Fabrication Of Three Dimensional Micro/nano Array-based Cancer Cell Biosensor

Cancer is one of the serious threats to the health of human beings nowadays,and restricts the improvement of human living quality.Early diagnosis of cancer is crucial to reducing the high lethality and patients' spending.Circulating tumor cells is one of the important indexes of cancer progression and prognosis.The operation of existing detection methods,such as the Cell Search system,are complicated and high-cost,Therefore,it is quite urgent to develop new methods to detect circulating tumor cellswith easy operation,high efficiency and low cost.In this thesis,nano-imprinting technique was applied to fabricate surfaces with various 3D micro/nano arrays.They were used as working electrode of electrochemical impedance analysis after the modification of amino benzene boric acid.Meanwhile,the influences of the morphology and size of the 3D micro/nano arrays on its ability to capture tumor cells was illustrated as well.The details are as follows:We designed and fabricated a series of 3D micro/nano arrays with different width and spacing on the IPS substrate.A thin gold film was fabricated by magnetron sputtering on the surface of substrate.Organic molecules containing benzene boric acid were modified on the surface of gold layer.The cancer cells can be captured by the interaction between the benzene boric acid and sialic acid,which is over expressed on the surface of cancer cells.The influences of the morphology and size of the 3D micro/nano arrays on its ability to capture tumor cells was studied.It can be found that when the width/interval size of the 3D array was in the range of2-16 ?m,cells capture efficiency increased with the decrease of the width/interval size.Meanwhile,when the depth of the arrays was in the range of 0.1 to 2 ?m,the cells capture efficiency increased with increasing depth.The morphology of the 3D structure also had an influence on the capture efficiency.The cylindrical structure can capture more cancer cells than cuboid structure.We chose the cylindrical structure with highest cells capture efficiency as a working electrode and study the relationship between the impedance change and concentration of tumor cells.It can be found that there was a linear relationship between the impedance and log CMCF-7 in both PBS solution and whole blood.There was still a good impedance signal response when the concentration of cancer cells is as low as 5 per milliliter,demonstrating that the prepared electrochemical impedance spectroscopy biosensorhas a good ability of detecting cancer cells.In summary,we prepared a biosensor for detecting cancer cells with good reproducibility,low cost,low detection limit and low environmental requirements,which was expected to detect circulating tumor cells in cancer patients clinically.