Cancer is one of the leading causes of death, second only to heart disease. Traditional cancer treatment (radiotherapy and chemotherapy, immunotherapy, and targeted therapy) is in need of new and synergistic modalities to increase survival, and tumor-treating fields (TTF) have been heralded as the "fourth modality" in cancer treatment. To date tumor-treating fields has been applied mostly to glioblastoma (FDA approved) and there is excitement to apply this therapy to other cancers, as evidenced by multiple ongoing clinical trials. This research will help to improve the understanding of the physical mechanisms by which this treatment works, discovering synergies with key chemotherapeutic and targeted molecular therapies, and optimizing it for each cancer cell type - and potentially to each patient's own tissue. Using a custom integrated circuit, we will develop sensors that can detect cells and image tissue using very high frequency electromagnetic fields (100-300 GHz) which have been shown to be effective at differentiating between tumor cells and healthy cells, and also between actively dividing cells and non-dividing cells. This will be used as a tool to detect the cell state during the application of tumor-treating fields to the cell. The hope is to both understand the biological reasons for the efficacy of tumor-treating fields and also to help optimize the voltage and frequency of the tumor-treating fields. This research opens the door to a future implantable device using the developed sensors that could in real time aid in the discovery of efficacious treatments - conveying instantaneous cellular response to therapy to allow real-time optimization of treatment for each patient - the ultimate goal of personalized medicine.
The proposed sensor platform integrates arrays of terahertz sensors for tissue-scale sub-cellular imaging into traditional Complementary Metal Oxide Semiconductor (CMOS) technology, allowing miniaturization and integration with other functions including on-chip signal processing and communication. Previous research has demonstrated that tumor cells can be identified without using any special markers or labels by measurement of the frequency dispersion of the dielectric constant. Most measurement platforms to date either measure cells in bulk or can only measure a single pixel at a time, and lack spatial resolution to measure sub-cellular structures. A true imaging platform that can measure the dielectric constant over a very small spatial resolution will be realized by leveraging the array-based nature of CMOS technology for imaging larger tissue areas - thereby permitting one to dynamically map the contents within a cell while using lower frequency electromagnetic (EM) fields to actuate the cell. Using frequencies over 100 GHz allows miniaturization of individual pixel elements, but this requires innovation to improve the sensitivity of the sensors. By simultaneously sensing the cells with high frequencies and activating the cells with low frequencies (so called Tumor Treating Fields), one will have the ability to actively manipulate and monitor cell division - key to cancer treatment. Tumor Treating Fields (TTF) have been shown to disrupt normal cell mitosis by interacting with strongly polarized molecules. Recently, TTF has been shown to be effective in treatment of certain kinds of cancers, most notably glioblastoma (GBM), a highly aggressive brain tumor. This is the first such advance in this disease in decades, and is synergistic with select chemotherapies. The proposed research investigates the ability to control, study and optimize EM fields on single cells within the context of a more complex tissue microenvironment, which is necessary to optimize TTF and select drug combinations but has heretofore been unattainable.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
