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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]

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]

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.)