Noncovalent functionalization of carbon nanotubes for highly specific electronic biosensors

Abstract

Novel nanomaterials for bioassay applications represent a rapidly progressing field of nanotechnology and nanobiotechnology. Here, we present an exploration of single-walled carbon nanotubes as a platform for investigating surface-protein and proteinprotein binding and developing highly specific electronic biomolecule detectors. Nonspecific binding on nanotubes, a phenomenon found with a wide range of proteins, is overcome by immobilization of polyethylene oxide chains. A general approach is then advanced to enable the selective recognition and binding of target proteins by conjugation of their specific receptors to polyethylene oxide-functionalized nanotubes. This scheme, combined with the sensitivity of nanotube electronic devices, enables highly specific electronic sensors for detecting clinically important biomolecules such as antibodies associated with human autoimmune diseases. R ecent years have witnessed significant interest in biological applications of novel inorganic nanomaterials such as nanocrystals (1, 2), nanowires (3), and nanotubes (4, 5) with the motivation to create new types of analytical tools for life science and biotechnology. Single-walled carbon nanotubes (SWNTs) are interesting molecular wires (diameter Ϸ1-2 nm) with unique electronic properties that have been spotlighted for future solid-state nanoelectronics (6, 7). Bridging nanotubes with biological systems, however, is a relatively unexplored area, with the exception of a few reports on nanotube probe tips for biological imaging (4), nonspecific binding (NSB) of proteins (8-10), functionalization chemistry for bioimmobilization on nanotube sidewalls (5), and one study on biocompatibility (11).Previously, we and others have shown that the electrical conductance of a nanotube is highly sensitive to its environment and varies significantly with changes in electrostatic charges and surface adsorption of various molecules (12)(13)(14). This research has hinted at possible SWNT-based miniature sensors for detecting biological molecules in fluids. Here, we systematically explore how nanotubes interact with and respond to various proteins in solution, how chemical functionalization can be used to tailor these interactions, and how the resulting understanding enables highly selective nanotube sensors for the electronic detection of proteins. Using atomic force microscopy (AFM) and quartz crystal microbalance (QCM) and electronic transport measurements, we first reveal that proteins in general exhibit a high degree of NSB on nanotubes, a phenomenon undesirable for potential biosensors. We then demonstrate a functionalization scheme involving irreversible adsorption of Tween 20 or triblock copolymer chains on nanotubes to prevent this general NSB, while at the same time enabling the binding of specific proteins of interest that can be detected electronically without the need for labeling. Further, we demonstrate specific detection of mAbs to the human autoantigen U1A, a prototype target of the autoimmune response in patients with systemic lupu...

Carbon Nanotubes for Electronic and Electrochemical Detection of Biomolecules

“…[20] Thus, there is enormous interest in utilizing CNTs for biosensor applications, where sensing motifs can be coupled to their optical [21,22] and electronic properties. [23] The incorporation of carbon nanotubes has the potential to address a variety of long-standing issues with respect to biosensing. In particular, the high surface area of single-walled CNTs (SWNTs), estimated as high as 1600 m 2 g −1 , [24] while maintaining electrical conductivity is of particular interest to achieve high biomolecule densities suitable for device miniaturization.…”

“…This is further amplified by an assortment of covalent and noncovalent functionalization strategies to link a variety of biological entities onto CNTs. [23,[37][38][39][40] The properties described above, along with excellent potential for device miniaturization, can allow CNTs to be key components of universal sensor platforms, where their unique optical and electronic properties are coupled with biorecognition and enzyme catalysis to enhance functionality.…”

DNA Functionalized Single-Walled Carbon Nanotubes for Electrochemical Detection

“…[7][8][9] However, for a more complete understanding about single-walled carbon nanotubes and also for many of their potential applications, functionalization and solubilization of nanotubes are required. Different approaches have been used to address this issue, [10][11][12][13][14] making it possible to carry out solution chemistry.…”

Integrated Single-Walled Carbon Nanotube/Microfluidic Devices for the Study of the Sensing Mechanism of Nanotube Sensors

“…The conduction of current through a semiconducting SWNT is greatly affected by the environment, a feature that has been exploited to develop chemical sensors both in the gas phase and in physiological solution. [1][2][3][4] For instance, the binding of proteins to SWNTs or to receptors immobilized on SWNTs can be detected by monitoring the conductance of nanotube field effect transistors (FETs) prepared by connecting two metal electrodes with a nanotube. [2][3][4] The combination of nanotube FETs with microfluidic channels offers unique advantages for sensor applications in a liquid.…”