CAREER: Microfluidic Separation Technologies for Cell Sorting

名称：SethuProposal#:1149059提出了一项研究，旨在开发用于分离白细胞（wbc）的小型化、便携式细胞分选技术，该技术具有分析、诊断或治疗价值，且分离过程诱导的变化（激活）最小。通常用于分离白细胞的分选技术依赖于使用抗体和基于离心的方法，这些方法与细胞活化有关。本项目介绍了两种新技术，它们利用细胞的物理和电荷属性，结合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，在高纵横比微流体通道中使用密度不匹配流体。该技术适用于自动分选白细胞亚群(即外周血单核细胞（PBMCs）和多形核细胞（PNMs）。第二种技术依赖于细胞表面能量的差异，通过相位分配引起初始分选，然后利用微通道中的惯性力放大这种分离。这项技术将用于分类特定的细胞群，如活化的白细胞和循环肿瘤细胞（CTCs）在循环中。完全依赖流动现象和物理/电荷属性来区分亚群，确保最小的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，适合在医疗或资源有限的环境中使用。该项目的成功离不开教育和推广活动，这些活动旨在激发少数民族和代表性不足群体对STEM领域的兴趣，并增加他们的参与。这将通过扩大和丰富先前与中央高中建立的伙伴关系来实现，中央高中是一所历史上少数民族大学，少数民族入学率为87%，女性入学率为60%。推广目标将通过长期的努力来实现，重点是在他们的高中和本科培训期间尽早吸引代表性不足的学生。中央高中医学磁体项目的学生将通过研讨会了解生物工程和就业机会；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成功的专业人士（榜样）的互动激励；介绍奖学金和经济援助计划，并提供参加有偿研究活动的机会。在他们的研究经历中，学生将接受来自全国黑人工程师协会（NSBE）和女性工程师协会（SWE）的本科生的个人指导，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，优先考虑在路易斯维尔大学注册的中央高中学生。除了这些活动外，PI还将与两名本地的HS科学教师合作，创建有关微流体的STEM模块，作为学习工具，以加强对科学基本概念的理解。这些已经在瓦尔登学校得到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。研究性学习也将被整合到本科和研究生阶段的所有课程中。最后，将维持一个实验室网站，向当地社区和其他人展示实验室的活动，作为招聘工具，传播研究和推广成果

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