Dual-modality field-effect/magnetic immunosensor chip for label-free biomarker detection (FEMIC)

用于无标记生物标志物检测的双模态场效应/磁性免疫传感器芯片 (FEMIC)

• 批准号: 445454801
• 负责人: Dr. Corinna Kaulen
• 金额: --
• 依托单位: Bioelektronik (IBI-3)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/445454801?language=en
• 关键词: Dual; modality; field; effect; magnetic

The main objective of the proposed project is the development of a reusable dual-modality field-effect/magnetic immunosensor chip for detection of multiple biomarkers. The semiconductor field-effect platform is very well-suited for label-free electrical detection of biomarkers by their molecular charge, whereas frequency mixing magnetic detection is a contactless technique probing the binding state of magnetic nanoparticles (MNPs). Such a combined immunosensor using two completely different transducer principles will drastically reduce possible false signals and thus, will provide a more reliable detection of target biomarkers. Only if signals recorded by both methods change in expected direction (Boolean logic AND gate), the result will be considered as positive.Advantages provided by the proposed concept include:- easy and low-cost fabrication of immunochips by using a simple immuno-sensitive field-effect capacitor (ImmunoFEC) as transducer;- the use of MNPs not only for magnetic detection but also for capturing and separation of target biomarkers from samples and their concentration on the immunochip surface;- capability for detection of biomarkers in both low- and high-ionic strength samples;- absence of non-specific adsorption of biomolecules on the ImmunoFEC surface because the immunochemical reaction event is separated from the sensing surface;- reusability and possibility of detection of multiple biomarkers using the same immunochip;- acceleration of adsorption of biomarker-antibody-conjugated MNPs by the magnet and a reduced time-to-result.ImmunoFECs modified with MNPs have not been used for label-free detection of protein biomarkers by their intrinsic molecular charge so far. The new approach shall be exemplarily examined for the detection of several clinically relevant biomarkers (e.g., glycated hemoglobin, hemoglobin, C-reactive protein). MNPs stabilized by hydrophilic coatings will be synthesized in different sizes and characterized according to their nonlinear magnetic responses. They will be conjugated with antibodies for specific biomarker detection. Physical and electrochemical characterization of ImmunoFECs will provide information on surface modification with biomarker-antibody-conjugated MNPs and regeneration steps. A theoretical model of how the ImmunoFEC modified with biomarker-antibody-conjugated MNPs works will be developed. Basic working characteristics (sensitivity, detection limit, specificity, reusability, etc.) of the dual-modality immunochip will be systematically studied and compared with theoretical predictions.The proposal might have distinct impact bringing field-effect and magnetic detection principle together for possible future diagnostic tools such as point-of-care applications. The intended collaboration enables target-oriented work on this multidisciplinary approach and combines complementary scientific expertise in a perfect match.

该项目的主要目标是开发可重复使用的双模场效应/磁免疫传感器芯片，用于检测多种生物标志物。半导体场效应平台非常适合通过分子电荷对生物标志物进行无标记电检测，而频率混合磁检测是一种探测磁性纳米颗粒（MNPs）结合状态的非接触技术。这种使用两种完全不同的传感器原理的组合免疫传感器将大大减少可能的假信号，因此，将提供更可靠的目标生物标志物检测。只有当两种方法记录的信号在预期方向（布尔逻辑与门）发生变化时，结果才被认为是正的。所提出的概念提供的优点包括：-使用简单的免疫敏感场效应电容器（ImmunoFEC）作为换能器，容易和低成本地制造免疫芯片；- MNPs不仅用于磁检测，还用于捕获和分离样品中的目标生物标志物及其在免疫芯片表面的浓度；-在低离子强度和高离子强度样品中检测生物标志物的能力；-免疫fec表面不存在生物分子的非特异性吸附，因为免疫化学反应事件与传感表面分离；-使用同一免疫芯片可重复使用和检测多种生物标志物的可能性；-加速磁体对生物标志物-抗体偶联MNPs的吸附，缩短获得结果的时间。到目前为止，用MNPs修饰的免疫fecs还没有通过其固有的分子电荷用于蛋白质生物标志物的无标记检测。新方法应用于几种临床相关生物标志物（如糖化血红蛋白、血红蛋白、c反应蛋白）的检测。由亲水性涂层稳定的MNPs可以合成不同尺寸的MNPs，并根据其非线性磁响应进行表征。它们将与抗体结合，用于特定的生物标志物检测。免疫fecs的物理和电化学表征将为生物标志物-抗体偶联MNPs的表面修饰和再生步骤提供信息。将建立一个生物标志物-抗体偶联MNPs修饰免疫fec的理论模型。系统研究双模免疫芯片的基本工作特性（灵敏度、检出限、特异性、可重用性等），并与理论预测进行比较。该提案可能会产生明显的影响，将场效应和磁检测原理结合在一起，为未来可能的诊断工具（如即时护理应用）提供帮助。预期的合作使这种多学科方法的目标导向工作成为可能，并将互补的科学专业知识完美地结合在一起。