The NanoBeamBalance: a passive, tensile-test device for the atomic force microscope.

An add-on device is presented, which significantly expands the force measurement capabilities of the atomic force microscope (AFM). The device consists of a completely passive mechanism, which translates the vertical motion of the AFM tip in force measurements into a horizontal motion of two sample support pads. The advantage is that it is much easier to deposit microscopic samples from suspension onto flat surfaces than to attach them reliably between tip and a surface. The working-principle and the design of the device is comprehensively described and demonstrated on the example of collagen fibres with a diameter of a few µm. Well-defined tensile measurements in longitudinal direction were performed, showing that the tensile stiffness of collagen fibres from rat tail tendon decreases by a factor of 5 when rehydrated from a dried sample and slowly increases upon cross-linking with glutaraldehyde.

Nanoscale scraping and dissection of collagen fibrils.

The main function of collagen is mechanical, hence there is a fundamental scientific interest in experimentally investigating the mechanical and structural properties of collagen fibrils on the nanometre scale. Here, we present a novel atomic force microscopy (AFM) based scraping technique that can dissect the outer layer of a biological specimen. Applied to individual collagen fibrils, the technique was successfully used to expose the fibril core and reveal the presence of a D-banding-like structure. AFM nanoindentation measurements of fibril shell and core indicated no significant differences in mechanical properties such as stiffness (reduced modulus), hardness, adhesion and adhesion work. This suggests that collagen fibrils are mechanically homogeneous structures. The scraping technique can be applied to other biological specimens, as demonstrated on the example of bacteria.

Back to basics: the development of a simple, homogenous, two-component dry-powder inhaler formulation for the delivery of budesonide using miscible vinyl polymers.

It was hypothesised that formulating a dry-powder inhaler (DPI) using a refined, smooth grade of lactose, without fines and a polymer coated drug microparticle should produce an homogeneous formulation in which aerosolization behaviour could be modified. Hence, the aim of this study was to develop a simple two component polymer coated-budesonide/lactose blend in which the drug microparticle adhesive forces could be optimised by modifying the drug coating in order to improve aerosolization from a DPI. Budesonide microparticles (1.83 +/- 0.03 microm) were coated with the vinyl polymers by adsorption and then spray-dried. The drug was blended with three different types of lactose, checked for uniformity of mixing and loaded into Pulvinal devices. The median volume particle size of all but one of the polymer coated microparticles remained below 4 microm after spray-drying and the content uniformity for all the blends >96%. Coating the budesonide with 0.01% poly(vinyl alcohol) increased the fine particle fraction (FPF) in the next generation impactor (NGI) from 29.1 +/- 0.7% to 52.8 +/- 1.0% and reduced the force of adhesion from 410 +/- 182 to 241 +/- 82 nN with smooth lactose. This illustrates that vinyl polymers could effectively modify adhesive interactions without the need for ternary components such as fines.