Biosensors and Bioelectronics: X最新文献

Over the last decade, a significant paradigm shift has been observed towards leveraging less invasive biological fluids—such as skin interstitial fluid (ISF), sweat, tears, and saliva—for health monitoring. This evolution seeks to transcend traditional, invasive blood-based methods, offering a more accessible approach to health monitoring for non-specialized personnel. Skin ISF, with its profound resemblance to blood, emerges as a pivotal medium for the real-time, minimally invasive tracking of a broad spectrum of biomarkers, thus becoming an invaluable asset for correlating with blood-based data. Our exploration delves deeply into the development of wearable molecular biosensors, spotlighting dermal sensors for their pivotal roles across both clinical and everyday health monitoring scenarios and underscoring their contributions to the holistic One Health initiative. In bringing forward the myriad challenges that permeate this field, we also project future directions, notably the potential of skin ISF as a promising candidate for continuous health tracking.

Moreover, this paper aims to catalyse further exploration and innovation by presenting a curated selection of seminal technological advancements. Amidst the saturated landscape of analytical literature on translational challenges, our approach distinctly seeks to highlight recent developments. In attracting a wider spectrum of research groups to this versatile domain, we endeavour to broaden the collective understanding of its trajectory and potential, mapping the evolution of wearable biosensor technology. This strategy not only illuminates the transformative impact of wearable biosensors in reshaping health diagnostics and personalized medicine but also fosters increased participation and progress within the field. Distinct from recent manuscripts in this domain, our review serves as a distillation of key concepts, elucidating pivotal papers that mark the latest advancements in wearable sensors. Through presenting a curated collection of landmark studies and offering our perspectives on the challenges and forward paths, this paper seeks to guide new entrants in the area. We delineate a division between wearable epidermal and subdermal sensors—focusing on the latter as the future frontier—thereby establishing a unique discourse within the ongoing narrative on wearable sensing technologies.

Extracellular histone proteins in the blood indicate a heightened risk of morbidity after trauma or in major illnesses such as sepsis. We present the development of an aptasensor for histone detection with an extended gate field-effect transistor (EGFET) configuration, which benefits from low power consumption, rapid response, and compatibility with miniaturized gold electrodes. Histones have a high isoelectric point and charge density, which cause them to physically adsorb to non-specific elements of the sensor that have available electrostatic charges. To combat this, the sensing surface is formed with a thiol-modified, high-affinity and histone-specific RNA aptamer sequence and by co-immobilizing with poly(ethylene glycol) methyl ether thiol (PEG) as a blocking agent. Surface plasmon resonance (SPR) is used to analyze aptamer and PEG immobilization strategies, confirm histone binding, and calculate kinetic binding constants. Through comparison of different blocking agents and time-dependent preparation, the ideal equilibrium dissociation constant (K_D) is estimated to be below 200 pM, which is the upper range of extracellular histone concentrations in critically ill patients with high mortality. The EGFET sensitivity of the optimized aptasensor is 6.65 mV/decade concentration change for histone H4 with a physiologically relevant 5 pM limit of detection. Selectivity tests with 100 nM bovine serum albumin (BSA) demonstrate a signal response that is 13-fold smaller than for histones. This EGFET aptasensor platform is suitable for future point-of-care monitoring of histone levels in critically ill patients, thus permitting the early detection of increased risk and the need for more aggressive interventional measures to prevent mortality.

This article has tried to provide an overview of the most sophisticated microfluidic biosensors for identifying nucleic acids and proteins at the site of treatment. Microfluidics, which also automates sample preparation and reduces processing time and reagent consumption, enables the analysis of small sample quantities. Microfluidics and biosensor technologies collaborate to provide diagnostics at the point of care with high throughput analysis, portability, and disposability. The high sensitivity and selectivity requirements, false response errors, and integration with other essential modules are some of the challenges posed by this merger. The broad categories of protein-based and DNA-based biosensor technology are covered in this review. Also, recent advancements in coupling the biosensors to microfluidics, the main challenges and potential solutions in deploying microfluidic biosensors for point-of-care diagnostics, and the most recent developments in these areas have been discussed.

PD1/PD-L1 checkpoint inhibitors are at the forefront of cancer immunotherapies. However, the overall response rate remains only 10–30%. Even among initial responders, drug resistance often occurs, which can lead to prolonged use of a futile therapy in the race with the fatal disease. It would be ideal to closely monitor key indicators of patients’ immune responsiveness, such as circulating PD-L1 levels. Traditional PD-L1 detection methods, such as ELISA, are limited in sensitivity and rely on core lab facilities, preventing their use for the regular monitoring. Electrochemical sensors exist as an attractive candidate for point-of-care tool, yet, streamlining multiple processes in a single platform remains a challenge. To overcome this challenge, this work integrated electrochemical sensor arrays into a digital microfluidic device to combine their distinct merits, so that soluble PD-L1 (sPD-L1) molecules can be rapidly detected in a programmed and automated manner. This new platform featured microscale electrochemical sensor arrays modified with electrically conductive 3D matrix, and can detect as low as 1 pg/mL sPD-L1 with high specificity. The sensors also have desired repeatability and can obtain reproducible results on different days. To demonstrate the functionality of the device to process more complex biofluids, we used the device to detect sPD-L1 molecules secreted by human breast cancer cell line in culture media directly and observed 2X increase in signal compared with control experiment. This novel platform holds promise for the close monitoring of sPD-L1 level in human physiological fluids to evaluate the efficacy of PD-1/PD-L1 immunotherapy.

Human adenosine deaminase acting on RNA1 (ADAR1) is an adenosine-to-inosine (A-to-I) RNA-editing enzyme involved in various types of cancer progression. ADAR1 has emerged as a novel prognostic biomarker for cancer. This study describes the application of a newly identified 70-nt DNA aptamer (Apt38483) against ADAR1 to develop a portable and simple electrochemical biosensor platform for the rapid and sensitive detection of ADAR1 in cell lysates. We selected an ADAR1-specific DNA aptamer from a randomized 70-nt single-stranded DNA library using a competitive in vitro selection method. ADAR1 in the cell lysate was sandwiched onto a bare carbon working electrode of an electro-chemically printed chip between the ADAR1 antibody and gold nanoparticles (40 nm) conjugated with Apt38483, followed by electrochemical analysis using differential pulse voltammetry (DPV) for sensor demonstration. A highly sensitive change in current was observed for as little as 0.53 nM ADAR1 in human embryonic kidney cell lysate. Thus, the merging of a novel DNA aptamer probe for ADAR1 with an electrochemical transduction method enabled the development of a simple, low-cost, and rapid method for the direct measurement of ADAR1 in cell lysates and indicated great potential for the development of an ADAR1 analysis platform, which would be useful in cancer prognosis.

Within this study we report a non-toxic nanomaterial suitable for Photodynamic Therapy (PDT) under hypoxic conditions. PDT relies on the production of reactive oxygen and nitrogen species that can lead to cancer cells death. Currently, PDT is limited by: the development of efficient photosensitizers that can produce these radicals in situ; and the oxygen level requirement. The produced Carbon Dots (Cdots) successfully destroy human melanoma cancer cells upon 5 min irradiation using 450 nm wavelength due to the in situ production of NO•. As such, this nanophotosensitizer is applicable regardless of the cells molecular oxygen levels. Additionally, this nanomaterial acts as a scavenging nanozyme biosensor allowing to follow-up, in situ, the released NO• concentration, thereby offering a tight control over the NO• concentration in real-time and, its maintenance within the therapeutic window. Hence, this work offers a novel theranostic and NO• scavenging nanozyme biosensing nanoplatform that allows high control for hypoxic-PDT cancer application even in low doses and with 5 min irradiation.

Metal-organic frameworks (MOFs) are an emerging class of nanomaterials with immense biomedical potential for their unique interactions with biological and organic materials. In this work, we select two candidate two-dimensional (2D) MOF systems based on Fe³⁺ and Ni²⁺ metal centers and 2-aminoterephthalate acid ligand (Fe-MOF and Ni-MOF) and evaluate their performance as an active interface for study of cell-interactions. 2D Fe-MOF and Ni-MOF were synthesized onto hydroxyl-modified gold and glass substrates using a layer-by-layer liquid-phase-epitaxy (LbL-LPE) growth at room temperature and used as active substrates (Fe-MOF/glass, Fe-MOF/Au, Ni-MOF/glass and Ni-MOF/Au, respectively) for MTT cell-proliferation and reactive oxygen species tests using the PC-12 cell-line in order to investigate the biocompatibility. Immunostaining and morphological analyses of PC-12 cells on MOF interfaces suggested a stronger cell-substrate interaction in comparison to glass and were further characterized using the Electrical Cell-substrate Impedance Sensing (ECIS) technique, here for the first time, employed to study cell attachment, spreading and proliferation on 2D Fe-MOF. The 2D Fe-MOF showed superior long-term stability in cell culture medium by recording impedance over 24 h, crucial to monitor cell-dynamics at a solid-liquid interface. A significant increase of interfacial impedance was observed in ECIS, due to PC-12 cells adhering onto 2D Fe-MOF, which was also confirmed by the focused ion beam etching followed by scanning electron microscopy. Our novel findings, therefore, suggest 2D MOFs as highly suitable platform for the study of cell-related interactions using electrical techniques and potentially pave the way for future use of MOFs for bioelectronics and biosensor applications.

In neurophysiological recording, reducing electrode impedance is crucial for enhancing the signal-to-noise ratio and achieving the desired spatial resolution. This study presents an approach to improve the performance of Au/Cr/glass electrodes by incorporating synthesized gold nanosheets without the need for additional adhesive material. We characterized the performance of the modified electrodes using electrochemical impedance spectroscopy and equivalent circuit analysis. Our findings showed an 81% reduction in mean impedance for the modified electrode, which was 0.85 kΩ at 1 kHz, compared to the unmodified electrode at 4.5 kΩ, an improvement attributed to the higher effective surface area of the modified electrode. Additionally, Scanning electron microscopy observations of PC12 cells cultured on the modified electrodes indicated favorable cell elongation and interaction with the rough surface. Stability studies indicated acceptable performance of the modified electrodes in solution environments. These results suggest that surface modification of electrodes with gold nanosheets could be a promising strategy for enhancing neural interface applications.

Sensitive on-site virus detection is a requirement for timely action against the spread of airborne infection since ultra-low in-air viral concentrations can readily infect individuals when inhaled. Here, we consider a fieldable biosensing process that incorporates a fast RNA enrichment step in order to concentrate viral RNA in a small volume prior to RT-qPCR. The enrichment approach uses electrophoresis in an RT-qPCR-compatible buffer, and allows for concentration of RNA by nearly 5-fold within only 10 min. In order to place this performance into context, we analyzed the minimum detectable concentration of a low-cost, fieldable, biosensing process that uses electrostatic precipitation for air sampling, heating for viral RNA extraction, and then RNA enrichment, followed by RT-qPCR. With enrichment, we estimated an in-air concentration of 5,654 genome copies (gc)/m${}^3$ with a 100% detection rate and an in-air concentration of 4,221 gc/m${}^3$ with a 78.6% detection rate. Given that the concentrations of common viruses, such as influenza and SARS-CoV-2, in several indoor spaces are between 5,800 and 37,000 gc/m${}^3$, we conclude that enrichment allows a detection that is sufficiently sensitive for practical applications.

In this research, we proposed an asymmetric rectangular slotted biosensor using photonic crystal fiber (PCF), which is subject to surface plasmon resonance (SPR). The proposed sensor utilizes only seven air holes, ensuring better fabrication feasibility and their properties are determined through finite element method (FEM)-based numerical analysis. To simplify the manufacturing process and ensure chemical stability, chemically impermeable gold (Au) strips are employed around the perimeter of the structure as the plasmonic material. With effective structural parameters, the maximum amplitude sensitivity for the proposed sensor is 663.13 ${\text{RIU}}^{-1}$, the maximum wavelength sensitivity is 204,000 nm/RIU, and the maximum wavelength resolution is 4.90 × 10⁻⁷ $\text{RIU}$ for the y-polarized mode. It also shows a high linearity of 0.9849. For the detection of sucrose content, it has a maximum wavelength sensitivity of 207070.71 nm/RIU and a maximum amplitude sensitivity of 662.80 ${\text{RIU}}^{-1}$. The newly introduced sensor can detect the refractive index (RI) of various analytes across a broad spectrum, ranging from 1.28 to 1.41. This extensive detection range allows the sensor to precisely measure sucrose concentrations up to 40%. This broad range enables the analysis of various analytes like sucrose, viruses, cancer cells, proteins, and numerous others.