Monitoring Cardiac Biomarkers with Aptamer-Based Molecular Pendulum Sensors.

Reagent-free electronic biosensors capable of analyzing disease markers directly in unprocessed body fluids will enable the development of simple & affordable devices for personalized healthcare monitoring. Here we report a powerful and versatile nucleic acid-based reagent-free electronic sensing system. The signal transduction is based on the kinetics of an electrode-tethered molecular pendulum-a rigid double stranded DNA with one of the strands displaying an analyte-binding aptamer and the other featuring a redox probe-that exhibits field-induced transport modulated by receptor occupancy. Using chronoamperometry, which enables the sensor to circumvent the conventional Debye length limitation, the binding of an analyte can be monitored as these species increase the hydrodynamic drag. The sensing platform demonstrates a low femtomolar quantification limit and minimal cross-reactivity in analyzing cardiac biomarkers in whole blood collected from patients with chronic heart failure.

Capillary-Assisted Molecular Pendulum Bioanalysis.

The development of robust biosensing strategies that can be easily implemented in everyday life remains a challenge for the future of modern biosensor research. While several reagentless approaches have attempted to address this challenge, they often achieve user-friendliness through sacrificing sensitivity or universality. While acceptable for certain applications, these trade-offs hinder the widespread adoption of reagentless biosensing technologies. Here, we report a novel approach to reagentless biosensing that achieves high sensitivity, rapid detection, and universality using the SARS-CoV-2 virus as a model target. Universality is achieved by using nanoscale molecular pendulums, which enables reagentless electrochemical biosensing through a variable antibody recognition element. Enhanced sensitivity and rapid detection are accomplished by incorporating the coffee-ring phenomenon into the sensing scheme, allowing for target preconcentration on a ring-shaped electrode. Using this approach, we obtained limits of detection of 1 fg/mL and 20 copies/mL for the SARS-CoV-2 nucleoproteins and viral particles, respectively. In addition, clinical sample analysis showed excellent agreement with Ct values from PCR-positive SARS-CoV-2 patients.

Photolysis Controls Atmospheric Budgets of Biogenic Secondary Organic Aerosol.

Secondary organic aerosol (SOA) accounts for a large fraction of the tropospheric particulate matter. Although SOA production rates and mechanisms have been extensively investigated, loss pathways remain uncertain. Most large-scale chemistry and transport models account for mechanical deposition of SOA but not chemical losses such as photolysis. There is also a paucity of laboratory measurements of SOA photolysis, which limits how well photolytic losses can be modeled. Here, we show, through a combined experimental and modeling approach, that photolytic loss of SOA mass significantly alters SOA budget predictions. Using environmental chamber experiments at variable relative humidity between 0 and 60%, we find that SOA produced from several biogenic volatile organic compounds undergoes photolysis-induced mass loss at rates between 0 and 2.2 ± 0.4% of nitrogen dioxide (NO2) photolysis, equivalent to average atmospheric lifetimes as short as 10 h. We incorporate our photolysis rates into a regional chemical transport model to test the sensitivity of predicted SOA mass concentrations to photolytic losses. The addition of photolysis causes a ∼50% reduction in biogenic SOA loadings over the Amazon, indicating that photolysis exerts a substantial control over the atmospheric SOA lifetime, with a likely dependence upon the SOA molecular composition and thus production mechanisms.

Shape-morphing nanocomposite origami.

Nature provides a vast array of solid materials that repeatedly and reversibly transform in shape in response to environmental variations. This property is essential, for example, for new energy-saving technologies, efficient collection of solar radiation, and thermal management. Here we report a similar shape-morphing mechanism using differential swelling of hydrophilic polyelectrolyte multilayer inkjets deposited on an LBL carbon nanotube (CNT) composite. The out-of-plane deflection can be precisely controlled, as predicted by theoretical analysis. We also demonstrate a controlled and stimuli-responsive twisting motion on a spiral-shaped LBL nanocomposite. By mimicking the motions achieved in nature, this method offers new opportunities for the design and fabrication of functional stimuli-responsive shape-morphing nanoscale and microscale structures for a variety of applications.

Artificial Intelligence in Point-of-Care Biosensing: Challenges and Opportunities.

The integration of artificial intelligence (AI) into point-of-care (POC) biosensing has the potential to revolutionize diagnostic methodologies by offering rapid, accurate, and accessible health assessment directly at the patient level. This review paper explores the transformative impact of AI technologies on POC biosensing, emphasizing recent computational advancements, ongoing challenges, and future prospects in the field. We provide an overview of core biosensing technologies and their use at the POC, highlighting ongoing issues and challenges that may be solved with AI. We follow with an overview of AI methodologies that can be applied to biosensing, including machine learning algorithms, neural networks, and data processing frameworks that facilitate real-time analytical decision-making. We explore the applications of AI at each stage of the biosensor development process, highlighting the diverse opportunities beyond simple data analysis procedures. We include a thorough analysis of outstanding challenges in the field of AI-assisted biosensing, focusing on the technical and ethical challenges regarding the widespread adoption of these technologies, such as data security, algorithmic bias, and regulatory compliance. Through this review, we aim to emphasize the role of AI in advancing POC biosensing and inform researchers, clinicians, and policymakers about the potential of these technologies in reshaping global healthcare landscapes.

Highly Stable Biotemplated InP/ZnSe/ZnS Quantum Dots for In Situ Bacterial Monitoring.

Despite their unique optical and electrical characteristics, traditional semiconductor quantum dots (QDs) made of heavy metals or carbon are not ideally suited for biomedical applications. Cytotoxicity and environmental concerns are key limiting factors affecting the adoption of QDs from laboratory research to real-world medical applications. Recently, advanced InP/ZnSe/ZnS QDs have emerged as alternatives to traditional QDs due to their low toxicity and optical properties; however, bioconjugation has remained a challenge due to surface chemistry limitations that can lead to instability in aqueous environments. Here, we report water-soluble, biotemplated InP/ZnSe/ZnS-aptamer quantum dots (QDAPTs) with long-term stability and high selectivity for targeting bacterial membrane proteins. QDAPTs show fast binding reaction kinetics (less than 5 min), high brightness, and high levels of stability (3 months) after biotemplating in aqueous solvents. We use these materials to demonstrate the detection of bacterial membrane proteins on common surfaces using a hand-held imaging device, which attests to the potential of this system for biomedical applications.

Self-Assembled Monolayer Transporters Enable Reagentless Analysis of Small Molecule Analytes.

The detection of small molecules beyond glucose remains an ongoing challenge in the field of biomolecular sensing owing to their small size, diverse structures, and lack of alternative non-enzymatic sensing methods. Here, we present a new reagentless electrochemical approach for small molecule detection that involves directed movement of electroactive analytes through a self-assembled monolayer to an electrode surface. Using this method, we demonstrate detection of several physiologically relevant small molecules as well as the capacity for the system to operate in several biological fluids. We anticipate that this mechanism will further improve our capacity for small molecule measurement and provide a new generalizable monolayer-based technique for electrochemical assessment of various electroactive analytes.

Spiky Gold Nanoparticles, a Nanoscale Approach to Enhanced Ex Vivo T-Cell Activation.

While existing synthetic technologies for ex vivo T-cell activation face challenges like suboptimal expansion rates and low effectiveness, artificial antigen-presenting cells (aAPCs) hold great promise for enhanced T-cell based therapies. In particular, gold nanoparticles (AuNPs), known for their biocompatibility, ease of synthesis, and versatile surface chemistry, are strong candidates for use as nanoscale aAPCs. In this study, we developed spiky AuNPs with branched geometries to present activating ligands to primary human T-cells. The special structure of spiky AuNPs enhances biomolecule loading capacity and significantly improves T-cell activation through multivalent binding of costimulatory ligands and receptors. Our spiky AuNPs outperform existing systems including Dynabeads and soluble activators by promoting greater polyclonal expansion of T-cells, boosting sustained cytokine production, and generating highly functional T-cells with reduced exhaustion. In addition, spiky AuNPs effectively activate and expand CD19 CAR-T cells while demonstrating increased in vitro cytotoxicity against target cells using fewer effector cells than Dynabeads. This study underscores the potential of spiky AuNPs as a powerful tool, bringing new opportunities to adoptive cell therapy applications.

Electrochemical Detection of Borrelia burgdorferi Using a Biomimetic Flow Cell System.

Lyme disease, caused by infection with pathogenic Borrelia bacteria, has emerged as a pervasive illness throughout North America and many other regions of the world in recent years, owing in part to climate-mediated habitat expansion of the tick vectors. Standard diagnostic testing has remained largely unchanged over the past several decades and is indirect, relying on detection of antibodies against the Borrelia pathogen, rather than detection of the pathogen itself. The development of new rapid, point-of-care tests for Lyme disease that directly detects the pathogen could drastically improve patient health by enabling faster and more frequent testing that could better inform patient treatment. Here, we describe a proof-of-concept electrochemical sensing approach to the detection of the Lyme disease-causing bacteria, which utilizes a biomimetic electrode to interact with the Borrelia bacteria that induce impedance alterations. In addition, the catch-bond mechanism between bacterial BBK32 protein and human fibronectin protein, which exhibits improved bond strength with increased tensile force, is tested within an electrochemical injection flow-cell to achieve Borrelia detection under shear stress.

Biomolecular sensors for advanced physiological monitoring.

Body-based biomolecular sensing systems, including wearable, implantable and consumable sensors allow comprehensive health-related monitoring. Glucose sensors have long dominated wearable bioanalysis applications owing to their robust continuous detection of glucose, which has not yet been achieved for other biomarkers. However, access to diverse biological fluids and the development of reagentless sensing approaches may enable the design of body-based sensing systems for various analytes. Importantly, enhancing the selectivity and sensitivity of biomolecular sensors is essential for biomarker detection in complex physiological conditions. In this Review, we discuss approaches for the signal amplification of biomolecular sensors, including techniques to overcome Debye and mass transport limitations, and selectivity improvement, such as the integration of artificial affinity recognition elements. We highlight reagentless sensing approaches that can enable sequential real-time measurements, for example, the implementation of thin-film transistors in wearable devices. In addition to sensor construction, careful consideration of physical, psychological and security concerns related to body-based sensor integration is required to ensure that the transition from the laboratory to the human body is as seamless as possible.

A magneto-activated nanoscale cytometry platform for molecular profiling of small extracellular vesicles.

Exosomal PD-L1 (exoPD-L1) has recently received significant attention as a biomarker predicting immunotherapeutic responses involving the PD1/PD-L1 pathway. However, current technologies for exosomal analysis rely primarily on bulk measurements that do not consider the heterogeneity found within exosomal subpopulations. Here, we present a nanoscale cytometry platform NanoEPIC, enabling phenotypic sorting and exoPD-L1 profiling from blood plasma. We highlight the efficacy of NanoEPIC in monitoring anti-PD-1 immunotherapy through the interrogation of exoPD-L1. NanoEPIC generates signature exoPD-L1 patterns in responders and non-responders. In mice treated with PD1-targeted immunotherapy, exoPD-L1 is correlated with tumor growth, PD-L1 burden in tumors, and the immune suppression of CD8+ tumor-infiltrating lymphocytes. Small extracellular vesicles (sEVs) with different PD-L1 expression levels display distinctive inhibitory effects on CD8 + T cells. NanoEPIC offers robust, high-throughput profiling of exosomal markers, enabling sEV subpopulation analysis. This platform holds the potential for enhanced cancer screening, personalized treatment, and therapeutic response monitoring.

A high-dimensional microfluidic approach for selection of aptamers with programmable binding affinities.

Aptamers are being applied as affinity reagents in analytical applications owing to their high stability, compact size and amenability to chemical modification. Generating aptamers with different binding affinities is desirable, but systematic evolution of ligands by exponential enrichment (SELEX), the standard for aptamer generation, is unable to quantitatively produce aptamers with desired binding affinities and requires multiple rounds of selection to eliminate false-positive hits. Here we introduce Pro-SELEX, an approach for the rapid discovery of aptamers with precisely defined binding affinities that combines efficient particle display, high-performance microfluidic sorting and high-content bioinformatics. Using the Pro-SELEX workflow, we were able to investigate the binding performance of individual aptamer candidates under different selective pressures in a single round of selection. Using human myeloperoxidase as a target, we demonstrate that aptamers with dissociation constants spanning a 20-fold range of affinities can be identified within one round of Pro-SELEX.

Multi-campaign ship and aircraft observations of marine cloud condensation nuclei and droplet concentrations.

In-situ marine cloud droplet number concentrations (CDNCs), cloud condensation nuclei (CCN), and CCN proxies, based on particle sizes and optical properties, are accumulated from seven field campaigns: ACTIVATE; NAAMES; CAMP2EX; ORACLES; SOCRATES; MARCUS; and CAPRICORN2. Each campaign involves aircraft measurements, ship-based measurements, or both. Measurements collected over the North and Central Atlantic, Indo-Pacific, and Southern Oceans, represent a range of clean to polluted conditions in various climate regimes. With the extensive range of environmental conditions sampled, this data collection is ideal for testing satellite remote detection methods of CDNC and CCN in marine environments. Remote measurement methods are vital to expanding the available data in these difficult-to-reach regions of the Earth and improving our understanding of aerosol-cloud interactions. The data collection includes particle composition and continental tracers to identify potential contributing CCN sources. Several of these campaigns include High Spectral Resolution Lidar (HSRL) and polarimetric imaging measurements and retrievals that will be the basis for the next generation of space-based remote sensors and, thus, can be utilized as satellite surrogates.

Harmonized and high-quality datasets of aerosol optical depth at a US continental site, 1997-2018.

Aerosol optical depth (AOD) characterizes the aerosol burden in the atmosphere, while its wavelength dependence is a sign of particle size. Long-term records of wavelength-resolved AOD with high quality and suitable continuity are required for climate change assessment. Typically, climate-related studies use AOD products provided by several, and perhaps different, ground-based instruments. The measurements from these instruments often have different accuracy and temporal resolution. To preserve the advantages of these products (high quality) and to reduce their disadvantages (patchy records), we generate a merged dataset obtained from four instruments deployed at a US continental site in which a nearly-continuous AOD record is found at two wavelengths (500 and 870 nm) with high quality and high temporal resolution (1-min) for a 21-yr period (1997-2018). The combined dataset addresses: (1) varying data quality and resolution mismatch of the individual AOD records, and (2) the uncertainty of the merged AOD and its relevance for user-specified needs. The generated dataset will be beneficial for a wide range of applications including aerosol-radiation interactions.

Lyme Disease Biosensors: A Potential Solution to a Diagnostic Dilemma.

Over the past four decades, Lyme disease has remained a virulent and pervasive illness, persisting throughout North America and many other regions of the world. Recent increases in illness in many countries has sparked a renewed interest in improved Lyme diagnostics. While current standards of diagnosis are acceptable for the late stages of the disease, it remains difficult to accurately diagnose early forms of the illness. In addition, current diagnostic methods tend to be relatively expensive and require a large degree of laboratory-based analysis. Biosensors represent the fusion of biological materials with chemical techniques to provide simple, inexpensive alternatives to traditional diagnostic methods. Lyme disease biosensors have the potential to better diagnose early stages of the illness and provide possible patients with an inexpensive, commercially available test. This review examines the current state of Lyme disease biosensing, with a focus on previous biosensor development and essential future considerations.

Nanostructured Cu2O Synthesized via Bipolar Electrochemistry.

Cuprous oxide (Cu2O) was synthesized for the first time via an open bipolar electrochemistry (BPE) approach and characterized in parallel with the commercially available material. As compared to the reference, Cu2O formed through a BPE reaction demonstrated a decrease in particle size; an increase in photocurrent; more efficient light scavenging; and structure-correlated changes in the flat band potential and charge carrier concentration. More importantly, as-synthesized oxides were all phase-pure, defect-free, and had an average crystallite size of 20 nm. Ultimately, this study demonstrates the impact of reaction conditions (e.g., applied potential, reaction time) on structure, morphology, surface chemistry, and photo-electrochemical activity of semiconducting oxides, and at the same time, the ability to maintain a green synthetic protocol and potentially create a scalable product. In the proposed BPE synthesis, we introduced a common food supplement (potassium gluconate) as a reducing and complexing agent, and as an electrolyte, allowing us to replace the more harmful reactants that are conventionally used in Cu2O production. In addition, in the BPE process very corrosive reactants, such as hydroxides and metal precursors (required for synthesis of oxides), are generated in situ in stoichiometric quantity, providing an alternative methodology to generate various nanostructured materials in high yields under mild conditions.

Novel polarization-sensitive micropulse lidar measurement technique.

Polarization-sensitive detection of elastic backscattered light is useful for detection of cloud phase and depolarizing aerosols. The U.S. Department of Energy's Atmospheric Radiation Measurement Program has deployed micropulse lidar (MPL) for over a decade, but without polarized detection. Adding an actively-controlled liquid crystal retarder provides the capability to identify depolarizing particles by alternately transmitting linearly and circularly polarized light. This represents a departure from established techniques, which transmit exclusively linear polarization or exclusively circular polarization. Mueller matrix calculations yield simple relationships between the well-known linear depolarization ratio delta(linear), the circular depolarization ratio delta(circ), and this MPL depolarization ratio delta(MPL).

Optical depth measurements by shadow-band radiometers and their uncertainties.

Shadow-band radiometers in general, and especially the Multi-Filter Rotating Shadow-band Radiometer (MFRSR), are widely used for atmospheric optical depth measurements. The major programs running MFRSR networks in the United States include the Department of Energy Atmospheric Radiation Measurement (ARM) Program, U.S. Department of Agriculture UV-B Monitoring and Research Program, National Oceanic and Atmospheric Administration Surface Radiation (SURFRAD) Network, and NASA Solar Irradiance Research Network (SIRN). We discuss a number of technical issues specific to shadow-band radiometers and their impact on the optical depth measurements. These problems include instrument tilt and misalignment, as well as some data processing artifacts. Techniques for data evaluation and automatic detection of some of these problems are described.