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The response of silicon-based MEMS diaphragms to applied pressure was studied to determine their ability to effectively measure the extent of blast overpressure. Different pressures (0-100 psi) were applied to silicon diaphragms of different diameters (1200, 1500, and 2200 μm) to study their mechanical response under both static and dynamic conditions using experimental and finite element analysis. A laser triangulation sensor was used to determine the diaphragm displacement as a function of blast pressure. High speed camera images were obtained to understand the response of the diaphragm at an applied blast pressure. Results show consistent behavior for deflections (10, 14, and 26 μm, respectively, at 40 psi) under dynamic conditions. Finite element analysis indicates that the dynamic deflection is larger than the corresponding static deflection for the same applied pressures. Burst strengths were not consistent, although the diaphragms fractured at their circumferential edges and showed a small degree of plastic deformation. It also appears that the diaphragm manifests a hemispherical as well as a conical deflection depending on applied blast pressures. [ABSTRACT FROM AUTHOR]

A package design, fabrication process, and assembly process to hermetically seal the microstructure area of a microoptoelectromechanical system (MOEMS) at the chip level is presented and evaluated. The packaged chip is fabricated using the Bosch deep reactive ion etching (DRIE) process on silicon on insulator (SOI) substrates. The packaging structures are formed during the batch fabrication of the MOEMS device. A hermetic seal is formed via an indium solder ring around the perimeter of the MOEMS chip that span channels etched in the silicon for optical fibers. The seal is made between the device chip, metallized optical fibers, and a cap chip with a fluxless soldering process. The integrity of the package is evaluated through die shear, fiber pull, and highly accelerated life testing (HALT). [ABSTRACT FROM AUTHOR]

The complexity of allorejection (cell activation, homing, and effector function) makes detailed studies difficult. We have developed a model of allograft rejection using purified monoclonal alloreactive effector cells. Immunodeficient C57Bl/6-Rag-1 (H-2b) recipients of Balb/c (H-2d) islet or skin grafts were reconstituted via adoptive transfer of splenocytes from 2C transgenic mice containing CD8+ cytotoxic effector cells directed against Ld. Recipients were assessed for engraftment, activation and homing of effector cells, and ability to reject grafts. Both unpurified 2C splenocytes and purified 2C/CD8+ cells durably reconstitute immunodeficient mice. Naïve 2C effector cells reject skin grafts, but not islet allografts. However, when effector cells are primed prior to reconstitution, islet allografts are rejected. Using this model, blockade of adhesion molecules LFA-1 and α4-integrin delayed infiltration of islet allografts and prolonged allograft survival. This model of allorejection may be useful to study the activation and homing of allospecific cells in vivo. [ABSTRACT FROM AUTHOR]

The bond layer is often the weakest link in the reliability of chip packages in the integrated circuit (IC) industry. Micro-electrical-mechanical systems (MEMS) packages are no exception to this trend. This paper presents a nondestructive methodology for determining delamination in chip-to-chip bonded MEMS. Experimental methods are used to determine the adhesive layer strength in samples subjected to environmental testing, and the reliability of the bonding layer is investigated. A simulation is performed using inputs from scanning acoustic microscopy, and simulation model results are correlated with the experimental die shear measurements to establish the validity of the nondestructive methodology for determining adhesive layer strength. [ABSTRACT FROM AUTHOR]

Focuses on a study of the multichip module which can be classified as a one-size, multielectronic technology domain structure. Information on nano-to-millimeter scale integrated systems; System requirements; Challenges in the evolution of In2m systems.

Discusses a class of electronic systems called Integrated nano to millimeter (In2m) systems. Common threads of In2m devices; System requirements; Challenges in the evolution of In2m systems.

Islet transplantation is a viable treatment alternative for a select group of patients with Type 1 diabetes. However, variables unique to the donor pancreas such as age, fibrosis and edema can influence the number and purity of the isolated islets. Thus, isolation of a sufficient number of islets for transplantation from the pancreas remains challenging due to the lack of methods enabling reproducible isolations. Islets were isolated from 38 consecutive deceased donors using the semi-automated Ricordi method of islet isolation and purified on a COBE 2991 cell processor using ficoll-based continuous density gradients. Three different gradient protocols were used. These included predefined gradient using different densities of ficoll (1.100 g/mL and 1.077 g/mL) mixed with HBSS (group 1), pre-defined gradient using single density ficoll (1.100 g/mL) mixed with University of Wisconsin solution (UW) (group 2), or variable gradient using single density ficoll (1.100 g/mL) with UW, with densities selected based on results of test gradients (group 3). Group 3 yielded better recovery of islets (74%) than groups 1 (43 %) or 2 (37%) (p=0.0144) (Fig. 1 ). Viability was significantly higher in groups 2 and 3 (p=0.0115). Purity was not significantly different among the groups. This method using a simple test gradient is a significant process improvement that can improve islet recovery without loss of viability or purity, and increase the number of islet products suitable for transplantation. [ABSTRACT FROM AUTHOR]

Although allogeneic human islet transplant has become a successful procedure within the last decade, reports of declining function in islet gratis have been discouraging. Attrition of islet graft function could be attributed to multiple variables including toxicity of immunosuppression, allo-immunity, autoimmunity and apoptosis of beta cells. Our experiments examine the role of amyloid formation in graft failure after islet transplantation with a unique human islet amyloid polypeptide (hIAPP) knock-in mouse model. Wild-type hIAPP alleles were knocked directly into the mouse IAPP locus, creating a WW genotype that corresponds to the human genotype. These knock-in animals produce physiologic levels of hIAPP that are under the physiologic control of the endogenous mouse IAPP promoter. Six hundred hand picked islets were isolated from WW mice and transplanted under the kidney capsule of athymic nude mice with streptozotocin induced diabetes (220mg/kg suspended in HBSS). Blood glucose levels were monitored, grafts were explanted and Thioflavin S staining was performed. Transplantation of 600 WW islets into diabetic athymic nude mice reversed diabetes and maintained euglycemia until explant. Average blood glucose values were 541 mg/dL on the day of transplant and 147 mg/dL for the 2 week study period (N=2). Thioflavin S staining showed amyloid formation in animals 14 days after transplantation. Our results suggest that initial amyloid formation may occur as an acute response to the stress of islet isolation, transplantation, and engraftment. This early deposition of human amyloid does not appear to alter the function of a large islet graft (600 islets). We are currently performing morphometric analysis of islet re-vascularization and apoptosis to examine any differences between WW and control grafts and evaluating the relationship between amyloid deposition and loss of function of the islet graft. [ABSTRACT FROM AUTHOR]

We are studying the role of islet amyloidogenesis in the pathogenesis of type 2 diabetes (T2D) and defining differences in amyloidogenicity and cytotoxicity between wild-type human islet amyloid polypeptide (hIAPPWT) and S20G mutant hIAPP (hIAPPS20G), associated with premature onset T2D in Asians. To define differences between hIAPPWT and hIAPPS20G, we created a mouse model via targeted gene transfer to allow physiologic comparison of these two proteins. We replaced the non-amyloidogenic mouse lAPP gene (M allele) with the hIAPPWT (W allele) and hIAPPS20G (G allele), providing for physiologic MAPP expression via the mouse IAPP promoter. Electron micrographs of WW and GG islets from founder animals on high fat diets for 12-14 mo revealed extensive intracellular amyloid deposits. Amyloid deposits were often present in cells with extensively distended endoplasmic reticulum (ER) and pycnotic nuclei, suggesting that amyloidogenesis might be accompanied by ER stress responses that could be linked to cell death by apoptosis. To examine whether ER stress responses were activated in b cells of knock-in mice, we isolated islets from 3 mo old C57B1/6 backbred (5th generation, 96.9% congenic) control MM and WW and GG knock-in mice maintained on standard diet and assessed the unfolded protein response (UPR) pathway by Western analyses of eIF2alpha phosphorylation and proteolytic activation of ATF6. Substantial phosphorylation of eIF2alpha and extensive proteolytic cleavage of ATF6 to their active forms was observed in knock-in WW and GG mice, but not in MM control mice, suggesting that significant protein folding/trafficking problems accrue in the islets of knock-in animals at relatively young ages even when maintained on a normal diet. The data suggest that lAPP misfolding in the ER leads to UPR activation that may result in increased beta cell dysfunction, apoptosis, eventual loss of beta cell mass, and development of T2D. [ABSTRACT FROM AUTHOR]