Dynamic and Fatigue Analysis of Healthy and Diseased Red Blood Cells

健康和患病红细胞的动态和疲劳分析

• 批准号: 1635312
• 负责人: Sarah Du
• 金额: $ 39.97万
• 依托单位: Florida Atlantic University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1635312&HistoricalAwards=false
• 关键词: Dynamic; Fatigue; Analysis; Healthy; Diseased

Red blood cells experience a tremendous amount of shearing, stretching and bending as they circulate through the body. Progressive damage occurs in the circulating cells before they are removed and replaced with new ones. Much of the research on cellular biomechanics focuses on a single application of load, which does not reproduce the dynamic repetitive loading that the cells experience in the body. This research will use a new microfluidic tool to apply repetitive cell loading to create a fundamental understanding of the mechanical origins of damage in circulating red blood cells. The results will provide quantitative links between cellular biomechanics and cell biology, thus advancing our understanding of the significantly shortened lifespan of transfused red blood cells and those made abnormal by diseases. The multidisciplinary approach will broaden participation of underrepresented groups in Science and Engineering. The PI is placing special emphasis on encouraging women students to participate research at the interface of engineering and life sciences.The objective of this research is to establish the fundamental correlations between the cellular dynamic and fatigue properties, the in vivo circulation history and influences from pathophysiological factors in human red blood cells. This work specifically addresses questions: (a) how to implement the dynamic viscoelasticity and fatigue measurements of individual cells at a relatively high throughput, and (b) how to quantify the pathophysiological influences on cellular biomechanics. This research will develop an experimental strategy for dynamic and fatigue measurement of single cells, by integrating knowledge and techniques of microfluidics, alternating current electrokinetics, digital modulation and biomechanics. The damage process in cell membranes caused by the mechanical forces in circulation is significantly analogous to material fatigue. Experimentally determined Wöhler curves in combination with Miner's rule will be used for remaining life prediction in red blood cells influenced by in vivo aging and sickle cell disease. Novelty of this research lies in the new experimental strategy and a new perspective in cellular biomechanics.

红细胞在体内循环时会经历大量的剪切、拉伸和弯曲。在循环细胞被移除并被新细胞取代之前，循环细胞会发生渐进性损伤。细胞生物力学的大部分研究集中在单一的负载应用上，这并不能再现细胞在体内经历的动态重复负载。这项研究将使用一种新的微流体工具来应用重复的细胞加载，以建立对循环红细胞损伤的机械起源的基本理解。这些结果将提供细胞生物力学和细胞生物学之间的定量联系，从而推进我们对输血红细胞寿命显著缩短以及疾病导致异常的理解。多学科方法将扩大科学和工程领域代表性不足的群体的参与。PI特别重视鼓励女学生参与工程学和生命科学领域的研究，这项研究的目的是建立细胞动力学和疲劳特性、体内循环史和人体红细胞病理生理因素影响之间的基本关系。这项工作具体解决的问题：（a）如何实现动态粘弹性和疲劳测量的单个细胞在一个相对较高的吞吐量，以及（B）如何量化的病理生理影响细胞生物力学。本研究将通过整合微流体、交流电动力学、数字调制和生物力学的知识和技术，开发单细胞动态和疲劳测量的实验策略。由循环中的机械力引起的细胞膜的损伤过程与材料疲劳非常相似。实验确定的Wöhler曲线结合Miner规则将用于受体内老化和镰状细胞病影响的红细胞的剩余寿命预测。本研究的新奇在于新的实验策略和细胞生物力学的新视角。

项目成果

Rapid electrical impedance detection of sickle cell vaso-occlusion in microfluidic device

微流控装置中镰状细胞血管闭塞的快速电阻抗检测

• DOI: 10.1007/s10544-023-00663-1
• 发表时间: 2023
• 期刊: Biomedical Microdevices
• 影响因子: 2.8
• 作者: Qiang, Yuhao;Dieujuste, Darryl;Liu, Jia;Alvarez, Ofelia
• 通讯作者: Alvarez, Ofelia

Electrical Impedance Characterization of Erythrocyte Response to Cyclic Hypoxia in Sickle Cell Disease

• DOI: 10.1021/acssensors.9b00263
• 发表时间: 2019-07-01
• 期刊: ACS SENSORS
• 影响因子: 8.9
• 作者: Liu, Jia;Qiang, Yuhao;Du, E.
• 通讯作者: Du, E.

Mechanical fatigue of human red blood cells

• DOI: 10.1073/pnas.1910336116
• 发表时间: 2019-10-01
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Qiang, Yuhao;Liu, Jia;Du, E.
• 通讯作者: Du, E.

Erythrocyte Membrane Failure by Electromechanical Stress

• DOI: 10.3390/app8020174
• 发表时间: 2018-02-01
• 期刊: APPLIED SCIENCES-BASEL
• 影响因子: 2.7
• 作者: Du, E.;Qiang, Yuhao;Liu, Jia
• 通讯作者: Liu, Jia

Dielectrophoresis Testing of Nonlinear Viscoelastic Behaviors of Human Red Blood Cells

人红细胞非线性粘弹性行为的介电泳测试

• DOI: 10.3390/mi9010021
• 发表时间: 2018
• 期刊: Micromachines
• 影响因子: 3.4
• 作者: Qiang, Y.