Circulating tumor cells and detection concept
Despite progress in early diagnosis and introduction of novel therapy, cancer will continue to be a leading cause of death during the coming decades. A major reason is the early blood borne spread of tumour cells, in many cases also before diagnosis. In fact, about 90 % of cancer-related deaths are caused by metastatic spread of the initial tumour.
Detection of occult tumour cells (OTC), e.g. circulating tumour cells (CTC) in peripheral blood may have a substantial impact on the prognosis and optimal disease management of patients with cancer. The major challenge in the detection and quantification of circulating tumour cells (CTCs) is their apparent extreme rarity in clinical samples; the desirable target range is below one tumour cell per ml of blood corresponding to a 107 – 108 dilution.
The project aim is to develop a new technique for fast detection of circulating tumour cells (CTC) in blood samples. Prospective tumour cells will be isolated, counted and identified based on detection of protein markers and transcripts. To accomplish this challenging goal, we will use a single-chip approach with microfluidic handling of single cells and a multiple parallel readout of a set of nanowires functionalised with different receptors. The goal is to reach a detection sensitivity of ~1 CTC per ml blood or better – as required in clinical cancer diagnostics.
The reason for using nanowires/nanoribbons as detection media is twofold: It allows very sensitive detection and provides easy upscaling for probing a large number of biomolecules simultaneously. The method is, furthermore, label-free, enabling direct electrical detection without adding fluorophores thus avoiding the complicated optical read-out scheme of many different channels.
The mechanism for sensing may be explained by charging effects when target molecules hybridise with antibodies/probes bound to the nanowire surface. This induces a depletion or an accumulation of carriers in the nanowire resulting in a change in current which may be detected. Acting like a gate in a MOS transistor, this provides an internal gain mechanism and a very high sensitivity may be achieved approaching the femto-molar (10-15 M) range.
In cancer diagnosis and treatment there is a clear need of minimally invasive techniques. Examples are non-surgical tumours of the lung, pancreas, liver, colo-rectal and also cancer with unknown primary tumour. The technology suggested here has the prospects of providing a diagnosis where routine diagnostic procedures are hazardous leaving many patients without a correct diagnosis. For these patients molecular markers contained in CTCs would help with diagnosis and also for therapeutic decisions. The presence of CTCs may also indicate prognosis as well as serve as read out of therapeutic efficacy.