CAREER: Acoustics Lab on a Chip for Comprehensive Biophysical Studies of Tumor Cells: Towards Personalized Cancer Diagnosis and Therapeutics

本CAREER提案的主要目标是开发表面声波设备沿着相关的化学和生物传感器，以研究细胞的生物力学特性及其与疾病的关系。应用于细胞水平的声波可用于阐明细胞的生物物理特性，并以当前技术不可能达到的准确性和灵敏度揭示诊断和治疗特征。本CAREER提案的研究目标是通过三个步骤来验证这一假设：1.设计、开发和表征集成有新型磁性细胞捕获和表面声波（SAW）换能器的单片细胞生物学芯片实验室（CBIs），2.研究和评估SAW用于非侵入性，对肿瘤细胞进行非接触式声致穿孔和转染研究，并识别每种细胞类型的独特声学特征，用于疾病诊断、治疗以及药物筛选测试，3.在集成了微流体和芯片电子的CMOS声学微流控芯片上进行细胞生物力学特性的系统研究，作为疾病类型和状态的函数。定量地了解细胞的机械特性及其与细胞健康的关系可以提供一种方法来优雅地区分细胞，而不使用可能需要改变其生化特性的化学传感技术。状态这些研究可以改变目前的医学状况，并有可能原位捕获和破坏循环肿瘤细胞，从而消除转移现象。此外，该项目将产生新的资源，在电气，生物医学工程，分子生物学，生物化学和癌症病理学领域的研究人员共享知识和合作。特别是在癌症诊断和治疗、细胞机械传导、机械生物学、微细加工、声波器件和集成电子学方面传播新的知识和科学。更广泛的影响：拟议的多学科项目预计将改变迈阿密大学（UM）的工程和生命科学教育，并将教育活动和尖端研究相结合。PI设想对生物纳米技术，MEMS和VLSI领域的下一代工程师和科学家的培训产生变革性影响。超过25%的学生是西班牙裔，UM很自豪能够在美国为西班牙裔服务的大学中排名第一。此外，工程学院在全国获得学士学位的女性比例排名第15位。在工程学方面。这种显著的多样性反映在PI研究小组的学生成员中。

The main objective of this CAREER proposal is to develop surface acoustic wave devices along with the associated chemical and biological sensors to study the bio-mechanical properties of cells and its relationship to disease. Acoustic waves applied at the cellular level can be used to elucidate biophysical properties of cells and reveal diagnostic as well as therapeutic signatures with accuracy and sensitivity that are not possible to attain in current technologies. The research objective of this CAREER proposal is to test this hypothesis in three steps: 1.Design, develop and characterize a monolithic cell biology lab-on-a-chip (LOC) integrated with novel magnetic cell capture and surface acoustic wave (SAW) transducers, 2.Study and evaluate the efficacy of SAWs for non-invasive, contactless sonoporation and transfection studies on tumor cells and identify the unique acoustic signature of each cell type for disease diagnostics, therapeutics as well as drug screening tests, 3.Carry out systematic studies of cell biomechanical properties as a function of disease type and state on a CMOS Acoustic LOC with integrated microfluidics and on chip electronics.Intellectual Merit: Quantitatively understanding the mechanical properties of cells and their relationship to the cells health may provide a method to elegantly differentiate between cells without using chemical sensing techniques that may require alteration of their biochemical state. These studies can transform the current state of medicine and potentially enable the in-situ capture and destruction of circulating tumor cells hence obliterating the metastasis phenomenon. In addition, this project will produce novel resources in sharing knowledge and collaboration of researchers in the fields of electrical, biomedical engineering, molecular biology, biochemistry and cancer pathology. In particular, new knowledge and science will be disseminated in cancer diagnosis and therapy, cellular mechanotransduction, mechanobiology, microfabrication, acoustic wave devices and integrated electronics.Broader Impacts: Proposed multidisciplinary project is expected to transform the engineering and life sciences education at University of Miami (UM) and integrate educational activities and cutting-edge research. The PI envisions a transformational effect on the training of next generation engineers and scientists in the discipline transcending fields of bionanotechnology, MEMS and VLSI. With over 25% of the students being of Hispanic descent, UM is proud to be ranked 1st among universities serving Hispanics in the United States. In addition, College of Engineering is ranked 15th in the nation for the percentage of women who were awarded a B.S. in engineering. This remarkable diversity is reflected in the student members of the PI's research group.