The ability to fabricate sensory systems capable of highly selective operation in complex fluid will undoubtedly underpin key future developments in healthcare. However, the abundance of (bio)molecules in these samples can significantly impede performance at the transducing interface where nonspecific adsorption (fouling) can both block specific signal (reducing sensitivity) and greatly reduce assay specificity. Herein, we aim to provide a comprehensive review discussing concepts and recent advances in the construction of antifouling sensors that are, through the use of chemical, physical, or biological engineering, capable of operating in complex sample matrix (e.g., serum). We specifically highlight a range of molecular approaches to the construction of solid sensory interfaces (planar and nanoparticulate) and their characterization and performance in diverse in vitro and in vivo analyte (e.g., proteins, nucleic acids, cells, neuronal transmitters) detection applications via derived selective optical or electrochemical strategies. We specifically highlight those sensors that are capable of detection in complex media or those based on novel architectures/approaches. Finally, we provide perspectives on future developments in this rapidly evolving field.

Metalloproteins and enzymes can be immobilized on SWNTs of different surface chemistry. The combination of high surface area, robust immobilization and inherent nanotube electrochemical properties is of promising application in bioelectrochemistry.

Electrical detection methodologies are likely to underpin the progressive drive towards miniaturised, sensitive and portable biomarker detection protocols. In being easily integrated within standard electronic microfabrication formats, and developing capability in microfluidics, the facile multiplexed detection of a range of proteins in a small analytical volume becomes entirely feasible with something costing just a few thousand pounds and benchtop or handheld in scale. In this review, we focus on recent important advances in label free assays of protein using a number of electrical methods, including those based on electrochemical impedance spectroscopy (EIS), amperometry/voltammetry, potentiometry, conductometry and field-effect methods. We introduce their mechanistic features and examples of application and sensitivity. The current state of the art, real world applications and challenges are outlined.

ObjectiveParkinson’s disease is characterised neuropathologically by α-synuclein aggregation. Currently, there is no blood test to predict the underlying pathology or distinguish Parkinson’s from atypical parkinsonian syndromes. We assessed the clinical utility of serum neuronal exosomes as biomarkers across the spectrum of Parkinson’s disease, multiple system atrophy and other proteinopathies.MethodsWe performed a cross-sectional study of 664 serum samples from the Oxford, Kiel and Brescia cohorts consisting of individuals with rapid eye movement sleep behavioural disorder, Parkinson’s disease, dementia with Lewy bodies, multiple system atrophy, frontotemporal dementia, progressive supranuclear palsy, corticobasal syndrome and controls. Longitudinal samples were analysed from Parkinson’s and control individuals. We developed poly(carboxybetaine-methacrylate) coated beads to isolate L1 cell adhesion molecule (L1CAM)-positive extracellular vesicles with characteristics of exosomes and used mass spectrometry or multiplexed electrochemiluminescence to measure exosomal proteins.ResultsMean neuron-derived exosomal α-synuclein was increased by twofold in prodromal and clinical Parkinson’s disease when compared with multiple system atrophy, controls or other neurodegenerative diseases. With 314 subjects in the training group and 105 in the validation group, exosomal α-synuclein exhibited a consistent performance (AUC=0.86) in separating clinical Parkinson’s disease from controls across populations. Exosomal clusterin was elevated in subjects with non-α-synuclein proteinopathies. Combined neuron-derived exosomal α-synuclein and clusterin measurement predicted Parkinson’s disease from other proteinopathies with AUC=0.98 and from multiple system atrophy with AUC=0.94. Longitudinal sample analysis showed that exosomal α-synuclein remains stably elevated with Parkinson’s disease progression.ConclusionsIncreased α-synuclein egress in serum neuronal exosomes precedes the diagnosis of Parkinson’s disease, persists with disease progression and in combination with clusterin predicts and differentiates Parkinson’s disease from atypical parkinsonism.

Redox active self-assembled monolayers inherently possess both electrochemically addressable and polarizable components. The latter will contribute, with additional parasitic terms, to the iR drop effects within any form of electronic analysis, potentially distorting results. A capacitive analysis of such interfaces (Electroactive Monolayer Capacitance Spectroscopy), presented here, enables a clean mapping of both the thermodynamic and kinetic faradaic characteristics in a single experimental run, with parasitic nonfaradaic contributions (polarization and resistance terms) both spectrally resolved and cleanly removed. The methodology enables a rapid and undistorted quantification of accessible redox site density of states (reported directly by redox capacitance), molecular surface coverage, electron transfer kinetics, and reorganization energies with comparatively little experimental effort. Exemplified here with electroactive copper protein and ferrocene films the approach is equally applicable to any redox active interface.