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，白细胞在人体抵御大量疾病(如败血症、癌症和其他慢性和急性疾病)中发挥着关键作用。最先进的医疗机构依赖笨重而昂贵的仪器，这些仪器需要人工处理样本和训练有素的技术人员来进行血液分析。在这项工作中，将开发一个支持人工智能的数据驱动生物传感器平台，用于血液学分析。它将基于多模式传感、集成微流控技术以及从全血样本执行自动样本处理的能力。此外，拟议的传感平台将配备实时测量能力和机器学习模型，以训练传感器数据，并根据需要提供可重构和资源优化。提出的动态可重构数据驱动生物传感器将促进生物医学研究，并将为人类的健康和福利带来巨大的潜力。这个跨学科项目将在传感器、系统和生物纳米技术领域培训本科生和研究生。该项目将使研究能够融入针对工科学生的教育努力中。PIS外展活动将包括通过教育讲座吸引K-12学生、当地医疗保健行业和普通公众，并使其在线可用于广泛传播知识。该提案将使下一代体外诊断平台的开发配备多模型传感和纳米条形码颗粒，以在全血样本中进行可重构的生物标志物选择。人类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在不同的疾病及其各自的发病机制中可能会发生变化。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控系统。生物传感平台将与包括电和光探测器在内的多模式传感相结合，这将允许纠正固有的设备到设备的差异，以提高传感器性能。与功能化纳米条形码颗粒结合的免疫细胞将通过阻抗检测器和智能手机图像传感器同时进行量化。此外，建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记物选择的可重新配置系统。一种集成的生物芯片将用于执行可重新配置的多路复用，并对患者血液样本中的多个炎症生物标志物进行量化。建议的传感器将使从一滴全血中进行多路细胞抗原分类的时间(TOR)不到30分钟。传感器将以患者临床样本为基准进行基准测试。此外，预计生物传感器平台将是通用的，可重新配置预功能化的墨盒，可以更换为不同的传染病。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.