Electrochemical sensors in breast cancer diagnostics and follow-up

Abstract

Purpose: The detection of tumor biomarkers can have a major contribution to the management of breast cancer. So far the only serum biomarker in current use in breast cancer is the cancer antigen 15-3 (CA15-3). This biomarker is used in advanced breast cancer to monitor patients and to help to identify treatment failure. The human epidermal growth factor receptor 2 (HER 2) is another biomarker whose characterization is usually made in tissue samples from primary tumour or metastasis and has been used as a prognostic factor but mainly as a target in immunotherapy treatment. Some previous studies suggest that the detection of the extracellular domain of HER2 (HER2-ECD) in blood can be a prognostic factor, with even better results than its detection in tissue. Recent techniques for circulating protein biomarker detection use immunoassays, but some are, for example, not sufficiently sensitive for the detection of low biomarker concentrations. To overcome some of these problems, electrochemical (bio)sensors, and especially the ones using voltammetric detection, can be adequate alternatives because of their high selectivity and sensitivity which allows early detection of many diseases. Furthermore, electrochemical (bio)sensors are excellent to be included into point-of-care devices due to their fast response, simplicity, low cost, easy miniaturization and integration into automatic systems. Another advantage is the possibility of combining individual sensors into multiplexed detection systems. Like this they can provide fast recording of biomarker profiles of tumours which can play an important role in early detection and personalized medicine.

Methods: Both individual as well as multiplexed electrochemical immunosensors were developed for the detection of CA15-3 and HER2-ECD. For this purpose a sandwich immunoassay was employed and the analytical signal was based on the voltammetric detection of enzymatically deposited silver. Screen-printed carbon electrodes (SPCEs) were used as the transducers. These SPCEs (working volume: ~40 μL) are widely employed in the construction of electrochemical (bio)sensors because of several reasons: simplicity and low cost, versatility of design, small dimensions and possibility of incorporation in portable systems, as well as adequate electroanalytical characteristics. These SPCEs were modified with gold nanoparticles (nAu) through the electrochemical deposition of ionic gold from a solution. The developed sensors were applied to the analysis of the selected biomarkers in spiked human serum samples.

Besides these immunosensors, a molecularly imprinted polymer (MIP) sensor was developed for the analysis of HER2-ECD. In this case a gold electrode was used as the transducer. The MIP was formed by surface imprinting and electrochemical impedance spectroscopy and voltammetry were used for detection purposes.

Results: For the immunoassays the following parameters were optimized: capture and detection antibody concentration, surface blocking, reaction mixtures and incubation times. The best limits of detection obtained were below the established cut-off values (25 U/mL and 15 ng/mL for CA15-3 and HER2-ECD, respectively). For the MIP sensor the most adequate polymer was chosen and the electropolymerization, template removal, and incubation conditions were optimized. The lowest HER2-ECD concentration that was analyzed was 50 µg/mL.

Conclusion: The obtained results indicate that the developed sensors could be promising tools in breast cancer diagnostics and follow-up. However, further studies should be conducted using patients' samples and the results of these assays should be validated with the established analysis procedures for these cancer biomarkers.

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Cite this article as:  Marques R, Pacheco J, Rama EC, Viswanathan S, Nouws H, Delerue-Matos C. Electrochemical sensors in breast cancer diagnostics and follow-up. Int J Cancer Ther Oncol 2015; 3(4):34012.

[This abstract was presented at the BIT’s 8^th Annual World Cancer Congress, which was held from May 15-17, 2015 in Beijing, China.]