In fact, the role of CTCs as a prognosis factor and their use for early detection of metastasis events are recognised for several tumours such as breast, colorectal, lung and prostate cancers [8�C12].Inclusion of the sequential follow-up of CTCs in clinical trials could provide information in the early stages about the therapeutic efficacy of the drugs against the presence of metastatic tumour cells. Likewise, elimination of these CTCs could represent an intermediate endpoint in clinical trials with antitumour drugs [13].To enrich or sort CTCs from peripheral blood, several approaches have been published, some of which are summarised in this review. CTCs enrichment methods are based on physical or biological cell properties such as size or specific marker expression.

Although most of the CTCs isolation techniques can be carried out in a semi-automated manner, they are laborious procedures with variable efficiency [14]. Besides, after the isolation process, a next step is required to identify CTCs with high specificity. This step is normally tedious and time-consuming, using techniques such as PCR, immunofluorescence, or flow cytometry [15]. To solve these limitations, detection approaches using sensor technology are being combined with traditional CTCs isolation procedures.Biosensors are defined as analytical devices composed of a recognition element of biological origin integrated into or associated with a physico-chemical transducer. The biological event produces a measurable change in a solution property, which the transducer converts into a quantifiable electrical signal [16].

Often, the term biosensor is used when the concentration of substances or other biological parameters are determined even where a biological recognition element is not used directly.Recognition elements include enzymes, immunoagents, DNA segments, and even whole cells, all of which are coupled to different modes of transduction [17]. The mode of transduction covers several approaches, including electrochemical, optical, and mass measurement. Some biosensors are considered point-of-care devices (POC). POC diagnostics are medical tools that can be used outside of a hospital setting and tend to be portable, fast, and relatively inexpensive [18]. More advantages of biosensor application are that they are easy to use, miniaturised (lab-on-a-chip devices), and offer robust results compared with classical analytical techniques such as immunohistochemistry or ELISA [19].

In the last years, several label-free biosensing technologies for the detection and monitoring of clinical relevant molecules such as glucose, hCG or cardiac markers for diabetes, pregnancy test, or cardiac diseases have been reported [20,21]. Currently, the use of biosensors for live CTCs Entinostat detection and monitoring is a challenge, taking into account the great biological heterogeneity of CTCs.