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.

该创新-技术转化伙伴关系（PFI-TT）项目更广泛的影响/商业潜力在于开发实用和快速的诊断技术平台。精密医学和液体活检等领域在医疗保健领域有着巨大的前景。他们依靠非常敏感的技术，可以检测人体内的微小分子。一个令人兴奋的进步被称为“数字检测”，它可以以令人难以置信的准确度分析单个分子，甚至比旧方法更好。提出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便宜和更广泛地使用。该项目将创建一个实用且具有成本效益的早期检测疾病的平台，这将对各种医疗应用非常有益，例如使用液体活检的小样本进行准确和早期诊断。该团队在原型设计、技术转化和商业化方面有着良好的记录。该项目将通过培训2名博士生和2名本科生进行技术开发和创业，为创造劳动力做出贡献。 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，该范式通过利用多种创新，经济实惠，实用且具有广泛的适应性。该技术基于干涉反射成像传感器（IRIS），可以动态检测数千个单独的生物纳米颗粒（病毒，外泌体）或标记有等离子体金纳米颗粒的单个生物分子，因为它们被捕获在传感器表面上。也许与这种技术转化努力相关的最重要的创新是本发明解决了传统干涉检测的局限性，传统干涉检测需要获取一堆图像，因此需要移动部件来区分单个纳米颗粒。数字检测的新模式，双像素多样性成像（PD）-IRIS，它引入了在单个图像帧而不是图像堆栈内对目标颗粒的必要光学特征进行编码。这一创新消除了移动部件，大大降低了读取器的复杂性，使其能够直接在无处不在的微孔板中进行数字检测-这是自动化的行业标准-实现了前所未有的高通量数字生物传感能力。该奖项反映了NSF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。