CAREER: Reconfigurable Microfluidic-Microbalance Sensors to Monitor and Optimize the Performance of Microphysiological Models

职业：可重构微流体-微平衡传感器，用于监测和优化微生理模型的性能

• 批准号: 1846911
• 负责人: Michael Daniele
• 金额: $ 50万
• 依托单位: North Carolina State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-15 至 2025-01-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1846911&HistoricalAwards=false
• 关键词: CAREER; Reconfigurable; Microfluidic; Microbalance; Sensors

Reconfigurable sensing-systems are adaptable platforms that can detect and quantify any target on-demand; however, such systems have not been translated and applied to fields of biosensing and biotechnology. New biosensing capabilities are needed for a paradigm shift in sensor design, from tailoring the sensor to fit a narrow range of targets and conditions, towards a more adaptable platform, wherein the sensor architecture is unvaried, while its performance is tuned to match a particular concentration and complexity of the biological analyte. This project aims to investigate and engineer a new generation of reconfigurable biosensor platforms that can be used to measure multiple circulating biomarkers and inform the development and analysis of microphysiological models. Microphysiological models replicate human organ function, and they are promising technologies for fundamental biological research and discovery of translatable biomarkers, pharmaceuticals, and regenerative therapies; however, due to the anatomical and cellular complexity of microphysiological models, a major challenge exists in measuring and analyzing the function and performance of such complex systems. Reconfigurable, multiplexed sensors will provide a new technique for the parallelization of monitoring microphysiological models, i.e. many microphysiological models and biomarkers can be operated, monitored, and analyzed simultaneously. Such a technology is poised to better our understanding of the fundamental development of any engineered large tissue, organ, or model. This knowledge will accelerate biotechnology research by reducing variability and providing more statistically powerful trials, better informing animal or clinical testing, and identifying new targets for investigation. The interdisciplinary nature of this project, combining microelectronics, microfluidics, data science, and tissue engineering will require equally interdisciplinary education and global engagement plan, which will be implemented by collaborating with high school STEM teachers through authentic summer research experiences and participating in the international SensUs Biosensors Research Competition for undergraduate and graduate students.The research objective of this proposal is to design, fabricate, and validate sensors for a reconfigurable, multiplexed microfluidic-microbalance system, which is comprised of an array of miniature quartz-crystal microbalances and integral microfluidics to characterize both biochemical and biophysical properties of microphysiological models. Specifically, the operational frequency, binding selectivity, and regeneration of the novel biosynthetic-recognition moieties will be investigated. Understanding these parameters will enable the microfluidic-microbalance platform to be reconfigured for different biomarkers; moreover, the multiplexed sensing can elucidate new correlations between sets of biomarkers and biological function. The proposed research will include (1) modelling of microfluidic delivery and operation of microfluidic-microbalance arrays in complex media, (2) microfabrication and experimental testing of sensor with novel biosynthetic-recognition elements, and (3) the development of the necessary hardware and computational algorithms to process the multiplexed data streams. To demonstrate these innovations, the sensors will be validated with a microphysiological model of human microvasculature to (1) extract, process, and biochemically analyze circulating media, (2) measure and correlate perfusion pressure and viscosity to microvascular development, and (3) harnesses these data streams to predict and optimize biological function of the model. This effort will be the foundation for new multiplexed sensing strategies to investigate microphysiological models and complex in vitro biological systems. Broadly, this research will illuminate a pathway for future research into innovative means of making sensors to monitor multiple biochemical analytes simultaneously, to be reconfigured for use in MPMs of different organs, and to generate data streams for the future development of machine learning methods to analyze and discover novel correlations between biomarkers.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.

可重新配置的传感系统是可以检测和量化任何目标的适应性平台。但是，此类系统尚未被翻译并应用于生物传感和生物技术领域。需要新的生物传感功能来实现传感器设计的范式变化，从调整传感器到适合狭窄的目标和条件，再到更适应性的平台，在该平台中，传感器架构是未变化的，而其性能则调整为匹配生物分析物的特定浓度和复杂性。该项目旨在调查和设计新一代可重构生物传感器平台，可用于测量多个循环生物标志物并为微生物生理模型的开发和分析提供信息。微生物生理模型复制了人体器官功能，它们是可转换生物标志物，药物和再生疗法的基本生物学研究和发现的有前途的技术；但是，由于微生物生理模型的解剖学和细胞复杂性，在测量和分析这种复杂系统的功能和性能时存在一个重大挑战。可重新配置的多路复用传感器将为监测微生物生理模型的并行化提供一种新技术，即可以同时操作，监测和分析许多微生物生理模型和生物标志物。这样的技术有望更好地理解任何工程大型组织，器官或模型的基本发展。这些知识将通过降低可变性并提供更统计学强大的试验，更好地为动物或临床测试提供信息，并确定调查的新目标，从而加速生物技术研究。该项目的跨学科性质，结合了微电学，微流体学，数据科学和组织工程，需要同样需要同样的跨学科教育和全球参与计划，该计划将通过与高中STEM教师通过合作，通过真实的夏季研究经验与高中型茎教师合作，并参与国际敏感的研究生竞争，以实现这一竞争。一个可重新配置的多重微流体微量平衡系统，该系统由一系列微型石英 - 晶体微量平衡和整体微能力组成，以表征微生物生理模型的生化和生物物理性质。具体而言，将研究新型生物合成识别部分的操作频率，结合选择性和再生。了解这些参数将使微流体微量平台能够重新配置不同的生物标志物。此外，多路复用传感可以阐明生物标志物和生物功能集之间的新相关性。拟议的研究将包括（1）在复杂培养基中微流体传递和微流体 - 微量平衡阵列的操作，（2）使用新型生物合成识别元件对传感器进行微生物化和实验测试的建模，（3）（3）必要的硬件和计算算法的开发来处理倍增数据流。为了证明这些创新，传感器将通过人类微举行的微生物生理模型进行验证（1）提取，过程和生化分析循环介质，（2）测量和将灌注压力和粘度与微血管发育相关，以及（3）在这些数据流中预测和最佳生物学功能。这项工作将是研究微观生理模型和复杂体外生物学系统的新的多重传感策略的基础。广泛地说，这项研究将阐明未来研究的途径，以使传感器同时监视多个生物化学分析物，以重新配置在不同器官的MPM中使用，以生成数据流，并为未来的机器学习方法开发来生成机器学习方法的未来开发，以通过评估奖励，并发现了nission nission dectory nissfory nissf and par eatory par nesfe satfe and par n s fews te nsf s fore nsf satifor nsf，基金会的智力优点和更广泛的影响评论标准。

项目成果

Toward the quantification of adeno-associated virus titer by electrochemical impedance spectroscopy

通过电化学阻抗谱定量腺相关病毒滴度

• DOI: 10.1109/biosensors58001.2023.10281105
• 发表时间: 2023
• 期刊: IEEE BioSensors
• 作者: Wang, Junhyeong;Hosseini, Mahshid;Shastry, Shriarjun;Barbieri, Eduardo;Chu, Wenning;Menegatti, Stefano;Daniele, Michael A.
• 通讯作者: Daniele, Michael A.

Microphysiological System for High-Throughput Computer Vision Measurement of Microtissue Contraction.

• DOI: 10.1021/acssensors.0c02172
• 发表时间: 2021-03-26
• 期刊: ACS SENSORS
• 影响因子: 8.9
• 作者: Martins, Ana Maria Gracioso;Wilkins, Michael D.;Ligler, Frances S.;Daniele, Michael A.;Freytes, Donald O.
• 通讯作者: Freytes, Donald O.

Monitoring of random microvessel network formation by in-line sensing of flow rates: A numerical and in vitro investigation

• DOI: 10.1016/j.sna.2021.112970
• 发表时间: 2021-11
• 期刊: Sensors and Actuators A-physical
• 影响因子: 4.6
• 作者: V. Pozdin;Patrick D. Erb;McKenna L. Downey;Kristina R. Rivera;M. Daniele

Towards electrochemical control of pH for regeneration of biosensors

用于生物传感器再生的 pH 值电化学控制

• DOI: 10.1109/biosensors58001.2023.10281061
• 发表时间: 2023
• 期刊: IEEE BioSensors
• 作者: Sharkey, Christopher;Twiddy, Jack;Peterson, Kaila L.;Aroche, Angélica F.;Menegatti, Stefano;Daniele, Michael A.
• 通讯作者: Daniele, Michael A.

Simple design for membrane-free microphysiological systems to model the blood-tissue barriers

用于模拟血液组织屏障的无膜微生理系统的简单设计

• DOI: 10.1016/j.ooc.2023.100032
• 发表时间: 2023
• 期刊: Organs-on-a-Chip
• 作者: Young, By Ashlyn;Deal, Halston;Rusch, Gabrielle;Pozdin, Vladimir A.;Brown, Ashley C.;Daniele, Michael
• 通讯作者: Daniele, Michael