# Exploring the Potential of Sensing for Breast Cancer Detection
## 5 Biosensors for Breast Cancer Detection
### Electrochemical Impedance Spectroscopy  
Electrochemical impedance spectroscopy (EIS) applies an external sinusoidal potential/current to an electrochemical system and measures the corresponding outcome sinusoidal potential/current [143; 144; 145]. The applied potential has several features, viz., amplitude, angular frequency, and time dependency, and the corresponding output current has similar characteristics. However, the output current experiences a phase shift from the input external potential [144]. So, to reiterate, the input and output signals should have the same angular frequency, but a phase shift or a phase angle may offset the output signal. A complete EIS experiment applies a sinusoidal potential with different frequencies instead of a single frequency, and corresponding output currents are measured. So, a frequency spectrum is observed instead of a single frequency. Fourier transform has been utilized to convert all input and output signals from the time domain to the frequency domain. The experimental setup is a frequency-dependent system, so the impedance is calculated by calculating the ratio of the frequency-dependent potential over the frequency-dependent current [145]. The phase angle and impedance are a function of frequency, and the associated plot is known as a body plot. Sometimes, a Nyquist plot is used to show the real and imaginary impedance. The time scale is a critical parameter in electrochemical processes [145], and in most cases, the time scale associated with different mechanisms cannot be recognized globally but can be recognized locally. For example, double-layer charging can occur in a few microseconds while diffusion can happen in a time scale of hundreds of milliseconds [144]. These two mechanisms have two distinct time scales for completion, but in electrochemistry, these two-time scales are not distinguishable. For example, in a DC voltammetry experiment, a step potential or a linear sweep is applied, and the corresponding measured current is the combination of different electrochemical processes occurring within a specific time. In that case, it is not easy to differentiate the current related to the double-layer charging or diffusion. So, DC voltammetry cannot provide a detailed picture of different mechanisms and their associated development time. On the other hand, EIS, in which oscillating perturbations are applied and corresponding currents are measured, can provide detailed pictures of individual internal mechanisms of the electrochemical reaction, and this EIS method is able to discern different electrochemical phenomena because they occur at different frequencies. EIS is widely used for direct monitoring of antibody-antigen connected reactions, DNA hybridization, and enzyme reactions, and the sensitivity of EIS can reach up to ug/mL to pg/mL [146; 147]. In [143], the authors employed the impedance spectroscopy method and differentiated early-stage, invasive, and metastasized human breast cancer lines MCF-7, MDA-MB-231, and MDA-MB-435, respectively, from the standard breast tissue cell line MCF-10A. They measured the impedance for both normal breast cells and three other cancerous cell lines over a frequency range of 100 Hz to 3.0 MHz and observed the following: (a) the magnitude of the impedance decreased with frequency; (b) the phase of the impedance initially decreased and further increased with frequency; (c) there was a significant difference between the standard cell line (for both magnitude and phase of the impedance) and the other three cancerous cell lines; (d) the magnitude and phase of the impedance decreased (increased) following the order MCF-10A, MCF-7, MDA-MB-231, and MDA-MB-435. In [148], authors identified the spectroscopic patterns for three different pathologic stages, viz., the early stage (MCF-7), invasive phase (MDA-MB-231), and metastasis (SK-BR-3), by employing bioimpedance spectroscopy under the consideration of magnetic nanoparticles.