Sensors & diagnostics最新文献

Iron, the most abundant transition metal in the body, regulates cellular function but can be harmful in excess, leading to reactive oxygen species production and cellular damage. Intracellular Fe²⁺ exerts a significant impact on cellular function, potentially contributing to various critical diseases. To address this, detection methods need high selectivity, sensitivity, and real-time monitoring capabilities, essential for comprehending disease progression. This necessitates advancements beyond conventional detection approaches. Frataxin, a crucial mitochondrial protein, is indispensable for sustaining life, contributing not only to iron metabolism but also to the formation of iron–sulfur clusters critical for cellular function. Its deficiency is implicated in neurodegenerative diseases. We have developed a nanosensor, based on fluorescence resonance energy transfer (FRET), designed to probe iron efflux mechanisms and facilitate dynamic monitoring of iron concentration and its spatial distribution within living cells. To construct this nanosensor, we strategically positioned CyaY, a bacterial frataxin ortholog, between ECFP and Venus, forming a FRET pair. This innovative nanosensor, designated as FeOS (iron optical sensor), demonstrates exceptional selectivity for iron and maintains stability under physiological pH conditions. Additionally, we engineered three mutant variants: I17C, AD10-I17C, and D76H, with A10D-I17C displaying the highest affinity for iron and a broad detection range. The distinguishing feature of this sensor is that it is genetically encoded, facilitating real-time detection of iron levels within living cells.

In many gas sensing tasks, we simply wish to become aware of gas compositions that deviate from normal, “business-as-usual” conditions. We provide a methodology, illustrated by example, to computationally predict the performance of a gas sensor array design for detecting anomalous gas compositions. Specifically, we consider a sensor array of two zeolitic imidazolate frameworks (ZIFs) as gravimetric sensing elements for detecting anomalous gas compositions in a fruit ripening room. First, we define the probability distribution of the concentrations of the key gas species (CO₂, C₂H₄, H₂O) we expect to encounter under normal conditions. Next, we construct a thermodynamic model to predict gas adsorption in the ZIF sensing elements in response to these gas compositions. Then, we generate a synthetic training data set of sensor array responses to “normal” gas compositions. Finally, we train a support vector data description to flag anomalous sensor array responses and test its false alarm and missed-anomaly rates under conceived anomalies. We find the performance of the anomaly detector diminishes with (i) greater variance in humidity, which can mask CO₂ and C₂H₄ anomalies or cause false alarms, (ii) higher levels of noise emanating from the transducers, and (iii) smaller training data sets. Our exploratory study is a step towards computational design of gas sensor arrays for anomaly detection.

Microfluidic chips designed to measure viscosity with extremely small amounts of liquids are expected to examine biological fluids, such as for the prediction of disease states and stress assessment, and for the evaluation of the physical properties of novel synthetic materials. However, these devices typically require sample volumes of several tens of μL or more, which has limitations when collecting biological samples from individuals nearly non-invasively. In this study, we fabricated a flow channel on a nonwoven fabric substrate with tailored hydrophilic and hydrophobic properties to enable viscosity measurements with the small-volume flow of aqueous solutions, such as 3 μL of saline. By measuring the electrical conductivity of the liquid using comb-shaped printed electrodes in contact with the flow path, we quantified the time and distance of liquid flow driven by capillary action to estimate solution viscosity. Using a mixture of glycerol and saline solution with varying viscosities, while maintaining a constant ion concentration, we demonstrated the capability to assess the relative viscosity of solutions. This was achieved by evaluating the correlation coefficient between the flow time and distance, and the net electrical conductivity, which is influenced by the viscosity and ion concentration of the solutions. This study lays the groundwork for developing a low-cost technique to measure the viscosity of solutions with a few μL, offering potential for routine health monitoring and disease prevention.

Effective monitoring of ocular drugs is crucial for personalized medicine and improving drug delivery efficacy. However, traditional methods face difficulties in detecting low drug concentrations in small volumes of ocular fluid, such as that found on the ocular surface. In this study, we used capture-SELEX to select aptamers for two commonly used ocular drugs, timolol maleate and atropine. We identified TMJ-1 and AT-1 aptamers with binding affinities of 3.4 μM timolol maleate and 10 μM atropine, respectively. Our label-free TMJ-1 biosensor using thioflavin T staining achieved a limit of detection (LOD) of 0.3 μM for timolol maleate. The AT-1 biosensor showed an LOD of 1 μM for atropine, and exhibited a 10-fold higher sensitivity compared to UV-visible spectroscopy. Future research in this area holds promise in enhancing drug delivery monitoring and improving the treatment of ocular diseases.

The constant need for cancer diagnosis in the early stages drives the development of contrast agents and imaging methods. Imaging agents have important roles in monitoring the progression and metastasis of cancers. Antibodies as biomolecules in conjugation with nanoparticles, radioisotopes, and drugs have been used as biomarkers for the early diagnosis/therapy of cancers due to their serum stability, affinity, and specificity. While antibodies are commonly used as nuclear medicine biomarkers, antibody-based contrast agent platforms have recently gained attention in X-ray computed tomography (CT) and magnetic resonance imaging (MRI). The developing antibody-based contrast agents have revolutionized cancer imaging techniques, particularly through MRI. Despite the promising advancements, some challenges and limitations need to be addressed for the extensive applications of these agents. Ongoing research is focused on overcoming challenges and limitations to enhance the efficiency and accuracy of these imaging methods. With continued advancements, antibody-based contrast agents hold immense potential in the early diagnosis and treatment of cancer. In this review, we summarize and categorize the recent progress in targeted imaging using antibody-based contrast agents by MRI and CT modalities.

Highly durable, stretchable, sensitive and biocompatible wearable strain sensors are crucial for healthcare, sports, and robotic applications. While strain sensor designs, fabrication and testing methods have been widely discussed by researchers, not many have discussed sensor improvements via implementing designs and protection layers that make the sensor more resilient. This paper will focus on sensor designs (straight line, U-shape, serpentine, and kirigami) and material selection that can provide better performance. Theoretical equations and calculations to indicate how the design shapes contribute to providing better performance are also included. An important aspect which is not often explored is having encapsulation layers which can significantly reduce the formation of cracks when the sensor is subjected to mechanical stress and bending. This review will include post-fabrication steps that are necessary to incorporate protection layers for wearable sensors. Due to the curvilinear shapes of wearable sensors that often need to be in close contact with human skin, reliability and durability testing often differs greatly from that of traditional strain sensors. Recent techniques for performance evaluation specific to wearable sensors such as cyclic stretching, bending, stretch till failure, washability, signal latency, and tensile tests were also discussed in detail. This includes experimental setup and duration of testing and its significance was described. To ensure device safety for the user, biocompatibility assessments need to be made. In this review, cytotoxicity test methods such as trypan blue, cell proliferation and MTT assay were compared and evaluated. By consolidating recent developments, this paper aims to provide researchers and practitioners with a comprehensive understanding of the advancements, and future directions in this rapidly evolving field.

Electrochemical aptamer-based (E-AB) sensors achieve detection and quantitation of biomedically relevant targets such as small molecule drugs and protein biomarkers in biological samples. E-ABs are usually fabricated on commercially available macroelectrodes which, although functional for rapid sensor prototyping, can be costly and are not compatible with the microliter sample volumes typically available in biorepositories for clinical validation studies. Seeking to develop a multi-point sensing platform for sensor validation in sample volumes characteristic of clinical studies, we report a protocol for in-house assembly of 3D-printed E-ABs. We employed a commercially available 3D stereolithographic printer (FormLabs, $5k USD) for electrochemical cell fabrication and directly embedded electrodes within the 3D-printed cell structure. This approach offers a reproducible and reusable electrode fabrication process resulting in four independent and simultaneous measurements for statistically weighted results. We demonstrate compatibility with aptamer sequences binding antibiotics and antineoplastic agents. We also demonstrate a proof-of-concept validation of serum vancomycin measurements using clinical samples. Our results demonstrate that 3D-printing can be used in conjunction with E-ABs for accessible, rapid, and statistically meaningful validation of E-AB sensors in biological matrices.

Monitoring of creatinine in human fluid has attracted considerable attention owing to the potential for diagnosis of chronic kidney disease. However, the detection of creatinine has been difficult owing to its electrochemical and optical inertness. In this approach, a highly selective and sensitive electrochemiluminescence (ECL) strategy based on homogeneous carbon quantum dots (CQDs) for the detection of creatinine was introduced. A copper(II) picrate complex was added at the surface of electrode to improve the selectivity of the sensor significantly by the formation of a Janovsky complex. A multi-pulse amperometric technique was applied as a very fast and reliable method for quantitative determination of creatinine. The calibration curve was acquired with a linear range from 1.0 × 10⁻⁸ to 1 × 10⁻⁵ M with a low detection limit of 8.7 × 10⁻⁹ M. The proposed creatinine sensing platform is experimentally very simple and shows high selectivity with a broad linear range of detection. Furthermore, the presented method can determine creatinine in real samples with excellent recoveries.

17β-Estradiol (E2) is one of the typical endocrine-disrupting compounds (EDCs), which plays a major role in facilitating the growth and regulating the balance of the human endocrine system. E2 contamination can cause environmental and health risks as E2 exposure can interfere with the endocrine system by binding to estrogen receptors. It is imperative to develop sensitive methods for E2 detection. Herein we developed a competitive enzyme-linked aptamer assay for E2 detection by using a newly reported high-affinity DNA aptamer as an affinity ligand. The complementary DNA (cDNA) of the anti-E2 aptamer is conjugated on a microplate. Horseradish peroxidase (HRP) is labeled on the aptamer probe. In the absence of E2, HRP-labeled aptamer is captured by cDNA, and HRP catalyzes the substrate into a product, generating an absorbance signal or chemiluminescence signal. In the presence of E2, E2 binds with the aptamer, causing displacement of HRP-labeled aptamer from the microplate and a decrease in signals. In absorbance-analysis mode, the detection limit of E2 reached 0.2 nmol L⁻¹ with a dynamic range from 0.2 nmol L⁻¹ to 20 μmol L⁻¹. In chemiluminescenceanalysis mode, this method enabled the quantification of E2 at 50 pmol L⁻¹, with a dynamic range from 50 pmol L⁻¹ to 50 μmol L⁻¹. This method could also detect E2 spiked in lake water samples, showing promise in practical applications.

Contact lenses offer a simple, cost-effective, and non-invasive method for in situ real-time analysis of various biomarkers. Electro-chemical sensors are integrated into contact lenses for analysis of various biomarkers. However, they suffer from rigid electronic components and connections, leading to eye irritation and biomarker concentration deviation. Here, a flexible and microfluidic integrated paper-based contact lens for colorimetric analysis of glucose was implemented. Facilitating a three-dimensional (3D) printer for lens fabrication eliminates cumbersome cleanroom processes and provides a simple, batch compatible process. Due to the capillary force of the filter paper, the sample was routed to detection chambers inside microchannels, and it allowed further colorimetric detection. The paper-embedded microfluidic contact lens successfully detects glucose down to 2 mM within ∼10 s. The small dimension of the microfluidic system enables detection of glucose levels as low as 5 μl. The results show the potential of the presented approach to analyze glucose concentration in a rapid manner. It is demonstrated that the fabricated contact lens can successfully detect glucose levels of diabetic patients.