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This study aimed to evaluate the oncological outcomes and surgical completeness of transoral robotic thyroidectomy (TORT) for papillary thyroid carcinoma (PTC) compared with conventional transcervical thyroidectomy.We analyzed 489 patients with PTC who underwent thyroidectomy with or without central neck dissection (CND; 311 conventional thyroidectomy and 178 TORT) between January 2017 and December 2021. Patients with gross invasion of the surrounding structures, revision or completion thyroidectomy, and lateral neck dissection were excluded. Propensity score-matched analysis was performed using eight covariates, including age, sex, extent of thyroidectomy, tumor size, extrathyroidal extension (ETE), radioactive iodine (RAI) ablation, lymphovascular invasion (LVI), and CND.Before propensity score matching (PSM), age, male-to-female ratio, and body mass index were lower in the TORT group. The ratio of total thyroidectomy and CND, tumor size and bilaterality, LVI, and RAI ablation were higher in the conventional group. PSM generated two matched groups of 100 patients each. After PSM, significant differences between the two groups in the baseline analysis disappeared. In the matched samples, the recurrence rate (2% and 0% in the conventional and TORT groups, respectively) and recurrence-free survival curves did not differ between the two groups. The mean thyroid-stimulating hormone (TSH)-stimulated thyroglobulin level in the RAI group and TSH-suppressed thyroglobulin level in the non-RAI group were not different between the two groups.The 5-year oncologic outcomes and surgical completeness of TORT were comparable with those of conventional thyroidectomy in patients with small, localized, low-risk PTC when performed by experienced surgeons.

Various methods based on gold nanoparticles (AuNPs) have been applied to enhance the photothermal effect. Among these methods, combining gold nanoparticles and stem cells has been suggested as a new technique for elevating the efficiency of photothermal therapy (PT) in terms of enhancing tumor targeting effect. However, to elicit the efficiency of PT using gold nanoparticles and stem cells, delivering large amounts of AuNPs into stem cells without loss should be considered.AuNPs, AuNPs-decorated silica nanoparticles, and silica-capped and AuNPs-decorated silica nanoparticles (SGSs) were synthesized and used to treat human mesenchymal stem cells (hMSCs). After evaluating physical properties of each nanoparticle, the concentration of each nanoparticle was estimated based on its cytotoxicity to hMSCs. The amount of AuNPs loss from each nanoparticle by exogenous physical stress was evaluated after exposing particles to a gentle shaking. After these experiments, in vitro and in vivo photothermal effects were then evaluated.SGS showed no cytotoxicity when it was used to treat hMSCs at concentration up to 20 μg/mL. After intravenous injection to tumor-bearing mice, SGS-laden hMSCs group showed significantly higher heat generation than other groups following laser irradiation. Furthermore, in vivo photothermal effect in the hMSC-SGS group was significantly enhanced than those in other groups in terms of tumor volume decrement and histological outcome.Our results suggest that additional silica layer in SGSs could protect AuNPs from physical stress induced AuNPs loss. The strategy applied in SGS may offer a prospective method to improve PT.

Background Recently, various studies have revealed that 3D cell spheroids have several advantages over 2D cells in stem cell culture. However, conventional 3D spheroid culture methods have some disadvantages and limitations such as time required for spheroid formation and complexity of the experimental process. Here, we used acoustic levitation as cell culture platform to overcome the limitation of conventional 3D culture methods. Methods In our anti-gravity bioreactor, continuous standing sonic waves created pressure field for 3D culture of human mesenchymal stem cells (hMSCs). hMSCs were trapped and aggerated in pressure field and consequently formed spheroids. The structure, viability, gene and protein expression of spheroids formed in the anti-gravity bioreactor were analyzed by electron microscope, immunostaining, polymerase chain reaction, and western blot. We injected hMSC spheroids fabricated by anti-gravity bioreactor into the mouse hindlimb ischemia model. Limb salvage was quantified to evaluate therapeutic efficacy of hMSC spheroids. Results The acoustic levitation in anti-gravity bioreactor made spheroids faster and more compact compared to the conventional hanging drop method, which resulted in the upregulation of angiogenic paracrine factors of hMSCs, such as vascular endothelial growth factor and angiopoietin 2. Injected hMSCs spheroids cultured in the anti-gravity bioreactor exhibited improved therapeutic efficacy, including the degree of limb salvage, capillary formation, and attenuation of fibrosis and inflammation, for mouse hindlimb ischemia model compared to spheroids formed by the conventional hanging drop method. Conclusion Our stem cell culture system using acoustic levitation will be proposed as a new platform for the future 3D cell culture system. Graphical Abstract

Teriparatide is an effective drug for the treatment of osteoporosis. This study examines the relationship between the drug delivery properties of the solid formulation with teriparatide and the pharmacokinetic properties of teriparatide in vivo.Teriparatide microneedles with different dissolution rates were prepared using sucrose and carboxymethylcellulose (CMC). There were three aspects of this study: (1) The dissolution rate of teriparatide from both formulations (sucrose and CMC) was measured in vitro. (2) After administration into porcine skin ex vivo, the diffusion rate of FITC-dextran was observed using a confocal microscope. (3) Pharmacokinetic studies were performed in rats and pharmacokinetic data compared with the release rate and the diffusion pattern.In the in vitro dissolution experiment, 80% of teriparatide was released within 30 min from the CMC MNs, whereas 80% of teriparatide was released within 10 min from the sucrose MNs. After 30 min, the fluorescence intensity on the surface of the MNs was 40% of the initial intensity for sucrose MNs and 90% for CMC MNs. In the pharmacokinetic study, the CWhen teriparatide is delivered into the skin using microneedles, the release rate from the solid formulation determines the drug's pharmacokinetic properties. The diffusion pattern of fluorescence into the skin can be used to anticipate the pharmacokinetic properties of the drug.

Microneedles (MNs), one of the transdermal drug delivery systems, have received extensive interest as an alternative to parenteral or parenteral administrations. For the successful drug delivery of coated MNs, the coated drug or chemical of MNs should be dissolved by skin's interstitial fluid and completely released from the MNs. Thus, the rapid disintegration of the drug from MNs plays a crucial role in ideal drug delivery of MNs. In this study, we developed the rapid disintegration coating formulation to reduce the application time of MN. The rapid disintegration MN was developed using polymers (PVA or HPMC), glycerol, croscarmellose sodium, tween 80, and Brij, as thickener, plasticizer, disintegrating agent, and surfactants, respectively. HPMC MN showed the burst release and rapid disintegration. Moreover, the drug from HPMC MN was successfully delivered into porcine skin within 1 min. In toxicological evaluation, the HPMC MN did not alter the liver and kidney function. Besides, HPMC MN did not induce the acute inflammation and change of skin structure after the application on rat skin. Thus, the coating formulation in this study could be one of the options for the development of safe and rapid disintegration MN.

Due to the continuously mutating nature of the H3N2 virus, two aspects were considered when preparing the H3N2 microneedle vaccines: (1) rapid preparation and (2) cross-protection against multiple antigenic variants. Previous methods of measuring hemagglutinin (HA) content required the standard antibody, thus rapid preparation of H3N2 microneedle vaccines targeting the mutant H3N2 was delayed as a result of lacking a standard antibody. In this study, H3N2 microneedle vaccines were prepared by high performance liquid chromatography (HPLC) without the use of an antibody, and the cross-protection of the vaccines against several antigenic variants was observed. The HA content measured by HPLC was compared with that measured by ELISA to observe the accuracy of the HPLC analysis of HA content. The cross-protection afforded by the H3N2 microneedle vaccines was evaluated against several antigenic variants in mice. Microneedle vaccines for the 2019–20 seasonal H3N2 influenza virus (19–20 A/KS/17) were prepared using a dip-coating process. The cross-protection of 19–20 A/KS/17 H3N2 microneedle vaccines against the 2015–16 seasonal H3N2 influenza virus in mice was investigated by monitoring body weight changes and survival rate. The neutralizing antibody against several H3N2 antigenic variants was evaluated using the plaque reduction neutralization test (PRNT). HA content in the solid microneedle vaccine formulation with trehalose post-exposure at 40℃ for 24 h was 48% and 43% from the initial HA content by HPLC and ELISA, respectively. The vaccine was administered to two groups of mice, one by microneedles and the other by intramuscular injection (IM). In vivo efficacies in the two groups were found to be similar, and cross-protection efficacy was also similar in both groups. HPLC exhibited good diagnostic performance with H3N2 microneedle vaccines and good agreement with ELISA. The H3N2 microneedle vaccines elicited a cross-protective immune response against the H3N2 antigenic variants. Here, we propose the use of HPLC for a more rapid approach in preparing H3N2 microneedle vaccines targeting H3N2 virus variants.

The oral mucosa is an effective site for vaccination. However, for oral mucosal vaccines, delivery of the right dose of vaccine is not possible due to the water-rich environment. In this study, the buccal mucosa, which is easy to access using a microneedle array in the oral cavity, was selected as the administration site. The immune responses to the use of microneedles to conventional transmucosal delivery were compared. In addition, the adjuvant effect of the addition of cholera toxin (CT) to the drug formulation was observed. Two kinds of patches were prepared: (1) Ovalbumin (OVA) was dip coated only on the tips of microneedles (C-OVA-MN) and (2) OVA was coated on the surface of a flat disk patch substrate without microneedles (C-OVA-D). The drug delivery properties of C-OVA-MN and C-OVA-D were investigated using fluorescent-labeled OVA (OVA/FITC). Each patch was administered to mice twice, 2 weeks apart, and then antibody titers were measured. A microneedle patch can deliver vaccine into the epithelium of the buccal mucosa in a short period of time compared to transmucosal delivery. A microneedle system of C-OVA-MN showed a high serum IgG titer. In addition, CT triggered CD8+ and CD4+ T cell-mediated immune responses. Through this study, we present the possibility of a new method of vaccination to the buccal mucosa using microneedles and CT adjuvant. Illustration of delivery of vaccine to the oral mucosal epithelium using a microneedle patch: Ovalbumin (OVA)-coated microneedle (C-OVA-MN) consists of tip, step, and coating formulation. Microneedle patch coated with OVA formulation is targeting buccal mucosa, which is easy to access in the oral cavity. OVA is delivered to the buccal epithelium precisely using a microneedle patch, and OVA is delivered by transmucosal route using a disk patch.

The phlorotannin compounds, dieckol and phlorofucofuroeckol (PFF), extracted from Ecklonia cava, have been suggested to exhibit anti-inflammatory, anti-adipogenic or anti-tumorigenic activity. However, role of dieckol or PFF in LPS/TLR-4 signaling that regulates cancer development still remains to be determined. Here we report that dieckol or PFF blocked lipopolysaccharide (LPS)-induced migration and invasion of human breast cancer MCF-7 or MDA-MB-231 cells by about 50% (p

Topology optimization is a shape optimization method connected with finite element (FE) structural analysis, and has recently received increasing attention owing to rapid evolution of additive manufacturing (AM). In this study, a rifle support for the sport biathlon is developed by combining three-dimensional (3D) scanning, FE analysis, topology optimization, and AM. Considering that the biathlon requires a stable shooting motion under hard breathing after a distance of cross-country skiing, the rifle support was designed to be fitted to a human body based on 3D scanning data. Topology optimization was then performed to reduce the part weight efficiently, and its structural safety and stiffness were evaluated by FE analyses considering the orthotropic material properties and the relevant printing directions. The optimized design and printing direction were showed 12.7% improvements in the specific stiffness and 23–43% improvements in the structural safety according to the direction. The final design was fabricated using a fused deposition modeling type 3D printer with acrylonitrile butadiene styrene filament. Compression tests were then performed to evaluate its structural safety, and the resulting relative critical force showed a 40% improvement in comparison with the original design.

A microneedle (MN) oral mucosal patch system was prepared to increase its adhesive strength, to improve the delivery of triamcinolone acetonide (TA) into the mucosa, and to protect the adhesive layer from mouth movement and saliva. The MN oral mucosal patch system consists of an adhesive layer containing TA and a backing layer. The adhesive layer consists of a base with a thickness of 50 μm, 300 μm long MNs, and 18% TA. After patches were attached to the tape-stripped porcine skin for a predetermined period of time, the adhesion of the patches was observed. TA was extracted from the skin, and the amount of TA was measured using high-performance chromatography. When the adhesive layer was applied for 10 s, the adhesive strength was 1.69 N mm/cm2 with microneedles and 0.41 N mm/cm2 without microneedles. An oral mucosal patch with MNs (TA MN-AL) delivered 42% more TA into the skin than an oral mucosal patch without MNs (TA AL). Also, as attachment time increased, the amount of TA delivered was significantly greater using a TA MN-AL compared to a TA AL. The addition of MNs can increase the adhesion of the oral mucosal patch to the mucosa and thus improve the efficiency of drug delivery.

Polydopamine (PDA) is a simple and versatile conformal coating material that has been proposed for a variety of uses; however in practice its performance is often hindered by poor mechanical properties and high roughness. Here, we show that blue-diode laser annealing dramatically improves mechanical performance and reduces roughness of PDA coatings. Laser-annealed PDA (LAPDA) was shown to be >100-fold more scratch resistant than pristine PDA and even better than hard inorganic substrates, which we attribute to partial graphitization and covalent coupling between PDA subunits during annealing. Moreover, laser annealing provides these benefits while preserving other attractive properties of PDA, as demonstrated by the superior biofouling resistance of antifouling polymer-grafted LAPDA compared to PDA modified with the same polymer. Our work suggests that laser annealing may allow the use of PDA in mechanically demanding applications previously considered inaccessible, without sacrificing the functional versatility that is so characteristic of PDA., The ability to alter surface chemistry on a variety of materials makes polydopamine (PDA) and excellent surface coating material, but weak wear resistance and high surface roughness limits its application. Here, the authors demonstrate a laser annealing process to improve the mechanical properties of PDA coatings.

To identify the protective effect of DJ-1 protein against oxidative stress-induced HepG2 cell death, we used cell-permeable wild type (WT) and a mutant (C106A Tat-DJ-1) protein. By using western blotting and fluorescence microscopy, we observed WT and C106A Tat-DJ-1 proteins were efficiently transduced into HepG2 cells. Transduced WT Tat-DJ-1 proteins increased cell survival and protected against DNA fragmentation and intracellular ROS generation levels in H2O2-exposed HepG2 cells. At the same time, transduced WT Tat-DJ-1 protein significantly inhibited NF-κB and MAPK (JNK and p38) activation as well as regulated the Bcl-2 and Bax expression levels. However, C106A Tat-DJ-1 protein did not show any protective effect against cell death responses in H2O2-exposed HepG2 cells. Oxidative stress-induced HepG2 cell death was significantly reduced by transduced WT Tat-DJ-1 protein, not by C106A Tat-DJ-1 protein. Thus, transduction of WT Tat-DJ-1 protein could be a novel strategy for promoting cell survival in situations of oxidative stress-induced HepG2 cell death.

This paper introduces a portable magnetic field generator for producing wireless induction heating, which has recently been introduced as one of the major thermal techniques in the point-of-care (POC) diagnostic method. To produce induction heating of thin metal structures in a microcentrifuge tube at any time and place, a portable magnetic field generating device was designed and fabricated using the fullbridge FET drive circuit based on a metal-oxide-semiconductor field-effect transistor (MOSFET) and pulse width modulation (PWM). A frequency of 312 kHz was set for effectively heating the micro-scale element, and a high-frequency magnetic field was produced by using a low-power device based on the full-bridge series resonance. Induction heating of two types of heating elements in a microcentrifuge tube was conducted using the new device, and thermal characteristics of induction heating were observed. The device induced eddy currents in both twisted and straight copper elements in the microtube; heating rates were approximately 6.5 J/sec and 3.8 J/sec, respectively. Output voltage of 160 W and magnetic intensity of 80.3 μT were generated by the working coil. This portable magnetic field generator weighs 450 g without a battery and consumes 3600 mAh of power. 70% of Salmonella cells in a concentration of 107 cells/mL was lysed for 15 sec of induction heating with a portable device. The authors conclude that a portable, low-power magnetic field generator can effectively induce heat in a micro-scale heating element, which provides simple and rapid thermal treatment at any time and place.

Dieckol, extracted from brown algae, Ecklonia cava, is suggested to elicit anti-inflammatory or anti-tumorigenic activities. However, dieckol-mediated regulatory mechanism for inflammatory response still remains elusive. Here, we show that dieckol suppressed lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) expression in mouse leukemic macrophage Raw264.7 cells. Also, dieckol decreased LPS-induced both nitric oxide (NO) production and iNOS promoter-driven transcriptional activity in a dose-dependent manner. On the other hand, LPS-mediated NF-κB activity was inhibited by dieckol treatment. Moreover, results revealed that dieckol diminished LPS-mediated p65 nuclear translocation or IκBα phosphorylation dose-dependently, and reduced LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs), significantly p38MAPK. Collectively, these findings suggest that dieckol acts as a negative regulator of LPS-mediated iNOS induction through suppression of NF-κB activity, implying a mechanistic role of dieckol in regulation of inflammatory response.

This study was conducted to fit the diameter-height data of Quercus glauca in Jeju Island, South Korea to the four commonly used stem taper equations and to evaluate the performance of the four stem taper models using four statistical criteria: Fit index (FI), root mean square error (RMSE), bias ( ), and absolute mean difference (AMD). Results showed that the Kozak02 stem taper equation provided the best FI (0.9847), RMSE(1.5745), (-0.0030 cm) and AMD (1.0990 cm) while Max and Burkhart model had the poorest performance among the four stem taper models based on the four evaluation statistics (FI : 0.9793, RMSE : 1.8272, : 0.3040 cm and AMD : 1.3060 cm). These stem taper equations can serve as a useful tool for forest managers in estimating the diameter outside bark at any given height, merchantable stem volumes and total stem volumes of the standing trees of Quercus glauca in the Gotjawal forests located in Mount Halla, Jeju Island, South Korea.

In this study, we developed an esophageal stent capable of sustained delivery of an anticancer drug, flu- orouracil (5-FU). The stents were coated with drug-loaded poly(lactic-co-glycolic acid) (PLGA) nanofibers (DPN) via the electrospinning method, which exhibited a sustained drug release for up to 6 days. To prolong drug release, we also added the nanofiber layers composed of PLGA alone (PN), surrounding the DPN layer, as a more resistive diffusion barrier, where a period of drug release could be extended to 21 days with the DPN layer topped with another 192 µm thick PN layer. Therefore, we envisioned longer period of drug release with the thicker PN layers, obtained simply with a longer collection time of PLGA nanofibers via electrospinning. Overall, we concluded that the drug-delivery esophageal stent prepared in this study is promising in the long-term treatment of dysphagia caused by esophageal cancer.

This paper demonstrates the development of a method for preparing micropatterned microdiscs in order to increase contact area with cells and to change the release pattern of drugs. The microdiscs were manufactured with hot embossing, where a polyurethane master structure was pressed onto both solid and porous microparticles made of polylactic-co-glycolic acid at various temperatures to form a micropattern on the microdiscs. Flat microdiscs were formed by hot embossing of porous microparticles; the porosity allowed space for flattening of the microdiscs. Three types of micro-grooves were patterned onto the flat microdiscs using prepared micropatterned molds: (1) 10 deep, 5 wide, and spaced 2 apart; (2) 10 deep, 9 wide, and spaced 5 apart; and (3) 10 deep, 50 wide, and spaced 50 apart. This novel microdisc preparation method using hot embossing to create micropatterns on flattened porous microparticles provides the opportunity for low-cost, rapid manufacture of microdiscs that can be used to control cell adhesion and drug delivery rates.

Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) appear to have increased intestinal permeability; it has been suggested that activation of protease-activated receptor-2 (PAR-2) receptors is responsible for this alteration. The aims of this study are to evaluate (1) if rectal (large bowel) permeability is increased in IBS-D and (2) if tryptase plays a critical role in the altered permeability. Rectal biopsies from 20 patients with IBS-D and 30 subjects without the condition (normal controls) were assessed for macromolecular permeability using horseradish peroxidase in Ussing chambers in the basal state and after addition of drugs to the basolateral side. Reverse-transcription polymerase chain reaction (RT-PCR) was performed using colonic biopsy tissues from patients with IBS-D and normal subjects. When tryptase was added to the basolateral (not mucosal) side of normal rectal biopsy tissues, permeability appeared to be proportional to the increase in tryptase concentration (P

We have designed and fabricated a microneedle array with electrical functionality with the final goal of electroporating skin's epidermal cells to increase their transfection by DNA vaccines. The microneedle array was made of polymethylmethacrylate (PMMA) by micromolding technology from a polydimethylsiloxane (PDMS) mold, followed by metal deposition, patterning using laser ablation, and electrodeposition. This microneedle array possessed sufficient mechanical strength to penetrate human skin in vivo and was also able to electroporate both red blood cells and human prostate cancer cells as an in vitro model to demonstrate cell membrane permeabilization. A computational model to predict the effective volume for electroporation with respect to applied voltages was constructed from finite element simulation. This study demonstrates the mechanical and electrical functionalities of the first MEMS-fabricated microneedle array for electroporation, designed for DNA vaccine delivery.

Ultrasonic welding can be used with micromolding to fabricate polymeric microstructures. We investigated whether these techniques are useful in fabricating polymeric microstructures from polymeric microparticles that encapsulate thermally sensitive compounds. We used a spray-drying method to prepare biodegradable polymer microparticles encapsulating the thermally sensitive compound, BSA and Vitamin B. The resulting polymeric structures were less than 7 μm in diameter. Morphological changes after increasing periods of application of ultrasonic energy could be categorized into four phases: loose connecting, dense connecting, porous packing, and solid structures. The stability of polymer structures encapsulating BSA was tested after increasing periods of applied energy. Few changes were seen after typical periods (under 1 min), but 10 % of BSA was denatured after 80 s (considered to be harsh conditions). More work is needed to optimize this novel method of microfabrication for delivery of other heat-sensitive protein and growth factors and the biological function of protein also need to be investigated in next experiment. However, it appears to a promising means of fabricating polymer microstructures for cell chips, tissue engineering, and drug delivery, in which protein must be encapsulated with minimal denaturation.

Conventional micromolding provides rapid and low-cost methods to fabricate polymer microstructures, but has limitations when producing sophisticated designs. To provide more versatile micromolding techniques, we developed methods based on filling micromolds with polymer microparticles, as opposed to polymer melts, to produce microstructures composed of multiple materials, having complex geometries, and made using mild processing conditions. Polymer microparticles of 1 to 30 microm in size were made from PLA, PGA and PLGA using established spray drying and emulsion techniques either with or without encapsulating model drug compounds. These polymer microparticles were filled into PDMS micromolds at room temperature and melted or bonded together to form microstructures according to different protocols. Porous microstructures were fabricated by ultrasonically welding microparticles together in the mold while maintaining the voids inherent in their packing structure. Multi-layered microstructures were fabricated to have different compositions of polymers and encapsulated compounds located in different regions of the microstructures. More complex arrowhead microstructures were fabricated in a two-step process using a single mold. To assess possible applications, microstructures were designed as microneedles for minimally invasive drug delivery. Multi-layer microneedles were shown to insert into cadaver tissue and, according to design, detach from their base substrate and remain embedded in the tissue for controlled release drug delivery over time. We conclude that polymer particle-based micromolding can encapsulate compounds within microstructures composed of multiple materials, having complex geometries, and made using mild processing conditions.

Intimal hyperplasia (IH) is characterized by vascular smooth muscle cell (VSMC) proliferation in the intima and subsequent accumulation of extracellular matrix. A variety of factors that might be considered as possible VSMC mitogens induce the specific gene expression of VSMC. This study was designed to identify differentially expressed mRNA by method using an mRNA differential display.A bilateral femoropopliteal reverse saphenous vein bypass was performed on both hind limbs of mongrel dogs. At 4 and 8 weeks after the implantation, the vein bypass grafts were harvested. The total RNAs were extracted from each specimen and transcribed into the cDNAs. Amplified cDNAs using 16 sets of primers were separated on DNA sequencing gel. Differentially displayed bands were excised from the gel, cloned, and then sequenced. The sequences were compared with the National Center of Biotechnology Information nonredundant sequence database using the Basic Local Alignment Search Tool (BLAST) program.Forty-three bands were cloned and sequenced. A computer search revealed that 11 of them had similarities to known genes while 32 cDNAs had no similarities to any registered DNA sequence.We found several genes to be related to IH. Some of them had already had their function and sequence identified whereas some of them have yet to be identified. Further studies are necessary to determine the precise relationship between these genes and IH.

A mathematical model for low pressure chemical vapor deposition in a single-wafer reactor in stagnation point flow has been developed to investigate the reactor performance. The transient transport equations for a simulated reactor include continuity, momentum, energy, and gaseous species balances. The model equations are simultaneously solved by using a numerical technique of orthogonal collocation on finite element method. Simulation studies have been performed to gain an understanding of tungsten low pressure chemical vapor deposition process. The model is then used to optimize the deposition rate and uniformity on a wafer, and the effects of operating conditions on deposition rate are studied to examine how system responses are affected by changes in process parameters. Deposition rate and uniformity calculated at the steady state are observed to be very sensitive to both temperature and total pressure. In addition, the model predictions for tungsten deposition from hydrogen reduction of tungsten hexafluoride have been compared with available experimental data in order to demonstrate the validity of the model.

A transient model of a single-wafer reactor in axisymmetric, stagnation point flow is used to study the effects of operating conditions on film thickness uniformity and composition uniformity across the wafer during low pressure chemical vapor deposition of tungsten silicide. Orthogonal collocation on finite elements is used to solve the transient model equations; continuity, momentum, energy and chemical species balances. A feature scale model for simultaneous Knudsen transport and heterogeneous reactions is used to predict film thickness in infinite trenches. Boundary conditions for the feature scale model are established using the reactor scale model. The use of a combined reactor scale and feature scale model is demonstrated to select deposition conditions which provide both good interwafer uniformity and good intrafeature uniformity. Film thickness and composition uniformity on a wafer are predicted using a model for a single-wafer reactor. Significant differences in step coverage predicted using partial pressures in the feed stream and partial pressures at the wafer surface were observed. Step coverage differences between the wafer center and the wafer edge were also significant under the operating conditions used in this study. Uniformities of interwafer and intrafeature step coverages inceased as either the wafer temperature or the partial pressure ratio of dichlorosilane to tungsten silicide in the feed was decreased.