Cancer cell metastasis is a leading cause of mortality whereby cancer cells migrate from a tumor and spread to distant sites in the body. Understanding metastasis requires a deeper understanding of biomechanics and mechanobiology at the cellular level. We have established the use of Atomic Force Microscopy to infer the mechanical properties of single cells in cultures by measurement of their Young’s modulus. Here we discuss the main advantages, challenges, technological limitations and applicability of AFM based cell mechanics studies along with other emerging high throughput techniques for the development of single cell mechanical based clinical assays for cancer detection and management.

Directed self-assembly (DSA) of block copolymers is a promising alternative nanolithographic technology aimed at producing sub-40 nm patterns. One important opportunity for DSA is the creation of periodic arrays of lines and spaces. The two most common methods for line-space applications are chemoepitaxy (typically using a lamella-forming PS-b-PMMA diblock) and graphoepitaxy (typically using cylinder-forming block copolymers with a Si-containing minority block). Mesoscale modeling, such as Self-Consistent Field Theory (SCFT), has by now become an important tool in formulation screening and predicting polymer morphologies and defect types and probabilities. Here, we use SCFT to study the morphology of cylinder-forming PS-b-PDMS diblocks in rectangular trenches with grafted PS-brushes. The targeted morphology is 2 cylinders per trench (3X multiplication). We compute phase diagrams and determine equilibrium morphologies as a function of brush thickness and guiding weir height. Using those equilibrium morphologies as starting points, we also compute structures and free energies of typical defects, including dislocation and disclination dipoles, broken lines, and bridges. The predicted defect structures and probabilities are in a reasonable qualitative agreement with recent experimental results.

We explore the impact of monovalent counter-ions on the molecular conformation of highly charged flexible polyelectrolytes for a range of molecular topologies (linear chains, stars, and unknotted and trefoil rings) by molecular dynamics simulations that include an explicit solvent having short range interaction with the polyelectrolyte. In particular, we investigate how the counter-ions near the polyelectrolytes with variable mass influence the average molecular shape. We also characterize the interfacially “bound” counter-ions by calculating the time-averaged number of interfacial counter-ions, as well as the degree to which the polyelectrolytes wrap around the counter-ions by calculating the number of contacts between the counter-ions and the polyelectrolyte.

Dislocations are line like crystal defects mediating plasticity in single crystals. In the current contribution we review classical continuum concepts of dislocation theory from a topological view point. Subsequently, we introduce a new measure for the density of jogs mutually impaired on each other by dislocations on different slip systems. This jog density is closely related to a topological measure of the interlinkage of the dislocations on the involved slip systems, known as relative helicity in other branches of physics.

The set of oscillatory resonance AFM modes is expanded with frequency modulation mode and frequency imaging in amplitude modulation mode. The backgrounds of these modes are discussed and their capabilities are compared on the practical examples. The data show how these techniques complement the amplitude modulation with phase imaging. The frequency imaging enhances the compositional mapping of heterogeneous samples. Frequency modulation mode provides a superior capability in imaging at low tip-sample forces.

Compositional imaging of several immiscible polymer blends was examined with the combination of AFM-based mechanical and electric modes with chemically-specific Raman mapping. Results showed that these methods substantially complement each other in comprehensive characterization of surface morphology by helping to identify a composition of top surface and sub-surface materials in polymer heterogeneous systems.

Silver nanostructures are directly grown on the apex of commercially available silicon AFM probes using our area-selective electroless deposition: the apex of a silicon AFM probe is irradiated using a focused ion beam (FIB), and then the FIB-irradiated AFM probe is exposed to a pure AgNO3 aqueous solution. With this method, a silver nanostructure selectively grows on the tip apex where the native oxide layer has been removed in response to FIB irradiation. Silver ions are reduced by the electrons flowing from the silicon probes into the solution through the FIB-irradiated area owing to the difference in Fermi energy between silicon and the solution. The morphology of the growing silver depends on the concentration of both AgNO3 and the electrons. The growth of a gold nanoflower is also demonstrated on the apex of a silicon AFM probe.

Liposome reinforced by adding cholesterol was synthesized using the dipalmitoyl-phosphatidylcholine (DPPC). Phase stability of the phospholipid bilayers was examined by FT-IR spectroscopy. The reinforced liposomes filled with ultrapure water or physiological saline were observed by the conventional TEM equipped with a mass spectrometer. It was confirmed that the liposomes filled with water or saline solution were stable in the vacuum at room temperature. However, during electron irradiation, water molecules escaped gradually, and a single crystal of rock salt precipitated in the liposome.

While the growth of pits in passive metals exposed to chloride solutions is well understood, the processes associated with the initiation and propagation of stable pits, versus pits that form and apparently re-passivate, are still a matter of conjecture. A major challenge in studying pit initiation using electron microscopy has been alteration of the structure and chemistry of the hydrated corrosion films upon transfer to the vacuum environment of the microscope. A recently developed technique uses a microfluidic liquid cell to maintain the aqueous environment in contact with the sample. This work uses such cells to directly observe pits initiating, and growing before reaching stability, in aluminum thin films under potentiostatic polarization in situ in the electron microscope. Polarization curves developed in the cell show good agreement with those observed under conventional electrochemical experimental conditions. We observed current transients representative of metastable pitting and were able to relate crystalline features found in situ with topographic features using atomic force microscopy (AFM). An accumulation of aluminum surrounding an initiated pit, combined with depth profiling using Auger electron spectroscopy suggests that aluminum metal is deposited during the pit initiation process, and may serve to reduce lateral dissolution of the aluminum film. Work is currently underway to determine if this observation is unique to the geometry of the microfluidics cell or if is a general result that occurs at the very beginning of pit initiation.

In an attempt to understand the structure and dynamics of ssDNA on graphene based surfaces, we performed all-atom implicit solvent molecular dynamics simulations of ssDNA on graphene and graphene oxide (GO) surfaces. Simulations indicate that adsorption of poly(A), poly(T) and poly (AT) have similar mechanisms of adsorption to free standing graphitic flakes, which are governed by a surface oxygen content. Specifically, higher oxygen content of a surface leads to decrease in persistence length of ssDNA. However, the role of DNA sequence on the physisorption mechanism is minimal.