Quantum dot biosensors; microfluidics-based manufacturing of a diagnostic tool

量子点(QD)代表了一种新的技术形式，目前正被用于检测和跟踪生命系统中的动态细胞事件。这项研究的目标是开发一种制造工艺，为细胞和细胞内水平的核酸诊断提供新的工具，最终实现疾病的早期检测，并监测疾病进展和治疗效果。要实现制造目标，需要两个技术平台：1.我们将设计和建造一个微流控反应器和合适的表面化学设备来生产QD-生物传感器。该反应器将基于固定化量子点的固相合成修饰。生物传感器将基于固定在量子点上的寡核苷酸，转导系统以荧光共振能量转移模式运行。生物传感器将是独立的，这意味着不需要荧光标记的核酸目标。小分子和多肽标签将与寡核苷酸共同固定在量子点上作为载体，选择性地将QD-生物传感器输送到靶细胞。我们将与我们的行业合作伙伴GL Chemtec合作，开发合成方法并验证反应堆产品的质量。2.我们将设计和建造一个单独的微流控工具，用于快速评估在反应堆中生产的QD-生物传感器的性能。微流控工具将允许对QD-生物传感器与单个活细胞之间的相互作用进行中等吞吐量的研究。这将允许对功能材料的性能进行评估，这将指导制造工艺设计的开发和优化，以提高QD-生物传感器的性能。

Quantum Dots (QDs) represent one newer form of technology that is now being exploited for the detection and tracking of dynamic cellular events in living systems. The goal of this research is to develop a manufacturing process that will offer a new tool for nucleic acid diagnostics at the cellular and intracellular levels, to ultimately enable the early detection of disease and to monitor disease progression and therapeutic efficacy. Two technology platforms are required to achieve the manufacturing goal: 1. We will design and construct a microfluidic reactor and suitable surface chemistries to produce QD-biosensors. The reactor will be based on solid-phase synthetic modification of immobilized QDs. Biosensors will be based on oligonucleotides that are immobilized on QDs, with the transduction system operated in fluorescence resonance energy transfer mode. The biosensors will be self-contained, meaning that fluorescently labelled nucleic acid targets are not required. Small molecule and peptide tags will be co-immobilized with oligonucleotides onto the QDs as a vector to selectively deliver QD-biosensors to targeted cells. In collaboration with our industry partner GL Chemtec, we will develop synthetic methodologies and validate the quality of the products from the reactor. 2. We will design and construct a separate microfluidic tool for rapid assessment of the performance of QD-biosensors produced in the reactor. The microfluidic tool will allow for moderate throughput investigation of the interactions between QD-biosensors and individual living cells. This will allow evaluation of the performance of the functional materials, which will guide development and optimization of the design of the manufacturing process to improve performance of QD-biosensors.