CAREER: Microfluidic Separation Technologies for Cell Sorting

职业：用于细胞分选的微流体分离技术

• 批准号: 1149059
• 负责人: Palaniappan Sethu
• 金额: $ 40.33万
• 依托单位: University of Louisville Research Foundation Inc
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1149059&HistoricalAwards=false
• 关键词: CAREER; Microfluidic; Separation; Technologies; Cell

Name:SethuProposal#:1149059Research targeted at developing miniaturized, portable cell sorting technologies for isolation of white blood cells (WBCs) containing analytic, diagnostic or therapeutic value with minimal isolation process induced changes (activation) is proposed. Commonly used sorting techniques for isolation of WBCs, rely on the use of antibody and centrifugation -based methods which are associated with cell activation. This project introduces two new techniques that exploit physical and charge based attributes of cells in conjunction with fluid flow phenomenon that develop in microfluidic channels to sort and separate cells. The first technique exploits differences in cell mass density in conjunction with inertial forces using density mismatched fluids in high-aspect ratio microfluidic channels. This technique is suitable for sorting sub-populations of WBCs (i.e.) peripheral blood mononuclear cells (PBMCs) from polymorphonuclear cells (PNMs) in an automated format. The second technique relies on differences in cell surface energy to cause initial sorting via phase partitioning and then amplifies this separation using inertial forces in microchannels. This technique will be used to sort specific cellular populations like activated WBCs and circulating tumor cells (CTCs) in circulation. Exclusive reliance on flow phenomenon and physical/charge attributes for discrimination into subpopulations ensures minimal cell loss or artifactual activation. Both of these techniques are fast, reliable, require minimal user intervention and are suitable for use in medical or resource limited settings. Integral to the success of this project are education and outreach activities seeking to stimulate the interest and increase the participation of minorities and underrepresented groups in STEM fields. This will be achieved through the expansion and enrichment of a partnership previously established with Central HS, a historically minority institution with 87% minority enrollment and 60% female enrollment. Outreach goals will be accomplished through long-term efforts focused on engaging underrepresented students early, during their HS and undergraduate training. Students within the medical magnet program at Central HS will be introduced to bioengineering and career opportunities through seminars; intellectually engaged via research demonstrations and hands-on activities; motivated through interactions with successful professionals in academia and industry (role models); introduced to scholarship and financial aid programs and offered opportunities to participate in paid research activities. During their research experience, students will receive individual mentorship from undergraduate students from the National Society of Black Engineers (NSBE) and the Society of Women Engineers (SWE) to establish a supportive peer community. Undergraduate research positions will be offered to incoming freshman from underrepresented groups, with priority given to students from Central HS enrolling at the University of Louisville. Complimentary to these activities, the PI will work with two local HS science teachers to create STEM modules on microfluidics as learning tools to enhance understanding of fundamental concepts in science. These learning modules already validated at Walden School will be implemented at Central HS and other schools within the Jefferson County Public School System (JCPS). Research-based learning will also be integrated into all courses taught at the undergraduate and graduate levels. Finally, a laboratory website will be maintained to expose activities in the lab to the local community and others, serve as a recruitment tool and disseminate research and outreach outcomes

名称：Sethu提案编号：1149059研究旨在开发小型化、便携式细胞分选技术，用于分离含有分析、诊断或治疗价值的白色血细胞（WBC），并将分离过程引起的变化（激活）降至最低。用于分离WBC的常用分选技术依赖于与细胞活化相关的基于抗体和离心的方法的使用。该项目介绍了两种新技术，利用细胞的物理和电荷属性，结合在微流体通道中发展的流体流动现象来分选和分离细胞。第一种技术利用细胞质量密度的差异结合惯性力，使用高纵横比微流体通道中的密度失配流体。该技术适用于分选WBC的亚群（即，来自多形核细胞（PNM）的外周血单核细胞（PBMC）。第二种技术依赖于细胞表面能的差异，通过相分离引起初始分选，然后使用微通道中的惯性力放大这种分离。该技术将用于分选特定的细胞群，如活化的WBC和循环中的循环肿瘤细胞（CTC）。完全依赖于流动现象和物理/电荷属性来区分亚群，确保了最小的细胞损失或人为激活。这两种技术都是快速、可靠的，需要最少的用户干预，适用于医疗或资源有限的环境。该项目成功的关键是开展教育和外联活动，以激发少数群体和代表性不足的群体对STEM领域的兴趣并增加其参与。这将通过扩大和丰富以前与中央HS建立的伙伴关系来实现，中央HS是一个历史上少数民族的机构，少数民族入学率为87%，女性入学率为60%。外联目标将通过长期的努力，专注于从事代表性不足的学生早期完成，在他们的HS和本科培训。在中央HS的医学磁铁计划内的学生将通过研讨会介绍生物工程和就业机会;通过研究演示和动手活动智力参与;通过与学术界和工业界成功的专业人士（榜样）的互动激励;介绍奖学金和财政援助计划，并提供机会参加有偿研究活动。在他们的研究经验，学生将获得来自黑人工程师（NSBE）和女工程师（SWE）的社会的本科生个人导师建立一个支持性的同龄人社区。本科研究职位将提供给来自代表性不足群体的新生，优先考虑来自中央房协在路易斯维尔大学入学的学生。作为对这些活动的补充，PI将与两名当地HS科学教师合作，创建微流体STEM模块作为学习工具，以加强对科学基本概念的理解。这些已在瓦尔登学校验证的学习模块将在中央HS和杰斐逊县公立学校系统（JCPS）内的其他学校实施。基于研究的学习也将被纳入本科和研究生阶段的所有课程。最后，将维持一个实验室网站，向当地社区和其他人介绍实验室的活动，作为招聘工具，并传播研究和外联成果

项目成果

Microfluidic inertia enhanced phase partitioning for enriching nucleated cell populations in blood

微流体惯性增强相分配以富集血液中的有核细胞群

• DOI: 10.1039/c2lc40663b
• 发表时间: 2013
• 期刊: Lab on a Chip
• 影响因子: 6.1
• 作者: Parichehreh, Vahidreza;Medepallai, Krishnakiran;Babbarwal, Karan;Sethu, Palaniappan
• 通讯作者: Sethu, Palaniappan

Low-stress Microfluidic Density-gradient Centrifugation for Blood Cell Sorting

• DOI: 10.1007/s10544-018-0323-3
• 发表时间: 2018-08-28
• 期刊: BIOMEDICAL MICRODEVICES
• 影响因子: 2.8
• 作者: Sun, Yuxi;Sethu, Palaniappan
• 通讯作者: Sethu, Palaniappan

A microfluidics-based technique for automated and rapid labeling of cells for flow cytometry

• DOI: 10.1088/0960-1317/24/3/034002
• 发表时间: 2014-03-01
• 期刊: JOURNAL OF MICROMECHANICS AND MICROENGINEERING
• 影响因子: 2.3
• 作者: Patibandla, Phani K.;Estrada, Rosendo;Sethu, Palaniappan
• 通讯作者: Sethu, Palaniappan