Atomic force microscopy as a tool applied to nano/biosensors

Abstract

This review article discusses and documents the basic concepts and principles of nano/biosensors. More specifically, we comment on the use of Chemical Force Microscopy (CFM) to study various aspects of architectural and chemical design details of specific molecules and polymers and its influence on the control of chemical interactions between the Atomic Force Microscopy (AFM) tip and the sample. This technique is based on the fabrication of nanomechanical cantilever sensors (NCS) and microcantilever-based biosensors (MC-B), which can provide, depending on the application, rapid, sensitive, simple and low-cost in situ detection. Besides, it can provide high repeatability and reproducibility. Here, we review the applications of CFM through some application examples which should function as methodological questions to understand and transform this tool into a reliable source of data. This section is followed by a description of the theoretical principle and usage of the functionalized NCS and MC-B technique in several fields, such as agriculture, biotechnology and immunoassay. Finally, we hope this review will help the reader to appreciate how important the tools CFM, NCS and MC-B are for characterization and understanding of systems on the atomic scale.

Keywords: atomic force microscopy; atomic force spectroscopy; nanoscience; nanosensors; nanotechnology.

Figure 1.

CFM principle: chemical tip modification with SAMs (Reprinted with permission [27]).

Figure 2.

Chemical force microscopy (CFM): principle and application to the probing of hydrophobic forces. Water contact angle (θ) values measured on mixed self-assembled monolayers (SAMs) of CH₃- and OH-terminated alkanethiols, plotted as a function of the molar fraction of CH₃-terminated alkanethiols (reprinted from [29] with permission).

Figure 3.

Force-displacement curves were formed. (A) tip is a far distance from the surface and there is no interaction; (B) the tip contacts the surface; (C) the cantilever is bent and a repulsive force (positive) is measured; (D) the cantilever holder is retracted from the surface and an adhesive (negative) interaction between the tip and surface is measured; (E) the pull-off point (reprinted from [9] with permission).

Figure 4.

A schematic diagram of an antigen-coated probe mapping specific interaction sites on a substrate patterned with three antibody species (reprinted from [26] with permission).

Figure 5.

Illustration of the displacement of the cantilever (h, w and l, thickness, width and the length of the cantilever, respectively).

Figure 6.

Sketch of the absorption-induced surface stress at the surface of cantilevers: (a) absorption and (b) penetration of target molecules into the sensing layer (reprinted from [38] with permission).

Figure 7.

Cantilevers (A) treated with Aqua regia; (B) coated with gold, removed from one side by a focused ion beam and (C) coated with gold and thin films of polymeric chromatographic stationary phases, removed from one side a focused ion beam (reprinted with permission [48]).

Figure 8.

(a) Simplified diagram of the functionalization of the silicon cantilever coated with polymer; (b) Chemical structure of methacrylonitrile; (c) Deflection of cantilever in response to sudden humidity change and (d) Dynamic sampling during linear humidification and desiccation (reprinted with permission [52]).

Figure 9.

The results of the HBV DNA assay with silicon-nanoparticle (SiNP) enhanced dynamic microcantilevers: (a) plots of the resonant frequency shifts acquired from the HBV DNA assay and the SiNP enhanced HBV DNA assay; (b) SEM image of the microcantilever surface with the captured SiNPs at 2.3 pM HBV target DNA, and the fluorescent images of the microcantilevers; (c) top side and (d) bottom side at 2.3 pM (reprinted from [72] with permission).