Cellular transfer and AFM imaging of cancer cells using Bioimprint

Currently, optical microscopy techniques are the primary method for cell surface visualization, with microscopic characteristics of cells traditionally used for diagnosis and classification of cancers [1]. However, because the differences in characteristics can be subtle, accurate detection can be challenging and ambiguous [2]. A drawback of analysis using focused light microscopy is the fundamental diffraction limit, which at its optimum imposes an attainable spatial limit of 180 nm in the focal plane and 500 nm along the optical axis [3,4].Imaging tools, such as the atomic force (AFM) and scanning electron (SEM) microscopes, are investigated for their ability to provide topographical information at a resolution far superior to optical methods [5,6]. Despite having the potential to image numerous diseases, cancers and pathogens, nanoscale analytical tools have not been efficiently utilized in mainstream biological research. Difficulties associated with imaging soft, living biological material in situ is challenging and remains a delicate and time consuming task, which while effective, is inefficient for the analysis and evaluation of large cell populations [7]. Predictions on the attainable resolution when imaging cell surfaces by AFM in liquid, regardless of living or fixed, is generally considered in be in the order of 50–500 nm [8-10]. Resolution limiting factors [11] include cell-to-substrate attachment, cell type, topographic complexity, surface composition and tip indentation into the soft biological material. In a probing-based imaging environment soft biomaterials are susceptible to structural movement and deformation caused by intermittent contact by the sharp AFM tip [12]. The tip apex is a crucial resolution limiting factor in AFM investigations and previous biological analysis has been limited to blunter probes for fear of membrane penetration [13].Time consuming preparation procedures used for air and vacuum imaging environments require dehydration and