Rapid Separation of B-lymphoma and Red Blood Cells by Optically-induced Electrokinetics

Description

Lymphoma patients have a significant risk of life-threatening complications arising from both the spreading of infections and metastasis of the cancer cells to other organs such as the spleen, kidneys, bones, and the nervous system. Therefore, finding a sensitive and specific early detection method for lymphoma is critical to saving lives and improving our understanding of other types of cancers. In the microscale, lymphoma is a cancer of thelymphocytes, which are several types of white blood cells that form part of the human immune system. Exploring the clinicopathological characteristics of lymphoma cells from patients is essential for revealing the pathologic properties of the malignant tissues of the patients, and for evaluating the prognosis of the patients in order to choose the best treatment for each patient. There are many types of lymphomas, and treatment for lymphoma patients might involve targeted drug therapy, chemotherapy, radiotherapy, and bone marrow transplantation. Survival rates after these treatments depend on the histology, type, and stage of the disease. However, different lymphoma patients exhibit distinctive drug resistance responses when presented with the same drug during targeted clinical therapy. Thus, exploring the characteristics of human lymphoma cells, such as the roughness and stiffness of the cells, is essential for understanding the cell pathology and deducing the appropriate corresponding medical therapy. However, extracting lymphoma cells from a patient’s bone marrow is extremely difficult, as the red blood cells (RBCs) mixed in the extracted biofluid outnumber the lymphoma cells. Currently, there is no gold standard technique in hospitals worldwide to efficiently differentiate the lymphoma cells from a much larger population of RBCs. Established technologies, including FACS (fluorescence activated cell sorting) and cell separation by centrifugation, still do not yield reliable and high-throughput extraction of lymphoma cells from bone marrows in general.The ultimate aim of our research team is to develop an integrated high-throughput and high-yield cell-extraction technology for obtaining lymphoma cells from bone marrow, and allow medical researchers to examine the pathology of the lymphoma cells in clinical environments. In this project, we will work with medical scientists to investigate a new technology that will efficiently separate B-lymphoma cells (cancerous B-lymphocytes) and RBCs. The following major objectives will be achieved in the next 3 years: 1) develop anoptically-induced electrokinetics(OEK) platform to allow rapid separation (~100um/sec cell manipulation speed) of lymphoma and red blood cells; 2) perform parametric experimental studies to identify optimal biofluidic media that allow effective separation of the cells using optically-induced electrokinetics, and at the same time, allow for the long-term viability of the cells in the media; 3) explore theoretical models and multi-physics simulations to elucidate the underlining relationship between optically-induced electrokinetics forces and the morphology and electrical properties of the cells. In order to achieve these major objectives of the project, an OEK chip will be integrated with customized microfluidic components, and along with specialized computer algorithms, anOEK platformwill be developed to automatically differentiate and separate B-lymphoma cells and RBCs.