Atomic Force Microscopy Based Tip-Enhanced Raman Spectroscopy in Biology

Abstract

Most biological phenomena occur at the nanometer scale, which is not accessible by the conventional optical techniques because of the optical diffraction limitation. Tip-enhanced Raman spectroscopy (TERS), one of the burgeoning probing techniques, not only can provide the topography characterization with high resolution, but also can deliver the chemical or molecular information of a sample beyond the optical diffraction limitation. Therefore, it has been widely used in various structural analyses pertaining to materials science, tissue engineering, biological processes and so on. Based on the different feedback mechanisms, TERS can be classified into three types: atomic force microscopy based TERS system (AFM-TERS), scanning tunneling microscopy based TERS system (STM-TERS) and shear force microscopy based TERS system (SFM-TERS). Among them, AFM-TERS is the most widely adopted feedback system by live biosamples because it can work in liquid and this allows the investigation of biological molecules under native conditions. In this review, we mainly focus on the applications of AFM-TERS in three biological systems: nucleic acids, proteins and pathogens. From the TERS characterization to the data analysis, this review demonstrates that AFM-TERS has great potential applications to visually characterizing the biomolecular structure and crucially detecting more nano-chemical information of biological systems.

Controllable Fabrication of Au-Coated AFM Probes via a Wet-Chemistry Procedure

“…In order to determine the TERS activity of our as-prepared probe, TERS enhancing performance of the probes should be detected. According to the calculation results of finite-difference time-domain (FDTD), the factors which can influence the TERS signal of a sample are not only probe but the substrate beneath the probe [ 27 ]. A metal substrate such as Au, Ag, or Cu will arise a stronger field enhancement owning to the sandwich-type assay called “gap mode.” Therefore, 50 nm Au film was chosen in our experiments as the substrate to test the TERS activities of the probes in Fig.…”

Atomic Force Microscopy Meets Biophysics, Bioengineering, Chemistry, and Materials Science

“…[44] Therefore, the combination of AFM (which can be operated in liquid conditions) with Raman spectroscopy can be usefult oi nvestigate both topographical and chemicalc hanges at the nanoscale for aw ide range of (biological) samples, such as fibril proteins, [45] carbon nanotubes, [46] DNA, [47] and cells. [48] More specifically,t ip-enhanced Ramans pectroscopy (TERS) [49] uses an apertureless probe to enhancet he Raman signal emitted by the sample molecules, which are separated from the probe by af ew nanometers, and am etallict ip that is irradiated along its apical axis by al aser with aw avelength in the visible region (l = 500-650 nm). Because the tip is sufficiently close to the sample, field enhancement is possible, leadingt om olecular excitation and registration of local Ramans pectra.…”

Optical Imaging of the Nanoscale Structure and Dynamics of Biological Membranes

“…[158][159][160] The fundamentals of the technique and recent advances beyond the measurement of cell membranes are discussed in several reviews. [161][162][163][164][165] The earliest applications of TERS for membrane studies include imaging model cell membranes (i.e., lipid bilayers), [166][167][168][169] bacterial 170,171 and viral surfaces. [172][173][174] In a recent study using TERS, Gram positive and negative bacterial species were differentiated based on the Raman signal of their membranes.…”