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

本提案是对NSF 01-157 NIRT类纳米科学与工程倡议的响应。我们提出了一个开发具有单分子检测能力的纳米级生物传感器的项目，更重要的是，提出了一种新的纳米级传感器功能化和组装技术。这些设备将由几个纳米级的积木组成：1)能够检测单个5 nm直径磁性纳米颗粒的超灵敏半导体霍尔梯度仪(磁检测)；2)基于新开发的半导体金属氧化物纳米带的纳米场效应晶体管(FET)(电检测)。我们将使用浸渍笔纳米光刻术(DPN)来使单个固态设备功能化，以检测特定的生物物质。此外，DPN修饰的固体基质将被用来从溶液中组装纳米级的构建块到特定的图案上。任何生物传感器的实用性取决于其：1)选择性，2)灵敏度，3)环境兼容性。我们最近已经证明，用GaAs/AlGaAs二维电子气制成的亚微米级霍尔梯度计，可以探测到直径为10 nm的单个磁性粒子。它们非常适合于检测标记有磁性纳米颗粒的吸附生物分子的存在。我们将利用InAs异质结来制作梯度计，以在环境条件下获得最佳性能。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来制造纳米级的FET。在这种情况下，吸附在功能化纳米带表面的带电分子可以通过测量纳米带结的电导变化来检测。利用DPN，纳米级霍尔梯度表面和纳米带FET沟道可以被功能化，从而为所需的生物分子创造特定的亲和力，这使得我们能够建立高选择性的传感器件。此外，通过表面模板化纳米组装策略，可以将多个纳米FET组装到衬底上或电路中的特定位置。在这种方法中，首先用与纳米带具有特定亲和力的化学结合基团对固体基质进行功能化，然后利用基质从其溶液中捕获纳米带。成功地实施所提出的程序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一种新的范式，可能会广泛应用于许多其他系统。为了实现所宣布的目标，我们组建了一个由来自三个机构的生物、物理、材料科学和电气工程方面的六名研究人员组成的团队。这个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，这一跨学科研究项目将为许多学生提供一个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.