Thermal characterization of SOI CMOS micro hot-plate gas sensors

This work reports on thermal characterization of SOI (silicon on insulator) CMOS (complementary metal oxide semiconductor) MEMS (micro electro mechanical system) gas sensors using a thermoreflectance (TR) thermography system. The sensors were fabricated in a CMOS foundry and the micro hot-plate structures were created by back-etching the CMOS processed wafers in a MEMS foundry using DRIE (deep reactive ion etch) process. The calibration and experimental details of the thermoreflectance based thermal imaging setup, used for these micro hot-plate gas sensor structures, are presented. Experimentally determined temperature of a micro hot-plate sensor, using TR thermography and built-in silicon resistive temperature sensor, is compared with that estimated using numerical simulations. The results confirm that TR based thermal imaging technique can be used to determine surface temperature of CMOS MEMS devices with a high accuracy. © 2010 EDA Publishing/THERMINIC.

Imbibition dynamics of nano-particulate ink-jet drops on micro-porous media

Ink-jet printing of nano-metallic colloidal fluids on to porous media such as coated papers has become a viable method to produce conductive tracks for low-cost, disposable printed electronic devices. However, the formation of well-defined and functional tracks on an absorbing surface is controlled by the drop imbibition dynamics in addition to the well-studied post-impact drop spreading behavior. This study represents the first investigation of the real-time imbibition of ink-jet deposited nano-Cu colloid drops on to coated paper substrates. In addition, the same ink was deposited on to a non-porous polymer surface as a control substrate. By using high-speed video imaging to capture the deposition of ink-jet drops, the time-scales of drop spreading and imbibition were quantified and compared with model predictions. The influences of the coating pore size on the bulk absorption rate and nano-Cu particle distribution have also been studied.

Imaging the femoral cortex: thickness, density and mass from clinical CT.

There is growing evidence that focal thinning of cortical bone in the proximal femur may predispose a hip to fracture. Detecting such defects in clinical CT is challenging, since cortices may be significantly thinner than the imaging system's point spread function. We recently proposed a model-fitting technique to measure sub-millimetre cortices, an ill-posed problem which was regularized by assuming a specific, fixed value for the cortical density. In this paper, we develop the work further by proposing and evaluating a more rigorous method for estimating the constant cortical density, and extend the paradigm to encompass the mapping of cortical mass (mineral mg/cm(2)) in addition to thickness. Density, thickness and mass estimates are evaluated on sixteen cadaveric femurs, with high resolution measurements from a micro-CT scanner providing the gold standard. The results demonstrate robust, accurate measurement of peak cortical density and cortical mass. Cortical thickness errors are confined to regions of thin cortex and are bounded by the extent to which the local density deviates from the peak, averaging 20% for 0.5mm cortex.

Imaging the femoral cortex: Thickness, density and mass from clinical CT

There is growing evidence that focal thinning of cortical bone in the proximal femur may predispose a hip to fracture. Detecting such defects in clinical CT is challenging, since cortices may be significantly thinner than the imaging system's point spread function. We recently proposed a model-fitting technique to measure sub-millimetre cortices, an ill-posed problem which was regularized by assuming a specific, fixed value for the cortical density. In this paper, we develop the work further by proposing and evaluating a more rigorous method for estimating the constant cortical density, and extend the paradigm to encompass the mapping of cortical mass (mineral mg/cm 2) in addition to thickness. Density, thickness and mass estimates are evaluated on sixteen cadaveric femurs, with high resolution measurements from a micro-CT scanner providing the gold standard. The results demonstrate robust, accurate measurement of peak cortical density and cortical mass. Cortical thickness errors are confined to regions of thin cortex and are bounded by the extent to which the local density deviates from the peak, averaging 20% for 0.5mm cortex. © 2012 Elsevier B.V.

X-ray observation of micro-failures in granular piles approaching an avalanche

An X-ray imaging technique is used to probe the stability of 3-dimensional granular packs in a slowly rotating drum. Well before the surface reaches the avalanche angle, we observe intermittent plastic events associated with collective rearrangements of the grains located in the vicinity of the free surface. The energy released by these discrete events grows as the system approaches the avalanche threshold. By testing various preparation methods, we show that the pre-avalanche dynamics is not solely controlled by the difference between the free surface inclination and the avalanche angle. As a consequence, the measure of the pre-avalanche dynamics is unlikely to serve as a tool for predicting macroscopic avalanches.

Imaging and optical properties of single core-shell GaAs-AlGaAs nanowires

We study the optical properties of a single core-shell GaAs-AlGaAs nanowire (grown by VLS method) using the technique of micro-photoluminescence and spatially-resolved photoluminescence imaging. We observe large linear polarization anisotropy in emission and excitation of nanowires.

A Prototype X-ray Framing Camera With Variable Exposure Time Based on Double-Gated Micro-Channel Plates

We present a novel X-ray frame camera with variable exposure time that is based on double-gated micro-channel plates (MCP). Two MCPs are connected so that their channels form a Chevron-MCP structure, and four parallel micro-strip lines (MSLs) are deposited on each surface of the Chevron-MCP. The MSLs on opposing surfaces of the Chevron-MCP are oriented normal to each other and subjected to high voltage. The MSLs on the input and output surfaces are fed high voltage pulses to form a gating action. In forming two-dimensional images, modifying the width of the gating pulse serves to set exposure times (ranging from ps to ms) and modifying the delay between each gating pulse serves to set capture times. This prototype provides a new tool for high-speed X-ray imaging, and this paper presents both simulations and experimental results obtained with the camera.

Research on micro-optical lenses fabrication technology

We present a detail investigation on the development of a series of gradient index (GRIN) optical glass microlens and polymer microlens and microlens arrays in our laboratory in recent years. The special glass material GRIN lenses have been fabricated mainly by using ion-exchange technology, which are applied to construct micro-optic devices and other applications. On one hand, we demonstrated the light propagation and imaging properties of GRIN lenses and the results analyzed. On the other hand, we have explored a drop-on-demand ink-jet printing method to produce microlens array using nano-scale polymer droplets involved with a uniform ultraviolet light and heat solidifying process. The experimental setup for manufacturing polymer microlens array and the performance of refractive microlens elements are also given in this paper. (C) 2006 Elsevier GmbH. All rights reserved.

Micro Insert: A Prototype Full-Ring PET Device for Improving the Image Resolution of a Small-Animal PET Scanner

A full-ring PET insert device should be able to enhance the image resolution of existing small-animal PET scanners. Methods: The device consists of 18 high-resolution PET detectors in a cylindric enclosure. Each detector contains a cerium-doped lutetium oxyorthosilicate array (12 x 12 crystals, 0.72 x 1.51 x 3.75 mm each) coupled to a position-sensitive photomultiplier tube via an optical fiber bundle made of 8 x 16 square multiclad fibers. Signals from the insert detectors are connected to the scanner through the electronics of the disabled first ring of detectors, which permits coincidence detection between the 2 systems. Energy resolution of a detector was measured using a Ge-68 point source, and a calibrated 68Ge point source stepped across the axial field of view (FOV) provided the sensitivity profile of the system. A Na-22 point source imaged at different offsets from the center characterized the in-plane resolution of the insert system. Imaging was then performed with a Derenzo phantom filled with 19.5 MBq of F-18-fluoride and imaged for 2 h; a 24.3-g mouse injected with 129.5 MBq of F-18-fluoride and imaged in 5 bed positions at 3.5 h after injection; and a 22.8-g mouse injected with 14.3 MBq of F-18-FDG and imaged for 2 h with electrocardiogram gating. Results: The energy resolution of a typical detector module at 511 keV is 19.0% +/- 3.1 %. The peak sensitivity of the system is approximately 2.67%. The image resolution of the system ranges from 1.0- to 1.8-mm full width at half maximum near the center of the FOV, depending on the type of coincidence events used for image reconstruction. Derenzo phantom and mouse bone images showed significant improvement in transaxial image resolution using the insert device. Mouse heart images demonstrated the gated imaging capability of the device. Conclusion: We have built a prototype full-ring insert device for a small-animal PET scanner to provide higher-resolution PET images within a reduced imaging FOV. Development of additional correction techniques are needed to achieve quantitative imaging with such an insert.

Investigation of micro-devices for neurobiological applications

The aim of this project is to integrate neuronal cell culture with commercial or in-house built micro-electrode arrays and MEMS devices. The resulting device is intended to support neuronal cell culture on its surface, expose specific portions of a neuronal population to different environments using microfluidic gradients and stimulate/record neuronal electrical activity using micro-electrode arrays. Additionally, through integration of chemical surface patterning, such device can be used to build neuronal cell networks of specific size, conformation and composition. The design of this device takes inspiration from the nervous system because its development and regeneration are heavily influenced by surface chemistry and fluidic gradients. Hence, this device is intended to be a step forward in neuroscience research because it utilizes similar concepts to those found in nature. The large part of this research revolved around solving technical issues associated with integration of biology, surface chemistry, electrophysiology and microfluidics. Commercially available microelectrode arrays (MEAs) are mechanically and chemically brittle making them unsuitable for certain surface modification and micro-fluidic integration techniques described in the literature. In order to successfully integrate all the aspects into one device, some techniques were heavily modified to ensure that their effects on MEA were minimal. In terms of experimental work, this thesis consists of 3 parts. The first part dealt with characterization and optimization of surface patterning and micro-fluidic perfusion. Through extensive image analysis, the optimal conditions required for micro-contact printing and micro-fluidic perfusion were determined. The second part used a number of optimized techniques and successfully applied these to culturing patterned neural cells on a range of substrates including: Pyrex, cyclo-olefin and SiN coated Pyrex. The second part also described culturing neurons on MEAs and recording electrophysiological activity. The third part of the thesis described integration of MEAs with patterned neuronal culture and microfluidic devices. Although integration of all methodologies proved difficult, a large amount of data relating to biocompatibility, neuronal patterning, electrophysiology and integration was collected. Original solutions were successfully applied to solve a number of issues relating to consistency of micro printing and microfluidic integration leading to successful integration of techniques and device components.

Micro and nanostructured impedance sensors for biological and biomedical applications

This thesis work covered the fabrication and characterisation of impedance sensors for biological applications aiming in particular to the cytotoxicity monitoring of cultured cells exposed to different kind of chemical compounds and drugs and to the identification of different types of biological tissue (fat, muscles, nerves) using a sensor fabricated on the tip of a commercially available needle during peripheral nerve block procedures. Gold impedance electrodes have been successfully fabricated for impedance measurement on cells cultured on the electrode surface which was modified with the fabrication of gold nanopillars. These nanostructures have a height of 60nm or 100nm and they have highly ordered layout as they are fabricated through the e-beam technique. The fabrication of the threedimensional structures on the interdigitated electrodes was supposed to improve the sensitivity of the ECIS (electric cell-substrate impedance sensing) measurement while monitoring the cytotoxicity effects of two different drugs (Antrodia Camphorata extract and Nicotine) on three different cell lines (HeLa, A549 and BALBc 3T3) cultured on the impedance devices and change the morphology of the cells growing on the nanostructured electrodes. The fabrication of the nanostructures was achieved combining techniques like UV lithography, metal lift-off, evaporation and e-beam lithography techniques. The electrodes were packaged using a pressure sensitive, medical grade adhesive double-sided tape. The electrodes were then characterised with the aid of AFM and SEM imaging which confirmed the success of the fabrication processes showing the nanopillars fabricated with the right layout and dimensions figures. The introduction of nanopillars on the impedance electrodes, however, did not improve much the sensitivity of the assay with the exception of tests carried out with Nicotine. HeLa and A549 cells appeared to grow in a different way on the two surfaces, while no differences where noticed on the BALBc 3T3 cells. Impedance measurements obtained with the dead cells on the negative control electrodes or the test electrodes with the drugs can be compared to those done on the electrodes containing just media in the tested volume (as no cells are attached and cover the electrode surface). The impedance figures recorded using these electrodes were between 1.5kΩ and 2.5 kΩ, while the figures recorded on confluent cell layers range between 4kΩ and 5.5kΩ with peaks of almost 7 kΩ if there was more than one layer of cells growing on each other. There was then a very clear separation between the values of living cell compared to the dead ones which was almost 2.5 - 3kΩ. In this way it was very easy to determine whether the drugs affected the cells normal life cycle on not. However, little or no differences were noticed in the impedance analysis carried out on the two different kinds of electrodes using cultured cells. An increase of sensitivity was noticed only in a couple of experiments carried out on A549 cells growing on the nanostructured electrodes and exposed to different concentration of a solution containing Nicotine. More experiments to achieve a higher number of statistical evidences will be needed to prove these findings with an absolute confidence. The smart needle project aimed to reduce the limitations of the Electrical Nerve Stimulation (ENS) and the Ultra Sound Guided peripheral nerve block techniques giving the clinicians an additional tool for performing correctly the peripheral nerve block. Bioimpedance, as measured at the needle tip, provides additional information on needle tip location, thereby facilitating detection of intraneural needle placement. Using the needle as a precision instrument and guidance tool may provide additional information as to needle tip location and enhance safety in regional anaesthesia. In the time analysis, with the frequency fixed at 10kHz and the samples kept at 12°C, the approximate range for muscle bioimpedance was 203 – 616 Ω, the approximate bioimpedance range for fat was 5.02 - 17.8 kΩ and the approximate range for connective tissue was 790 Ω – 1.55 kΩ. While when the samples were heated at 37°C and measured again at 10kHz, the approximate bioimpedance range for muscle was 100-175Ω. The approximate bioimpedance range of fat was 627 Ω - 3.2 kΩ and the range for connective tissue was 221-540Ω. In the experiments done on the fresh slaughtered lamb carcass, replicating a scenario close to the real application, the impedance values recorded for fat were around 17 kΩ, for muscle and lean tissue around 1.3 kΩ while the nervous structures had an impedance value of 2.9 kΩ. With the data collected during this research, it was possible to conclude that measurements of bioimpedance at the needle tip location can give valuable information to the clinicians performing a peripheral nerve block procedure as the separation (in terms of impedance figures) was very marked between the different type of tissues. It is then feasible to use an impedance electrode fabricated on the needle tip to differentiate several tissues from the nerve tissue. Currently, several different methods are being studied to fabricate an impedance electrode on the surface of a commercially available needle used for the peripheral nerve block procedure.

A low-cost, portable, and quantitative spectral imaging system for application to biological tissues.

The ability of diffuse reflectance spectroscopy to extract quantitative biological composition of tissues has been used to discern tissue types in both pre-clinical and clinical cancer studies. Typically, diffuse reflectance spectroscopy systems are designed for single-point measurements. Clinically, an imaging system would provide valuable spatial information on tissue composition. While it is feasible to build a multiplexed fiber-optic probe based spectral imaging system, these systems suffer from drawbacks with respect to cost and size. To address these we developed a compact and low cost system using a broadband light source with an 8-slot filter wheel for illumination and silicon photodiodes for detection. The spectral imaging system was tested on a set of tissue mimicking liquid phantoms which yielded an optical property extraction accuracy of 6.40 +/- 7.78% for the absorption coefficient (micro(a)) and 11.37 +/- 19.62% for the wavelength-averaged reduced scattering coefficient (micro(s)').

Spanning the scales of granular materials through microscopic force imaging.

If you walk on sand, it supports your weight. How do the disordered forces between particles in sand organize, to keep you from sinking? This simple question is surprisingly difficult to answer experimentally: measuring forces in three dimensions, between deeply buried grains, is challenging. Here we describe experiments in which we have succeeded in measuring forces inside a granular packing subject to controlled deformations. We connect the measured micro-scale forces to the macro-scale packing force response with an averaging, mean field calculation. This calculation explains how the combination of packing structure and contact deformations produce the observed nontrivial mechanical response of the packing, revealing a surprising microscopic particle deformation enhancement mechanism.

In vivo small animal micro-CT using nanoparticle contrast agents.

Computed tomography (CT) is one of the most valuable modalities for in vivo imaging because it is fast, high-resolution, cost-effective, and non-invasive. Moreover, CT is heavily used not only in the clinic (for both diagnostics and treatment planning) but also in preclinical research as micro-CT. Although CT is inherently effective for lung and bone imaging, soft tissue imaging requires the use of contrast agents. For small animal micro-CT, nanoparticle contrast agents are used in order to avoid rapid renal clearance. A variety of nanoparticles have been used for micro-CT imaging, but the majority of research has focused on the use of iodine-containing nanoparticles and gold nanoparticles. Both nanoparticle types can act as highly effective blood pool contrast agents or can be targeted using a wide variety of targeting mechanisms. CT imaging can be further enhanced by adding spectral capabilities to separate multiple co-injected nanoparticles in vivo. Spectral CT, using both energy-integrating and energy-resolving detectors, has been used with multiple contrast agents to enable functional and molecular imaging. This review focuses on new developments for in vivo small animal micro-CT using novel nanoparticle probes applied in preclinical research.

High-Resolution CT for Small-Animal Imaging Research

Preclinical imaging has a critical role in phenotyping, in drug discovery, and in providing a basic understanding of mechanisms of disease. Translating imaging methods from humans to small animals is not an easy task. The purpose of this work is to review high-resolution computed tomography (CT) also known as micro-CT for small-animal imaging. We present the principles, the technologies, the image quality parameters, and the types of applications. We show that micro-CT can be used to provide not only morphological but also functional information such as cardiac function or vascular permeability. Another way in which micro-CT can be used in the study of both function and anatomy is by combining it with other imaging modalities, such as positron emission tomography or single-photon emission tomography. Compared to other modalities, micro-CT imaging is usually regarded as being able to provide higher throughput at lower cost and higher resolution. The limitations are usually associated with the relatively poor contrast mechanisms and the radiation damage, although the use of novel nanoparticle-based contrast agents and careful design of studies can address these limitations.