Abstract
Since its invention, atomic force microscopy (AFM) has come forth as a powerful member of the “scanning probe microscopy” (SPM) family and an unparallel platform for high-resolution imaging and characterization for inorganic and organic samples, especially biomolecules, biosensors, proteins, DNA, and live cells. AFM characterizes any sample by measuring interaction force between the AFM cantilever tip (the probe) and the sample surface, and it is advantageous over other SPM and electron micron microscopy techniques as it can visualize and characterize samples in liquid, ambient air, and vacuum. Therefore, it permits visualization of three-dimensional surface profiles of biological specimens in the near-physiological environment without sacrificing their native structures and functions and without using laborious sample preparation protocols such as freeze-drying, staining, metal coating, staining, or labeling. Biosensors are devices comprising a biological or biologically extracted material (assimilated in a physicochemical transducer) that are utilized to yield electronic signal proportional to the specific analyte concentration. These devices utilize particular biochemical reactions moderated by isolated tissues, enzymes, organelles, and immune system for detecting chemical compounds via thermal, optical, or electrical signals. Other than performing high-resolution imaging and nanomechanical characterization (e.g., determining Young’s modulus, adhesion, and deformation) of biosensors, AFM cantilever (with a ligand functionalized tip) can be transformed into a biosensor (microcantilever-based biosensors) to probe interactions with a particular receptors of choice on live cells at a single-molecule level (using AFM-based single-molecule force spectroscopy techniques) and determine interaction forces and binding kinetics of ligand receptor interactions. Targeted drug delivery systems or vehicles composed of nanoparticles are crucial in novel therapeutics. These systems leverage the idea of targeted delivery of the drug to the desired locations to reduce side effects. AFM is becoming an extremely useful tool in figuring out the topographical and nanomechanical properties of these nanoparticles and other drug delivery carriers. AFM also helps determine binding probabilities and interaction forces of these drug delivery carriers with the targeted receptors and choose the better agent for drug delivery vehicle by introducing competitive binding. In this review, we summarize contributions made by us and other researchers so far that showcase AFM as biosensors, to characterize other sensors, to improve drug delivery approaches, and to discuss future possibilities.
Highlights
Understanding the process of biosensing, characterizing biosensors (Pontinha et al, 2011; Kim et al, 2015; ChiorceaPaquim et al, 2018; Chiorcea-Paquim et al, 2018), measuring interaction forces between ligand–receptor pairs (Sarkar et al, 2019), and utilizing self-assembled nanoparticles and other drug delivery carriers to improve drug delivery approaches are of utmost importance in the field of biomedicine, nanotechnology (Goldsbury and Scheuring 2002; Wu et al, 2002; Kreplak 2016), and biophysics
Imaging modes where the probe is scanned over the surface of the substrate, the cantilever tip is first approached toward the substrate until tip–sample contact happens and retracted in Atomic force microscopy (AFM) dynamic force spectroscopy (AFM-DFS) (Sulchek et al, 2005; Neuert et al, 2006; Thormann et al, 2006; Diezemann and Janshoff 2008; Alessandrini et al, 2012; Sengupta et al, 2014; Sluysmans et al, 2018; Ju 2019; Reiter-Scherer et al, 2019; Alhalhooly et al, 2021) and single-molecule force spectroscopy (AFM-SMFS) experiments
AFM results of these measurements have been compared to similar techniques (DLS and transmission EM (TEM)/SEM) for validation in multiple research studies conducted till date, and AFM seemed to produce more accurate measurements than these techniques
Summary
AFM characterizes any sample by measuring interaction force between the AFM cantilever tip (the probe) and the sample surface, and it is advantageous over other SPM and electron micron microscopy techniques as it can visualize and characterize samples in liquid, ambient air, and vacuum. It permits visualization of three-dimensional surface profiles of biological specimens in the near-physiological environment without sacrificing their native structures and functions and without using laborious sample preparation protocols such as freeze-drying, staining, metal coating, staining, or labeling.
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