Abstract
Tracking of biological and physiological processes on the nanoscale is a central part of the growing field of nanomedicine. Although atomic force microscopy (AFM) is one of the most appropriate techniques in this area, investigations in non-transparent fluids such as human blood are not possible with conventional AFMs due to limitations caused by the optical readout. Here, we show a promising approach based on self-sensing cantilevers (SSC) as a replacement for optical readout in biological AFM imaging. Piezo-resistors, in the form of a Wheatstone bridge, are embedded into the cantilever, whereas two of them are placed at the bending edge. This enables the deflection of the cantilever to be precisely recorded by measuring the changes in resistance. Furthermore, the conventional acoustic or magnetic vibration excitation in intermittent contact mode can be replaced by a thermal excitation using a heating loop. We show further developments of existing approaches enabling stable measurements in turbid liquids. Different readout and excitation methods are compared under various environmental conditions, ranging from dry state to human blood. To demonstrate the applicability of our laser-free bio-AFM for nanomedical research, we have selected the hemostatic process of blood coagulation as well as ultra-flat red blood cells in different turbid fluids. Furthermore, the effects on noise and scanning speed of different media are compared. The technical realization is shown (1) on a conventional optical beam deflection (OBD)-based AFM, where we replaced the optical part by a new SSC nose cone, and (2) on an all-electric AFM, which we adapted for measurements in turbid liquids.
Highlights
Atomic force microscopy (AFM), invented in the late 1980s, has become an invaluable tool in nanoscience
The implementation of the self-sensing technology in an optical beam deflection (OBD)-based AFM and the use of the AFSEM® system, a sensing cantilevers (SSC)-based AFM, which we adapted for fluid measurements
The technical challenge to perform biological AFM imaging in turbid liquids is solved
Summary
Atomic force microscopy (AFM), invented in the late 1980s, has become an invaluable tool in nanoscience. In the life sciences, the unique possibility of molecular resolution under (almost) physiological conditions is convincing, justifying the importance of AFM in the study of physiological processes at the single molecule level. This unique possibility was and still is the basis for many successful research projects in which nature has been followed in its work [1,2,3,4,5], opening the window to physiology and nanomedicine. A prerequisite for all these studies was the possibility to perform investigations in transparent liquids (e.g., physiological buffers). A large number of important questions can be answered by measurements
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