Sensors & diagnostics最新文献

In this study, transparent humidity sensors and conducting electrodes (TCEs) were fabricated using a highly interconnected gold nanoparticle network (Au nanonetwork) via a simple solution approach. Here, the direct reduction of metal anions at lower temperatures (5 °C) followed by the addition of a non-polar solvent facilitates the cold welding of nanoparticles at junctions and yields an interconnected Au nanonetwork at the liquid–liquid interface. The formed Au nanonetwork is cautiously transferred to the desired flexible, stretchable, and transparent substrates for various applications. As the synthesis involves no capping agents, the prepared nanonetworks offer high conductivity without further chemical or thermal treatments. The fabricated Au nanonetwork is highly crystalline and thermally stable, with excellent mechanical robustness towards various deformations. Using an Au-1L (1-layer) nanonetwork, a highly transparent (>85%) humidity sensor is fabricated with short response and recovery times (1.1 s and 1.3 s). The Au-1L sensor is studied systematically for various humidity changes (40% to 90%) and breath conditions (normal/deep, hydrated/dehydrated, breathing/blowing, etc.) and exhibits high selectivity toward humidity. Notably, the sensing device offered a stable response for more than a year demonstrating its robustness for prolonged use.

The introduction of surface-enhanced Raman scattering (SERS) in lateral flow assays (LFA) has been recently exploited to increase the sensitivity and quantification capabilities of these rapid tests. Herein, we took advantage of a SERS–LFA combination to improve LFAs designed to test for P. gingivalis, a biomarker for oral health. We have demonstrated a limit of detection (LOD) < 10 ng mL⁻¹, which is within the range of concentration needed to monitor oral health. By comparison, conventional colorimetric LFAs achieve an LOD ≈ 100 ng mL⁻¹, generating a lower diagnostic sensitivity. To achieve this enhanced sensitivity, we optimized the materials used in the SERS–LFA, investigating nanostars (NS) differing in size and material composition and comparing them to commercial gold nanoparticles, as a benchmark. We found that large (56 nm) NSs with a silver coating were the most sensitive nanomaterials for SERS–LFA. To prove the applicability of this SERS–LFA to point-of-care (POC) settings, we tested the optimized LFA with a portable Raman system prototype designed to work on LFAs with 3D-printed cartridges and a line-shaped laser illumination. Using this prototype, we achieved the same LOD observed with the traditional benchtop Raman system. The use of a portable Raman system has brought the SERS–LFA technology closer to the POC use.

Circulating tumour cells (CTCs) are cancer cells shed from a primary tumour which intravasate into the blood stream and have the potential to extravasate into distant tissues, seeding metastatic lesions. As such, they can offer important insight into cancer progression with their presence generally associated with a poor prognosis. The detection and enumeration of CTCs is, therefore, critical to guiding clinical decisions during treatment and providing information on disease state. CTC isolation has been investigated using a plethora of methodologies, of which immunomagnetic capture and microfluidic size-based filtration are the most impactful to date. However, the isolation and detection of CTCs from whole blood comes with many technical barriers, such as those presented by the phenotypic heterogeneity of cell surface markers, with morphological similarity to healthy blood cells, and their low relative abundance (∼1 CTC/1 billion blood cells). At present, the majority of reported methods dissociate CTC isolation from detection, a workflow which undoubtedly contributes to loss from an already sparse population. This review focuses on developments wherein isolation and detection have been integrated into a single-step, microfluidic configuration, reducing CTC loss, increasing throughput, and enabling an on-chip CTC analysis with minimal operator intervention. Particular attention is given to immune-affinity, microfluidic CTC isolation, coupled to optical, physical, and electrochemical CTC detection (quantitative or otherwise).

Phosgene (carbonyl dichloride, COCl₂) is an extremely toxic and hazardous chemical warfare agent (CWA; schedule 3 substance) that poses significant threats to public safety and human well-being. Simultaneously, it is a commonly employed reagent in chemical synthesis in laboratories and industrial settings. Therefore, monitoring phosgene concentration levels is essential for handling them within the workplace and for safeguarding public security. Activity-based fluorescent probes are the most effective real-time detection methods currently used for the detection of CWAs. Reaction-based sensing offers excellent temporal and spatial resolution, minimal side effects, and quick response times. Recently, a plethora of reaction-based fluorescent probes have been designed for the detection of phosgene. This review provides an overview of the latest developments using amino-1,8-naphthalimide-based small-molecule fluorescent probes designed for phosgene detection/sensing. Additionally, we investigate the existing challenges and prospects in the field of reaction-based fluorescent probes for phosgene detection. Herein, various fluorescence sensors are categorized based on their reactions with phosgene, and each section highlights the reaction sites, sensing mechanisms, structure–function relationships, photophysical performances, and practical applications of these sensors. It is our aspiration that this review will provide valuable insights into the advancement of cutting-edge fluorescent probes tailored for phosgene detection and sensing.

The study systematically explores the connection between analyte particle size and the hot-spot in Au nanoparticle (NP) dimer systems. Contrary to the conventional understanding tied to localized surface plasmon resonance (LSPR), we show that depending on the analyte particle's size, the location to produce surface-enhanced Raman scattering (SERS), defined as effective hot-spot, is different from the gap based hot-spot, where the electric field reaches maximum intensity, and the corresponding resonant wavelength is also shifted significantly from LSPR wavelength. This effective hot-spot occurs primarily at the point where the Au NP contacts the analyte particle, covering a larger area than the traditional hot-spot and having a significantly smaller enhancement factor. Moreover, different effective hot-spots can be activated under various polarizations. The local electric field versus distance relationship decays significantly slower, complicating the interpretation of SERS spectra of large analyte particles. This complexity offers tunability, allowing for a more precise representation of unique molecular features of the analyte. Consequently, our findings demonstrate the necessity for SERS substrate design rules to be contingent on analyte particle size. Although interpreting SERS spectra is intricate, it can be refined to effectively capture distinctive molecular characteristics. These insights pave a new way to tailor SERS substrate design specifically catering to large analyte particles.

Optimizing paper immunoassay conditions for diagnostic accuracy is often achieved by tuning running conditions in a trial and error manner. We developed an approach to use machine learning (ML) in the optimization process, demonstrating it on a COVID-19 assay to detect IgG and IgM antibodies for both SARS CoV-2 spike and nucleocapsid proteins. The multiplexed test had a multicolor readout by using red and blue gold nanoparticles. Spike and nucleocapsid proteins were immobilized on a nitrocellulose strip at different locations, and the assay was run with red nanoparticles conjugated to anti-IgG and blue nanostars conjugated to anti-IgM. The spatial location of the signal indicated whether the antibody present was anti-spike or anti-nucleocapsid, and the test area color indicated the antibody type (IgG vs. IgM). Linear discriminant analysis (LDA) and ML were used to evaluate the test accuracy, and then used iteratively to modify running conditions (presence of quencher molecules, nanoparticle types, washes) until the test accuracy reached 100%. The resulting assay could be trained to distinguish between 9 different antibody profiles indicative of different disease cases (prior infection vs. vaccinated, early/mid/late stage post infection). Results show that supervised learning can accelerate test development, and that using the test as a selective array rather than a specific sensor could enable rapid immunoassays to obtain more complex information.

Magnetoelastic sensors, which are wirelessly activated and interrogated via magnetic fields, have gained popularity for monitoring physical parameters such as mass loading and stress. The functionalization of the sensor surface has facilitated the development of biosensing devices with the capacity to monitor chemical/biological quantities such as liquid pH, bacteria, and cell growth in biological environments. In this study, melt electrowriting (MEW) is used for the first time to integrate user-defined microstructures onto the surface of magnetoelastic sensors, aiming to enhance their cell growth monitoring performance. Specifically, MEW is used to define specific topographies on the sensor surface, which enable custom control of attachment, distribution, and alignment of cells along the sensor surface. This technique holds potential for engineering tissues with predefined physical structures, as well as for the development of advanced monitoring systems for tracking the growth of adherent cells in real-time.

Cytokines and acute-phase proteins are promising biomarkers for inflammatory disease. Despite its potential, early diagnosis based on these biomarkers remains challenging without technology enabling highly sensitive protein detection immediately after sample collection, because of the low abundance and short half-life of these proteins in bodily fluids. Enzyme-linked immunosorbent assay (ELISA) is a gold-standard method for such protein analysis, but it often requires labor-intensive and time-consuming sample handling and as well as a bulky benchtop platereader, limiting its utility in the clinical site. We developed a portable microfluidic immunoassay device capable of sensitive, quantitative, and high-throughput protein detection at point-of-need. The portable microfluidic system performs eight magnetic bead-based sandwich immunoassays from raw samples in 40 min. An innovative bead actuation strategy was incorporated into the system to automate multiple sample handling steps with minimal user intervention. The device enables quantitative protein analysis with picomolar sensitivity, as demonstrated using human samples spiked with interleukin-6 and C-reactive protein. The affinity-based assays are highly specific to the target without cross-reactivity. Therefore, we envision the reported device offering ultrasensitive and field-deployable immunoassay tests for timely and accurate clinical diagnosis.

Gadolinium (Gd)-based contrast agents (CAs) are widely used to enhance anatomical details in magnetic resonance imaging (MRI). Significant research has expanded the field of CAs into bioresponsive CAs by modulating the signal to image and monitor biochemical processes, such as pH. In this work, we introduce the modular, dynamic actuation mechanism of DNA-based nanostructures as a new way to modulate the MRI signal based on the rotational correlation time, τ_R. We combined a pH-responsive oligonucleotide (i-motif) and a clinical standard CA (Gd-DOTA) to develop a pH-responsive MRI CA. The i-motif folds into a quadruplex under acidic conditions and was incorporated onto gold nanoparticles (iM-GNP) to achieve increased relaxivity, r₁, compared to the unbound i-motif. In vitro, iM-GNP resulted in a significant increase in r₁ over a decreasing pH range (7.5–4.5) with a calculated pK_a = 5.88 ± 0.01 and a 16.7% change per 0.1 pH unit. In comparison, a control CA with a non-responsive DNA strand (T₃₃-GNP) did not show a significant change in r₁ over the same pH range. The iM-GNP was further evaluated in 20% human serum and demonstrated a 28.14 ± 11.2% increase in signal from neutral pH to acidic pH. This approach paves a path for novel programmable, dynamic DNA-based complexes for τ_R-modulated bioresponsive MRI CAs.

As a reversible and reusable fluorescent material possessing excellent durability for detecting and visualizing moisture and water droplets, we have designed and synthesized a PET (photo-induced electron transfer)-type fluorescent monomer KT-2 composed of anthracene fluorophore-(aminomethyl)-4-cyanophenylboronic acid pinacol ester (AminoMeCNPhenylBPin) with a 3-(triethoxysilyl)propyl group on the amino moiety and achieved preparation of drop-cast poly(KT-2-co-TEOS or GPTMS)silsesquioxane (SQ) films on glass substrates via the sol–gel reaction of KT-2 and tetraethoxysilane (TEOS) or (3-glycidyloxypropyl)trimethoxysilane (GPTMS). KT-2 exhibited enhancement of the fluorescence emission with the increase in water content in various solvents (less polar, polar, protic, and aprotic solvents) due to the formation of the PET inactive (fluorescent) species KT-2W by the interaction with water molecules. The detection limit (DL) of KT-2 for water in the low water content region below 1.0 wt% in the solvents was 0.015–0.020 wt%, indicating that KT-2 can act as a PET-type fluorescent sensor for a trace amount of water in solvents. Indeed, it was found that the poly(KT-2-co-TEOS or GPTMS)SQ films exhibited a reversible fluorescence off–on switching between the PET active state under a dry process and the PET inactive state under a wet process. Actually, the poly(KT-2-co-TEOS or GPTMS)SQ films initially exhibited a weak blue emission under a dry process but visually apparent blue emission upon exposure to moisture (under a wet process). In particular, the poly(KT-2-co-TEOS)SQ film displays superior reversible switching performance with a huge change in the fluorescence intensity in the dry–wet process compared with the poly(KT-2-co-GPTMS)SQ film. This result is attributed to the fact based on the measurements of water contact angles and the roughness on the film surfaces that the poly(KT-2-co-TEOS)SQ film with a pitted uneven structure has large amounts of KT-2 units on the surface which make it possible to form the PET inactive KT-2W structure by the interaction with water molecules. Herein, we propose that PET-type fluorescent sensor-immobilized glass substrates are one of the most promising and convenient functional dye materials based on a fluorescence off–on switching system for detecting and visualizing moisture and water droplets.