A Novel Bioimpedance Sensor for Intracellular Hemoglobin Analysis in Single Sickle Cells

用于单镰状细胞胞内血红蛋白分析的新型生物阻抗传感器

• 批准号: 2032730
• 负责人: Sarah Du
• 金额: $ 40.27万
• 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: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2032730&HistoricalAwards=false
• 关键词: Novel; Bioimpedance; Sensor; Intracellular; Hemoglobin

Sickle cell disease is an inherited red blood cell disorder that affects hemoglobin, the oxygen-carrying protein inside the red blood cells. Sickle hemoglobin is the fundamental cause of abnormalities in sickle cell shape, deformability and blood flow behavior, leading to various symptoms and complications. Variabilities in complications and disease severity are expected over time. A major challenge in understanding the extreme heterogeneities of sickle cell disease is the inability to measure the sickle hemoglobin within the single sickle cells. This research aims to overcome this challenge by developing a microfabricated sensor that can measure the amount of abnormal sickle hemoglobin without breaking down cell membranes. This interdisciplinary project provides research training to women and underrepresented minority students, in biosensing, cell biophysics, microfabrication, and microfluidics. The research findings and technological development are incorporated into course development and disseminated to students at undergraduate and graduate levels. Sickle cell disease is known for its extreme heterogeneities in cell morphology, deformability, hemorheology, and severity of clinical symptoms and complications, which are linked to the intracellular hemoglobin variations. This project develops a microfluidics-based single-cell assay of intracellular sickle hemoglobin, using a sequential bioimpedance sensing of sickle cells under controlled oxygen levels in a microflow cytometry setting. Integration of hypoxic microenvironment with impedance sensing allows selective measurement of intracellular sickle hemoglobin variant from the induced cell sickling process in single cells. Three research objectives include: (i) establishment of a bioimpedance analysis of hemoglobin solution; (ii) design and development of a sequential impedance sensing of sickle cells under low and high oxygen levels; (iii) modeling of single cell bioimpedance and method validation for characterization of cell volume, membrane and intracellular hemoglobin composition from the multi-frequency impedance signal of single sickle cells.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.

镰状细胞病是一种遗传性红细胞疾病，影响血红蛋白，红细胞内的携氧蛋白。镰状血红蛋白是镰状细胞形状、变形性和血流行为异常的根本原因，导致各种症状和并发症。预计随着时间的推移，并发症和疾病严重程度会发生变化。理解镰状细胞病的极端异质性的一个主要挑战是无法测量单个镰状细胞内的镰状血红蛋白。这项研究旨在通过开发一种微型传感器来克服这一挑战，该传感器可以在不破坏细胞膜的情况下测量异常镰状血红蛋白的量。这个跨学科项目为妇女和代表性不足的少数民族学生提供生物传感，细胞生物物理学，微制造和微流体方面的研究培训。研究结果和技术发展被纳入课程开发，并传播给本科生和研究生。镰状细胞病以其细胞形态学、变形性、血液流变学以及临床症状和并发症的严重程度的极端异质性而闻名，这与细胞内血红蛋白的变化有关。该项目开发了一种基于微流体的细胞内镰状血红蛋白的单细胞测定，在微流式细胞仪设置中在受控的氧水平下使用镰状细胞的顺序生物阻抗传感。缺氧微环境与阻抗传感的集成允许从单细胞中诱导的细胞镰状化过程中选择性地测量细胞内镰状血红蛋白变体。三个研究目标包括：（i）建立血红蛋白溶液的生物阻抗分析;（ii）设计和开发低氧和高氧水平下镰状细胞的顺序阻抗传感;（iii）单细胞生物阻抗的建模和用于表征细胞体积的方法验证，膜和细胞内血红蛋白组成的多，该奖项反映了NSF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。

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

Dielectric spectroscopy of red blood cells in sickle cell disease

• DOI: 10.1002/elps.202000143
• 发表时间: 2021-02-03
• 期刊: ELECTROPHORESIS
• 影响因子: 2.9
• 作者: Liu, Jia;Qiang, Yuhao;Du, E.
• 通讯作者: Du, E.