Fabrication of antibody functionalized silk fibroin micro-well arrays using reactive inkjet printing for circulating tumour cell capture

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Cancer is a group of diseases caused by the abnormal growth of cells and can potentially spread to other parts of the body. It has been the major threat to human health worldwide, counting for 8.2 million deaths (2012). In UK, there are 0.3 million new cancer patients every year with more than 200 types of cancers of which breast, lung, colon and prostate cancers are the most common types. Some of the cancers such as prostate cancer have no early symptoms making the prognosis extremely difficult. Therefore, effective tools for early detection of cancer are highly desired and can greatly increase the chances for successful treatment or extend the lifetime. Circulating tumour cells (CTCs) are cell seeds that have shed from a primary tumour and circulate in the blood stream and can subsequent growth into additional tumours. Isolation and characterization of CTCs have been proved to be effective in cancer prognosis. However, this task is extremely challenging due to the significant low abundance of CTCs in blood (a few to tens in a millilitre of blood which contains millions of white and red blood cells). Currently, CellSearch is the only FDA approved CTC capture device that require specific equipment to perform the analysis and are not able to discriminate from different types of cancers. Furthermore, the captured CTCs on the filter membrane need to be transferred to a cell culture plate for enumeration/characterization. Hence, there is an urgent need to develop efficient high throughput screen devices/methods that can screen multiple cancers in one test with excellent sensitivity.The proposed research, envisaging this challenging task and urgent needs, seeks to harness the emerging additive manufacturing technology (reactive inkjet printing, RIJ) and the FDA approved biomaterial (regenerated silk fibroin, RSF) for the fabrication of antibody functionalized micro-well arrays for the capture and sorting of CTCs. The advantages of RIJ are not only the computer assisted design (CAD) that offers the precise delivery of pico-litres (1e-12 litre) of ink at predetermined locations allowing the fabrication of complex micro arrays but also the alternate delivery of different antibody inks (through different print heads) that allows the functionalization of different micro-wells with different cancer biomarker antibodies. The fabricated devices will not only allow us to efficiently capture the rare CTCs but also allow us to discriminate different types of cancer cells, providing a promising tool for efficient cancer diagnosis. The project also extends the knowledge and skills of employing emerging additive manufacturing technology for cost-effective manufacturing of high value products. Therefore, this project firmly aligns with EPSRC priority themes of Healthcare technologies (novel diagnostic tools) and Manufacturing the future and will have significant impact to cancer diagnosis and medical device manufacturing industry.