CAREER: Optoelectronic lab-on-a-chip technology for high content automated multiparametric physiological analyses of live cells

职业：用于活细胞高内涵自动化多参数生理分析的光电芯片实验室技术

• 批准号: 2339030
• 负责人: Luyao Lu
• 金额: $ 50万
• 依托单位: George Washington University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-09-01 至 2029-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2339030&HistoricalAwards=false
• 关键词: CAREER; Optoelectronic; lab; chip; technology

In vitro live cells such as stem cells are powerful models to replicate human (patho)physiology and enable detailed analysis of cell function, cellular mechanisms of action, and responses to interventions and therapeutics. The widespread acceptance of these cell models, coupled with their growing commercial availability and ease of deriving patient-specific cells, have underscored their potential to revolutionize our understanding of human physiology and function. To date, however, limited techniques exist for comprehensive investigation of the properties of such cell models over time, which greatly impedes their translation for physiology investigations, disease modeling, and pharmacology research. This project will address these technical challenges and develop automated lab-on-a-chip platforms for comprehensive chronic monitoring and control of cell physiology. This will be accomplished via innovations in materials, device fabrication, circuit design, software development, and system integration. The research results represent important steps towards the next generation lab-on-a-chip health monitoring and modulation systems. If successful, the outcomes will significantly simplify the operation, expand the possibilities, and create new opportunities in many programs of biomedical research, in which automated lab-on-a-chip devices with reduced human exposure are highly demanded. The education activities will integrate with the technical developments through multidisciplinary training of female and underrepresented students in bioelectronics research, introduction of new undergraduate courses on optoelectronic biomedical systems. Outreach plans involve lectures and designing pedagogical demonstration kits to educate K-12 students as well as active research participation by local high school students.This project will develop and validate automated lab-on-a-chip platforms that allow for direct high-content, real-time, multiparametric interrogation of multiple parallel live cell properties and their interplay at meaningful levels of spatiotemporal precision inside standard cell culture environment. The project includes three research objectives: (1) explore cellular-scale components for crosstalk-free electrical recording, stimulation, and triple-parametric fluorescence recording of in vitro live cell function. The structure-property relationships of those components will be investigated to optimize the device performance. Optical and electrochemical modeling will be performed to yield fundamental insights into their characteristics; (2) develop compact lab-on-a-chip platforms for automated, long-term, multiparametric probing of live cell models under controlled cultivation conditions. The full compatibility with incubator culturing environment is beneficial for work with dangerous pathogens, such as COVID-19, toxic substances, and radioactivity. Advanced hardware and software designs will enable independent control of each modality, fast measurement, and data analysis. This will eliminate the need of significant technical expertise to manually analyze the high-content data generated, dramatically save the time efforts, reduce error, and improve accuracy for the experimenters; (3) validate the platforms via rigorous benchtop measurements and high-content on-chip screening of induced pluripotent stem cells-derived neurons. The performance will be benchmarked against commercial systems. The technology and new knowledge in this project will impact the broad biomedical engineering community, including elucidating disease mechanisms, drug testing, personalized medicine, organs-on-chip.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.

体外活细胞（例如干细胞）是复制人（PATHO）生理学的强大模型，并能够详细分析细胞功能，细胞作用机理以及对干预措施和治疗剂的反应。这些细胞模型的广泛接受，以及它们不断增长的商业可用性和易于得出患者特异性细胞的易用性，强调了它们的潜力，以彻底改变我们对人类生理学和功能的理解。然而，迄今为止，对于随着时间的推移，对此类细胞模型的性质进行了全面研究，存在有限的技术，这极大地阻碍了它们在生理研究，疾病建模和药理学研究中的翻译。该项目将应对这些技术挑战，并开发自动化的实验室芯片平台，以全面的长期监测和控制细胞生理学。这将通过材料，设备制造，电路设计，软件开发和系统集成的创新来实现。研究结果代表了朝着下一代实验室芯片健康监测和调制系统的重要步骤。如果成功，结果将大大简化运营，扩大可能性并在许多生物医学研究计划中创造新的机会，在这些计划中，高度要求自动化的实验室芯片设备自动化的芯片设备减少。教育活动将通过对女性和代表性不足的学生研究的多学科培训，在生物电子研究中的多学科培训，介绍有关光电生物医学系统的新本科课程的跨学科培训。 Outreach plans involve lectures and designing pedagogical demonstration kits to educate K-12 students as well as active research participation by local high school students.This project will develop and validate automated lab-on-a-chip platforms that allow for direct high-content, real-time, multiparametric interrogation of multiple parallel live cell properties and their interplay at meaningful levels of spatiotemporal precision inside standard cell culture environment.该项目包括三个研究目标：（1）探索用于无串扰的电记录，刺激和三个参数荧光记录的细胞尺度成分。将研究这些组件的结构质地关系，以优化设备性能。将进行光学和电化学建模，以产生对其特征的基本见解； （2）开发紧凑的实验室芯片平台，用于在受控培养条件下对活细胞模型进行自动，长期的多参数探测。与孵化器培养环境的完全兼容性对使用危险病原体（例如Covid-19，有毒物质和放射性）的工作有益。高级硬件和软件设计将使每个模式，快速测量和数据分析能够独立控制。这将消除需要大量技术专长来手动分析生成的高内含物数据，大大节省时间努力，减少错误并提高实验者的准确性； （3）通过严格的台式测量值和对诱导多能干细胞衍生的神经元的片上筛选验证平台。性能将针对商业系统进行基准测试。该项目中的技术和新知识将影响广泛的生物医学工程社区，包括阐明疾病机制，药物测试，个性化医学，芯片上的器官。这项奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子优点和更广泛的影响审查标准来通过评估来通过评估来支持的。