Collaborative Research: Optimization of Sperm Sorting in Microfluidic Channels Using Coarse-Grained Modeling

合作研究：使用粗粒度模型优化微流体通道中的精子分选

• 批准号: 1309933
• 负责人: Erkan Tuzel
• 金额: $ 29.3万
• 依托单位: Worcester Polytechnic Institute
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1309933&HistoricalAwards=false
• 关键词: Collaborative; Research; Optimization; Sperm; Sorting

5.3 million American couples of reproductive age are affected by infertility. Among these cases, male factors account for up to 50%, necessitating the identification of key parameters dictating male fertility, including sperm count, morphology and motility. Assisted reproductive technologies (ARTs) have emerged as powerful tools to address male infertility problems in modern clinical practice. In vitro fertilization (IVF) with or without intra cytoplasmic sperm injection (ICSI) has become the most widely used assisted reproductive technology (ART) in modern clinical practice to overcome male infertility challenges. One of the obstacles of IVF and ICSI lies in identifying and isolating the most motile, and healthiest sperm from semen samples that have low sperm counts (oligozoospermia), low sperm motility (oligospermaesthenia). Selection of the best performing sperm based in the selection criteria including motility is the keystone for successful outcomes of fertilization and full term pregnancy. However, it remains a clinical challenge to select the most motile normal/healthy sperm. The researchers propose to develop a GPU accelerated computational framework that will enable the multi-scale coarsegrained modeling of sperm motility in micro-channels. Towards achieving this goal, they will develop a computationally efficient model of sperm motility and interactions, and design acomputer-optimized space-constrained microfluidic sorting (SCMS) system, integrated with a lensless technology, for rapid monitoring, selection and sorting of sperm. As they are utilizing such microchip technology, the proposed device can be easily transformed into a scalable device composed of multiplexed channels. In the long term, this computational platform can be used to design micro-fluidic devices for the selection and sorting of not only spermatozoa, but also other types of biological entities, such as circulating tumors cells (CTCs) or HIV from blood. The broader impacts of this proposal include educational and scientific outcomes that will open new avenues for physical and biological research and have a considerable impact on fundamental and applied science, education, and medicine. This proposal will facilitate the participation of undergraduates in year round research activities, and directly support the training of graduate students at the interface between physics, engineering and medicine at Harvard, MIT and WPI. The PIs will actively participate in recruitment efforts to broaden theparticipation of underrepresented groups in the biological, physical sciences, and engineering by attending national meetings and via Harvard's underrepresented minority program. They will continue to advise undergraduates through the Undergraduate Research Opportunities Program(UROP) and the mandatory senior theses (MQPs) at WPI. The PIs will also develop graduate courses, and arrange field trips with local high schools in educating students about computational biophysics and microfluidics research. At the national and international level, the PIs will educate the students and the public at other institutions on technological and scientific challenges by giving lectures at NSF supported international summer schools, and by organizing hands-on workshops.

5.3美国有1000万对育龄夫妇受到不孕症的影响。在这些病例中，男性因素占50%，因此有必要确定决定男性生育力的关键参数，包括精子数量、形态和活力。在现代临床实践中，辅助生殖技术（ART）已成为解决男性不育问题的有力工具。有或没有胞质内单精子注射（ICSI）的体外受精（IVF）已成为现代临床实践中最广泛使用的辅助生殖技术（ART），以克服男性不育的挑战。IVF和ICSI的障碍之一在于从精子数量低（少精子症），精子活力低（少精子症）的精液样本中识别和分离出最活跃，最健康的精子。根据包括活力在内的选择标准选择表现最好的精子是受精和足月妊娠成功结局的关键。然而，选择最活跃的正常/健康精子仍然是一个临床挑战。研究人员建议开发一个GPU加速的计算框架，该框架将实现微通道中精子运动的多尺度粗粒度建模。为了实现这一目标，他们将开发一个计算效率高的精子运动和相互作用模型，并设计计算机优化的空间约束微流体分选（SCMS）系统，与无透镜技术相结合，用于快速监测，选择和分选精子。由于他们利用这种微芯片技术，所提出的设备可以很容易地转换成由多路复用通道组成的可扩展设备。从长远来看，这种计算平台可用于设计微流体设备，不仅用于精子的选择和分选，还用于其他类型的生物实体，如循环肿瘤细胞（CTC）或血液中的HIV。该提案的更广泛影响包括教育和科学成果，这将为物理和生物研究开辟新的途径，并对基础和应用科学、教育和医学产生重大影响。该提案将促进本科生参与全年的研究活动，并直接支持哈佛、麻省理工学院和WPI在物理学、工程学和医学之间接口的研究生培训。PI将积极参与招聘工作，通过参加国家会议和哈佛代表性不足的少数民族计划，扩大生物，物理科学和工程领域代表性不足的群体的参与。他们将继续通过本科生研究机会计划（UROP）和WPI的强制性高级论文（MQPs）为本科生提供建议。PI还将开发研究生课程，并与当地高中安排实地考察，教育学生有关计算生物物理学和微流体研究。在国家和国际一级，PI将通过在NSF支持的国际暑期学校举办讲座和组织实践研讨会，教育其他机构的学生和公众了解技术和科学挑战。