High Sensitivity 3D Plasmonic Biosensor Enhanced by Electric Field and Shear Flow

Description

In Hong Kong, cancer causes more than 30% of deaths in 2015 and it is considered to be one of the most deadly diseases. Many new cases of cancer are diagnosed each year. In 2016, new cancer cases exceeded 1.6 million in US and close to 600,000 cancer deaths were reported. Early diagnosis and screening can greatly improve the cancer survival rate. Therefore it is important to be able to detect cancer at an early stage even when the obvious symptoms have not yet occurred.While cancer affects people of all ages, the incidence rate increases rapidly with age for most cancers. In Hong Kong, the life expectancy is currently at 79.5 years old, which is among the top three in the world. The proportion of elderly at age 65 and over is expected to reach 27% in 2033. Therefore, early detection and treatment of cancer related diseases become more important as it affects a growing number of people in Hong Kong and in the world. It is known that 90% of cancer deaths result from metastases that involve cancer cells spreading from the primary tumor to surrounding tissues or to organs at a distant. The spreading of cancer is due to cancer cell detachment from the primary tumor site and moves into the blood or lymphatic vessels. Circulating tumor cells (CTCs) are tumor cells that circulate in patients’ blood vessels and they are considered as predictive biomarker for metastatic development and recurrence. However, CTCs are in very low concentration (~10 CTCs/ml) in cancer patients, and they are difficult to be detected for early cancer diagnosis.In addition to CTCs, exosomes could also be released from the primary tumor but they are more abundant and could be used for early cancer detection. Exosomes carry the same mRNA, DNA, and signal lipids as the primary tumor and they are small vesicles with typical size range of 30 to 300 nm. It is believed that cancer cells often release more exosomes compared to normal cells, and they could be used as biomarkers related to cancer development. Despite such clinical potential for early detection of tumors, capturing and detecting exosomes is challenging due to their small size and low buoyant density.Therefore, we propose to develop a microsystem with nanometer size threedimensional (3D) plasmonic biosensors that have high sensitivity to detect low concentration exosomes. The 3D plasmonic nanostructures will include different plasmonic designs such as Au nanodots, nanosquares, nanobars, nanorings, and nanoholes stacked on top of one another to provide the hybrid-coupling effect of the Fano resonance and Fabry-Perot cavity modes. With multiple layers of nanostructures, it is expected that these 3D plasmonic biosensors could result in higher sensitivity and figure of merit with tunable resonance peaks in visible and near-infrared regions for early detection of exosomes in low concentration.To enhance the detection efficiency, the 3D plasmonic sensor array will be integrated with asymmetrical electrodes to provide electric field induced dielectrophoresis (DEP) force and nanogratings to promote flow induced shear force in a microfluidic platform for effective capturing of exosomes. In combination with the 3D plasmonic biosensors and the external forces due to DEP and shear flow, low concentration exosomes in the form of nanometer size vesicles could be detected during the early stage of cancer development. The early cancer screening through sensing low concentration exosomes allows timely treatment of cancer that could greatly increase patient survival rate.