There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

Current medical imaging technologies allow visualization of tissue anatomy in the human body at resolutions ranging from 100 micrometers to 1 millimeter. These technologies are generally not sensitive enough to detect early-stage tissue abnormalities associated with diseases such as cancer and atherosclerosis, which require micrometer-scale resolution. Here, optical coherence tomography was adapted to allow high-speed visualization of tissue in a living animal with a catheter-endoscope 1 millimeter in diameter. This method, referred to as "optical biopsy," was used to obtain cross-sectional images of the rabbit gastrointestinal and respiratory tracts at 10-micrometer resolution.

In Vivo Endoscopic Optical Biopsy with Optical Coherence Tomography

Hydrogel microparticles (HMPs) are promising for biomedical applications, ranging from the therapeutic delivery of cells and drugs to the production of scaffolds for tissue repair and bioinks for 3D printing. Biologics (cells and drugs) can be encapsulated into HMPs of predefined shapes and sizes using a variety of fabrication techniques (batch emulsion, microfluidics, lithography, electrohydrodynamic (EHD) spraying and mechanical fragmentation). HMPs can be formulated in suspensions to deliver therapeutics, as aggregates of particles (granular hydrogels) to form microporous scaffolds that promote cell infiltration or embedded within a bulk hydrogel to obtain multiscale behaviours. HMP suspensions and granular hydrogels can be injected for minimally invasive delivery of biologics, and they exhibit modular properties when comprised of mixtures of distinct HMP populations. In this Review, we discuss the fabrication techniques that are available for fabricating HMPs, as well as the multiscale behaviours of HMP systems and their functional properties, highlighting their advantages over traditional bulk hydrogels. Furthermore, we discuss applications of HMPs in the fields of cell delivery, drug delivery, scaffold design and biofabrication.

Hydrogel microparticles for biomedical applications.

Microbubble size isolation by differential centrifugation.

The effects of confinement on glass transition temperature (Tg) and physical aging are measured in polystyrene (PS), poly(methyl methacrylate) (PMMA), and poly(2-vinyl pyridine) (P2VP) nanocomposites containing 10- to 15-nm-diameter silica nanospheres or 47-nm-diameter alumina nanospheres. Nanocomposites are made by spin coating films from sonicated solutions of polymer, nanofiller, and dye. The Tgs and physical aging rates are measured by fluorescence of trace levels of dye in the films. At 0.1–10 vol % nanofiller, Tg values can be enhanced or depressed relative to neat, bulk Tg (Tg,bulk) or invariant with nanofiller content. For alumina nanocomposites, Tg increases relative to Tg,bulk by as much as 16 K in P2VP, decreases by as much as 5 K in PMMA, and is invariant in PS. By analogy with thin polymer films, these results are explained by wetted P2VP–nanofiller interfaces with attractive interactions, nonwetted PMMA–nanofiller interfaces (free space at the interface), and wetted PS–nanofiller interfaces lacking attractive interactions, respectively. The presence of wetted or nonwetted interfaces is controlled by choice of solvent. For example, 0.1–0.6 vol % silica/PMMA nanocomposites exhibit Tg enhancements as large as 5 K or Tg reductions as large as 17 K relative to Tg,bulk when films are made from methyl ethyl ketone or acetic acid solutions, respectively. A factor of 17 reduction of physical aging rate relative to that of neat, bulk P2VP is demonstrated in a 4 vol % alumina/P2VP nanocomposite. This suggests that a strategy for achieving nonequilibrium, glassy polymeric systems that are stable or nearly stable to physical aging is to incorporate well-dispersed nanoparticles possessing attractive interfacial interactions with the polymer. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 2935–2943, 2006

http://absimage.aps.org/image/MAR06/MWS_MAR06-2005-001949.pdf

Polymer-Nanoparticle Interfacial Interactions in Polymer Nanocomposites: Confinement Effects on Glass Transition Temperature and Suppression of Physical Aging.

Two new methods for preparing phospholipid coated microbubble suspensions are elucidated. Firstly, co-axial electrohydrodynamic atomisation was utilized to generate 3–7 µm diameter microbubbles. Secondly, a specially designed and constructed T-junction device was used to prepare monodisperse microbubbles. Characteristics of microbubbles prepared by these two methods are compared with those obtained by sonication of the phospholipid suspension.

Novel methods for preparing phospholipid coated microbubbles.

The nonlinear response of gas bubbles to acoustic excitation is an important phenomenon in both the biomedical and engineering sciences. In medical ultrasound imaging, for example, microbubbles are used as contrast agents on account of their ability to scatter ultrasound nonlinearly. Increasing the degree of nonlinearity, however, normally requires an increase in the amplitude of excitation, which may also result in violent behaviour such as inertial cavitation and bubble fragmentation. These effects may be highly undesirable, particularly in biomedical applications, and the aim of this work was to investigate alternative means of enhancing nonlinear behaviour. In this preliminary report, it is shown through theoretical simulation and experimental verification that depositing nanoparticles on the surface of a bubble increases the nonlinear character of its response significantly at low excitation amplitudes. This is due to the fact that close packing of the nanoparticles restricts bubble compression.

/pdf/increasing-the-nonlinear-character-of-microbubble-3m4xa47dyi.pdf

Increasing the nonlinear character of microbubble oscillations at low acoustic pressures

There has recently been considerable interest in the development of devices for the preparation of monodisperse microbubble suspensions for use as ultrasound contrast agents and drug delivery vehicles. These applications require not only a high degree of bubble uniformity but also a maximum bubble size of 8 μm, and this provides a strong motivation for developing an improved understanding of the process of bubble formation in a given device. The aim of this work was to investigate bubble formation in a T-junction device and determine the influence of the different processing parameters upon bubble size, in particular, liquid viscosity. Images of air bubble formation in a specially designed T-junction were recorded using a high-speed camera for different ratios of liquid to gas flow rate (Ql/Qg) and different liquid viscosities (μl). It was found that theoretical predictions of the flow profile in the focal region based on analysis of axisymmetric Stokes flow were accurate to within 6% when compared with t...

Dynamics of bubble formation in highly viscous liquids.

Uniform spherical chitosan particles of size 100 mPa s results in particles >10 μm diameter. In this study, by reducing surface tension of a high viscosity chitosan suspension, it was found that smaller diameter particles could be prepared. Chitosan solutions were electrosprayed in the stable cone-jet mode to systematically study the relationship between particle diameter, viscosity and surface tension. Increasing viscosity resulted in larger diameter particles with a broad size distribution, but decreasing surface tension had the opposite effect. Results show that a chitosan solution having a viscosity of ~80 mPa s can be used to prepare chitosan particles of diameter ~2.5 μm which on drying reduced to particles of 500 nm.

Novel electrohydrodynamic preparation of porous chitosan particles for drug delivery.

This paper presents an experimental investigation on surface and subsurface characterisation of micro-machined single-crystal silicon with (100) orientation. Full immersion slot milling was conducted using solid cubic boron nitride (CBN) and diamond-coated fine grain tungsten carbide micro-end mills with a uniform tool diameter of 0.5 mm. The micro-machining experiments were carried out on an ultra-precision micro-machining centre. Formal design of experiments (DoE) techniques were applied to design and analysis of the machining process. Surface roughness, edge chipping formation and subsurface residual stress under varying machining conditions were characterised using white light interferometry, SEM and Raman microspectroscopy. Tens of nanometre-level surface roughness can be achieved under the certain machining conditions, and influences of variation of cutting parameters including cutting speeds, feedrate and axial depth of cut on surface roughness were analysed using analysis of variance (ANOVA) method. Raman microspectroscopy studies show that compressive subsurface residual stress and amorphous phase transformation were observed on most of the micro-machined subsurface, which provides evidence of ductile mode cutting. Surface and subsurface characterisation studies show that the primary material removal mode is ductile or partial ductile using lower feedrate for both tools, and diamond-coated tools can produce better surface quality. Silicon brain implants were fabricated with good dimensional accuracy and edge quality using the optimised machining conditions, which demonstrated that micro-milling is an effective process for fabrication of silicon components at a few tens to a few hundreds of micron scale.

/pdf/surface-and-subsurface-characterisation-in-micro-milling-of-981i19yfji.pdf

Ketan Pancholi

Papers

Novel methods for preparing phospholipid coated microbubbles.

Increasing the nonlinear character of microbubble oscillations at low acoustic pressures

Dynamics of bubble formation in highly viscous liquids.

Novel electrohydrodynamic preparation of porous chitosan particles for drug delivery.

Surface and subsurface characterisation in micro-milling of monocrystalline silicon