PFI-TT: High-Throughput Digital Biosensing: Future Of Molecular Diagnostics

PFI-TT：高通量数字生物传感：分子诊断的未来

• 批准号: 2329817
• 负责人: Selim Unlu
• 金额: $ 55万
• 依托单位: Trustees of Boston University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2329817&HistoricalAwards=false
• 关键词: PFI; TT; Throughput; Digital; Biosensing

The broader impact/commercial potential of this Partnerships for Innovation - Technology Translation (PFI-TT) project is in the development of a practical and fast diagnostic technology platform. Areas like precision medicine and liquid biopsies hold great promise in the field of healthcare. They rely on very sensitive technologies that can detect tiny molecules in human bodies. One exciting advancement is called "digital detection," which can analyze individual molecules with incredible accuracy, even better than older methods. The proposed single-molecule counting technology has the potential to revolutionize disease diagnosis because it could make advanced diagnostic tools more affordable and widely available. The project will create a practical and cost-effective platform for detecting diseases early on, which will be incredibly beneficial for various medical applications, like accurate and early diagnosis using small samples from liquid biopsies. The team has a proven track record of prototyping, technology translation, and commercialization. The project will make a contribution to workforce creation by training 2 PhD students and 2 undergraduate students in technology development and entrepreneurship. The proposed project builds on more than a decade-long cutting-edge basic and applied research effort and develops a new paradigm of Digital Biosensing that is affordable, practical, and broadly adaptable by exploiting multiple innovations. The technology is based on Interferometric Reflectance Imaging Sensor (IRIS), which can dynamically detect thousands of individual biological nanoparticles (viruses, exosomes) or single biomolecules labeled with plasmonic gold nanoparticles as they are captured on the sensor surface. Perhaps the most significant innovation relevant to this Technology Translation effort is the invention to address the limitations of the conventional interferometric detection that requires acquisition of a stack of images, thus, necessitating moving parts, to distinguish individual nanoparticles. The new modality of digital detection, ʻpixel-diversityʻ (PD)-IRIS, that introduces encoding the necessary optical signatures of target particles within a single image frame rather than an image stack. This innovation eliminates moving parts and drastically reduces the complexity of the reader enabling digital detection directly in ubiquitous microwell plates – an industry standard for automation – achieving an unprecedented capability of High-throughput Digital Biosensing.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.

这种创新合作伙伴关系的更广泛的影响/商业潜力 - 技术翻译（PFI -TT）项目是在实用且快速诊断的技术平台的开发中。 Precision Medicine和液体活检等领域在医疗保健领域拥有巨大的希望。他们依靠非常敏感的技术，可以检测人体中的微小分子。一个令人兴奋的进步称为“数字检测”，它可以以令人难以置信的精度分析单个分子，甚至比旧方法更好。拟议的单分子计数技术有可能彻底改变疾病诊断，因为它可以使先进的诊断工具更实惠和广泛使用。该项目将创建一个实用且具有成本效益的平台，用于早期检测疾病，这将对各种医疗应用非常有益，例如使用液体活检中的小样本进行精确和早期诊断。该团队具有原型制作，技术翻译和商业化的良好记录。该项目将通过培训2名博士学位学生和2名技术发展和企业家的本科生为劳动力创造做出贡献。拟议的项目建立在长达十多年的尖端基础和应用研究工作的基础上，并开发了一种新的数字生物传感范式，通过利用多个创新，这些范式是负担得起，实用且广泛适应的。该技术基于干涉反射率成像传感器（IRIS），该传感器可以动态检测成千上万的单个生物纳米颗粒（病毒，外泌体）或单个生物分子在传感器表面捕获时，它们被捕获为血浆金纳米粒子。也许与此技术翻译工作相关的最重要的创新是解决需要获取一堆图像的常规干涉检测局限性的发明，因此，需要堆叠图像，从而区分各个纳米颗粒。数字检测的新模态``pd-doverity''（PD）-IRI，它引入了单个图像框架内的目标粒子的必要光学签名，而不是图像堆栈。这项创新消除了活动部位，并大大降低了无处不在的微型小台板中直接实现数字检测的复杂性（一种自动化行业标准） - 实现了前所未有的数字生物传感器的前所未有的能力，这反映了NSF的法定任务和审查的良好依据，这是通过评估良好的依据来评估的。