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

具有嵌入式纳米传感器的片上实验室，用于高通量分析

• 批准号: RGPIN-2018-06232
• 负责人: Mahshid, Sara
• 金额: $ 2.04万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=714162
• 关键词: Lab; chip; embedded; nanosensors; throughput

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.

该计划的愿景是推进芯片实验室诊断的集成，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实验室设施中进行的，这一过程缓慢且昂贵。因此，在护理点快速准确地诊断致病性和遗传性疾病（例如癌症）是一项全球性挑战，但却是至关重要的必要性。片上实验室 (LOC) 设备提供了一个自动化系统，可实现纳米级生物反应的完整循环，与标准实验室方案相比，可实现快速分析。然而，在芯片上识别遗传性疾病或疾病状态，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）。当前的 LOC 技术受到传感器分辨率和灵敏度的限制，因为难以将检测位点的目标分子浓缩到足够高的水平。 该研究计划将重点关注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限制，来设计 LOC 技术的新方法。纳米结构可以通过显着放大检测位点来提高传感器分辨率。此外，所提出的电/流体样品传输可以通过提供片上纳米级样品制备、浓缩和多重诊断来显着提高检测的速度和灵敏度。该研究将解决一些基本问题，包括：纳米结构与流体装置的最佳界面；传感探针（DNA、抗体）的片上固定；使用 DEP 驱动在 LOC 中进行目标分离、制备和浓缩。首先，该研究项目旨在通过结合电沉积和光刻来设计集成制造方法，在流体通道上创建专门设计的灌木状纳米岛（SNI），用于捕获探针（DNA和抗体）的片上和选择性固定。其次，该项目旨在将 SNI 检测平台与横向电场集成在开放式 LOC 配置中，并具有可寻址流体技术，以探索目标分子的捕获效率和浓度以及多重检测。 这项工作的成功完成将代表着在创建用于早期多重诊断的新一代自动化工具和提高患者生存率方面迈出的重要一步，特别是在偏远地区或家庭护理中。该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疗。