Micro-fabrication of bio-MEMS based force sensor to measure the force response of living cells

Understanding how a living cell behaves has become a very important topic in today’s research field. Hence, different sensors and testing devices have been designed to test the mechanical properties of these living cells. This thesis presents a method of micro-fabricating a bio-MEMS based force sensor which is used to measure the force response of living cells. Initially, the basic concepts of MEMS have been discussed and the different micro-fabrication techniques used to manufacture various MEMS devices have been described. There have been many MEMS based devices manufactured and employed for testing many nano-materials and bio-materials. Each of the MEMS based devices described in this thesis use a novel concept of testing the specimens. The different specimens tested are nano-tubes, nano-wires, thin film membranes and biological living cells. Hence, these different devices used for material testing and cell mechanics have been explained. The micro-fabrication techniques used to fabricate this force sensor has been described and the experiments preformed to successfully characterize each step in the fabrication have been explained. The fabrication of this force sensor is based on the facilities available at Michigan Technological University. There are some interesting and uncommon concepts in MEMS which have been observed during this fabrication. These concepts in MEMS which have been observed are shown in multiple SEM images.

The development of a novel Bio-MEMS filtration chip for the separation of specific cells in fluid suspension

In the clinical/microbiological laboratory there are currently several ways of separating specific cells from a fluid suspension. Conventionally cells can be separated based on size, density, electrical charge, light-scattering properties, and antigenic surface properties. Separating cells using these parameters can require complex technologies and specialist equipment. This paper proposes new Bio-MEMS (microelectromechanical systems) filtration chips manufactured using deep reactive ion etching (DRIE) technology that, when used in conjunction with an optical microscope and a syringe, can filter and grade cells for size without the requirement for additional expensive equipment. These chips also offer great versatility in terms of design and their low cost allows them to be disposable, eliminating sample contamination. The pumping mechanism, unlike many other current filtration techniques, leaves samples mechanically and chemically undamaged. In this paper the principles behind harnessing passive pumping are explored, modelled, and validated against empirical data, and their integration into a microfluidic device to separate cells from a mixed population suspension is described. The design, means of manufacture, and results from preliminary tests are also presented. © IMechE 2007.

Development of a Lab-on-a-Chip Device for Rapid Nanotoxicity Assessment In Vitro

Increasing useof nanomaterials in consumer products and biomedical applications creates the possibilities of intentional/unintentional exposure to humans and the environment. Beyond the physiological limit, the nanomaterialexposure to humans can induce toxicity. It is difficult to define toxicity of nanoparticles on humans as it varies by nanomaterialcomposition, size, surface properties and the target organ/cell line. Traditional tests for nanomaterialtoxicity assessment are mostly based on bulk-colorimetric assays. In many studies, nanomaterials have found to interfere with assay-dye to produce false results and usually require several hours or days to collect results. Therefore, there is a clear need for alternative tools that can provide accurate, rapid, and sensitive measure of initial nanomaterialscreening. Recent advancement in single cell studies has suggested discovering cell properties not found earlier in traditional bulk assays. A complex phenomenon, like nanotoxicity, may become clearer when studied at the single cell level, including with small colonies of cells. Advances in lab-on-a-chip techniques have played a significant role in drug discoveries and biosensor applications, however, rarely explored for nanomaterialtoxicity assessment. We presented such cell-integrated chip-based approach that provided quantitative and rapid response of cellhealth, through electrochemical measurements. Moreover, the novel design of the device presented in this study was capable of capturing and analyzing the cells at a single cell and small cell-population level. We examined the change in exocytosis (i.e. neurotransmitterrelease) properties of a single PC12 cell, when exposed to CuOand TiO2 nanoparticles. We found both nanomaterials to interfere with the cell exocytosis function. We also studied the whole-cell response of a single-cell and a small cell-population simultaneously in real-time for the first time. The presented study can be a reference to the future research in the direction of nanotoxicity assessment to develop miniature, simple, and cost-effective tool for fast, quantitative measurements at high throughput level. The designed lab-on-a-chip device and measurement techniques utilized in the present work can be applied for the assessment of othernanoparticles' toxicity, as well.

Graded Meshes In Bio-thermal Problems With Transmission-line Modeling Method.

In this study, the transmission-line modeling (TLM) applied to bio-thermal problems was improved by incorporating several novel computational techniques, which include application of graded meshes which resulted in 9 times faster in computational time and uses only a fraction (16%) of the computational resources used by regular meshes in analyzing heat flow through heterogeneous media. Graded meshes, unlike regular meshes, allow heat sources to be modeled in all segments of the mesh. A new boundary condition that considers thermal properties and thus resulting in a more realistic modeling of complex problems is introduced. Also, a new way of calculating an error parameter is introduced. The calculated temperatures between nodes were compared against the results obtained from the literature and agreed within less than 1% difference. It is reasonable, therefore, to conclude that the improved TLM model described herein has great potential in heat transfer of biological systems.

Crescimento e desempenho motor em pre-escolares de Itapira SP : um enfoque bio-social-cultural

Universidade Estadual de Campinas. Faculdade de Educação Física

Comparação dos estados nutricionais dos alunos do ensino medio da cidade de Los Angeles VIII. Região de Bio-Bio, Chile : (1991-2000)

Universidade Estadual de Campinas . Faculdade de Educação Física

MEMS-based incandescent microlamps for integrated optics applications

In this work we present the fabrication and operation of incandescent microlamps for integrated optics applications. This microlamp emits white and infrared light from a chromium resistor embedded in a free-standing silicon oxynitride (SiO(x)N(y)) cantilever that can be coupled to an optical waveguide. In fact, the chromium resistor is sandwiched between layers of SiO(x)N(y) that isolate it from the atmosphere, while electric current heats the resistor to incandescent temperatures. The same SiO(x)N(y) material used in the microlamp fabrication is also used to produce the optical waveguides to allow a monolithic integration of light source and optical circuit. Front-side bulk micromachining of the silicon substrate in potassium hydroxide (KOH) solution is used to fabricate the cantilevers that thermally isolate the resistors from the substrate, thus reducing the heat transfer and the current required to light the lamp.

Bio-Dis and the Paddle Dissolution Apparatuses Applied to the Release Characterization of Ketoprofen from Hypromellose Matrices

The purposes of this work were: (1) to comparatively evaluate the effects of hypromellose viscosity grade and content on ketoprofen release from matrix tablets, using Bio-Dis and the paddle apparatuses, (2) to investigate the influence of the pH of the dissolution medium on drug release. Furthermore, since direct compression had not shown to be appropriate to obtain the matrices under study, it was also an objective (3) to evaluate the impact of granulation on drug release process. Six formulations of ketoprofen matrix tablets were obtained by compression, with or without previous granulation, varying the content and viscosity grade of hypromellose. Dissolution tests were carried out at a fixed pH, in each experiment, with the paddle method (pH 4.5, 6.0, 6.8, or 7.2), while a pH gradient was used in Bio-Dis (pH 1.2 to 7.2). The higher the hypromellose viscosity grade and content were, the lower the amount of ketoprofen released was in both apparatuses, the content effect being more expressive. Drug dissolution enhanced with the increase of the pH of the medium due to its pH-dependent solubility. Granulation caused an increase in drug dissolution and modified the mechanism of the release process.

BIO Logical Agents: Norms, Beliefs, Intentions in Defeasible Logic

In this paper we follow the BOID (Belief, Obligation, Intention, Desire) architecture to describe agents and agent types in Defeasible Logic. We argue, in particular, that the introduction of obligations can provide a new reading of the concepts of intention and intentionality. Then we examine the notion of social agent (i.e., an agent where obligations prevail over intentions) and discuss some computational and philosophical issues related to it. We show that the notion of social agent either requires more complex computations or has some philosophical drawbacks.

Determination of mechanical properties of PECVD silicon nitride thin films for tunable MEMS Fabry-Pérot optical filters

This paper reports an investigation on techniques for determining elastic modulus and intrinsic stress gradient in plasma-enhanced chemical vapor deposition (PECVD) silicon nitride thin films. The elastic property of the silicon nitride thin films was determined using the nanoindentation method on silicon nitride/silicon bilayer systems. A simple empirical formula was developed to deconvolute the film elastic modulus. The intrinsic stress gradient in the films was determined by using micrometric cantilever beams, cross-membrane structures and mechanical simulation. The deflections of the silicon nitride thin film cantilever beams and cross-membranes caused by in-thickness stress gradients were measured using optical interference microscopy. Finite-element beam models were built to compute the deflection induced by the stress gradient. Matching the deflection computed under a given gradient with that measured experimentally on fabricated samples allows the stress gradient of the PECVD silicon nitride thin films introduced from the fabrication process to be evaluated.

Characterization of mechanical properties of silicon nitride thin films for MEMS devices by nanoindentation

An experimental investigation of mechanical properties of thin films using nanoindentation was reported. Silicon nitride thin films with different thicknesses were deposited using plasma enhanced chemical vapor deposition (PECVD) on Si substrate. Nanoindentation was used to measure their elastic modulus and hardness. The results indicated that for a film/substrate bilayer system, the measured mechanical properties are significantly affected by the substrate properties. Empirical formulas were proposed for deconvoluting the film properties from the measured bilayer properties.

Twelve-month Outcomes After Coronary Stenting With the Genous (TM) Bio-Engineered R Stent (TM) in Diabetic Patients from the e-HEALING Registry

Objectives: We compared 12-month outcomes, regarding ischemic events, repeat intervention, and ST, between diabetic and nondiabetic patients treated with the Genous (TM) EPC capturing R stent (TM) during routine nonurgent percutaneous coronary intervention (PCI) using data from the multicenter, prospective worldwide e-HEALING registry. Background: Diabetic patients have an increased risk for restenosis and stent thrombosis (ST). Methods: In the 4,996 patient e-HEALING registry, 273 were insulin requiring diabetics (IRD), 963 were non-IRD (NIRD), and 3,703 were nondiabetics. The 12-month primary outcome was target vessel failure (TVF), defined as target vessel-related cardiac death or myocardial infarction (MI) and target vessel revascularization. Secondary outcomes were the composite of cardiac death, MI or target lesion revascularization (TLR), and individual outcomes including ST. Cumulative event rates were estimated with the Kaplan-Meier method and compared with a log-rank test. Results: TVF rates were respectively 13.4% in IRD, 9.0% in NIRD, and 7.9% in nondiabetics (P < 0.01). This was mainly driven by a higher mortality hazard in IRD (P < 0.001) and NIRD (P = 0.07), compared with nondiabetics. TLR rates were comparable in NIRD and nondiabetics, but significantly higher in IRD (P = 0.04). No difference was observed in ST. Conclusion: The 1-year results of the Genous stent in a real-world population of diabetics show higher TVF rates in diabetics compared with nondiabetics, mainly driven by a higher mortality hazard. IRD is associated with a significant higher TLR hazard. Definite or probable ST in all diabetic patients was comparable with nondiabetics. (J Interven Cardiol 2011;24:285-294)

Clinical results after coronary stenting with the Genous (TM) Bio-engineered R stent (TM): 12-month outcomes of the e-HEALING (Healthy Endothelial Accelerated Lining Inhibits Neointimal Growth) worldwide registry

Aims: e-HEALING is a worldwide, internet-based registry designed to capture post marketing clinical data on the use of the Genous (TM) EPC capturing R stent (TM). Rapid restoration of a healthy endothelial layer after stent placement by capturing circulating endothelial progenitor cells may reduce both stent thrombosis (ST) and in-stent-restenosis. Methods and results: We planned a 5,000 patient registry with >= 1 lesion suitable for stenting. The 12-month primary outcome was target vessel failure (TVF), defined as target vessel-related cardiac death or myocardial infarction (MI) and target vessel revascularisation. Secondary outcomes were the composite of cardiac death, MI or target lesion revascularisation (TLR), and individual outcomes including ST. A total of 4,939 patients received >= 1 Genous stent between 2005 and 2007. Baseline characteristics showed a median age of 63 years, 79% males, 25% diabetics, and 37% with prior MI. A total of 49% of lesions treated were ACC/AHA type B2 or C; 1.1 stents per lesion were used. At 12 months, TVF occurred in 8.4% and the composite of cardiac death, MI or TLR in 7.9%. Twelve-month TLR and ST were 5.7% and 1.1%, respectively. Conclusions: Coronary stenting with the Genous results in good clinical outcomes, and low incidences of repeat revascularisation and ST.