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Fundamental Limitations of Atomic Force Microscopy for Soft Materials Research

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Scanning Probe Microscopy (SPM) is a broad class of measurement techniques that allowthe precise manipulation of sensory equipment for studying physical phenomena at the surfaces of materials at scales ranging from Angstroms () to micrometers (). Here, we focus on the Atomic Force Microscope (AFM), an SPM technique that allows researchers to measure the mechanical properties (softness or stiffness). This device, which requires a strong background in applied physics, has become a popular tool in fields such as biology as it enables researchers to quantitatively describe the biological function of systems, such as cells, in terms of their mechanical behavior. Here, we provide a new perspective which seeks to demonstrate a need for further care and rigor in the interpretation of data collected with this device with a specific focus on its application in measuring the mechanical properties of soft materials ( softer than Aluminum). Primarily, we categorize these errors into three classes which organize the structure of the thesis. First, we demonstrate the limitations of existing techniques used to extract the mechanical properties of a material from data obtained with typical AFM experiments. This analysis spans Chapter 3 and 4. As an addition, we also demonstrate the application of these techniques on several materials of interest, namely cancer cells, as seen in Chapter 3. Second, we discuss how the types of experiments being performed impose fundamental limitations on the quality and quantity of information that can be obtained about a material. In Chapter 4, we show how these limitations can be reverse engineered to design experiments that provide more optimal information about a material’s mechanical properties. Third, we investigate the inapplicability of existing physical theories in faithfully describing the AFM measurement process. In Chapter 5,7we consider the deleterious effects of performing AFM measurements in a fluid, as would benecessary for in vitro investigation of cells. In Chapter 6, we propose an efficient and generalized framework which serves as a foundation for the development of new physical theories which directly account for the effects of distance dependent surface forces. Although the work is driven from a theoretical basis, simple experiments are performed whenever feasible to provide a basic demonstration of the ideas developed here. Finally, a rugged theoretical background is given in Chapter 2. This review is by no means comprehensive, rather it serves to provide the essentials to support the ideas in the following chapters. Interested readers can be directed to further technical details by following the references.

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