NIRT: Development, Functionalization, and Assembly of Nanoscale Biological Sensors

该提案是响应纳米尺度科学与工程计划，NSF 01-157，类别NIRT而收到的。我们提出了一个项目，开发具有单分子检测能力的纳米级生物传感器，更重要的是，这些传感器的纳米级功能化和组装的新技术。该装置将由几个纳米级构件组成：1)超灵敏的半导体霍尔梯度仪，能够检测单个直径为5纳米的磁性纳米颗粒（磁检测）；2)基于新型半导体金属氧化物纳米带的纳米场效应晶体管（FET）（电检测）。我们将采用浸笔纳米光刻（DPN）功能化单个固态器件来检测特定的生物物质。此外，dpn装饰的固体衬底将用于将纳米级构建块组装到溶液的特定图案上。任何生物传感器的实用性都取决于其：1)选择性，2)灵敏度，3)环境兼容性。我们最近展示了由GaAs/AlGaAs二维电子气体制成的亚微米霍尔梯度仪，可以检测单个直径为10纳米的磁颗粒。它们非常适合于检测被磁性纳米颗粒标记的吸附生物分子的存在。为了在环境条件下获得最佳性能，我们将利用InAs异质结构制造梯度仪。对于生物分子的电检测，我们打算用一组金属氧化物纳米带制造纳米级场效应晶体管。在这种情况下，可以通过测量纳米带连接处的电导率变化来检测吸附在功能化纳米带表面的带电分子。利用DPN，纳米霍尔梯度计表面和纳米带场效应晶体管通道可以功能化，从而对所需的生物分子产生特定的亲和力，从而使我们能够构建高选择性的传感器件。此外，多个纳米fet可以通过表面模板纳米组装策略组装到衬底上的特定位置或电路中。在这种方法中，固体底物将首先被与纳米带具有特定亲和力的化学结合基团功能化，然后底物将被用来从溶液中捕获纳米带。该计划的成功实施不仅将产生几种具有直接应用价值的高灵敏度新型生物传感器，而且还将为生物传感器的制造和组装创造新的范例，这可能广泛适用于许多其他系统。为了完成既定的目标，我们已经组建了一个由来自三个机构的生物学、物理学、材料科学和电气工程方面的六名研究人员组成的团队。该团队提供了独特的跨学科组合，并拥有项目所需的所有专业知识和工具。此外，这个跨学科的研究项目将为许多学生提供与其他学科的研究人员合作的宝贵机会。

This proposal was received in response to Nanoscale Science and Engineering initiative, NSF 01-157, category NIRT. We propose a project to develop nanoscale biological sensors with single molecule detection capability and, more importantly, a novel technique for nanoscale functionalization and assembly of these sensors. The devices will consist of several nanoscale building blocks: 1) ultra-sensitive semiconductor Hall gradiometer capable of detecting a single 5-nm diameter magnetic nanoparticle (magnetic detection); 2) nanoscale field effect transistor (FET) based on newly developed semiconducting metal oxide nanobelts (electrical detection). We will employ dip-pen nanolithography (DPN) to functionalize individual solid state devices to detect specific biological substances. Furthermore, DPN-decorated solid substrates will be utilized to assemble nanoscale building blocks onto specific patterns from solution.The practicality of any biological sensor is governed by its: 1) selectivity, 2) sensitivity, and 3) environmental compatibility. We have recently demonstrated that sub-micrometer Hall gradiometers, made out of GaAs/AlGaAs two-dimensional electron gas, can detect a single 10-nm-diameter magnetic particle. They are ideally suited for detecting the presence of adsorbed biomolecules tagged with magnetic nanoparticles. We will fabricate gradiometers out of InAs heterostructures for the optimal performance under ambient conditions. For electrical detection of biological molecules, we intend to fabricate nanoscale FET's from a group of metal oxide nanobelts. In this case, charged molecules adsorbed on the functionalized nanobelt surfaces can be detected by measuring the conductivity change of the nanobelt junctions.Utilizing DPN, the nanoscale Hall gradiometer surface and nanobelt FET channel can be functionalized to create specific affinity for desired biomolecules, which allows us to build highly selective sensing devices. Furthermore, multiple nano-FET's can be assembled onto specific locations on a substrate or in a circuit via surface-templated nano-assembly strategy. In this method, the solid substrate will be first functionalized with chemical binding groups with specific affinity to the nanobelts, and then the substrates will be used to capture the nanobelts from their solution.Successful execution of the proposed program will not only produce several highly sensitive novel biosensors with immediate application values, but also create a new paradigm for biosensor fabrication and assembly that may be widely applicable in many other systems. To accomplish the stated goals, we have assembled a team of six researchers in biology, physics, materials science, and electrical engineering from three institutions. This team provides a unique interdisciplinary combination and possesses all the necessary expertise and tools for the project. In addition, this interdisciplinary research project will provide many students a valuable opportunity to collaborate with researchers in other disciplines.