Lab-on-chip with embedded nanosensors for high throughput analysis

该计划的愿景是推进芯片上实验室诊断的集成，以实现高通量和单分子水平的生物分子定量检测。目前，85%的诊断测试是在中央实验室设施中在专业实验室人员的帮助下进行的，这一过程缓慢且昂贵。因此，在护理地点对病原性和遗传性疾病(如癌症)进行快速和准确的诊断是一项全球性的挑战，但也是一项关键的必要性。芯片上实验室(LOC)设备提供了一个在纳米尺度上完成生物反应循环的自动化系统，与标准的实验室方案相比，可以实现快速分析。然而，在芯片上识别遗传疾病或疾病状态，特别是在早期阶段，需要在单个单分子水平上动态操作和浓缩少量目标分子(蛋白质、DNA或RNA)。目前的LOC技术受到传感器分辨率和灵敏度的限制，因为很难在足够高的水平上将目标分子集中在检测位置。*本研究计划将重点放在通过将纳米结构材料与电/流体样品输送系统协同结合来设计LOC技术的新方法，以克服这些限制。纳米结构可以通过显著放大检测位置来提高传感器的分辨率。此外，通过提供芯片上纳米尺度的样品制备、浓缩和多重诊断，所提出的电子/液体样品传输可以显著提高检测的速度和灵敏度。这项研究将解决基本问题，包括：纳米结构与流体设备的最佳接口；传感探针(DNA、抗体)的芯片上固定化；使用DEP驱动的靶标分离、制备和在LOC中的浓度。首先，这项研究计划旨在通过将电沉积和光刻技术相结合来设计集成制造方法，在流体通道上创建有目的地设计的灌木状纳米岛(SNI)，用于芯片上捕获探针(DNA和抗体)的选择性固定。其次，本项目旨在将SNI检测平台与横向电场集成在开放访问的LOC配置中，并采用可寻址流体来探索目标分子的捕获效率和浓度以及多路检测。*这项工作的成功完成将代表着朝着创建新一代自动化工具的重要步骤，这些工具用于早期多路诊断并提高患者的存活率，特别是在偏远地区或在家庭护理中。这一计划的广泛影响提供了许多有吸引力的应用，包括医疗保健、疾病诊断、药物发现和个性化医学。

The vision of this program is to advance the integration of lab-on-chip diagnostics for high throughput and quantitative detection of biomolecules at single-molecule level. Presently, 85% of the diagnostics tests are performed in centralized lab facilities with the aid of professional lab personnel a process which is slow and expensive. Therefore, rapid and accurate diagnostics of pathogenic and genetic disease (such as cancer) at point-of-care is a global challenge, but a critical necessity. Lab-on-chip (LOC) devices provide an automated system for complete cycle of biological reactions at the nano scale, resulting in rapid analysis compared to standard laboratory protocols. However, identifying genetic disorders or disease states on-chip, in particular at early-stage, requires dynamic manipulation and concentration of a small number of target molecules (protein, DNA or RNA) at individual single-molecules level. Current LOC technologies are limited by sensor resolution and sensitivity, due to the difficulty of concentrating target molecules at the detection sites in high enough levels.***This research program will focus on the engineering of new approaches in LOC technology via synergistically combining nanostructured materials with electric/fluidic sample delivery systems to overcome limitations. Nanostructures can boost the sensor resolution by significant amplification of the detection sites. In addition, proposed electric/fluidic sample delivery can significantly improve the speed and sensitivity of detection by providing on-chip nanoscale sample preparation, concentration and multiplex diagnosis. The research will address fundamental questions including: optimal interface of nanostructures with fluidic devices; on-chip immobilization of sensing probes (DNA, antibody); target isolation, preparation and concentration in LOCs using DEP actuation. First, this research program aims at engineering integrated fabrication methods by combining electrodeposition and lithography to create purposefully-designed shrub-like nano-islands (SNI) on fluidic channels for on-chip and selective immobilization of capturing probes (DNA and antibodies). Second, this program aims at integrating the SNI detection platform with a transverse electric filed in an open-access LOC configuration with addressable fluidics to explore the trapping efficiency and concentration of the target molecules and multiplexed detection. ***Successful completion of this work will represent significant steps towards the creation of new generation of automated tools for early-stage multiplexed diagnostics and increasing the survival rate of the patients, particularly in remote locations, or in home-care. The wide implication of this program offers many attractive applications including health care, disease diagnostics, drug discovery and personalized medicine.