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

这一创新-技术转化伙伴关系(PFI-TT)项目的更广泛影响/商业潜力是开发一个实用和快速的诊断技术平台。精准医学和液体活组织检查等领域在医疗保健领域前景广阔。他们依靠非常敏感的技术来检测人体中的微小分子。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精度分析单个分子，甚至比旧的方法更好。拟议的单分子计数技术有可能给疾病诊断带来革命性的变化，因为它可以使先进的诊断工具变得更加负担得起和更广泛地获得。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，例如使用液体活组织检查的小样本进行准确和早期诊断。该团队在原型制作、技术转换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名本科生在技术开发和创业方面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成果的基础上，并通过利用多种创新开发出一种负担得起、实用且具有广泛适应性的数字生物传感新范式。这项技术基于干涉反射成像传感器(IRIS)，当它们被捕获到传感器表面时，可以动态检测数千个单独的生物纳米颗粒(病毒、外切体)或标记有血浆金纳米颗粒的单个生物分子。也许与这项技术转换工作相关的最重要的创新是这项发明，它解决了传统干涉检测的局限性，这种检测需要采集一叠图像，从而需要移动部件来区分单个纳米颗粒。新的数字检测方式，ʻ像素多样性ʻ(PD)-IRIS，引入了在单个图像帧而不是图像堆栈中对目标粒子的必要光学特征进行编码。这一创新消除了移动部件并极大地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(自动化的行业标准)中进行数字检测，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。

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.