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，以实现单分子水平生物分子的高通量和定量检测。目前，85%的诊断测试是在专业实验室人员的帮助下在集中的实验室设施中进行的，这一过程既缓慢又昂贵。因此，在医疗点快速准确地诊断致病性和遗传性疾病（如癌症）是一项全球性挑战，但也是一项至关重要的必要性。芯片实验室（LOC）设备提供了一个自动化系统，可以在纳米尺度上完成生物反应的完整循环，与标准实验室方案相比，可以进行快速分析。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集中少量靶分子（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，因为难以在检测位点将目标分子集中到足够高的水平。***该研究项目将重点关注LOC技术新方法的工程设计，通过将纳米结构材料与电/流体样品输送系统协同结合来克服局限性。纳米结构可以通过显著放大检测位点来提高传感器的分辨率。此外，通过提供片上纳米级样品制备、浓缩和多重诊断，所提出的电/流控送样可以显著提高检测速度和灵敏度。该研究将解决以下基本问题：纳米结构与流体器件的最佳界面；传感探针（DNA、抗体）的片上固定化；利用DEP驱动LOCs中目标的分离、制备和浓缩。首先，本研究项目旨在通过结合电沉积和光刻技术的工程集成制造方法，在流体通道上创建有目的地设计的灌木状纳米岛（SNI），用于芯片上和选择性固定捕获探针（DNA和抗体）。其次，本项目旨在将SNI检测平台与具有可寻址流体的开放访问LOC配置中的横向电场集成在一起，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标志着为早期多路诊断创造新一代自动化工具和提高患者生存率迈出重要一步，特别是在偏远地区或家庭护理中。该计划的广泛含义提供了许多有吸引力的应用，包括卫生保健，疾病诊断，药物发现和个性化医疗。

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.