A biosensor capable of identifying low quantities of breast cancer cells by electrical impedance spectroscopy
Breast cancer (BC) is a malignant disease with a high prevalence worldwide. The main cause of death is not the primary tumor, but instead the spread of tumor cells to distant sites. The aim of the present study was to examine a new method for the detection of cancer cells in aqueous medium using bioimpedance spectroscopy assisted with magnetic nanoparticles (MNP’s) exposure to a constant magnetic field. The spectroscopic patterns were identified for three breast cancer cell lines. Each BC cell line represents a different pathologic stage: the early stage (MCF-7), invasive phase (MDA-MB-231) and metastasis (SK-BR-3). For this purpose, bioimpedance measurements were carried out at a certain frequency range with the aid of nanoprobes, consisting of magnetic nanoparticles (MNPs) coupled to a monoclonal antibody. The antibody was specific for the predominant cell surface protein for each cell line, which was identified by using RT-qPCR and flow cytometry. Accordingly, EpCAM corresponds to MCF-7, MUC-1 to MDA-MB-231, and HER-2 to SK-BR-3. Despite their low concentrations, BC cells could be detected by impedance spectroscopy. Hence, this methodology should permit the monitoring of circulating tumor cells (CTC) and therefore help to prevent recurrences and metastatic processes during BC treatment.
Optical and impedimetric study of genetically modified cells for diclofenac sensing
Whole-cell biosensors, based on genetically modified yeast cells, were employed to detect anthropogenic micropollutants (e.g. drugs). Specific stimuli, e.g. traces of drugs, lead to the induction of fluorescence in the respective cells. Receptors of the cells detect specific signal molecules and induce the formation of fluorescent proteins. In this work, genetically modified cells of the yeast Saccharomyces cerevisiae BY4741 were confined in a four-chamber microfluidic cell, providing an optical monitoring of the cell behaviour and their supply with the nutrients. The measurements of the time-dependent fluorescence intensity were performed with different concentrations of the drug diclofenac, and the sensitivity of yeast cells to diclofenac was demonstrated. Cell viability was monitored by simultaneous impedance recording.
Electrochemical live monitoring of tumor cell migration out of micro-tumors on an innovative multiwell high-dense microelectrode array
Understanding of cell migration and spreading out of tumor tissue is of great interest concerning the mechanism and causes of tumor malignancy and metastases. Although there are methods available for studying cell migration on monolayer cell cultures like transwell assays, novel techniques for monitoring cell spreading out of 3D organoids or tumor tissue samples are highly required. In this context, we developed an innovative high-dense microelectrode array for impedimetric monitoring of cell migration from 3D tumor cultures. For a proof of concept, a strongly migrating breast cancer cell line (MDA-MB-231) and two malignant melanoma cell lines (T30.6.9, T12.8.10ZII) were used for generating viable micro-tumor models. The migration propensity was determined by impedimetric monitoring over 144 hours, correlated by microscopy and validated by transwell assays. The impedimetric analysis of covered electrodes and the relative impedance maximum values revealed extended information regarding the contribution of proliferative effects. More strikingly, using reference populations of mitomycin C treated spheroids where proliferation was suppressed, distinction of proliferation and migration was possible. Therefore, our high-dense microelectrode array based impedimetric migration monitoring has the capability for an automated quantitative analysis system that can be easily scaled up as well as integrated in lab on chip devices.
The joint research project PhenoCor deals with the development of a medical diagnostic device (Clinical Multi Electrode Array, cMEA) for a better and more precise in-vitro stratifization, model-based therapy planning and clinical safety pharmacology for patients suffering from a genetically caused heart disease.
Our partners of the University of Leipzig and the University Clinic in Dresden are focusing on the assay and experimental design Sciospec`s role is to develop and build a massiv-multichannel system combining electro-physiological potential recording (EPR), electrical impedance spectroscopy (EIS), electrical impedance tomography (EIT) and complex stimulation within the same system. The system allows for fully simultaneous acquisition of impedance or potential signals on up to 512 electrodes in combination with up to 4 independent complex stimulation injections. This opens up new possibilities for monitoring highly dynamic and spatially distributed electro-physiological phenomena and allows in-depth insights into complex cell interactions. An application-specific sensor adapter brings together the measurement system and the newly designed high density sensor array with an innovative contacting scheme.
Find out more about the PCOR system.
PhenoCor is supported by the Free State of Saxony and the European Union (SMWA/EFRE).
Project number: 100387683