ACS Sensors最新文献

Lung cancer remains a global health concern, demanding the development of noninvasive, prompt, selective, and point-of-care diagnostic tools. Correspondingly, breath analysis using nanobiosensors has emerged as a promising noninvasive nose-on-chip technique for the early detection of lung cancer through monitoring diversified biomarkers such as volatile organic compounds/gases in exhaled breath. This comprehensive review summarizes the state-of-the-art breath-based lung cancer diagnosis employing chemiresistive-module nanobiosensors supported by theoretical findings. It unveils the fundamental mechanisms and biological basis of breath biomarker generation associated with lung cancer, technological advancements, and clinical implementation of nanobiosensor-based breath analysis. It explores the merits, challenges, and potential alternate solutions in implementing these nanobiosensors in clinical settings, including standardization, biocompatibility/toxicity analysis, green and sustainable technologies, life-cycle assessment, and scheming regulatory modalities. It highlights nanobiosensors' role in facilitating precise, real-time, and on-site detection of lung cancer through breath analysis, leading to improved patient outcomes, enhanced clinical management, and remote personalized monitoring. Additionally, integrating these biosensors with artificial intelligence, machine learning, Internet-of-things, bioinformatics, and omics technologies is discussed, providing insights into the prospects of intelligent nose-on-chip lung cancer sniffing nanobiosensors. Overall, this review consolidates knowledge on breathomic biosensor-based lung cancer screening, shedding light on its significance and potential applications in advancing state-of-the-art medical diagnostics to reduce the burden on hospitals and save human lives.

In this study, we introduce a new separation of phases-based activity reporter of kinase (SPARK) for AMP-activated kinase (AMPK), named AMPK-SPARK, which reports the AMPK activation by forming bright fluorescent clusters. Furthermore, we introduce a dual reporter system, named GCaMP-AMPK-SPARK, by incorporating a single-fluorescent protein (FP)-based Ca²⁺ biosensor, GCaMP6f, into our initial design, enabling simultaneous monitoring of Ca²⁺ levels and AMPK activity. This system offers the essential quality of information by single-channel fluorescence microscopy without the need for coexpression of different biosensors and elaborate filter layouts to overcome spectral limitations. We used AMPK-SPARK to map endogenous AMPK activity in different cell types and visualized the dynamics of AMPK activation in response to various stimuli. Using GCaMP-AMPK-SPARK, we revealed cell-to-cell heterogeneities in AMPK activation by Ca²⁺ mobilization. We anticipate that this dual reporter strategy can be employed to study the intricate interplays between different signaling networks and kinase activities.

Antithrombin (AT) deficiency in the extracorporeal circulation during cardiac surgery leads to uncontrolled inflammation and vascular damage in patients. AT levels decrease in sepsis, major trauma, extracorporeal membrane oxygenation, and eclampsia. Monitoring plasma AT levels facilitates the accurate restoration of AT to baseline values through precise supplementation. Traditional methods of chromogenic assay and enzyme-linked immunosorbent assay (ELISA) kits encounter challenges, such as interference, inconsistency, and delayed response times, making real-time, reliable antithrombin monitoring a clinical gap. To address this critical need, we develop a heparin-bead extraction enhanced fluoroGenic aptamer-thrombin composite reporter (HExGATOR) for the rapid, sensitive, and precise detection of functional AT in plasma. Our design employs thrombin-binding aptamers and a fluorescence "turn on" technology such that a signal is produced upon the interaction of AT with the otherwise "turned off" aptamer-thrombin complex. The prominent signal-background interference originating from plasma is remarkably diminished by using a heparin-bead solid-phase extraction of AT. We achieved highly sensitive and rapid detection of AT in 5 to 20 min with a limit of detection of 15.11 nM. This approach offers a promising alternative to traditional AT tests in clinical settings, potentially facilitating personalized anticoagulant therapy.

Breast cancer is a major challenge in the field of oncology, with around 2.3 million cases and around 670,000 deaths globally based on the GLOBOCAN 2022 data. Despite having advanced technologies, breast cancer remains the major type of cancer among women. This review highlights various collagen signatures and the role of different collagen types in breast tumor development, progression, and metastasis, along with the use of photoacoustic spectroscopy to offer insights into future cancer diagnostic applications without the need for surgery or other invasive techniques. Through mapping of the tumor microenvironment and spotlighting key components and their absorption wavelengths, we emphasize the need for extensive preclinical and clinical investigations.

Cardiovascular diseases (CVDs) are a predominant global health concern, accounting for over 17.9 million deaths in 2019, representing approximately 32% of all global fatalities. In North America and Europe, over a million adults undergo cardiac surgeries annually. Despite the benefits, such surgeries pose risks and require precise postsurgery monitoring. However, during the postdischarge period, where monitoring infrastructures are limited, continuous monitoring of vital signals is hindered. In this area, the introduction of implantable electronics is altering medical practices by enabling real-time and out-of-hospital monitoring of physiological signals and biological information postsurgery. The multimodal implantable bioelectronic platforms have the capability of continuous heart sensing and stimulation, in both postsurgery and out-of-hospital settings. Furthermore, with the emergence of machine learning algorithms into healthcare devices, next-generation implantables will benefit artificial intelligence (AI) and connectivity with skin-interfaced electronics to provide more precise and user-specific results. This Review outlines recent advancements in implantable bioelectronics and their utilization in cardiovascular health monitoring, highlighting their transformative deployment in sensing and stimulation to the heart toward reaching truly personalized healthcare platforms compatible with the Sustainable Development Goal 3.4 of the WHO 2030 observatory roadmap. This Review also discusses the challenges and future prospects of these devices.

This study introduces a novel deep learning framework for lung health evaluation using exhaled gas. The framework synergistically integrates pyramid pooling and a dual-encoder network, leveraging SHapley Additive exPlanations (SHAP) derived feature importance to enhance its predictive capability. The framework is specifically designed to effectively distinguish between smokers, individuals with chronic obstructive pulmonary disease (COPD), and control subjects. The pyramid pooling structure aggregates multilevel global information by pooling features at four scales. SHAP assesses feature importance from the eight sensors. Two encoder architectures handle different feature sets based on their importance, optimizing performance. Besides, the model's robustness is enhanced using the sliding window technique and white noise augmentation on the original data. In 5-fold cross-validation, the model achieved an average accuracy of 96.40%, surpassing that of a single encoder pyramid pooling model by 10.77%. Further optimization of filters in the transformer convolutional layer and pooling size in the pyramid module increased the accuracy to 98.46%. This study offers an efficient tool for identifying the effects of smoking and COPD, as well as a novel approach to utilizing deep learning technology to address complex biomedical issues.

Mapping of O₂ with luminescent sensors within intact animals is challenging due to attenuation of excitation and emission light caused by tissue absorption and scattering as well as interfering background fluorescence. Here we show the application of luminescent O₂ sensor nanoparticles (∼50-70 nm) composed of the O₂ indicator platinum(II) tetra(4-fluoro)phenyltetrabenzoporphyrin (PtTPTBPF) immobilized in poly(methyl methacrylate-co-methacrylic acid) (PMMA-MA). We injected the sensor nanoparticles into the gastrovascular system of intact colony fractions of reef-building tropical corals that harbor photosynthetic microalgae in their tissues. The sensor nanoparticles are excited by red LED light (617 nm) and emit in the near-infrared (780 nm), which enhances the transmission of excitation and emission light through biological materials. This enabled us to map the internal O₂ concentration via time-domain luminescence lifetime imaging through the outer tissue layers across several coral polyps in flowing seawater. After injection, nanoparticles dispersed within the coral tissue for several hours. While luminescence intensity imaging showed some local aggregation of sensor particles, lifetime imaging showed a more homogeneous O₂ distribution across a larger area of the coral colony. Local stimulation of symbiont photosynthesis in corals induced oxygenation of illuminated tissue areas and formation of lateral O₂ gradients toward surrounding respiring tissues, which were dissipated rapidly after the onset of darkness. Such measurements are key to improving our understanding of how corals regulate their internal chemical microenvironment and metabolic activity, and how they are affected by environmental stress such as ocean warming, acidification, and deoxygenation. Our experimental approach can also be adapted for in vivo O₂ imaging in other natural systems such as biofilms, plant and animal tissues, as well as in organoids and other cell constructs, where imaging internal O₂ conditions are relevant and challenging due to high optical density and background fluorescence.

Fluorescent protein-based pH biosensors enable the tracking of pH changes during protein trafficking and, in particular, exocytosis. The recent development of chemogenetic reporters combining synthetic fluorophores with self-labeling protein tags offers a versatile alternative to fluorescent proteins that combines the diversity of chemical probes and indicators with the selectivity of the genetic encoding. However, this hybrid protein labeling strategy does not avoid common drawbacks of organic fluorophores such as the risk of off-target signal due to unbound molecules. Here, we describe a novel fluorogenic and chemogenetic pH sensor based on a cell-permeable molecular pH indicator called pHluo-Halo-1, whose fluorescence can be locally activated in cells by reaction with HaloTag, ensuring excellent signal selectivity in wash-free imaging experiments. pHluo-Halo-1 was selected out of a series of four fluorogenic molecular rotor structures based on protein chromophore analogues. It displays good pH sensitivity with a pK_a of 6.3 well-suited to monitor pH variations during exocytosis and an excellent labeling selectivity in cells. It was applied to follow the secretion of CD63-HaloTag fusion proteins using TIRF microscopy. We anticipate that this strategy based on the combination of a tunable and chemically accessible fluorogenic probe with a well-established protein tag will open new possibilities for the development of versatile alternatives to fluorescent proteins for elucidating the dynamics and regulatory mechanisms of proteins in living cells.