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：SethuProposal#：1149059 建议进行研究，旨在开发小型化、便携式细胞分选技术，用于分离具有分析、诊断或治疗价值的白细胞 (WBC)，同时将分离过程引起的变化（激活）降至最低。用于分离白细胞的常用分选技术依赖于与细胞活化相关的抗体和基于离心的方法的使用。该项目引入了两种新技术，利用细胞的物理和基于电荷的属性以及微流体通道中发展的流体流动现象来分类和分离细胞。第一种技术利用高纵横比微流体通道中密度不匹配的流体结合细胞质量密度的差异和惯性力。该技术适用于以自动化方式从多形核细胞 (PNM) 中分选 WBC（即外周血单核细胞 (PBMC)）亚群。第二种技术依赖于细胞表面能的差异，通过相分配进行初始分选，然后利用微通道中的惯性力放大这种分离。该技术将用于对循环中的特定细胞群进行分类，例如激活的白细胞和循环肿瘤细胞（CTC）。完全依赖流动现象和物理/电荷属性来区分亚群，确保最大限度地减少细胞损失或人为激活。这两种技术都快速、可靠，需要最少的用户干预，并且适合在医疗或资源有限的环境中使用。该项目成功的一个重要组成部分是教育和外展活动，旨在激发少数群体和弱势群体对 STEM 领域的兴趣并增加他们的参与。这将通过扩大和丰富之前与 Central HS 建立的合作伙伴关系来实现，Central HS 是一所历史悠久的少数族裔机构，其中 87% 为少数族裔入学，60% 为女性入学。外展目标将通过长期努力来实现，重点是在高中和本科生培训期间尽早吸引代表性不足的学生。中央高中医学磁石项目的学生将通过研讨会了解生物工程和职业机会；通过研究演示和实践活动进行智力参与；通过与学术界和工业界的成功专业人士（榜样）的互动来激励；介绍了奖学金和经济援助计划，并提供了参与付费研究活动的机会。在研究期间，学生将接受来自美国黑人工程师协会（NSBE）和女性工程师协会（SWE）本科生的个人指导，以建立一个支持性的同伴社区。本科研究职位将提供给来自代表性不足群体的新生，并优先考虑在路易斯维尔大学就读的中央高中学生。作为对这些活动的补充，PI 将与两名当地高中科学教师合作，创建有关微流体的 STEM 模块，作为学习工具，以增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高中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融入本科生和研究生级别的所有课程中。最后，将维护一个实验室网站，向当地社区和其他人展示实验室的活动，作为招聘工具并传播研究和推广成果

项目成果

Inertial lift enhanced phase partitioning for continuous microfluidic surface energy based sorting of particles

用于基于连续微流体表面能的颗粒分选的惯性升力增强相分配

• DOI: 10.1039/c2lc21034g
• 发表时间: 2012-01
• 期刊: Lab on a Chip
• 影响因子: 6.1
• 作者: Parichehreh, Vahidreza;Sethu, Palaniappan
• 通讯作者: Sethu, Palaniappan

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: 2013-01
• 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

Review: Microfluidics technologies for blood-based cancer liquid biopsies

评论：用于基于血液的癌症液体活检的微流体技术

• DOI: 10.1016/j.aca.2017.12.050
• 发表时间: 2018-07
• 期刊: Analytica Chimica Acta
• 影响因子: 6.2
• 作者: Sun, Yuxi;Haglund, Thomas A.;Rogers, Aaron J.;Ghanim, Asem F.;Sethu, Palaniappan
• 通讯作者: Sethu, Palaniappan

Microfluidic Adaptation of Density-Gradient Centrifugation for Isolation of Particles and Cells

用于分离颗粒和细胞的密度梯度离心的微流体适应

• DOI: 10.3390/bioengineering4030067
• 发表时间: 2017-08-02
• 期刊: Bioengineering
• 作者: Yuxi Sun;P. Sethu
• 通讯作者: P. Sethu

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

一种基于微流体的技术，用于自动快速标记流式细胞术细胞

• DOI: 10.1088/0960-1317/24/3/034002
• 发表时间: 2014-03
• 期刊: Journal of Micromechanics and Microengineering
• 影响因子: 2.3
• 作者: Patibandla, Phani K;Estrada, Rosendo;Kannan, Manasaa;Sethu, Palaniappan
• 通讯作者: Sethu, Palaniappan