Exceptional Points Enhanced Acoustic Sensing of Biological Cells

该奖项支持的研究调查了对细胞机械生物标志物高灵敏度测量的新型生物传感概念的基本理解。生物标记物是生物细胞状态或状态的可测量指标，与细胞功能和健康的变化密切相关。因此，测量多种细胞力学特性作为生物标志物的能力将有利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，异常点是发生在以平衡增益和损失为特征的非厄米物理系统中的高度敏感动态状态。该项目的长期研究目标是采用传感方案高通量测量单个细胞的机械生物标志物，用于基础研究和临床应用。研究结果还将有助于pi的长期教育和推广目标，通过说明工程的深远影响，激励学生学习科学和工程。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动力学概念为生物医学做出贡献。这项研究的结果将有益于美国的健康和社会，影响声学传感、疾病诊断和细胞生物学等领域。该项目将研究与以下相关的基础研究问题：具有不同机械特性（刚度、密度、压缩性和粘度）的生物细胞如何与沿基底传播的声波相互作用，细胞及其特性变化引起的扰动如何打破与异常点相关的动态平衡。以及相应的频率分裂机制如何量化细胞特性的变化，从而形成一种新的声学生物传感技术的基础。项目目标将通过两项研究任务来完成：(1)调查细胞波相互作用和声学基底异常点生成的基础研究；(2)基于点的声学生物传感的实验研究和概念验证。这个项目将导致在理解表面声波和细胞之间的相互作用方面取得进展。具有腔体的表面声波基底中异常点产生的研究是这项工作的一个新方面，它将探索具有腔-细胞共振的多种波模式的相互作用，它们的耦合和杂交。分析、数值和实验研究将探索异常点感知细胞物理特性的敏感性，这将为感知开辟新的途径。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值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.