Nanosensor for detecting cancer in blood

Looking for cancer biomarkers in blood is a promising method for detecting metastatic cancer. It is less demanding than imaging techniques like MRI (magnetic resonance imaging). The main challenge to overcome is the extremely low concentrations of these markers making it difficult to detect them. Researchers of the University of Twente and Wageningen University developed a nanosensor able to accurately detect biomarkers for cancer in an extremely broad range of concentrations: from 10 particles per microliter to a million particles per microliter. With their nanosensor, the researchers made it to the cover of Nano Letters, a journal of the American Chemical Society.
Tumor-derived extracellular vesicles (tdEVs) are attracting much attention due to their potential as cancer biomarkers. Although tdEVs are significantly more abundant in blood than other cancer biomarkers, their concentration compared to other blood components remains relatively low. The presence of particles in blood with a similar size as that of tdEVs asks not only for a sensitive but also a selective sensor.

Two Nanoscale Combs

On the nanoscale, the sensor looks like two ‘combs’ woven into each other, that leaves gaps between the ‘teeth’ – the electrodes – of around 120 nanometers. This small gap size provides amplification of the signal. The sensor has two levels of selection and two levels of amplification. This gives it the selectivity and sensitivity to accurately detect particles at low concentration. “The most unique feature of this sensor is that its sensitivity spans over six orders of magnitude. In contrast to other sensors, it covers most of the clinically relevant range for tdEV detection in blood”, says Dilu Mathew, one of the researchers at NanoElectronics group at University of Twente.

Schematic illustration of tdEV sensing using a sandwich immunoassay and redox cycling on nIDEs resulting in a two-level selectivity and a two-level amplification

exosomes

tdEVs are captured using C-AE tethered to electrodes (first level of selectivity). The binding of R-AE to the tdEVs completes the antibody–antigen-antibody sandwich (second-level selectivity), after which the enzyme ALP is introduced using a biotin–SAV interaction. ALP provides an enzymatic amplification of pAPP to pAP by substrate cleavage (first-level amplification), which is followed by an electrochemical signal amplification via the oxidation of pAP to pQI and subsequent redox cycling thereof between the nIDE electrodes (second-level amplification).

Future Work

Mathew, winner of the Metrohm Young Chemist Award 2018, is currently working on a new sensor. He says: “The goal is to make a sensor that is able to detect a single tdEV in small amount of blood.” His colleague Pepijn Beekman adds: “In the lab we’ve already shown that we can detect individual nanoparticles.”

Dilu and Pepijn are working on their start-up ECsens, which was announced winner in the prototype category of the UT Entrepreneurial Challenge 2019 and winner of the 4TU Impact Challenge. ECsens will join the ministry of Foreign Affairs on a trade mission to the World Expo in Dubai next year. They were also announced winner of the UT in the Media Prize for PhD-students.

Source – University of Twente

Mathew DG, Beekman P, Lemay SG, Zuilhof H, Le Gac S, van der Wiel WG. (2020) Electrochemical Detection of Tumor-Derived Extracellular Vesicles on Nanointerdigitated Electrodes. Nano Lett 20(2):820-828. [article]

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