Multi-Modal Data-Driven Platform for Multiplexed Cellular Antigen Classification using Nano-electronic Barcoded Particles for Whole Blood Applications

该项目旨在开发一个可以对人类白细胞进行分类的平台，白细胞在人体防御败血症、癌症和其他慢性和急性疾病等多种疾病方面发挥着关键作用。最先进的医疗保健设施依赖于体积庞大且价格昂贵的仪器，这些仪器需要手工取样处理和训练有素的技术人员来进行血液分析。在这项工作中，将开发用于血液学分析的人工智能数据驱动生物传感器平台。它将基于多模态传感，集成微流体，以及对全血样本进行自动样品处理的能力。此外，所提出的传感平台将配备实时测量能力和机器学习模型来训练传感器数据，并根据需要提供可重构性和资源优化。提出的动态可重构数据驱动生物传感器将推动生物医学研究，并将有巨大的潜力造福人类健康和福祉。这个跨学科项目将培养传感器、系统和生物纳米技术领域的本科生和研究生。该项目将使研究与针对工程专业学生的教育工作相结合。私人事务处的外联活动将包括通过教育讲座吸引小学至12年级学生、当地保健行业和公众参与，并在网上提供这些讲座，以便广泛传播知识。该提案将使下一代体外诊断平台的发展成为可能，该平台配备了多模型传感和纳米条形码颗粒，可以在全血样本中进行可重构的生物标志物选择。人体血细胞在免疫系统对感染的反应中起着关键作用。这些免疫细胞在全血中的浓度及其膜受体密度可能在不同的疾病及其各自的发病机制中发生变化。需要对细胞分类的异质性进行量化，以便为医院环境中的患者提供个性化的诊断和监测系统。生物传感平台将与多模态传感集成，包括电气和光学探测器，这将允许纠正固有的设备到设备的变化，以提高传感器的性能。与功能化纳米条形码粒子结合的免疫细胞将与阻抗检测器和智能手机图像传感器同时定量。此外，拟议的生物传感器将配备使用机器学习的实时数据分析，以实现资源优化和生物标志物选择的可重构系统。集成的生物芯片将用于执行可重构的多路复用，并量化来自患者血液样本的多种炎症生物标志物。该传感器将在不到30分钟的时间内从一滴全血中进行多重细胞抗原分类。传感器将以患者临床样本作为基准。此外，设想生物传感器平台是通用的和可重构的，具有预功能化的墨盒，可以替换为不同的传染病。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This project is to develop a platform that can classify human leukocytes, which play a critical role in the body’s defense against a plethora of diseases like sepsis, cancer, and other chronic and acute diseases. State-of-the-art healthcare facilities rely on bulky and costly instruments which require manual sample processing and highly trained technical staff to perform blood analysis. In this work, an artificial intelligence enabled data-driven biosensor platform will be developed for hematology analysis. It will be based on multi-modal sensing, integrated microfluidics, and the ability to perform automated sample processing from whole blood samples. Furthermore, the proposed sensing platform will be equipped with real-time measurement capability and machine learning models to train the sensors data and provide reconfigurability and resource optimization as required. The proposed dynamic reconfigurable data driven biosensor will advance biomedical research and will have great potential to benefit human health and welfare. This cross disciplinary project will train undergraduate and graduate students in areas of sensors, systems, and bionanotechnology. The project will enable the integration of research into educational efforts directed towards engineering students. The PIs outreach activities will include engaging K-12 students, the local health-care industry, and the general public through educational lectures and making them available online for broad dissemination of knowledge. The proposal will enable the development of a next generation in-vitro diagnostic platform equipped with multi-model sensing and nano-barcoded particles to perform reconfigurable biomarker selection in whole blood samples. Human blood cells play a critical role in immune system activation in response to infections. The concentration of these immune cells in whole blood and their membrane receptor densities may change in different diseases and their respective pathogenesis. The heterogeneity of the cellular classification needs to be quantified to provide a personalized diagnostics and monitoring system for patients in a hospital setting. The biosensing platform will be integrated with multi-modal sensing including electrical and optical detectors which will allow to correct for inherent device-to-device variation to improve sensor performance. Immune cells conjugated with functionalized nano-barcoded particles will be quantified simultaneously with an impedance detector and smartphone image sensor. Further, the proposed biosensor will be equipped with real-time data analysis using machine learning to enable a reconfigurable system for resource optimization and biomarker selection. An integrated biochip will be used to perform reconfigurable multiplexing and quantify multiple inflammatory biomarkers from patient blood samples. The proposed sensor will enable multiplexed cellular antigen classification from a drop of whole blood with time to result (TOR) for less than 30 minutes. Sensors will be benchmarked with patient clinical samples. Furthermore, it is envisioned that the biosensor platform to be generic and reconfigurable with pre-functionalized cartridges that can be swapped out for different infectious diseases.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.