A lab-on-a-chip for characterising and sorting cancer cells

At present, more than one person dies from cancer every three minutes in the UK, or more than 440 per day, or more than 162,000 per annum. The projection of new cancer cases rises from about 298,000 per annum in 2007, to 432,000 by 2030 - an increase of 45% in the UK alone. The rise is explained almost entirely by the expected increase in the number of people living in the UK and the ageing population.

The dominant cause of cancer-associated mortality is tumour metastasis. At some point in their growth, solid tumours start to shed tumour cells into the bloodstream. These cells are called circulating tumour cells (CTCs), which have been considered as seeds spreading through the bloodstream to metastatic sites. CTCs are also treated as surrogates allowing doctors to determine the course of therapy and watch how a cancer evolves.

CTCs express considerable marker expression heterogeneity which has been recently recognised as a mechanism of resistance to systematic therapy. This project aims to reveal the characterisation of single CTCs by developing next generation lab-on-a-chip integrating microwave, ultrasonic and microfluidic technologies, which will characterise single CTCs and provide their real-time and label-free information for subsequent analyses.

The lab-on-a-chip will measure the dielectric properties of single CTCs, allowing the association to cellular morphology, proliferation, metabolism, cytoskeleton, viability, and cytoplasm. This project will develop a hybrid device to facilitate monitoring the cancer progression and treatment effectiveness, and reveal the makeup of CTCs to address specific mutations and phenotypic alterations, which will act as the first step to understand CTCs' behaviours in metastasis.

The proposed project will benefit a range of parties who are related to cancer research, by its contribution in advancing the knowledge of cancer metastasis and cancer biology. Meanwhile, the proposed research aligns with the efforts of the UK academic base to keep its leading in the area of cancer detection and CTC characterisation, which will have impact on:
i. Cancer patients. The proposed research will enable associating the dielectric signature to the molecular and phenotypic events of CTCs, which provides the opportunity to monitor cancer progression over time and facilitate appropriate modifications to a patient's therapy, potentially enhance their prognosis and quality of life.
ii. Health professionals in cancer care. Dielectric signature of the patient's CTCs can be used as an indicative factor for the presence and severity of metastasis. Professionals can implement a test for CTC to understand the progression in order to guide cancer care.
iii. Biologists. The knowledge of single CTC will be the supplement information for cancer biologists to study genetic heterogeneity of CTCs. Analysing the functional, molecular, and genetic alterations in CTCs can be implemented in real-time diagnosis and treatment.
iv. Cancer pharmaceutical industries. There are many applications of the potential use of CTCs as pharmacodynamics and predictive biomarkers, and their application in revealing drug resistance in real-time. The single CTCs analysis can target 'liquid biopsy' serving as a companion diagnosis for the pharmaceutical industry by incorporating CTCs based biomarkers as endpoints in future clinical trial design.
v. Cancer detection device manufacturers. The proposed project paves the way of developing a label-free and real-time miniature device integrating the CTC detection and analysis.
vi. National / International health services. Surveillance CTCs can identify patients at risk of recurrence before clinical evidence of disease in most patients and results in a reduced disease burden at relapse. Transformative technology developed from the potential outcome of the proposed project will be able to supplement biopsy in certain circumstances and predict disease progression, which will reduce substantial costs of cancer management.