npj Biosensing最新文献

Von Willebrand Disease (VWD) is characterized by improper blood clotting, resulting from qualitative or quantitative changes in Von Willebrand factor (VWF). Diagnosis of VWD currently relies on measuring both the concentration of VWF and its activity by the binding ability to several different proteins, each of which are currently quantified separately. As such, the current diagnosis of VWD is complex and expensive, requiring multiple tests for a positive clinical determination. To address this challenge, we report a multiplexed biosensor that simultaneously measures VWF concentration and binding activity in plasma, enabling rapid diagnosis of VWD and discrimination among multiple subtypes. Using an 18-plex photonic ring resonator in a disposable, lateral flow assay-like format as the core technology, capture of VWF by an immobilized monoclonal antibody results in a red shift in resonance, which is referenced to a nonspecific binding control. Other ring resonators on the chip, functionalized with binding partners of VWF, allow simultaneous measurement of VWF binding to collagen, Factor VIII, and the GP1b receptor. Evaluation of a panel of 37 single-donor human plasma samples previously analyzed using FDA clinically approved assays demonstrated that the sensor has comparable concentration results and was able to accurately identify several categories of VWD (type 1, 2 A, and type 3).

The reactivation of heterotrimeric protein phosphatase 2A (PP2A) through small molecule activators is of interest to therapeutic intervention due to its dysregulation, which is linked to chronic conditions. This study focuses on the PP2A scaffold subunit PR65 and a small molecule activator, ATUX-8385, designed to bind directly to this subunit. Using a label-free single-molecule approach with nanoaperture optical tweezers (NOT), we quantify its binding, obtaining a dissociation constant of 13.6 ± 2.5 μM, consistent with ensemble fluorescence anisotropy results but challenging to achieve with other methods due to low affinity. Single-molecule NOT measurements reveal that binding increases optical scattering, indicating PR65 elongation. This interpretation is supported by all-atom molecular dynamics simulations showing PR65 adopts more extended conformations upon binding. This work highlights NOT's utility in quantifying binding kinetics and structural impact, offering insights valuable for drug discovery.

Cuffless noninvasive blood pressure (BP) measurement could enable early unobtrusive detection of abnormal BP patterns, but when the sensor is placed on a location away from heart level (such as the arm), its accuracy is compromised by variations in the position of the sensor relative to heart level; such positional variations produce hydrostatic pressure changes that can cause swings in tens of mmHg in the measured BP if uncorrected. A standard method to correct for changes in hydrostatic pressure makes use of a bulky fluid-filled tube connecting heart level to the sensor. Here, we present an alternative method to correct for variations in hydrostatic pressure using unobtrusive wearable inertial sensors. This method, called IMU-Track, analyzes motion information with a deep learning model; for sensors placed on the arm, IMU-Track calculates parameterized arm-pose coordinates, which are then used to correct the measured BP. We demonstrated IMU-Track for BP measurements derived from pulse transit time, acquired using electrocardiography and finger photoplethysmography, with validation data collected across 20 participants. Across these participants, for the hand heights of 25 cm below or above the heart, mean absolute errors were reduced for systolic BP from 13.5 ± 1.1 and 9.6 ± 1.1 to 5.9 ± 0.7 and 5.9 ± 0.5 mmHg, respectively, and were reduced for diastolic BP from 15.0 ± 1.0 and 11.5 ± 1.5 to 6.8 ± 0.5 and 7.8 ± 0.8, respectively. On a commercial smartphone, the arm-tracking inference time was ~134 ms, sufficiently fast for real-time hydrostatic pressure correction. This method for correcting hydrostatic pressure may enable accurate passive cuffless BP monitors placed at positions away from heart level that accommodate everyday movements.

Rapid antibiotic susceptibility tests (AST) are vital for the effective treatment of disease, necessitating the development of analytical tools to address unmet needs in healthcare. Leveraging the sensitivity of plasmonic nanosensors and isotopic labelling has the potential to accelerate AST. Here, we developed surface-enhanced Raman scattering (SERS)-based nanofibre sensors and heavy water [deuterium oxide (D₂O)] labelling (SERS-DIP) for detecting the minimum inhibitory concentration (MIC) and AST for trimethoprim (TMP) against E. coli. SERS-DIP rapidly detected the MIC of TMP for the susceptible strain in 2 h. TMP-resistant cells retained the metabolic activity regardless of TMP levels, confirming the resistance phenotype. Kinetic analysis of D uptake by resistant cells treated with TMP (2 × MIC) revealed increasing D levels proportional to peak redshifts over time, confirmed by machine learning-driven data exploration. Our results demonstrate the utility of nanofibre-enabled SERS-DIP for robust AST, uncovering new spectral biomarkers that may impact clinical medicine.

Neurodegenerative diseases involve the progressive loss of neurons in the brain and nervous system, leading to functional decline. Early detection is critical for improving outcomes and advancing therapies. Optical biosensors, some of which offer rapid, label-free, and ultra-sensitive detection, have been applied to early diagnosis and drug screening. This review examines the principles and performance of different optical biosensors used for diagnosing neurodegenerative diseases and discusses potential future advancements.

The blood test is one of the most performed investigations in clinical practice, with samples typically analysed in a centralised laboratory. Many of these tests monitor routine conditions that would benefit from a point-of-care approach, reducing the burden on practitioners, patients and healthcare systems. Such a decentralised model requires the development of sophisticated, yet easy-to-use technology; however, platforms that combine high-performance with low-cost and simplicity remain scarce. Moreover, most research papers only address a subset of requirements and study specific aspects in isolation. A systems approach that considers the interplay between each element of the technology is clearly required to develop a coherent solution. Here, we present such a systems approach in the context of testing for C-reactive protein (CRP), a commonly requested test in clinical practise that indicates inflammation and is particularly relevant for monitoring patients with chronic diseases, e.g. those with rheumatoid arthritis or who are undergoing cancer therapy. The approach we take here features an entirely passive microfluidic cartridge for blood separation, integrated with a high-performance sensing platform which we have tested in a real-world context. The device is compatible with a handheld detection unit and is simple to use yet can accurately detect CRP levels at clinically relevant levels.

This perspective discusses the present and future role of artificial intelligence (AI) and machine learning (ML) in surface-enhanced Raman scattering (SERS) sensing. Our goal is to guide the reader through current applications, mainly focused on discriminative approaches aimed at developing new and improved SERS diagnostic capabilities, towards the future role of AI in SERS sensing, with the use of generative approaches to design new materials and biomaterials.

Parkinson's Disease (PD) is an age-progressive disorder caused by misfolding of alpha-synuclein (α-Syn) that can begin years before clinical symptoms appear, making early diagnosis crucial for timely intervention. In this study, a novel antibody-functionalized Organic Electrolyte-Gated Field-Effect-Transistor (Ab-OEGFET) biosensor was implemented to detect α-Syn levels in blood serum samples from an A53T Transgenic (TG) mouse line. PD-like pathology was examined in blood serum using Ab-OEGFET devices and in brain tissue samples using Western Blot and immunohistochemistry. Different forms (monomeric, phosphorylated, oligomeric) of α-Syn were identified in low volumes of blood serum samples collected from TG and Wild Type (WT) populations of mice at ages 2, 5 and 8 months, and the biosensor response was correlated to Blot and immunohistochemistry results. The Ab-OEGFETs performance in this study is a promising result towards a minimally invasive blood biomarker-based multianalyte testing strategy for early screening of PD and similar neurodegenerative disease pathologies.

Nanoplasmonic optical antennas function as sensors and actuators, facilitating rapid and selective on-site molecular diagnostics for personalized precision medicine. Here, we highlight advancements in plasmonic biosensors and actuators within point-of-care diagnostics platforms, including optical trapping, cell lysis and ultrafast photonic polymerase chain reaction. Furthermore, we discuss nanoplasmonic optical sensing technologies, and commercial optical diagnostic systems. Nanoplasmonic optical antennas are essential to photonic sample-to-answer systems, significantly enhancing advancing preventive, personalized, and precision medicine.

Parkinson's disease (PD), dementia with Lewy bodies (DLB), and other synucleinopathies are characterized by the accumulation of abnormal, self-propagating aggregates of α-synuclein. RT-QuIC or seed amplification assays are currently showing unprecedented diagnostic sensitivities and specificities for synucleinopathies even in prodromal phases years in advance of the onset of Parkinsonian signs or dementia. However, commonly used α-synuclein seed amplification assays take ≥48 h to perform as applied to patients' diagnostic biospecimens. Here, we report the development of a faster α-synuclein RT-QuIC assay that is as analytically sensitive as prior assays of this type, but can be completed in ≤12 h for brain, skin, and intestinal mucosa, with positive signals often arising in <5 h. CSF assays took a few hours longer. Our same-day α-synuclein RT-QuIC (sdRT-QuIC) assay should increase the practicality, cost-effectiveness, and throughput of measurements of pathological forms of α-synuclein for fundamental research, clinical diagnosis, and therapeutics development.