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Accurate monitoring of small molecules and precise characterization of the secretory ability of neurons are essential for effective diagnosis of neurological diseases. However, existing technologies for monitoring small molecules only provide approximate results. Plasmonic‐based biosensors are a potential solution in this biological application. Nevertheless, optical sensing nanoparticles require precise control of interparticle distance, particle shape and morphology, which can be challenging. This article discovers that the trapping of small molecules to aptamers induces a conformational change that alters the nanostructure of irregularly shaped Au nanoclusters (NCs) and aptamers due to the strong structure‐property relationships of Au NC‐aptamers. This change can be detected via resonance Rayleigh scattering (RRS) intensity in the dark‐field. This new technology overcomes the challenges of precise control of individual nanoparticles and the difficulty of small spectral peak shifts. The Au NC‐aptamers sensing device has a detection limit of 0.112 pm for dopamine, and this work detects 0.226 pm of dopamine surrounding a single epileptic neuron in polarization, which is more than those of healthy neurons. Overall, this easy‐to‐fabricate Au NC‐aptamers‐based technology has a high potential for monitoring small molecules and determining the secretory ability of single neurons, which is not possible using traditional technologies. [ABSTRACT FROM AUTHOR]

Knowledge of the antibody response to the third dose of inactivated SARS-CoV-2 vaccines is crucial because it is the subject of one of the largest global vaccination programs. This study integrated microsampling with optical biosensors to profile neutralizing antibodies (NAbs) in fifteen vaccinated healthy donors, followed by the application of machine learning to predict antibody response at given timepoints. Over a nine-month duration, microsampling and venipuncture were conducted at seven individual timepoints. A refined iteration of a fiber optic biolayer interferometry (FO-BLI) biosensor was designed, enabling rapid multiplexed biosensing of the NAbs of both wild-type and Omicron SARS-CoV-2 variants in minutes. Findings revealed a strong correlation (Pearson r of 0.919, specificity of 100%) between wild-type variant NAb levels in microsamples and sera. Following the third dose, sera NAb levels of the wild-type variant increased 2.9-fold after seven days and 3.3-fold within a month, subsequently waning and becoming undetectable after three months. Considerable but incomplete evasion of the latest Omicron subvariants from booster vaccine-elicited NAbs was confirmed, although a higher number of binding antibodies (BAbs) was identified by another rapid FO-BLI biosensor in minutes. Significantly, FO-BLI highly correlated with a pseudovirus neutralization assay in identifying neutralizing capacities (Pearson r of 0.983). Additionally, machine learning demonstrated exceptional accuracy in predicting antibody levels, with an error level of <5% for both NAbs and BAbs across multiple timepoints. Microsample-driven biosensing enables individuals to access their results within hours of self-collection, while precise models could guide personalized vaccination strategies. The technology's innate adaptability means it has the potential for effective translation in disease prevention and vaccine development. [ABSTRACT FROM AUTHOR]

Superantigens are virulence factors secreted by microorganisms that can cause various immune diseases, such as overactivating the immune system, resulting in cytokine storms, rheumatoid arthritis, and multiple sclerosis. Some studies have demonstrated that superantigens do not require intracellular processing and instated bind as intact proteins to the antigen-binding groove of major histocompatibility complex II on antigen-presenting cells, resulting in the activation of T cells with different T-cell receptor Vβ and subsequent overstimulation. To combat superantigen-mediated diseases, researchers have employed different approaches, such as antibodies and simulated peptides. However, due to the complex nature of superantigens, these approaches have not been entirely successful in achieving optimal therapeutic outcomes. CD28 interacts with members of the B7 molecule family to activate T cells. Its mimicking peptide has been suggested as a potential candidate to block superantigens, but it can lead to reduced T-cell activity while increasing the host's infection risk. Thus, this review focuses on the use of drug delivery methods to accurately target and block superantigens, while reducing the adverse effects associated with CD28 mimic peptides. We believe that this method has the potential to provide an effective and safe therapeutic strategy for superantigen-mediated diseases. [ABSTRACT FROM AUTHOR]

The effective control of infectious diseases, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, depends on the availability of rapid and accurate monitoring techniques. However, conventional SARS-CoV-2 detection technologies do not support continuous self-detection and may lead to cross-infection when utilized in medical institutions. In this study, we introduce a prototype of a mask biosensor designed for the long-term collection and self-detection of SARS-CoV-2. The biosensor utilizes the average resonance Rayleigh scattering intensity of Au nanocluster-aptamers. The inter-mask surface serves as a medium for the long-term collection and concentration enhancement of SARS-CoV-2, while the heterogeneous-nucleation nanoclusters (NCs) contribute to the exceptional stability of Au NCs for up to 48 h, facilitated by the adhesion of Ti NCs. Additionally, the biosensors based on Au NC-aptamers exhibited high sensitivity for up to 1 h. Moreover, through the implementation of a support vector machine classifier, a significant number of point signals can be collected and differentiated, leading to improved biosensor accuracy. These biosensors offer a complementary wearable device-based method for diagnosing SARS-CoV-2, with a limit of detection of 103 copies. Given their flexibility, the proposed biosensors possess tremendous potential for the continuous collection and sensitive self-detection of SARS-CoV-2 variants and other infectious pathogens. [ABSTRACT FROM AUTHOR]

The recent COVID-19 pandemic has caused tremendous damage to the social economy and people's health. Some major issues fighting COVID-19 include early and accurate diagnosis and the shortage of ventilator machines for critical patients. In this manuscript, we describe a novel solution to deal with COVID-19: portable biosensing and wearable photoacoustic imaging for early and accurate diagnosis of infection and magnetic neuromodulation or minimally invasive electrical stimulation to replace traditional ventilation. The solution is a closed-loop system in that the three modules are integrated together and form a loop to cover all-phase strategies for fighting COVID-19. The proposed technique can guarantee ubiquitous and onsite detection, and an electrical hypoglossal stimulator can be more effective in helping severe patients and reducing complications caused by ventilators. [ABSTRACT FROM AUTHOR]

Tests for SARS-CoV-2 are crucial for the mass surveillance of the incidence of infection. The long waiting time for classic nucleic acid test results highlights the importance of developing alternative rapid biosensing methods. Herein, we propose a fiber-optic biolayer interferometry-based biosensor (FO-BLI) to detect SARS-CoV-2 spike proteins, extracellular domain (ECD), and receptor-binding domain (RBD) in artificial samples in 13 min. The FO-BLI biosensor utilized an antibody pair to capture and detect the spike proteins. The secondary antibody conjugated with horseradish peroxidase (HRP) reacted with the enzyme substrate for signal amplification. Two types of substrates, 3,3′-diaminobenzidine (DAB) and an advanced 3-Amino-9-ethylcarbazole (i.e., AMEC), were applied to evaluate their capabilities in enhancing signals and reaching high sensitivity. After careful comparison, the AMEC-based FO-BLI biosensor showed better assay performance, which detected ECD at a concentration of 32–720 pM and RBD of 12.5–400 pM in artificial saliva and serum, respectively. The limit of detection (LoD) for SARS-CoV-2 ECD and RBD was defined to be 36 pM and 12.5 pM, respectively. Morphology of the metal precipitates generated by the AMEC-HRP reaction in the fiber tips was observed using field emission scanning electron microscopy (SEM). Collectively, the developed FO-BLI biosensor has the potential to rapidly detect SARS-CoV-2 antigens and provide guidance for "sample-collect and result-out on-site" mode. [ABSTRACT FROM AUTHOR]

Cost-effective, rapid, and sensitive detection of SARS-CoV-2, in high-throughput, is crucial in controlling the COVID-19 epidemic. In this study, we proposed a vertical microcavity and localized surface plasmon resonance hybrid biosensor for SARS-CoV-2 detection in artificial saliva and assessed its efficacy. The proposed biosensor monitors the valley shifts in the reflectance spectrum, as induced by changes in the refractive index within the proximity of the sensor surface. A low-cost and fast method was developed to form nanoporous gold (NPG) with different surface morphologies on the vertical microcavity wafer, followed by immobilization with the SARS-CoV-2 antibody for capturing the virus. Modeling and simulation were conducted to optimize the microcavity structure and the NPG parameters. Simulation results revealed that NPG-deposited sensors performed better in resonance quality and in sensitivity compared to gold-deposited and pure microcavity sensors. The experiment confirmed the effect of NPG surface morphology on the biosensor sensitivity as demonstrated by simulation. Pre-clinical validation revealed that 40% porosity led to the highest sensitivity for SARS-CoV-2 pseudovirus at 319 copies/mL in artificial saliva. The proposed automatic biosensing system delivered the results of 100 samples within 30 min, demonstrating its potential for on-site coronavirus detection with sufficient sensitivity. [ABSTRACT FROM AUTHOR]

Functional synapses in the central nervous system depend on a chemical signal exchange process that involves neurotransmitter delivery between neurons and receptor cells in the neuro system. Abnormal neurotransmitter levels and distributions can cause intractable diseases involving descending/ascending modulatory pathways or dysfunctional organs. The detection of abnormal neurotransmitter levels is one of the most promising techniques in the diagnosis of brain diseases. Also, numerous effective methods for the detection of neurotransmitters in vivo have been fabricated. Nowadays, electrochemical, optical, magnetic, and microdialysis methods are among the main techniques used to detect neurotransmitters. Herein, we review current techniques for detecting eight types of neurotransmitters with a focus on in vivo neurotransmitter tracking methods intended for the real-time diagnosis of brain disorders. [ABSTRACT FROM AUTHOR]

Background and Aim Therapeutic drug monitoring is used to optimise adalimumab therapy in patients with Crohn's disease [CD]. However, the interindividual variability in drug absorption and the quantitative effect on drug clearance of anti-adalimumab antibodies [AAA], measured with a drug-resistant assay, are unclear. We aimed to characterise adalimumab population pharmacokinetics [PopPK] and identify determinants of interindividual variability in patients with CD. Methods In a prospective multicentre open-label cohort study in 28 patients with CD starting adalimumab therapy peak, intermediate, and trough serum samples were analysed for adalimumab and AAA concentrations using a drug resistant assay. Adalimumab concentration-time data were analysed by non-linear mixed effects modelling and were adequately described by a PopPK model with first-order absorption and one-compartment disposition with linear elimination. Clinical remission at Week 12 [W12] was defined as a Harvey-Bradshaw index ≤4. Results The absorption rate, volume of distribution, and clearance estimates of a typical patient were respectively 0.343 /day, 7.8 L, and 0.330 L/day. A 4-fold difference in the range of adalimumab concentrations was observed 7 days after the first dose and found to be inversely correlated with baseline lean body weight [LBW], soluble tumour necrosis factor [s-TNF], and s-TNF receptor-1 whereas positive AAA and higher LBW were found to be important predictors of accelerated clearance. An adalimumab concentration at W12 of >7.3 µg/mL was significantly associated with achieving clinical remission at W12. Conclusion Variability in subcutaneous drug absorption is an important contributor to the observed interindividual variability in adalimumab concentrations, in addition to drug clearance [ClinicalTrials.gov NCT02450513]. [ABSTRACT FROM AUTHOR]

Summary: Background: Proactive testing of adalimumab serum levels is debated. Aim: To study the association between adalimumab serum levels at week 4 and the development of anti‐adalimumab drug antibodies and long‐term outcome in anti‐TNF naive Crohn's disease patients. Methods: Serum samples from 116 biologically naive Crohn's disease patients with active disease were prospectively collected at baseline, and weeks 4 and 12. Adalimumab serum levels were measured using the RIDA®QUICK adalimumab lateral flow assay and anti‐adalimumab drug antibodies were determined using a drug‐resistant assay. Pharmacokinetic data were studied in relation to clinical outcome. Patients who stopped adalimumab by week 12 due to persisting symptoms were considered primary non‐responders, whereas initial improvement with increasing symptoms after week 12 was considered loss of response. Adalimumab continuation until the end of follow‐up was considered sustained clinical benefit. Results: Patients with low serum levels at week 4 (<8.3 μg/mL) were at significantly higher risk of being anti‐adalimumab positive by week 12 (46.7% vs 13.0%, P = 0.009). After a median follow‐up of 89 weeks, dose‐escalation and sustained clinical benefit were observed in 37.1% and 48.3% of patients. The 21.4% of patients who were anti‐adalimumab drug antibody positive by week 12, had a significantly higher need of dose escalation (P < 0.001), and experienced sustained clinical benefit less frequently due to primary non‐response or secondary loss of response (P = 0.02). Conclusions: Our findings support early monitoring of adalimumab serum levels to guide dose optimisation, which may prevent immunogenicity and influence long‐term outcome. We validated a novel lateral flow assay for quantitative determination of adalimumab levels, facilitating physicians to optimise therapy immediately at the outpatient clinic. [ABSTRACT FROM AUTHOR]

Abstract: Therapeutic drug monitoring of adalimumab is recommended to improve therapeutic outcome in patients with Crohn's disease. Performing an ELISA requires a rather long time‐to‐result and the necessity of collecting multiple samples to decrease the cost per adalimumab determination. In this study, we aim to develop and validate a rapid assay suitable for measuring a single adalimumab serum sample using a fiber‐optic surface plasmon resonance (FO‐SPR) based sensor. Therefore, we have immobilized MA‐ADM28B8 as capture antibody on an FO‐probe and conjugated MA‐ADM40D8 as detecting antibody to gold nanoparticles. A dose–response curve ranging from 2.5 to 40 ng/mL adalimumab was obtained in 1/400 diluted serum. Serum samples of patients with adalimumab concentrations between 1 and 16 μg/mL were measured whereas the negative control, a sample spiked with infliximab at a concentration of 16 μg/mL, showed no significant signal. Using a pre‐functionalized FO‐probe, the technology requires less than 45 minutes for measuring a single sample. Comparison of measurements between the biosensor and the ELISA revealed an excellent agreement with a Pearson r coefficient of 0.99 and an intra‐class coefficient of 0.99. The reduced assay time and the possibility of measuring a single sample are major advantages compared to the ELISA. The developed and validated optical adalimumab biosensor could be a valuable point‐of‐care diagnostic tool for adalimumab quantification in patients with Crohn's disease. [ABSTRACT FROM AUTHOR]

On-site monitoring of carbamazepine (CBZ) that allows rapid, sensitive, automatic, and high-throughput detection directly from whole blood is of urgent demand in current clinical practice for precision medicine. Herein, we developed two types (being indirect vs. direct) of fiber-optic biolayer interferometry (FO-BLI) biosensors for on-site CBZ monitoring. The indirect FO-BLI biosensor preincubated samples with monoclonal antibodies towards CBZ (MA-CBZ), and the mixture competes with immobilized CBZ to bind towards MA-CBZ. The direct FO-BLI biosensor used sample CBZ and CBZ-horseradish peroxidase (CBZ-HRP) conjugate to directly compete for binding with immobilized MA-CBZ, followed by a metal precipitate 3,3′-diaminobenzidine to amplify the signals. Indirect FO-BLI detected CBZ within its therapeutic range and was regenerated up to 12 times with negligible baseline drift, but reported results in 25 min. However, Direct FO-BLI achieved CBZ detection in approximately 7.5 min, down to as low as 10 ng/mL, with good accuracy, specificity and negligible matric interference using a high-salt buffer. Validation of Direct FO-BLI using six paired sera and whole blood from epileptic patients showed excellent agreement with ultra-performance liquid chromatography. Being automated and able to achieve high throughput, Direct FO-BLI proved itself to be more effective for integration into the clinic by delivering CBZ values from whole blood within minutes. [ABSTRACT FROM AUTHOR]

• A method for vedolizumab concentration measurements in dried blood spots (DBS) was developed. • The method was clinically validated using paired DBS and serum samples from VDZ-treated patients. • Vedolizumab concentrations in DBS extracts strongly correlated with serum concentrations. • Vedolizumab DBS can be used for intensive sampling to gain more insight in its pharmacokinetics. An association between vedolizumab (VDZ) trough concentrations and therapeutic outcome has been observed in patients with inflammatory bowel diseases. VDZ samples are typically collected via venous sampling for therapeutic drug monitoring (TDM), but can alternatively be collected via dried blood spot (DBS) samples, which can be used for intensive sampling to investigate pharmacokinetic profiles. Therefore, we have developed a DBS method for determining VDZ concentrations and validated this method by comparing VDZ measurements in paired DBS and venous patient samples. First, VDZ was spiked in citrated whole blood and spotted on filter paper. After drying, DBS were extracted and VDZ concentrations were determined in the extracts using ELISA. For clinical validation, 41 paired DBS and serum samples were collected from 19 VDZ-treated patients. VDZ concentrations measured in DBS extracts strongly correlated with serum concentrations (Pearson r = 0.978, p < 0.0001). No significant impact of the hematocrit value was observed on the VDZ DBS/serum concentration ratios. Additionally, the VDZ DBS/serum ratio was calculated in nine individual patients, which was, in general, shown to be stable over time. VDZ DBS sampling is a robust method that can be used as an alternative to venous blood collection for TDM of VDZ. VDZ concentrations in DBS highly correlated with VDZ serum concentrations over a broad concentration range, allowing DBS to be used for intensive sampling to gain more insight in VDZ pharmacokinetics. [ABSTRACT FROM AUTHOR]

High sensitivity and high quality-factor are crucial for achieving outstanding sensing performance in photonic biosensors. However, strong optical field confinement and high light-biomolecule interactions on photonic surfaces are usually contradictory and challenging to satisfy simultaneously. Here, a distinctive configuration for addressing this issue is reported: embedding a nanophotonic metasurface inside a micro vertical cavity as a meta-channel (metacavity) biosensor. The analyte solution serves as the cavity medium, thereby maximizing the light-analyte interaction. Simulation validation is conducted to optimize the metacavity with high structural robustness and remarkable optical and sensing properties. Large-scale low-cost metacavity biosensors are realized by combining anodic aluminum oxide template technique and wafer bonding. Experimentally, the metacavity biosensor demonstrates a notable quality-factor (maximum 4140) and high bulk refractometric sensitivity (450 nm RIU -1 ), resulting in an unprecedented figure-of-merit (1670 RIU -1 ). Moreover, the metacavity biosensor achieves high surface sensitivity, together with a detection-limit of 119 viral copies mL -1 for label-free severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus sensing, revealing remarkable performance in both bulk and surface sensing., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Chips-based platforms intended for single-cell manipulation are considered powerful tools to analyze intercellular interactions and cellular functions. Although the conventional cell co-culture models could investigate cell communication to some extent, the role of a single cell requires further analysis. In this study, a precise intercellular interaction model was built using a microelectrode array [microelectrode array (MEA)]-based and dielectrophoresis-driven single-cell manipulation chip. The integrated platform enabled precise manipulation of single cells, which were either trapped on or transferred between electrodes. Each electrode was controlled independently to record the corresponding cellular electrophysiology. Multiple parameters were explored to investigate their effects on cell manipulation including the diameter and depth of microwells, the geometry of cells, and the voltage amplitude of the control signal. Under the optimized microenvironment, the chip was further evaluated using 293T and neural cells to investigate the influence of electric field on cells. An examination of the inappropriate use of electric fields on cells revealed the occurrence of oncosis. In the end of the study, electrophysiology of single neurons and network of neurons, both differentiated from human induced pluripotent stem cells (iPSC), was recorded and compared to demonstrate the functionality of the chip. The obtained preliminary results extended the nature growing model to the controllable level, satisfying the expectation of introducing more elaborated intercellular interaction models., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Wang, Huang, Zhao, Su, Li, Bian and Sawan.)

Increasing population is suffering from neurological disorders nowadays, with no effective therapy available to treat them. Explicit knowledge of network of neurons (NoN) in the human brain is key to understanding the pathology of neurological diseases. Research in NoN developed slower than expected due to the complexity of the human brain and the ethical considerations for in vivo studies. However, advances in nanomaterials and micro-/nano-microfabrication have opened up the chances for a deeper understanding of NoN ex vivo , one step closer to in vivo studies. This review therefore summarizes the latest advances in lab-on-chip microsystems for ex vivo NoN studies by focusing on the advanced materials, techniques, and models for ex vivo NoN studies. The essential methods for constructing lab-on-chip models are microfluidics and microelectrode arrays. Through combination with functional biomaterials and biocompatible materials, the microfluidics and microelectrode arrays enable the development of various models for ex vivo NoN studies. This review also includes the state-of-the-art brain slide and organoid-on-chip models. The end of this review discusses the previous issues and future perspectives for NoN studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Rong, Bian and Sawan.)

Background and Aim: Therapeutic drug monitoring is used to optimise adalimumab therapy in patients with Crohn's disease [CD]. However, the interindividual variability in drug absorption and the quantitative effect on drug clearance of anti-adalimumab antibodies [AAA], measured with a drug-resistant assay, are unclear. We aimed to characterise adalimumab population pharmacokinetics [PopPK] and identify determinants of interindividual variability in patients with CD., Methods: In a prospective multicentre open-label cohort study in 28 patients with CD starting adalimumab therapy peak, intermediate, and trough serum samples were analysed for adalimumab and AAA concentrations using a drug resistant assay. Adalimumab concentration-time data were analysed by non-linear mixed effects modelling and were adequately described by a PopPK model with first-order absorption and one-compartment disposition with linear elimination. Clinical remission at Week 12 [W12] was defined as a Harvey-Bradshaw index ≤4., Results: The absorption rate, volume of distribution, and clearance estimates of a typical patient were respectively 0.343 /day, 7.8 L, and 0.330 L/day. A 4-fold difference in the range of adalimumab concentrations was observed 7 days after the first dose and found to be inversely correlated with baseline lean body weight [LBW], soluble tumour necrosis factor [s-TNF], and s-TNF receptor-1 whereas positive AAA and higher LBW were found to be important predictors of accelerated clearance. An adalimumab concentration at W12 of >7.3 µg/mL was significantly associated with achieving clinical remission at W12., Conclusion: Variability in subcutaneous drug absorption is an important contributor to the observed interindividual variability in adalimumab concentrations, in addition to drug clearance [ClinicalTrials.gov NCT02450513]., (Copyright © 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Proactive testing of adalimumab serum levels is debated., Aim: To study the association between adalimumab serum levels at week 4 and the development of anti-adalimumab drug antibodies and long-term outcome in anti-TNF naive Crohn's disease patients., Methods: Serum samples from 116 biologically naive Crohn's disease patients with active disease were prospectively collected at baseline, and weeks 4 and 12. Adalimumab serum levels were measured using the RIDA ® QUICK adalimumab lateral flow assay and anti-adalimumab drug antibodies were determined using a drug-resistant assay. Pharmacokinetic data were studied in relation to clinical outcome. Patients who stopped adalimumab by week 12 due to persisting symptoms were considered primary non-responders, whereas initial improvement with increasing symptoms after week 12 was considered loss of response. Adalimumab continuation until the end of follow-up was considered sustained clinical benefit., Results: Patients with low serum levels at week 4 (<8.3 μg/mL) were at significantly higher risk of being anti-adalimumab positive by week 12 (46.7% vs 13.0%, P = 0.009). After a median follow-up of 89 weeks, dose-escalation and sustained clinical benefit were observed in 37.1% and 48.3% of patients. The 21.4% of patients who were anti-adalimumab drug antibody positive by week 12, had a significantly higher need of dose escalation (P < 0.001), and experienced sustained clinical benefit less frequently due to primary non-response or secondary loss of response (P = 0.02)., Conclusions: Our findings support early monitoring of adalimumab serum levels to guide dose optimisation, which may prevent immunogenicity and influence long-term outcome. We validated a novel lateral flow assay for quantitative determination of adalimumab levels, facilitating physicians to optimise therapy immediately at the outpatient clinic., (© 2018 John Wiley & Sons Ltd.)