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Cell therapy is targeted at many organs, but locally or systemically delivered cells are shortly able to survive resulting from the immune/inflammation reactions and irregular cell targeting. Here we explore the multimodal nanoparticle having anti-inflammation and magnetic guidance for successful cell transplantation. We design magnetic resonance (MR)-active glycyrrhizin-chitosan coated superparamagnetic iron oxide nanoparticle (SPIO@Chitosan-GL) to inhibit release of inflammatory damage-associated molecular pattern (DAMP) protein and to offer noninvasive monitoring after intrahepatic transplantation of pancreatic islets and mesenchymal stem cell (MSC) spheroids. Intracellular delivered SPIO@Chitosan-GL is not cytotoxic to pancreatic islets and MSC spheroids and attenuate DAMP release from them. Also, therapeutic cells labeled with SPIO@Chitosan-GL are magnetically localized to the intended lobe of liver during transplantation procedure. If necessary, partial hepatectomy can be performed to remove the localized therapeutic cells for protection of the remaining liver lobes from systemic inflammation. Therapeutically, the cells selectively localized in the liver can treat blood glucose in diabetic mice to normal levels with DAMP modulation, and are visualized using in vivo MR imaging for over 4 weeks. Collectively, DAMP-modulating SPIO@Chitosan-GL can be used in multimodal nanomedince for attenuating the inflammation reaction by transplanted cells and for noninvasively long-term monitoring of transplanted cells.

Many groups are working to improve the results of clinical allogeneic islet transplantation in a primate model. However, few studies have focused on the optimal islet dose for achieving normal glycemia without exogenous insulin after transplantation in primate models or on the relationship between rejection and islet amyloid polypeptide (IAPP) expression. We evaluated the dose (10,000, 20,000, and > 25,000 islet equivalents (IEQ)/kg) needed to achieve normal glycemia without exogenous insulin after transplantation using eleven cynomolgus monkeys, and we analyzed the characteristics exhibited in the islets after transplantation. 10,000 IEQ/kg (N = 2) failed to control blood glucose level, despite injection with the highest dose of exogenous insulin, and 20,000 IEQ/kg group (N = 5) achieved unstable control, with a high insulin requirement. However, 25,000 IEQ/kg (N = 4) achieved normal glycemia without exogenous insulin and maintained it for more than 60 days. Immunohistochemistry results from staining islets found in liver biopsies indicated that as the number of transplanted islets decreased, the amount of IAPP accumulation within the islets increased, which accelerated CD3+ T cell infiltration. In conclusion, the optimal transplantation dose for achieving a normal glycemia without exogenous insulin in our cynomolgus monkey model was > 25,000 IEQ/kg, and the accumulation of IAPP early after transplantation, which depends on the transplanted islet dose, can be considered one factor in rejection.

Many groups are working to improve the results of clinical allogeneic islet transplantation in a primate model. However, few studies have focused on the optimal islet dose for achieving normal glycemia without exogenous insulin after transplantation in primate models or on the relationship between rejection and islet amyloid polypeptide (IAPP) expression. We evaluated the dose (group 1/10,000, group 2/20,000, and group 3/>25,000 islet equivalents (IEQ)/kg) needed to achieve normal glycemia without exogenous insulin after transplantation using eleven cynomolgus monkeys, and we analyzed the characteristics exhibited in the islets after transplantation. Group 1 (n2) failed to control blood glucose level, despite injection with the highest dose of exogenous insulin, and group 2 (n5) achieved unstable control, with a high insulin requirement. However, group 3 (n4) achieved normal glycemia without exogenous insulin and maintained it for more than 60 days. Immunohistochemistry results from staining islets found in liver biopsies indicated that as the number of transplanted islets decreased, the amount of IAPP accumulation within the islets increased, which accelerated immune cell infiltration. In conclusion, the marginal transplantation dose for achieving a normal glycemia without exogenous insulin in our cynomolgus monkey model was >25,000 IEQ/kg, and the accumulation of IAPP early after transplantation, which depends on the transplanted islet dose, can be considered one factor in rejection.

Inhibition of mitochondrial reactive oxygen species (ROS) and subsequent damage-associated molecular patterns (DAMPs)-induced inflammatory responses could be a novel target in clinical islet transplantation. We investigated the protective effects of NecroX-7, a novel clinical-grade necrosis inhibitor that specifically targets mitochondrial ROS, against primary islet graft failure. Islets from heterozygote human islet amyloid polypeptide transgenic (hIAPP+/- ) mice and nonhuman primates (NHPs) were isolated or cultured with or without NecroX-7 in serum-deprived medium. Supplementation with NecroX-7 during hIAPP+/- mouse islet isolation markedly increased islet viability and adenosine triphosphate content, and attenuated ROS, transcription of c-Jun N-terminal kinases, high mobility group box 1, interleukin-1beta (IL-1 β ), IL-6, and tumor necrosis factor-alpha. Supplementation of NecroX-7 during serum-deprived culture also protected hIAPP+/- mouse and NHP islets against impaired viability, serum deprivation-induced ROS, proinflammatory response, and accumulation of toxic IAPP oligomer. Supplementation with NecroX-7 during isolation or serum-deprived culture of hIAPP+/- mouse and NHP islets also improved posttransplant glycemia in the recipient streptozotocin-induced diabetic hIAPP-/- mice and BALB/c-nu/nu mice, respectively. In conclusion, pretransplant administration of NecroX-7 during islet isolation and serum-deprived culture suppressed mitochondrial ROS injury, generation of DAMPs-induced proinflammatory responses, and accumulation of toxic IAPP oligomers ex vivo, and improved posttransplant glycemia in vivo.

Intraportal pancreatic islet transplantation incurs huge cell losses during its early stages due to instant blood-mediated inflammatory reactions (IBMIRs), which may also drive regulation of the adaptive immune system. Therefore, a method that evades IBMIR will improve clinical islet transplantation. We used a layer-by-layer approach to shield non-human primate (NHP) islets with polyethylene glycol (nano-shielded islets, NSIs) and polyethylene glycol plus heparin (heparin nano-shielded islets; HNSIs). Islets ranging from 10,000 to 20,000 IEQ/kg body weight were transplanted into 19 cynomolgus monkeys (n = 4, control; n = 5, NSI; and n = 10, HNSI). The mean C-peptide positive graft survival times were 68.5, 64 and 108 days for the control, NSI and HNSI groups, respectively (P = 0.012). HNSI also reduced the factors responsible for IBMIR in vitro. Based on these data, HNSIs in conjunction with clinically established immunosuppressive drug regimens will result in superior outcomes compared to those achieved with the current protocol for clinical islet transplantation.

Background Macrophages play important roles in xenograft rejection. Here, we investigated whether overexpression of human CD200 or CD47 in porcine endothelial cells (PEC) can suppress macrophages activation in xenogeneic immune responses. Methods PECs and human macrophages were incubated together, harvested, and analyzed for in vitro macrophage phagocytic and cytotoxicity activity, and cytokine release. Next, PECs were injected into renal subcapsular space of humanized mice. On day 10 posttransplantation, we analyzed xenograft survival and perigraft inflammatory cell infiltrations in PEC-to-humanized mouse transplantation. Results PECs highly expressing human CD200, CD47, or both CD47/CD200 were established by lentiviral vector transduction. Both CD200 and CD47 suppressed in vitro macrophage phagocytic and cytotoxic activity against PECs; decreased TNF-α, IL-1β, and IL-6 secretion; and increased IL-10 secretion. However, simultaneous overexpression of CD200 and CD47 did not show additive effects. Next, PECs were transplanted into NOD-scid IL-2Rg null mice, and human monocytes and lymphocytes were adoptively transferred 1 day after xenotransplantation. PEC xenograft cell death and apoptosis were decreased in the CD200-PEC and CD47/CD200-PEC groups. Perigraft infiltration of human T cells was suppressed by CD47; CD200 suppressed infiltration of human macrophages to a greater extent than CD47; and the CD47/CD200-PEC group exhibited the lowest level of leukocyte infiltration. In summary, overexpression of CD200 in PECs suppressed xenogeneic activation of human macrophages and improved survival of PEC xenografts in humanized mice; however, coexpression of CD200 and CD47 did not show additive effects. Conclusions Therefore, overexpression of human CD200 in donor pigs could constitute a promising strategy for overcoming xenograft rejection.

Apoptosis during engraftment and inflammation induce poor islet xenograft survival. We aimed to determine whether overexpression of human heme oxygenase-1 (HO-1) or soluble tumor necrosis factor-α receptor type I with human IgG1 Fc (sTNF-αR-Fc) in porcine islets could improve islet xenograft survival. Adult porcine islets were transduced with adenovirus containing human HO-1, sTNF-αR-Fc, sTNF-αR-Fc/HO-1 or green fluorescent protein (control). Humanized mice were generated by injecting human cord blood-derived CD34(+) stem cells into NOD-scid-IL-2Rγ(null) mice. Both HO-1 and sTNF-αR-Fc reduced islet apoptosis under in vitro hypoxia or cytokine stimuli and suppressed RANTES induction without compromising insulin secretion. Introduction of either gene into islets prolonged islet xenograft survival in pig-to-humanized mice transplantation. The sTNF-αR-Fc/HO-1 group showed the best glucose tolerance. Target genes were successfully expressed in islet xenografts. Perigraft infiltration of macrophages and T cells was suppressed with decreased expression of RANTES, tumor necrosis factor-α and IL-6 in treatment groups; however, frequency of pig-specific interferon-γ-producing T cells was not decreased, and humoral response was not significant in any group. Early apoptosis of islet cells was suppressed in the treatment groups. In conclusion, overexpression of HO-1 or sTNF-αR-Fc in porcine islets improved islet xenograft survival by suppressing both apoptosis and inflammation. HO-1 or sTNF-αR-Fc transgenic pigs have potential for islet xenotransplantation.

Oxidative stress generated during islet isolation, culture, and transplantation causes islet cell damage mediated by hypoxia, reactive oxygen species (ROS) and inflammatory responses. We investigated the protective effects of NecroX-7, a novel ROS scavenger, during isolation and/or culture of islets. For ex vivo studies, islets from heterozygote human islet amyloid polypeptide (hIAPP+/-) mice and C57BL/6J mice were isolated by collagenase with and without supplementation with 20 uM of NecroX-7. Supplementation with NecroX-7 provided markedly increased islet viability and ATP contents, and attenuated ROS, transcription of c-Jun N-terminal kinases, high mobility group box-1 (HMGB1) and proinflammatory cytokines including interleukin-1beta (IL-1b), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-a). Transplantation of islets, which is derived from islet isolation method using supplementation with NecroX-7, into syngeneic subrenal subcapsular of hIAPP+/- mice also improved post-transplant blood glucose levels. Also, NecroX-7 protected RINm5F cells from t-BHP-induced and serum deprivation induced toxicity in in vitro culture by dose-dependent manner from 0.1 uM to 20 uM. Supplementation of medium with NecroX-7 during serum-deprived culture condition also improved impaired viability and serum deprivation-induced ROS in islets from hIAPP+/- mice by dose-dependent manner from 0.1 uM to 20 uM. These findings suggest that NecroX-7 supplementation during the islet isolation and/or culture process suppressed inflammatory responses and ROS induced by serum deprivation and provides a potential benefit to improve post-transplantation outcomes. Disclosure Y. Kwon: None. H. Lee: None. H. Kim: None. G. Kim: None. S. Jin: None. M. Lee: None. J. Kim: None.

Background Porcine islet xenotransplantation is considered an attractive alternative treatment for type 1 diabetes mellitus. However, it is largely limited because of initial rejection due to Instant Blood-Mediated Inflammatory Reaction (IBMIR), oxidative stress, and inflammatory responses. Recently, soluble tumor necrosis factor-ɑ receptor type I (sTNF-αR) and heme oxygenase (HO)-1 genes (HO-1/sTNF-αR) have been shown to improve the viability and functionality of porcine islets after transplantation. Methods In this study, genetically modified mesenchymal stem cells (MSCs) expressing the HO-1/sTNF-αR genes (HO-1/sTNF-αR-MSC) were developed using an adenoviral system, and porcine islet viability and function were confirmed by in vitro tests such as GSIS, AO/PI, and the ADP/ATP ratio after coculturing with HO-1/sTNF-αR-MSCs. Subsequently, isolated porcine islets were transplanted underneath the kidney capsule of diabetic humanized mice without MSCs, with MSCs or with HO-1/sTNF-αR-MSCs. Results According to the results, the HO-1/sTNF-αR-MSC-treated group exhibited improved survival of porcine islets and could reverse hyperglycemia more than porcine islets not treated with MSCs or islets cotransplanted with MSCs. Moreover, the HO-1/sTNF-αR-MSC group maintained its morphological characteristics and the insulin secretion pattern of transplanted porcine islets similar to endogenous islets in immunocompetent humanized mice. Conclusions Our results suggest that HO-1/sTNF-αR-MSCs are efficient tools for porcine islet xenotransplantation, and this study may provide basic information for pre-clinical animal models and future clinical trials of porcine islet xenotransplantation.

Islet transplantation is as effective as but also less immunogenic than pancreas transplantation for the treatment of type 1 diabetes mellitus. However, as the complete elimination of immunogenicity still remains a major obstacle in islet transplantation, layer-by-layer encapsulation (LbL) of pancreatic islets using biocompatible polymers offers a rational approach to reducing host immune response towards transplanted islets. We investigated the effect of LbL of non-human primate (NHP) islets on reducing immunogenicity as a preclinical model since NHPs have close phylogenetic and immunological relationship with humans. LbL with three-layers of polyethylene glycol (PEG) molecules (SH-6-arm-PEG-NHS, 6-arm-PEG-catechol and linear PEG-SH) showed a uniform nano-shielding on islets without the loss of viability or function of islets. An immunosuppressive drug protocol was also combined to improve the survival rate of the transplanted islets in vivo. A xenorecipient (C57BL/6 mice) of LbL islet transplanted along with our immunosuppressive drug protocol showed 100% survival rate for 150 days after transplantation. On the other hand, naked islet recipients showed poor survival time of 5.5 ± 1.4 days without drugs and 77.5 ± 42 days with the drug protocol. Immunohistochemistry of the transplanted grafts and serum cytokine concentration demonstrated less immunogenicity in the LbL islet transplanted recipients compared with the naked islet ones.

Meralgia paresthetica (MP) is generally caused by entrapment of the lateral femoral cutaneous nerve (LFCN), and presents with pain and paresthesia in the anterolateral thigh. This paper describes a patient who had MP-like symptoms as a result of continuous epidural analgesia after total knee arthroplasty. The patient with pre-existing left foraminal stenosis at L3-L4 and disc herniations at L4-5 did not complain of paresthesia or pain during the combined spinal-epidural anesthetic procedure. However, during epidural analgesia on the second post-operative day, he complained of paresthesia and pain in the anterolateral thigh of the contralateral leg. Electromyography showed a neurogenic lesion at the level of L3. Although an ultrasound-guided diagnostic block of the LFCN was performed twice post-operatively, the patient's symptoms persisted. The symptoms gradually resolved 12 months after the surgery. In our case, we suggest that the continuous epidural infusate caused neural ischemia of the L3 nerve root by a compressive effect.

Ferumoxytol is the only clinically available ultrasmall superparamagnetic iron oxide. However, the labeling efficacy of islet magnetic resonance imaging (MRI) using ferumoxytol is not suitable for use in clinical pancreatic islet transplantation (PIT). We evaluated the feasibility of pancreatic islet MRI using ferumoxytol through multi-layer surface modification. A four-layer nanoshield with poly (ethylene) glycol (PEG, 2 layers), ferumoxytol, and heparin was formed on the pancreatic islets. We compared pancreatic islet function, viability, and labeling efficacy of control, ferumoxytol alone-labeled, heparin-PEGylated, and ferumoxytol-heparin-PEGylated islets. With optimization of the ferumoxytol concentration during the ferumoxytol-heparin-PEGylation process, the labeling contrast in ex vivo MRI of ferumoxytol-heparin-PEGylated pancreatic islets was stronger than that of pancreatic islets labeled with ferumoxytol alone, without decreasing ex vivo islet viability or function. In a syngeneic mouse renal subcapsular PIT model, heparin-PEGylation and ferumoxytol-heparin-PEGylation delayed the revascularization of pancreatic islet grafts but did not impair glucose tolerance or revascularization of pancreatic islet grafts four weeks post-transplantation. Pancreatic islet visibility after labeling was also confirmed in a syngeneic mouse intraportal PIT model and in preliminary analysis of a non-human primate intraportal PIT model. In conclusion, multi-layer islet surface modification is a promising option for pancreatic islet MRI in intraportal PIT.

Live imaging is a powerful technique that can be used to characterize the fate and location of stem cells in animal models. Here we investigated the characteristics and in vitro cytotoxicity of human mesenchymal stem cells (MSCs) labeled with silica-coated magnetic nanoparticles incorporating rhodamine B isothiocyanate, MNPs@SiO 2 (RITC). We also conducted various in vivo–uptake tests with nanoparticle-labeled human MSCs. MNPs@SiO 2 (RITC) showed photostability against ultraviolet light exposure and were nontoxic to human MSCs, based on the MTT, apoptosis, and cell cycle arrest assays. In addition, MNPs@SiO 2 (RITC) did not affect the surface phenotype or morphology of human MSCs. We also demonstrated that MNPs@SiO 2 (RITC) have stable retention properties in MSCs in vitro. Furthermore, using optical and magnetic resonance imaging, we successfully detected a visible signal from labeled human MSCs that were transplanted into NOD.CB17-Prkdc SCID (NOD-SCID) mice. These results demonstrate that MNPs@SiO 2 (RITC) are biocompatible and useful tools for human MSC labeling and bioimaging. From the Clinical Editor The characteristics and in vitro cytotoxicity of human mesenchymal stem cells (MSCs) labeled with silica-coated magnetic nanoparticles incorporating rhodamine B isothiocyanate, RITC were investigated in this study. RITC showed photostability against ultraviolet light exposure and was nontoxic to human MSCs. Using both optical and magnetic resonance imaging, successful detection of signal from labeled human MSCs transplanted into mice is demonstrated.

In this paper we proposed a new source-drain structure for N-type MOSFET which can suppress the output resistance reduction of a device in saturation region due to soft break down leakage at high drain voltage when the gate is biased around relatively low voltage. When a device is generally used as a switch at high gate bias the current level is very important for the operation. but in electronic circuit like an amplifier we should mainly consider the output resistance for the stable voltage gain and the operation at low gate bias. Hence with T-SUPREM simulator we designed devices that operate at low gate bias and high gate bias respectively without a extra photo mask layer and ion-implantation steps. As a result the soft break down leakage due to impact ionization is reduced remarkably and the output resistance increases about 3 times in the device that operates at the low gate bias. Also it is expected that electronic circuit designers can easily design a circuit using the offered N-type MOSFET device with the better output resistance.

In this paper, effects of the trench angle() on the breakdown voltage according to the process parameters of p-base region and doping concentrations of n-drift region in a Trench Gate IGBT (TIGBT) device were analyzed by computer simulation. Processes parameters used by variables are diffusion temperature, implant dose of p-base region and doping concentration of n-drift region, and aspects of breakdown voltage change with change of each parameter were examined. As diffusion temperature of the p-base region increases, depth of the p-base region increases and effect of the diffusion temperature on the breakdown voltage is very low in the case of small trench angle() but that is increases 134.8 % in the case of high trench angle(). Moreover, as implant dose of the p-base region increases, doping concentration of the p-base region increases and effect of the implant dose on the breakdown voltage is very low in the case of small trench angle() but that is increases 232.1 % in the case of high trench angle(). These phenomenons is why electric field concentrated in the trench is distributed to the p-base region as the diffusion temperature and implant dose of the p-base increase. However, effect of the doping concentration variation in the n-drift region on the breakdown voltage varies just 9.3 % as trench angle increases from to . This is why magnitude of electric field concentrated in the trench changes, but direction of that doesn`t change. In this paper, respective reasons were analyzed through the electric field concentration analysis by computer simulation.

Both human soluble tumor necrosis factor-α receptor-Fc (sTNF-αR-Fc) and heme oxygenase-1 (HO-1) transgenic pigs have been generated previously for xenotransplantation. Here, we investigated whether overexpression of sTNF-αR-Fc or HO-1 in pig islets prolongs islet xenograft survival. Adult porcine islets were isolated from human sTNF-αR-Fc or HO-1 transgenic and wild type pigs, and were transplanted into diabetic nude mice. Effects of the expression of both genes on islet apoptosis, chemokine expression, cellular infiltration, antibody production, and islet xenograft survival were analyzed. Human sTNF-αR-Fc transgenic pigs successfully expressed sTNF-αR-Fc in the islets; human HO-1 transgenic pigs expressed significant levels of HO-1 in the islets. Pig-to-mouse islet xenograft survival was significantly prolonged in both the sTNF-αR-Fc and HO-1 groups compared with that in the wild type group. Both the sTNF-αR-Fc and HO-1 groups exhibited suppressed intragraft expression of monocyte chemoattractant protein-1 (MCP-1) and decreased perigraft infiltration of immune cells. However, there was no difference in the anti-pig antibody levels between the groups. Apoptosis of islet cells during the early engraftment was suppressed only in the HO-1 group. Porcine islets from both sTNF-αR-Fc and HO-1 transgenic pigs prolonged xenograft survival by suppressing islet cell apoptosis or secondary inflammatory responses following islet death, indicating that these transgenic pigs might have applications in successful islet xenotransplantation.

Background Given the fragility of adult porcine islets, reduction of shearing stress in islet purification using histidine-tryptophan-ketoglutarate (HTK) solution and iodixanol could be an effective strategy. We examined the effect of ductal preservation with HTK solution and an islet purification protocol that utilizes HTK solution and iodixanol in adult porcine islet isolation. Methods Islets were isolated with a modified Ricordi method using adult Prestige World Genetics (PWG) and Yucatan pigs. The discontinuous density gradient was composed of either HTK solution/iodixanol (n = 23, iodixanol group) or Hank's balanced salt solution (HBSS)/Ficoll (n = 17, Ficoll group). In the iodixanol group, ductal injection of HTK solution was performed before purification. Results In PWG pigs, significantly higher islet yield after purification (3480 ± 214.2 islet equivalent [IEQ]/g, P = .003) and higher recovery rate (85.45% ± 3.49%, P = .0043) were obtained from the HTK/iodixanol group as compared to the HBSS/Ficoll group (1905 ± 323.2 IEQ/g, and 67.22% ± 4.77%, respectively). Similar results were obtained in Yucatan pigs with greater body weight. Conclusion Ductal preservation and iodixanol-based islet purification using HTK solution improved the yield of adult porcine islet isolation compared to the conventional method using HBSS and Ficoll. The results of this study support the feasibility of an adult porcine islet isolation protocol using HTK solution and iodixanol, which have the favorable physical properties.

A new double offset-implanted (DOI) technology, which can effectively suppress the gate-induced drain-leakage (GIDL) current of buried-channel PMOS transistor in small-size CMOS devices, is proposed and developed with a 0.12-/spl mu/m single-gate low-power SRAM device. The DOI scheme is characterized by the usage of the silicon nitride etch-stopper for the formation of borderless W-contact as offset spacer without supplementing auxiliary processes at p+ source/drain (S/D) implantation process after the n+ S/D one. It is assured that the DOI technology makes the gate-to-S/D overlap controllable, so that the GIDL current of PMOS transistor can remarkably be reduced. Furthermore, the enhancement of CMOS transistor performance was possible by reducing the sidewall reoxidation thickness of the gate-poly Si and optimizing the implantation conditions with this technology.

An equivalent islet number (EIN) greater than 300,000 is necessary for islet cell transplantation for a recipient who weighs about 60 kg. The aim of this study is to identify factors that affect isolation outcome. The most significant independent predictor for successful islet isolation from deceased donors was low international normalized ratio (INR).

A planar edge termination technique of trenched field limiting ring is investigated by using 2-dimensional numerical analysis and simulation. The better voltage blocking capability and reliability can be obtained by trenching the field-limiting ring site which would be implanted. The trench etch step makes the junction depth deeper so that junction curvature effect and surface breakdown are less happened. The numerical analyses reveal two facts that the trenched field limiting ring has smaller maximum electric field and the electric field peak is deeper from the substrate surface, hence silicon dioxide layer can be protected. Therefore the voltage blocking capability and reliability of the new structure can be improved. The simulated results for 1700 V power devices by using TMA MEDICI show that the trenched field limiting ring can have smaller critical electric field and accomplish near 30% increase of breakdown voltage in comparison with the conventional structure. The proposed structure is more efficient to support voltage and more easy to gain the optimized design. Moreover, the fabrication of trenched field-limiting ring is relatively simple because the trench etch step uses the same mask of p+ field-ring implantation step. Extensive device simulations as well as qualitative analyses confirm these conclusions.

A trench gate insulated gate bipolar transistor(IGBT) employing a shielding layer, which improves the breakdown voltage characteristic is proposed and verified by 2D numerical simulation. The shielding layer concept is proposed to alleviate the electric field of concentrated on the trench bottom corner. By simulation results, we verified that a shielding layer reduced the electric fields not only in the gate oxide but in the p-base region. Compared with conventional trench gate IGBT, about 33% increment of forward breakdown voltages are achieved.

In this paper we introduced the shielding layer concept in order to alleviate the electric field of concentrated on the trench bottom corner. The shielded trench gate IGBT is a trench gate IGBT with a P+ shielding layer bottom of a trench gate. By simulation results, we verified that a shielding layer reduced the electric fields not only in the gate oxide but in the p-base region. Compared with conventional trench gate IGBT, about 33% increment of forward breakdown voltages are achieved.

In this paper, we propose a new structure that improves the on-state voltage drop along with the switching speed in insulated gate bipolar transistors(IGBTs), which is widely applied in high voltage semiconductors. The proposed structure is unique that the collector area is divided by SiO2 regions, whereas in existing IGBTs, the collector has a planar P+ structure. The process and device simulation results show remarkably improved on-state and switching characteristics. The current and electric field distributions indicate that the segmented collector structure increases the electric field near the SiO2 edge which leads to an increase in electron current and finally a decrease in on-state voltage drop to 30% ~ 40%. Also, since the area of the P+ region decreases compared to existing structures, the hole injection decreases which leads to an improved switching speed to 30%.

A novel simple shallow trench isolation technology, SSTI, has been developed. SSTI consists of direct trench etching masked only with the photoresist, trench oxidation, liner SiN deposition, CVD oxide trench fill, densification, and high selectivity CMP. CMP stops at the liner SiN with a residual SiN thickness range of less than 2 nm and without micro-scratching. High selectivity CMP eliminates the field recess variation which is one of the drawbacks of conventional STI. SSTI is a promising candidate for future isolation technology.

In order to develop a Shallow Trench Isolation (STI) which does not have trench corner induced degradation of the gate oxide, its integrities were evaluated with rounded, non-rounded top corner, and an addition of CVD SiO/sub 2/ spacer. In the experiment, we found that the rounded and SiO/sub 2/ spacered STI showed the best result meaning no harmful influence of the corner to the gate oxide integrity. Also, etch-back processes of the filled CVD SiO/sub 2/ were modified to eliminate the degradation of the gate oxide by a stress concentration at top corner kinks.

Densification methods using H/sub 2/O and N/sub 2/ ambient annealing of the filled CVD oxide for quarter micron STI are compared. Although the H/sub 2/O ambient oxidation is more effective in terms of the resistance against the HF etching, volume expansion by the trench sidewall oxidation generates a large amount of stress in the narrow isolation region. However, an N/sub 2/ gas ambient annealing at high temperature shows a low stress and a low HF etch rate which enable us to fabricate the stable quarter micron STI.