Exceptional Points Enhanced Acoustic Sensing of Biological Cells

该奖项支持对用于细胞机械生物标记物高灵敏度测量的新生物传感概念的基本了解进行调查的研究。生物标记物，或生物标记物，是生物细胞状态或条件的可测量指标，并可与细胞功能和健康的变化密切相关。因此，能够测量多种细胞的力学性质作为生物标志物将有助于生物学研究和临床应用，如癌症研究、药物筛选/发现和免疫学。本项目中的声学传感概念依赖于异常点的检测，异常点是发生在非埃尔米特物理系统中的高度敏感的动态状态，其特征是增益和损耗平衡。该项目的长期研究目标是将该传感方案用于高通量测量单个细胞的机械生物标记物，用于基础研究和临床应用。研究结果也将有助于私人投资机构的长期教育和外展目标，即通过说明工程学的深远影响，激发学生对科学和工程的兴趣。项目活动还将具体说明工程师如何通过声学传感和基本波力学概念为生物医学做出贡献。这项研究的结果将造福于美国的健康和社会，影响到声传感、疾病诊断和细胞生物学领域。该项目将调查与具有不同机械属性(硬度、密度、可压缩性和粘性)的生物细胞如何与沿基质传播的声波相互作用、由细胞及其特性变化引起的扰动如何打破与例外点相关的动态平衡以及相应的频率分裂机制如何量化细胞特性的变化从而形成新的声生物传感技术的基础研究问题。项目目标将通过两项研究任务实现：(1)细胞-波相互作用的调查和声学基质中特殊点产生的基础研究；(2)基于特殊点的声生物传感的实验研究和概念验证。该项目将促进对声表面波与细胞相互作用的理解。研究具有腔体的声表面波衬底中异常点的产生是这项工作的一个新方面，它将探索多个波模与腔体-细胞共振的相互作用、它们的耦合和杂交。分析、数值和实验研究将探索细胞物理属性的例外点感测的敏感性，这将为感测开辟新的途径。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

This award supports research that investigates the fundamentals understanding of a novel biosensing concept for high-sensitivity measurement of cell mechanical biomarkers. Biomarkers, or biological markers, are measurable indicators of a biological cell state or condition and can be closely associated with changes in functionality and health of cells. Thus, the ability to measure multiple cell mechanical properties as biomarkers will benefit biological research and clinical applications such as cancer studies, drug screening/discovery, and immunology. The acoustic sensing concept in this project relies on the detection of exceptional points, which are highly sensitive dynamic states that occur in non-Hermitian physical systems characterized by balanced gain and loss. The long-term research goal of the project is to employ the sensing scheme for measuring mechanical biomarkers of individual cells in high throughput for both fundamental studies and clinical applications. The research findings will also contribute to the PIs’ long-term education and outreach goals of motivating students toward science and engineering, by illustrating far reaching implications of engineering. The project activities will also specifically illustrate how engineers contribute to biomedicine through acoustic sensing and fundamental wave mechanics concepts. Results from this research will benefit the US health and society, impacting the fields of acoustic sensing, disease diagnosis, and cellular biology.The project will investigate fundamental research questions related to how biological cells with different mechanical properties (stiffness, density, compressibility and viscosity) interact with acoustic waves propagating along a substrate, how perturbations caused by the cell and by changes in its properties can break the dynamic equilibrium associated with exceptional points, and how the corresponding frequency splitting mechanism can quantify changes in the cell properties and thus form the basis for a novel acoustic biosensing technique. The project objectives will be accomplished through two research tasks: (1) investigation of cell-wave interaction and fundamental studies on exceptional point generation in acoustic substrates; and (2) experimental investigations, and proof-of-concept of exceptional point-based acoustic biosensing. This project will lead to advances in the understanding of the interaction between surface acoustic waves and a cell. The study of exceptional points generation in surface acoustic waves substrates with a cavity is a novel aspect of the work, which will explore the interaction of multiple wave modes with cavity-cell resonances, their coupling and hybridization. Analytical, numerical, and experimental studies will explore the sensitivity of exceptional points sensing of the cell’s physical properties, which will open new pathways for sensing.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.