Microwells with Integrated Plasmonic Sensors and Narrow Channels to Study Cell Passage

Description

Cancer is a severe disease, with many new cases and deaths every year. For example, the American Cancer Society reported 1.9 million new cancer cases and 609,260 cancer deaths in 2022. According to the global cancer statistics from the International Agency of Research on Cancer, 19 million cancer cases and 10 million cancer deaths were observed in 2020 worldwide, compared with 17 million cancer cases and 9.5 million cancer deaths in 2018. About 20% of people will develop cancer during their lifetime. Further down the road, cancer cases are expected to rise to 30.2 million by 2040. With an improved understanding of cancer and improved diagnostic techniques and treatments, cancer survival has increased significantly throughout the world. During the past 20 years from 2001 to 2020, cancer death rates have been reduced by 27%. In the United States, deaths per 100,000 population have decreased from 196.5 to 144.1 and are targeted to be reduced further to 122.7 by 2030. Cancer should be diagnosed and treated during its early stages to attain high survival rates in patients with cancer. Cancer cells can migrate and spread beyond their originated sites and grow in distant areas of the body, resulting in metastatic cancer. Once metastasis occurs, cancer is difficult to treat and has decreased survival rate. For example, metastatic lung cancer has an extremely low 5-year survival rate of 7%. Therefore,understanding how cancer and normal cells squeeze through small passages will be beneficial to gain the needed knowledge in cancer metastasis.  We propose to develop micro- and nanotechnologies to form deep microwells with connecting channels to mimic a confined microenvironment similar to an extracellular matrix. In theseprecisely engineered platforms, highly sensitive nanoplasmonic sensors will be nanoimprinted in the microwells to detect nano-sized filopodium extensions from cell membranes as they migrate through the narrow channels.This process is similar to cancer metastasis as cells squeeze through small openings and migrate to other organs. The resonance peak shifts monitored by the nanoplasmonic sensors will be related to the reach of filopodia and the probability of cell passage. Moreover, the surface conditions in the platforms will be tuned by modifying the chemical coating and surface morphology to control cells squeezing through the channels in the presence of different cell types. The findings obtained in this project will providesignificant insights into cancer metastasis and cell separation, perhaps leading to early cancer diagnosis and effective treatments in the future.