TERACELL: Integrated Microwave-to-Terahertz Sensors for label-free circulating tumour cell detection

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Label-free detection of circulating tumour cells (CTCs) is considered to be one of the holy grails of biosensing. CTCs are malignant cells shed into the bloodstream from a tumour, which have the potential to establish metastases. The separation and subsequent characterization of these cells is of vital importance for cancer diagnosis and development of personalized cancer therapies. Biochemical CTC separation methods have proven to be highly inefficient and, therefore, preventive screening by sole blood analysis is currently not reliable. Microwave-to-terahertz dielectric measurements were successfully used for the identification of cancer cells; their capability for tumour tissue imaging is clinically established as a viable alternative to X-rays and MRI. The frequency range from 10 GHz up to about 1 THz is extremely promising for the detection of single tumour cells. Due to the diminishing cell membrane polarization effects, the cell membrane becomes transparent, but cell scattering is still negligible, in contrast to that found in the visible and near/medium-infrared range. Due to the high electromagnetic absorption of water up to about 1 THz, electromagnetic resonators with high quality factors and highly concentrated electric field within a small integrated microfluidic reservoir (previously demonstrated by the team), which essentially contains one cell at a time, represent an ideal system for fast and accurate dielectric measurements. This is because the single cell lies within their natural liquid environment. In order to tackle the problem of extremely low abundance of CTCs in blood samples, we intend to combine microfluidic separation techniques with integrated microwave-to-terahertz resonators on one chip or as a multichip combination, aiming towards a lab-on-chip approach for clinical applications. In order to achieve this ambitious goal, within this three-year project, we suggest a multidisciplinary approach, based on the expertise of the associated members of Imperial's Centre for Terahertz Science and Engineering (made up of academics and researchers from the Depts. of Materials, Electrical and Electronic Engineering and Physics), along with selected groups from dedicated areas of Life Sciences (which includes cancer cell biology and cell biosensing), plus the expertise of oncologists from Imperial's Faculty of Medicine. A variety of tumour cell suspension of defined concentration based on whole blood, serum or water being derived from a murine model will be our gold standard approach for the generation of a database of dielectric properties of different types of tumour cells, for the optimization of different sensor chip approaches, and for the development of cell detection methods. As a key milestone, towards the end of the project, we will demonstrate CTC detection in human blood samples.As the main engineering challenge of this project, three different electromagnetic resonator approaches will be investigated, based on our previous work on silicon MEMS technology for nanolitre liquid measurements: dielectric resonators, photonic crystals and spoof plasmon-based metamaterials. Advanced micro- and nano-machining techniques like deep reactive ion etching, e-beam lithography and focussed ion-beam etching will be employed for the manufacturing of fully-integrated (sub-) THz resonator-microfluidic systems.On the way towards the grand challenge of CTC detection, we intend to investigate two potential applications, which may generate clinical impact on a shorter timescale: Label-free detection of leukaemia cells within a murine model and bladder cancer cell detection in human urine samples. In both cases, the expected cell abundance is much higher than in the case of CTC, but the methods of dielectric cell recognition are identical to CTC detection. Follow-up projects including clinical studies plus stronger involvement of industry are likely to be launched during the time-span of this project.