantitate the propellant, HFA-134a, in breath up to 30 min after using an asthma inhaler, enabling the use of a point-of-care device to monitor exhaled breath for the presence of propellants. We also demonstrate via simulations that the same approach can be leveraged to detect and identify next-generation propellants, specifically HFA-152a. As a result, we provide evidence that a single point-of-care THz sensor can detect when individuals have used pressure-mediated dose inhalers (pMDIs) without further modification of the hardware.

Terahertz Spectroscopic Molecular Sensor for Rapid and Highly Specific Quantitative Analytical Gas Sensing.

Quantitative analytical gas sampling is of great importance in a range of environmental, safety, and scientific applications. In this article, we present the design, operation, and performance of a recently developed tabletop terahertz (THz) spectroscopic molecular sensor capable of rapid (minutes) and sensitive detection of polar gaseous analytes with near "absolute" specificity. A novel double-coil absorption cell design and an array of room-temperature sorbent-based preconcentration modules facilitate quantitative THz detection of light polar volatile compounds, which often challenge the capabilities of established gas sensing techniques. Acetone, ethanol, methanol, acetaldehyde, formaldehyde, and isoprene are detected at low parts-per-billion to high parts-per-trillion levels. This work evaluates performance-limiting factors for THz spectroscopy-based chemical identification: (1) spectral signal to noise and (2) preconcentrator efficiency.

Microfluidic Thermal Flowmeters for Drug Injection Monitoring.

This paper presents a microfluidic thermal flowmeter for monitoring injection pumps, which is essential to ensure proper patient treatment and reduce medication errors that can lead to severe injury or death. The standard gravimetric method for flow-rate monitoring requires a great deal of preparation and laboratory equipment and is impractical in clinics. Therefore, an alternative to the standard method suitable for remote, small-scale, and frequent infusion-pump monitoring is in great demand. Here, we propose a miniaturized thermal flowmeter consisting of a silicon substrate, a platinum heater layer on a silicon dioxide thin-membrane, and a polymer microchannel to provide accurate flow-rate measurement. The present thermal flowmeter is fabricated by the micromachining and micromolding process and exhibits sensitivity, linearity, and uncertainty of 0.722 mW/(g/h), 98.7%, and (2.36 ± 0.80)%, respectively, in the flow-rate range of 0.5-2.5 g/h when the flowmeter is operated in the constant temperature mode with the channel width of 0.5 mm. The measurement range of flow rate can be easily adjusted by changing the cross-sectional microchannel dimension. The present miniaturized thermal flowmeter shows a high potential for infusion-pump calibration in clinical settings.

Electrochemical biosensor for rapid detection of fungal contamination in fuel systems.

There is an increased demand for real-time monitoring of biological and biochemical processes. While most sensor research focuses on physiological conditions, less has been done towards developing real-time biosensors that can operate in and survive exposure to extreme environments and harsh chemicals such as fuel. One interesting application is monitoring microbial load in fuel tanks to prevent both fuel spoilage and biocorrosion. We developed a comprehensive method to enable the first reagentless, real-time, microbial sensor platform that is also fuel resistant. We first identified an extracellular protein epitope conserved in fuel-degrading fungi then used this epitope to develop a suitable biorecognition element (BRE) through biopanning of a 7-mer phage displayed peptide library. After demonstrating the BRE's affinity to fungi using molecular and fluorescence assays, we incorporated the BRE into a reagentless, real-time electrochemical sensing platform based on a self-assembled monolayer of peptide BREs and redox reporters. Finally, we incorporated this real-time electrochemical sensing platform into a microfluidic device. We demonstrated detection of Yarrowia lipolytica as low as 1 × 104 CFU/mL in a bath cell, and demonstrate a microfluidic cell that functions even after exposure to jet fuel. In summary, this work describes development of a fuel-resistant biosensor for monitoring microbial growth in extreme environments.

Laser-Fabricated 2D Molybdenum Disulfide Electronic Sensor Arrays for Rapid, Low-Cost, Ultrasensitive Detection of Influenza A and SARS-Cov-2.

Multiplex electronic antigen sensors for detection of SARS-Cov-2 spike glycoproteins and hemagglutinin from influenza A are fabricated using scalable processes for straightforward transition to economical mass-production. The sensors utilize the sensitivity and surface chemistry of a 2D MoS2 transducer for attachment of antibody fragments in a conformation favorable for antigen binding with no need for additional linker molecules. To make the devices, ultra-thin layers (3 nm) of amorphous MoS2 are sputtered over pre-patterned metal electrical contacts on a glass chip at room temperature. The amorphous MoS2 is then laser annealed to create an array of semiconducting 2H-MoS2 transducer regions between metal contacts. The semiconducting crystalline MoS2 region is functionalized with monoclonal antibody fragments complementary to either SARS-CoV-2 S1 spike protein or influenza A hemagglutinin. Quartz crystal microbalance experiments indicate strong binding and maintenance of antigen avidity for antibody fragments bound to MoS2. Electrical resistance measurements of sensors exposed to antigen concentrations ranging from 2-20 000 pg mL-1 reveal selective responses. Sensor architecture is adjusted to produce an array of sensors on a single chip suited for detection of analyte concentrations spanning six orders of magnitude from pg mL-1 to µg mL-1.

Biomarkers and Detection Platforms for Human Health and Performance Monitoring: A Review.

Human health and performance monitoring (HHPM) is imperative to provide information necessary for protecting, sustaining, evaluating, and improving personnel in various occupational sectors, such as industry, academy, sports, recreation, and military. While various commercially wearable sensors are on the market with their capability of "quantitative assessments" on human health, physical, and psychological states, their sensing is mostly based on physical traits, and thus lacks precision in HHPM. Minimally or noninvasive biomarkers detectable from the human body, such as body fluid (e.g., sweat, tear, urine, and interstitial fluid), exhaled breath, and skin surface, can provide abundant additional information to the HHPM. Detecting these biomarkers with novel or existing sensor technologies is emerging as critical human monitoring research. This review provides a broad perspective on the state of the art biosensor technologies for HHPM, including the list of biomarkers and their physiochemical/physical characteristics, fundamental sensing principles, and high-performance sensing transducers. Further, this paper expands to the additional scope on the key technical challenges in applying the current HHPM system to the real field.

Myopericarditis in a Young Adult Secondary to COVID-19 Vaccination.

We present the case of a healthy 29-year-old male with no significant medical history who presented with electrocardiogram findings consistent with pericarditis and elevated troponin levels, commonly seen in myocarditis, after receiving his second Pfizer-BioNTec vaccination for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). The patient had significant clinical improvement shortly after receiving aspirin and colchicine and was discharged home with these medications. His laboratory findings returned to baseline less than 2 weeks after his illness. While this case highlights the importance of diagnosis, intervention selection, and treatment of myopericarditis amid ongoing global vaccination campaigns, it should be emphasized that the benefits of vaccination considerably outweigh the risks.

Impact of Self-Assembled Monolayer Design and Electrochemical Factors on Impedance-Based Biosensing.

Real-time sensing of proteins, especially in wearable devices, remains a substantial challenge due to the need to convert a binding event into a measurable signal that is compatible with the chosen analytical instrumentation. Impedance spectroscopy enables real-time detection via either measuring electrostatic interactions or electron transfer reactions while simultaneously being amenable to miniaturization for integration into wearable form-factors. To create a more robust methodology for optimizing impedance-based sensors, additional fundamental studies exploring components influencing the design and implementation of these sensors are needed. This investigation addresses a sub-set of these issues by combining optical and electrochemical characterization to validate impedance-based sensor performance as a function of (1) biorecognition element density, (2) self-assembled monolayer chain length, (3) self-assembled monolayer charge density, (4) the electrochemical sensing mechanism and (5) the redox reporter selection. Using a pre-existing lysozyme aptamer and lysozyme analyte combination, we demonstrate a number of design criteria to advance the state-of-the-art in protein sensing. For this model system we demonstrated the following: First, denser self-assembled monolayers yielded substantially improved sensing results. Second, self-assembled monolayer composition, including both thickness and charge density, changed the observed peak position and peak current. Third, single frequency measurements, while less informative, can be optimized to replace multi-frequency measurements and in some cases (such as that with zwitterionic self-assembled monolayers) are preferred. Finally, various redox reporters traditionally not used in impedance sensing should be further explored. Collectively, these results can help limit bottlenecks associated with device development, enabling realization of next-generation impedance-based biosensing with customize sensor design for the specific application.

Air2Liquid Method for Selective, Sensitive Detection of Gas-Phase Organophosphates.

Environmental hazards typically are encountered in the gaseous phase; however, selective sensing modalities for identifying and quantitating compounds of interest in an inexpensive, pseudo-real-time format are severely lacking. Here, we present a novel proof-of-concept that combines an Air2Liquid sampler in conjunction with an oil-in-water microfluidic assay for detection of organophosphates. We believe this proof-of-concept will enable development of a new platform technology for semivolatile detection that we have demonstrated to detect 50 pmoles (2 ppb) of neurotoxic organophosphates.

Portable Skin Analyzers with Simultaneous Measurements of Transepidermal Water Loss, Skin Conductance and Skin Hardness.

Simultaneous measurement of skin physiological and physical properties are important for the diagnosis of skin diseases and monitoring of human performance, since it provides more comprehensive understanding on the skin conditions. Current skin analysis devices, however, require each of probes and unique protocols for the measurement of individual skin properties, resulting in inconvenience and increase of measurement uncertainty. This paper presents a pen-type skin analyzing device capable tomeasure three key skin properties at the same time: transepidermal water loss (TEWL), skin conductance, and skin hardness. It uses a single truncated hollow cone (THC) probe integrated with a humidity sensor, paired electrodes, and a load cell for the multimodal assessment of the skin properties. The present device measured TEWL with a sensitivity of 0.0068 (%/s)/(g/m2/h) and a linearity of 99.63%, conductance with a sensitivity of 1.02 µS/µS and a linearity of 99.36%, and hardness with a sensitivity of 0.98 Shore 00/Shore 00 and a linearity of 99.85%, within the appropriate ranges for the human skin. The present pen-type device has a high potential for the skin health diagnosis as well as the human performance monitoring applications.

Achievements and Challenges for Real-Time Sensing of Analytes in Sweat within Wearable Platforms.

Physiological sensors in a wearable form have rapidly emerged on the market due to technological breakthroughs and have become nearly ubiquitous with the Apple Watch, FitBit, and other wearable devices. While these wearables mostly monitor simple biometric signatures, new devices that can report on the human readiness level through sensing molecular biomarkers are critical to optimizing the human factor in both commercial sectors and the Department of Defense. The military is particularly interested in real-time, wearable, minimally invasive monitoring of fatigue and human performance to improve the readiness and performance of the war fighter. However, very few devices have ventured into the realm of reporting directly on biomarkers of interest. Primarily this is because of the difficulties of sampling biological fluids in real-time and providing accurate readouts using highly selective and sensitive sensors. When additional restrictions to only use sweat, an excretory fluid, are enforced to minimize invasiveness, the demands on sensors becomes even greater due to the dilution of the biomarkers of interest, as well as variability in salinity, pH, and other physicochemical variables which directly impact the read-out of real-time biosensors. This Account will provide a synopsis not only on exemplary demonstrations and technological achievements toward implementation of real-time, wearable sweat sensors but also on defining problems that still remain toward implementation in wearable devices that can detect molecular biomarkers for real world applications. First, the authors describe the composition of minimally invasive biofluids and then identify what biomarkers are of interest as biophysical indicators. This Account then reviews demonstrated techniques for extracting biofluids from the site of generation and transport to the sensor developed by the authors. Included in this discussion is a detailed description on biosensing recognition elements and transducers developed by the authors to enable generation of selective electrochemical sensing platforms. The authors also discuss ongoing efforts to identify biorecognition elements and the chemistries necessary to enable high affinity, selective biorecognition elements. Finally, this Account presents the requirements for wearable, real-time sensors to be (1) highly stable, (2) portable, (3) reagentless, (4) continuous, and (5) responsive in real-time, before delving into specific methodologies to sense classes of biomarkers that have been explored by academia, government laboratories, and industry. Each platform has its areas of greatest utility, but also come with corresponding weaknesses: (1) ion selective electrodes are robust and have been demonstrated in wearables but are limited to detection of ions, (2) enzymatic sensors enable indirect detection of metabolites and have been demonstrated in wearables, but the compounds that can be detected are limited to a subset of small molecules and the sensors are sensitive to flow, (3) impedance-based sensors can detect a wide range of compounds but require further research and development for deployment in wearables. In conclusion, while substantial progress has been made toward wearable molecular biosensors, substantial barriers remain and need to be solved to enable deployment of minimally invasive, wearable biomarker monitoring devices that can accurately report on psychophysiological status.

Chemically Enhanced Polymer-Coated Carbon Nanotube Electronic Gas Sensor for Isopropyl Alcohol Detection.

Breathing-air quality within commercial airline cabins has come under increased scrutiny because of the identification of volatile organic compounds (VOCs) from the engine bleed air used to provide oxygen to cabins. Ideally, a sensor would be placed within the bleed air pipe itself, enabling detection before it permeated through and contaminated the entire cabin. Current gas-phase sensors suffer from issues with selectivity, do not have the appropriate form factor, or are too complex for commercial deployment. Here, we chose isopropyl alcohol (IPA), a main component of de-icer spray used in the aerospace community, as a target analyte: IPA exposure has been hypothesized to be a key component of aerotoxic syndrome in pre, during, and postflight. IPAs proposed mechanism of action is that of an anesthetic and central nervous system depressant. In this work, we describe IPA sensor development by showing (1) the integration of a polymer as an IPA capture matrix, (2) the adoption of a redox chemical additives as an IPA oxidizer, and (3) the application of carbon nanotubes as an electronic sensing conduit. We demonstrate the ability to not only detect IPA at 100-10 000 ppm in unfiltered, laboratory air but also discriminate among IPA, isoprene, and acetone, especially in comparison to a typical photoionization detector. Overall, we show an electronic device that operates at room temperature and responds preferentially to IPA, where the increase in the resistance corresponds directly to the concentration of IPA. Ultimately, this study opens up the pathway to selective electronic sensors that can enable real-time monitoring in a variety of environments for the force health prevention and protection, and the potential through future work to enable low parts-per-million and possibly high parts-per-billion selective detection of gas-phase VOCs of interest.

Insight on Structure of Water and Ice Next to Graphene Using Surface-Sensitive Spectroscopy.

The water/graphene interface has received considerable attention in the past decade due to its relevance in various potential applications including energy storage, sensing, desalination, and catalysis. Most of our knowledge about the interfacial water structure next to graphene stems from simulations, which use experimentally measured water contact angles (WCAs) on graphene (or graphite) to estimate the water-graphene interaction strength. However, the existence of a wide spectrum of reported WCAs on supported graphene and graphitic surfaces makes it difficult to interpret the water-graphene interactions. Here, we have used surface-sensitive infrared-visible sum frequency generation (SFG) spectroscopy to probe the interfacial water structure next to graphene supported on a sapphire substrate. In addition, the ice nucleation properties of graphene have been explored by performing in situ freezing experiments as graphitic surfaces are considered good ice nucleators. For graphene supported on sapphire, we observed a strong SFG peak associated with highly coordinated, ordered water next to graphene. Similar ordering was not detected next to bare sapphire, implying that the observed ordering of water molecules in the former case is a consequence of the presence of graphene. Our analysis indicates that graphene behaves like a hydrophobic (or negatively charged) surface, leading to enhanced ordering of water molecules. Although liquid water orders next to graphene, the ice formed is proton disordered. This research sheds light on water-graphene interactions relevant in optimizing the performance of graphene in various applications.

Peptide interactions with zigzag edges in graphene.

Recognition and manipulation of graphene edges enable the control of physical properties of graphene-based devices. Recently, the authors have identified a peptide that preferentially binds to graphene edges from a combinatorial peptide library. In this study, the authors examine the functional basis for the edge binding peptide using experimental and computational methods. The effect of amino acid substitution, sequence context, and solution pH value on the binding of the peptide to graphene has been investigated. The N-terminus glutamic acid residue plays a key role in recognizing and binding to graphene edges. The protonation, substitution, and positional context of the glutamic acid residue impact graphene edge-binding. Our findings provide insights into the binding mechanisms and the design of peptides for recognizing and functionalizing graphene edges.

Geometrical assembly of ultrastable protein templates for nanomaterials.

The fabrication of nanoscale devices requires architectural templates on which to position functional molecules in complex arrangements. Protein scaffolds are particularly promising templates for nanomaterials due to inherent molecular recognition and self-assembly capabilities combined with genetically encoded functionalities. However, difficulties in engineering protein quaternary structure into stable and well-ordered shapes have hampered progress. Here we report the development of an ultrastable biomolecular construction kit for the assembly of filamentous proteins into geometrically defined templates of controllable size and symmetry. The strategy combines redesign of protein-protein interaction specificity with the creation of tunable connector proteins that govern the assembly and projection angles of the filaments. The functionality of these nanoarchitectures is illustrated by incorporation of nanoparticles at specific locations and orientations to create hybrid materials such as conductive nanowires. These new structural components facilitate the manufacturing of nanomaterials with diverse shapes and functional properties over a wide range of processing conditions.

Recent Advances in Two-Dimensional Materials beyond Graphene.

The isolation of graphene in 2004 from graphite was a defining moment for the "birth" of a field: two-dimensional (2D) materials. In recent years, there has been a rapidly increasing number of papers focusing on non-graphene layered materials, including transition-metal dichalcogenides (TMDs), because of the new properties and applications that emerge upon 2D confinement. Here, we review significant recent advances and important new developments in 2D materials "beyond graphene". We provide insight into the theoretical modeling and understanding of the van der Waals (vdW) forces that hold together the 2D layers in bulk solids, as well as their excitonic properties and growth morphologies. Additionally, we highlight recent breakthroughs in TMD synthesis and characterization and discuss the newest families of 2D materials, including monoelement 2D materials (i.e., silicene, phosphorene, etc.) and transition metal carbide- and carbon nitride-based MXenes. We then discuss the doping and functionalization of 2D materials beyond graphene that enable device applications, followed by advances in electronic, optoelectronic, and magnetic devices and theory. Finally, we provide perspectives on the future of 2D materials beyond graphene.

Approach to multifunctional device platform with epitaxial graphene on transition metal oxide.

Heterostructures consisting of two-dimensional materials have shown new physical phenomena, novel electronic and optical properties, and new device concepts not observed in bulk material systems or purely three dimensional heterostructures. These new effects originated mostly from the van der Waals interaction between the different layers. Here we report that a new optical and electronic device platform can be provided by heterostructures of 2D graphene with a metal oxide (TiO2). Our novel direct synthesis of graphene/TiO2 heterostructure is achieved by C60 deposition on transition Ti metal surface using a molecular beam epitaxy approach and O2 intercalation method, which is compatible with wafer scale growth of heterostructures. As-grown heterostructures exhibit inherent photosensitivity in the visible light spectrum with high photo responsivity. The photo sensitivity is 25 times higher than that of reported graphene photo detectors. The improved responsivity is attributed to optical transitions between O 2p orbitals in the valence band of TiO2 and C 2p orbitals in the conduction band of graphene enabled by Coulomb interactions at the interface. In addition, this heterostructure provides a platform for realization of bottom gated graphene field effect devices with graphene and TiO2 playing the roles of channel and gate dielectric layers, respectively.