本项目针对肺癌早期预警的重大需求，研究气泡液体活检新技术和新方法。在前期跨尺度传感界面和微流控工作基础上，提出高分子无电沉积和框架核酸精确组装策略，以微气泡为模板，构建球形微纳协同分子识别界面，研制兼容光电检测、集成微流控阵列的气泡液体活检系统，用于肺癌靶标的高灵敏、高特异性多指标联合检测，降低假阳性。深入研究气泡自聚集效应、探针分子在气泡表面的作用机制，以及纳米结构对气泡界面性能和分子结合动力学调控的科学问题。藉此构建集主动运输、分子识别、靶标捕获、界面重构和原位检测于一体的气泡实验室分析平台，其特点是气泡自驱动捕获生物靶标，自聚集重构分子界面增强信号，并自动与背景基质分离，解决了传统微纳米颗粒在分离检测时过度依赖外场力和多步信号放大的局限。预期构筑多功能气泡微纳协同分子界面，在高性能气泡液体活检关键技术取得突破，实现靶标高效分离和多元检测，建立肺癌早期预警模型，提升肺癌的精准诊疗水平。

This proposal aims to developing new techniques and approaches of liquid biopsies mediated by bubbles to fulfill the unmet need of lung cancer early warning. On the basis of our previous advancement in engineering of trans-scale biosensing interface and microfluidics, this proposal will use macromolecule-aided electroless metal deposition and precise assembly of framework nucleic acids (FNAs) to engineer spherical and synergic micro- and nano-scale molecular interface templated with microbubbles. Such a functional interface is compatible with optical and electric detection schemes, and could be integrated with microfluidic array for construction of bubble-mediated liquid-biospy platforms. These platforms enable highly sensitive, specific and combined detection of multiple markers of lung cancer and thus minimize the false positives. This proposal also suggests the exploration of self-aggregation effect and the oriented conjugation and ordered assembly of biomolecules on bubble surface, and the modulation of nanostructuring on the sensing performance of bubble interface and molecular binding kinetics. The result allows to engineer a “lab-on-a-bubble” platform that integrates with bubble-mediated multiple functions, such as active transport, molecular recognition, target capturing, interface reconfiguration and in-situ detection. This bubble platform is featured with self-driven target capturing, reconfigurable bubble network interface through self-aggregation for signal enhancement and self-separation from the bulk solution. These merits address the long-lasting challenge in conventional separation and detection application of micro- and nano-particles that heavily relied on external magnetic, centrifugal forces and multistep signal amplification. This proposal is expected to engineer multifunctional bubbles with synergic micro- and nano-scale molecular interface, develop high-performance bubble-mediated key techniques of liquid biopsy for highly efficient marker separation and multiplexed detection, and establish early-warning model of lung cancer to promote its precision theranostics.