A challenge in cancer patient care is to monitor the response to treatment. Nowadays, most of the established approaches use tissue staining, which implies their invasive collection through, e.g., biopsies of the primary tumour. Patient follow-up therefore requires serial biopsies, making it very unpleasant for the patient. Alternatively, in vivo imaging approaches using MRI and PET-CT are used, with an essential limitation that they can only detect tumours of at least 1 cm. Moreover, high cost, radiation problems (PET-CT), and/or allergic reactions render these tests unsuitable for repeated use. Nonetheless, more frequent monitoring of the patient to study the treatment efficacy is crucial for making a more accurate prognosis and prescribing personalised treatment. In that context, NanoDisc aims at providing a robust and easy-to-use, non-invasive biosensing platform, for both highly sensitive and selective cancer marker detection in blood.
Currently, circulating tumour cells (CTC) are being used for liquid biopsies. However, we will examine tumour-derived extracellular vesicles (td-EVs), since they are much more available in blood compared to CTCs (∽103 higher). EVs are small (50 nm – 1 μm), membrane-enclosed carriers, which are produced by all cells. Nonetheless, the limit of detection (LOD) of td-EVs using state-of-the-art techniques is several orders of magnitude higher than their clinically relevant concentrations (104 td-EVs/ml) in blood. Consequently, to have a precise quantification of td-EVs, an ultra-selective device is required, that can also measure ultralow concentrations.
We propose an array of nanoscale electrodes for the label-free electrochemical detection of td-EVs with high sensitivity and specificity, down to the single td-EV level. For specific detection, the nanoelectrodes will be functionalised with antibodies targeting td-EVs. One of the main challenges at such low concentrations however, is the diffusion time of the biomarkers to the electrodes, which is relatively large for EVs. Therefore, in our approach, we will take advantage of the electrophoretic force. Owing to the oxidation reaction at the nanoelectrode, the td-EVs are attracted onto the electrode, making the transport 1011 times faster. Expectedly, other biomolecules will also be attracted to the nanoelectrode. Therefore, an antifouling layer is necessary on the nanoelectrodes to ensure highly selective detection.
This project combines the expertise of the University of Twente (UT) in the fields of nanoelectronic biosensors and td-EV analysis and of Wageningen University & Research (WUR) in the field of surface modification. All partners already intensely collaborate, and preliminary results point towards successful outcome of the project.
We expect NanoDisc to have an unprecedented LOD, which will be a major step for the implementation of personalised medicine, which is one of the 4Ps in the European roadmap to systems medicine as devised by CASyM and H2020.