EAGER: Nanopipette-based immunosensor

Mirkin 1251232智能优点固态纳米孔已被广泛用于从库尔特计数器到DNA测序设备的不同传感应用中。 这些多功能传感器可以检测不同大小的分析物，从单个分子到细菌。 然而，大多数报道的纳米孔的应用是定性的，并且它们的物理尺寸和几何形状通常不适合于在微环境中的原位测量。 该提案旨在开发一种新的生物传感器平台，用于基于纳米尺寸移液管的抗体和蛋白质生物标志物的检测。 与纳米孔一样，移液管可以检测进入其孔径的分析物，并部分阻断流过其中的离子电流。然而，纳米移液管提供了几个重要的优点，包括易于制造，小的物理尺寸和针状几何形状，使其适合作为扫描电化学显微镜（SECM）的探针。 金属纳米粒子的易位将被用作模型系统，以建立纳米移液管连续脉冲传感的原理。 通过彻底表征移液管的尺寸和几何形状，我们将证明记录的单颗粒事件的频率和颗粒到孔的扩散通量之间的定量关系。 这将能够定量测定溶液中的分析物种类。 在裸金属颗粒的概念验证实验之后，我们将致力于抗体的检测和定量（例如，抗花生抗体）和癌症生物标志物（例如，前列腺特异性抗原（PSA）。 总体而言，拟议的工作将导致开发一种新的生物传感平台，用于在单个生物分子或单个纳米颗粒水平上进行定量分析。 这一潜在的变革性概念可能会导致生物电分析化学的范式转变。更广泛的影响所提出的生物传感方法可以基于检测低浓度的抗体和蛋白质生物标志物来实现过敏、癌症和其他疾病的准确诊断。 它可以在生物医学测试中找到其他应用，包括DNA测序。 参与该项目的研究生和博士后研究员将获得传感器，电化学，生物分析化学和纳米科学的多学科研究经验。 这项研究的结果将通过出版物和专业介绍广泛传播。 所要求的资金将使我们能够为纽约市立大学正在进行的努力做出贡献，以招募代表性不足的少数STEM学生并参与其多样性举措。 该项目将为本科生和高中生提供研究机会。

Mirkin1251232Intellectual Merit Solid-state nanopores have been widely employed in different sensing applications from Coulter counter to DNA sequencing devices. These versatile sensors can detect analytes of different size ranging from single molecules to bacteria. However, most reported applications of nanopores are qualitative, and their physical size and geometry are often not suitable for in situ measurements in microenvironments. This proposal is aimed at developing a new biosensor platform for the detection of antibodies and protein biomarkers based on the use of nanometer-sized pipettes. Like a nanopore, a pipette can sense the analyte that enters its aperture and partially blocks the ion current flowing through it. However, a nanopipette offers several important advantages including the ease of fabrication, small physical size, and needle-like geometry that makes it suitable as a probe for scanning electrochemical microscopy (SECM). The translocation of metal nanoparticles will be used as a model system to establish the principles of resistive-pulse sensing with nanopipettes. By thoroughly characterizing the pipette size and geometry, we will demonstrate the quantitative relationship between the frequency of the recorded single particle events and the diffusion flux of particles to the orifice. This will enable quantitative determination of analyte species in solution. Following proof-of-concept experiments with bare metal particles, we will work on the detection and quantitation of antibodies (e.g., antipeanut antibody) attached to nanoparticles and cancer biomarkers (e.g., prostate specific antigen, PSA). Overall, the proposed work will result in the development of a new biosensing platform for quantitative analysis at the level of single biomolecules or single nanoparticles. This potentially transformative concept can cause the paradigm shift in bioelectroanalytical chemistry.Broader Impacts The proposed approach to biosensing can enable accurate diagnostics of allergies, cancer and other diseases based on the detection of low concentrations of antibodies and protein biomarkers. It can find other applications in biomedical testing including DNA sequencing.The requested support is mostly for graduate and postdoctoral stipends. The graduate students and postdoctoral fellows involved in this project will get multidisciplinary research experience in sensors, electrochemistry, bioanalytical chemistry and nanoscience. The results of this research will be broadly disseminated through publications and professional presentations. The requested funds will enable us to contribute to ongoing CUNY efforts to recruit underrepresented minority STEM students and participate in its diversity initiatives. This project will provide research opportunities to undergraduates and high school students.