Several neurodegenerative diseases have been linked to proteins or peptides that are prone to aggregate in different brain regions. Aggregation of amyloid-β (Aβ) peptides is recognized as the main cause of Alzheimer's disease (AD) progression, leading to the formation of toxic Aβ oligomers and amyloid fibrils. The molecular mechanism of Aβ aggregation is complex and still not fully understood. Nanopore technology provides a new way to obtain kinetic and morphological aspects of Aβ aggregation at a single-molecule scale without labeling by detecting the electrochemical signal of the peptides when they pass through the hole. Here, we investigate the influence of nanoscale geometry (conical and bulletlike shape) of a track-etched nanopore pore and the effect of molecular crowding (polyethylene glycol-functionalized pores) on Aβ fibril sensing and analysis. Various Aβ fibril samples that differed by their length were produced by sonication of fibrils obtained in the presence of epigallocatechin gallate. The conical nanopore functionalized with polyethylene glycol (PEG) 5 kDa is suitable for discrimination of the fibril size from relative current blockade. The bullet-like-shaped nanopore enhances the amplitude of the current and increases the dwell time, allowing us to well discern the fibrils. Finally, the nanopore crowded with PEG 20 kDa enhances the relative current blockade and increases the dwell time; however, the discrimination is not improved compared to the "bullet-shaped" nanopore.

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Solid‐state nanopores are an emerging technology used as a high‐throughput, label‐free analytical method for the characterization of protein aggregation in an aqueous solution. In this work, we used Levodopamine to coat a silicon nitride nanopore surface that was fabricated through a dielectric breakdown in order to reduce the unspecific adsorption. The coating of inner nanopore wall by investigation of the translocation of heparin. The functionalized nanopore was used to investigate the aggregation of amyloid‐β and α‐synuclein, two biomarkers of degenerative diseases. In the first application, we demonstrate that the α‐synuclein WT is more prone to form dimers than the variant A53T. In the second one, we show for the Aβ(42)‐E22Δ (Osaka mutant) that the addition of Aβ(42)‐WT monomers increases the polymorphism of oligomers, while the incubation with Aβ(42)‐WT fibrils generates larger aggregates.

Breast cancer is the leading cancer type for women with two million new yearly infections and more than half a million dead worldwide. Human Epidermal Receptor 2 (HER2) is a prominent breast cancer biomarker that indicates aggressive cancer and is often associated with a bad prognosis and low survival rates. However, current detection methods for HER2 are often time-consuming, expensive, and require a high level of expertise. Biosensors are devices that turn biological interaction into a readable electronic signal; they are known for their high specificity and selectivity for low concentration, as well as their low cost and ease of use, thus making them a better alternative to traditional methods. Also, saliva is becoming a better alternative to blood for the detection of biomarkers due to its non-invasive collection in large quantities with simple collection methods with a richness in disease biomarkers including HER2. Thus, this project aims to develop a label-free, low cost, electrochemical biosensor for the detection of HER2 in saliva. This was done by first depositing diazonium salt onto a screen-printed electrode (SPE) through cyclic voltammetry, then immobilizing anti-HER2 antibodies on the activated SPE using 1-ethyl-3-(3-dimethylamino) propyl carbodiimide/N-hydroxysuccinimide. HER2 biomarker concentrations were detected using electrochemical impedance spectroscopy inside a microfluidic system. The biosensor showed a higher linear detection of HER2 (Y = 0.0062X + 0.1066/R2 = 0.9909) in its physiological concentration range of 5 and 40 pg/mL when compared to other interference proteins: Epidermal Growth Factor Receptor (Y = 0.0016X + 0.0188/R2 = 0.8072) and Human Epidermal Receptor 3 (Y = (0.0035X + 0.0225/R2 = 0.1302). The biosensor was then used to detect 10 pg/mL of HER2 concentration in real saliva using the standard addition methods (Y = 0.0118X + 0.1282/R2 = 0.9876).

Breast Cancer is one of the world’s most notorious diseases affecting two million women in 2018 worldwide. It is a highly heterogeneous disease, making it difficult to treat. However, its linear progression makes it a candidate for early screening programs, and the earlier its detection the higher the chance of recovery. However, one key hurdle for breast cancer screening is the fact that most screening techniques are expensive, time-consuming, and cumbersome, making them impractical for use in several parts of the world. One current trend in breast cancer detection has pointed to a possible solution, the use of salivary breast cancer biomarkers. Saliva is an attractive medium for diagnosis because it is readily available in large quantities, easy to obtain at low cost, and contains all the biomarkers present in blood, albeit in lower quantities. Affinity sensors are devices that detect molecules through their interactions with biological recognition molecules. Their low cost, high sensitivity, and selectivity, as well as rapid detection time make them an attractive alternative to traditional means of detection. In this review article, we discuss the current status of breast cancer diagnosis, its salivary biomarkers, as well as the current trends in the development of affinity sensors for their detection.

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