High-yield Process Research Articles

Encapsulation of ɣ-Aminobutyric Acid Compounds Extracted from Germinated Brown Rice by Freeze-Drying Technique

Gamma-aminobutyric acid (GABA) from plants has several bioactivities, such as neurotransmission, anti-cancer cell proliferation, and blood pressure control. Its bioactivities vary when exposed to pH, heat, and ultraviolet. This study analyzed the protective effect of the GABA encapsulation technique using gum arabic (GA) and maltodextrin (MD) and the freeze-drying method. The impact of different ratios of the wall material GA and MD on morphology, GABA content, antioxidant activity, encapsulation efficiency, process yield, and physical properties were analyzed. Results showed that the structure of encapsulated GABA powder was similar to broken glass pieces of various sizes and irregular shapes. The highest GABA content and encapsulation efficiency were, respectively, 90.77 mg/g and 84.36% when using the wall material GA:MD ratio of 2:2. The encapsulated powder’s antioxidant activity was 1.09–1.80 g of encapsulation powder for each formula, which showed no significant difference. GA and MD as the wall material in a 2:2 (w/w) ratio showed the lowest bulk density. The high amount of MD showed the highest Hausner ratio (HR), and Carr’s index (CI) showed high encapsulation efficiency and process yield. The stability of encapsulated GABA powder can be kept in clear glass with a screw cap at 35 °C for 42 days compared to the non-encapsulated one, which can be preserved for only 18 days under the same condition. In conclusion, this study demonstrated that the freeze-drying process for GABA encapsulation preserved GABA component extracts from brown rice while increasing its potential beneficial properties. Using a wall material GA:MD ratio of 2:2 resulted in the maximum GABA content, solubility, and encapsulation efficiency while having the lowest bulk density.

Production of few-layer graphene and boron nitride nano onions via lamp ablation

Abstract Few-layer graphene, and separately, boron nitride nano onions have been synthesised by a novel lamp ablation method which is a one-step, high-yield process that is catalyst-free, devoid of toxic reagents, with short reaction times, and potentially scalable. The precursor for the few-layer graphene is graphite flake, while that of boron nitride nano onions is hexagonal boron nitride powder. Product nanostructures are characterised by high-resolution transmission electron microscopy (HRTEM), energy-dispersive X-ray spectroscopy (EDS) and electron energy loss spectroscopy (EELS). We also report on our commercialisation trajectory to translate promising research findings in the laboratory to the market. For the few-layer graphene product, it is presently on a pre-commercial pilot plant phase.

Scaleable production of highly loaded protein nanoparticles for immune modulation

Immune modulation and desensitization is a growing field of research and clinical investigation that requires precise delivery of antigens to immune system cells. Nanoparticles (NPs) have emerged as excellent candidates for antigen delivery, particularly in immune desensitization applications. NP-encapsulated protein antigens enable the delivery of protein and co-encapsulated adjuvant to antigen-presenting cells without systemic exposure and allergic response. Here, we show a method for producing poly(lactide-co-glycolide) (PLG) NPs in an efficient, high-yield, and large-scale inhomogeneous precipitation process. The process enables the production of compositionally complex PLG NPs containing protein while also incorporating DNA and E. coli phospholipids as integral adjuvants in the NP vehicle. Orally delivered PLG NPs activate the murine immune system, and encapsulated peanut allergen protein elicits approximately 10-fold lower levels of basophil activation than does unencapsulated protein in basophils isolated from peanut-allergic patients. This efficacy and safety evidence makes these PLG NPs excellent candidates for clinical applications.

OREATE as a High Yield and Purity Electrochemical Process for Transition and Rare Earth Metal Recovery

Developing a process that can consistently convert transition and rare earth metal oxides to chemically pure metals in near quantitative yield will have significant impact in many levels, from fundamental science to national security-related applications. Traditional separation methods of lanthanides and actinides from aqueous media have been based on liquid-liquid extractions that have proven to be quite efficient, though they are expensive and require complex engineering. Likewise, separation by pyro-chemistry provides a good recovery performance but requires the use of high temperatures that adds technological difficulties to the process. An alternative method that has grown interest in the last few years is the utilization of the difference in the metals’ reduction potentials from ionic state to metallic state. However, this electrochemical approach requires more negative reduction potentials than hydrogen evolution, which requires a very challenging control of their electrolytic deposition onto solid cathodes.In recent years, our team at LANL has been working on the development of OREATE (Oxide Reduction by Electrochemical Amalgamation and Thermal Extraction). OREATE is a holistic electrochemical approach that involves an initial step wherein the metal oxide is dissolved and chlorinated into an acidic medium. The dissolved metal cation is then electrochemically amalgamated via reduction using a mercury pool cathode. Finally, mercury's high vapor pressure allows an easy thermal extraction process to obtain the metal. From the conceptual perspective and preliminary results, the OREATE process appears easier and simpler than traditional separation methods and is suitable for small- and large-scale preparation of high purity metals.The results obtained using Cerium (Ce) as a surrogate metal demonstrated near quantitative yield of the electrochemical amalgamation (yield > 99%), almost complete mercury recovery during the thermal extraction (Hg recovery > 99.5%), and high purity of the Ce metal product (purity > 99%). Moreover, a variety of system parameters such as the pH of the buffered solution, concentration of cerium, reduction potential, and temperature were explored to evaluate the effect that the scaling up of the OREATE process may have on reaction rate, current efficiency, process yield, and temperature management.

Ionic liquid and ultrasound as a fast and innovative combination for improved extraction of Chlorella sorokiniana-derived carotenoids

Chlorella sorokiniana is a microalgae with high amounts of carotenoids, but the extraction methods need to be improved. This work hypothesized that the combination of ionic liquids (ILs) and ultrasound would provide a fast and efficient process for carotenoid extraction, allowing for the reuse of ILs in several extractive cycles. This study aimed to develop an improved ILs/ultrasound-based method for extracting carotenoids from C. sorokiniana. The potential reuse of ILs in five consecutive extraction cycles and the recovery of carotenoids was also examined. Moreover, the antioxidant activity of the carotenoid extracts and their effects on metabolic cell viability and cell death were investigated using HT22 neuronal cells. Initial tests with four ILs and acetone as a control were carried out in an ultrasonic probe. The ILs (1-butyl-3-methylimidazolium chloride [BMIM][Cl]; 1-hexyl-3-methylimidazolium chloride [HMIM][Cl]) were selected for the 25−1 fractional experimental design. The maximized parameters obtained in the experimental design were the following: IL ([HMIM][Cl]), a 1:10 solid-liquid ratio, a 1:4 IL-cosolvent ratio, and two repetitions of extraction with 7.5 min (with an extraction yield of 1.29 mg·g‐1 of dry matter). A total of 11 carotenoids were separated, and nine were identified, the major ones being lutein and β-carotene. [HMIM][Cl] recyclability using resin Amberlite XAD-7HP was efficient for at least five cycles. On average, 91 % of the IL was recovered, and the pigment yield increased by 40 %. The antioxidant activities of the extracts obtained using [HMIM][Cl] and acetone were 1.65 μmol and 2.32 μmol of α-tocopherol, respectively. Both extracts (≤ 4.0 μg·mL‐1) exhibited no significant toxicity to HT22 cells. The proposed method is an innovative and improved approach for carotenoid extraction from C. sorokiniana due to its short extraction times and high process yield. [HMIM][Cl] demonstrated stability in reuse cycles and proved to have the potential for obtaining carotenoids from C. sorokiniana.

Coriolopsis trogii MUT3379: A Novel Cell Factory for High-Yield Laccase Production

Coriolopsis trogii is a basidiomycete fungus which utilizes a large array of lignin-modifying enzymes to colonize and decompose dead wood. Its extracellular enzymatic arsenal includes laccases, i.e., polyphenol oxidases of relevant interest for different industrial applications thanks to their ability to oxidize a diverse range of natural and synthetic compounds. In this work, the production of laccases in C. trogii MUT3379 was explored and improved. From an initial production of ca. 10,000 U L−1, the fermentation process was gradually optimized, reaching a final yield of ca. 200,000 U L−1. An SDS-PAGE analysis of the secretome highlighted the presence of a main protein of ca. 60 kDa showing laccase activity, which was designated as Lac3379-1 once its primary sequence was established by tandem mass spectrometry. The characterization of Lac3379-1 revealed a remarkable enzymatic stability in the presence of surfactants and solvents and a diversified activity on a broad range of substrates, positioning it as an interesting tool for diverse biotechnological applications. The high-yield and robust production process indicates C. trogii MUT3379 as a promising cell factory for laccases, offering new perspectives for industrial applications of lignin-modifying enzymes.

Parallel Multifactorial Process Optimization and Intensification for High-Yield Production of Live YF17D-Vectored Zika Vaccine.

The live-attenuated yellow fever 17D strain is a potent vaccine and viral vector. Its manufacture is based on embryonated chicken eggs or adherent Vero cells. Both processes are unsuitable for rapid and scalable supply. Here, we introduce a high-throughput workflow to identify suspension cells that are fit for the high-yield production of live YF17D-based vaccines in an intensified upstream process. The use of an automated parallel ambr15 microbioreactor system for screening and process optimization has led to the identification of two promising cell lines (AGE1.CR.pIX and HEKDyn) and the establishment of optimized production conditions, which have resulted in a >100-fold increase in virus titers compared to the current state of the art using adherent Vero cells. The process can readily be scaled up from the microbioreactor scale (15 mL) to 1 L stirred tank bioreactors. The viruses produced are genetically stable and maintain their favorable safety and immunogenicity profile, as demonstrated by the absence of neurovirulence in suckling BALB/c mice and consistent seroprotection in AG129 mice. In conclusion, the presented workflow allows for the rapid establishment of a robust, scalable, and high-yield process for the production of live-attenuated orthoflavivirus vaccines, which outperforms current standards. The approach described here can serve as a model for the development of scalable processes and the optimization of yields for other virus-based vaccines that face challenges in meeting growing demands.

Development of semi-dried goat meat jerky using tenderizers considering the preferences of the elderly.

Elderly people avoid eating red meat and dried meat product due to its texture and stiffness; they deprive them of rich sources of nutrients. In addition, food-related diseases are exponentially increasing due to using synthetic additives in food products. Therefore, this research aimed to develop semi-dried goat meat jerky considering geriatric preferences by using natural tenderizers and nitrate. Four treatments were formulated negative control (NC [synthetic nitrite without tenderizers]), positive control (PC [Swiss chard without tenderizers]), T1 (Swiss chard with pineapple powder), and T2 (Swiss chard with pineapple and tomato powder). T1 and T2 had higher processing yield, and rehydration capacity compared with NC and PC. The fat content of T1 and T2 was lower than the control groups. Moisture was significantly higher in T1, NC, and T2 than in PC (p < 0.05). T2 showed the lowest water activity (0.87), lowest shear force (4.82 kgf), and lowest total plate count (TPC). The lowest pH and thiobarbituric acid reactive substances (TBARS) were observed in T1 and T2. T1 showed the lowest lightness and the maximum redness (p < 0.05) while PC showed the lowest yellowness. During the storage period, moisture and pH decreased, and TPC and TBARS significantly increased whereas water activity is stable regardless of the treatment. The results of the myofibrillar fragmentation index (MFI) and sodium dodecyl sulfate-polyacrylamide gel revealed that T1 and T2 more effectively converted protein to polypeptides. In addition, tenderizers positively affected thrombogenicity, atherogenicity, and hypocholesterolemic/hypercholesterolemic indices. T2 observed the highest overall sensory acceptance by reducing goaty flavor. Overall, jerky treated with tenderizers is easily chewable and digestible for the elderly due to its tenderness and essential fatty acids that would be senior-friendly food.

Efficient Alcoholysis of Poly(ethylene terephthalate) by Using Supercritical Carbon Dioxide as a Green Solvent.

In order to reduce the environmental impact of poly(ethylene terephthalate) (PET) plastic waste, supercritical fluids were used to facilitate effective recovery via improved solvent effects. This work focuses on the mechanisms of supercritical CO2 (ScCO2) during the alcoholysis processing of PET using systematic experiments and molecular dynamics (MD) simulations. The results of the alcoholysis experiment indicated that PET chips can be completely depolymerized within only an hour at 473 K assisted with ScCO2 at an optimal molar ratio of CO2/ethanol of 0.2. Random scission of PET dominates the early stage of the depolymerization reaction process, while specific scission dominates the following stage. Correspondingly, molecular dynamics (MD) simulations revealed that the solubilization and self-diffusion properties of ScCO2 facilitate the transportation of alcohol molecules into the bulk phase of PET, which leads to an accelerated diffusion of both oligomers and small molecules in the system. However, the presence of excessive CO2 has a negative impact on depolymerization by weakening the hydrogen bonding between polyester chain segments and ethanol, as well as decreasing the swelling degree of PET. These data provide a deep understanding of PET degradation by alcohols and the enhancement of ScCO2. It should be expected to achieve an efficient and high-yield depolymerization process of wasted polyesters assisted with ScCO2 at a relatively low temperature.

Probing single electrons across 300-mm spin qubit wafers

Building a fault-tolerant quantum computer will require vast numbers of physical qubits. For qubit technologies based on solid-state electronic devices1–3, integrating millions of qubits in a single processor will require device fabrication to reach a scale comparable to that of the modern complementary metal–oxide–semiconductor (CMOS) industry. Equally important, the scale of cryogenic device testing must keep pace to enable efficient device screening and to improve statistical metrics such as qubit yield and voltage variation. Spin qubits1,4,5 based on electrons in Si have shown impressive control fidelities6–9 but have historically been challenged by yield and process variation10–12. Here we present a testing process using a cryogenic 300-mm wafer prober13 to collect high-volume data on the performance of hundreds of industry-manufactured spin qubit devices at 1.6 K. This testing method provides fast feedback to enable optimization of the CMOS-compatible fabrication process, leading to high yield and low process variation. Using this system, we automate measurements of the operating point of spin qubits and investigate the transitions of single electrons across full wafers. We analyse the random variation in single-electron operating voltages and find that the optimized fabrication process leads to low levels of disorder at the 300-mm scale. Together, these results demonstrate the advances that can be achieved through the application of CMOS-industry techniques to the fabrication and measurement of spin qubit devices.

Investigation of Crystallization Growth Characteristics of Mg(OH)2 Crystals under Unconstrained Conditions.

Utilizing MgO as the precursor and deionized water as the solvent, this study synthesized nanoparticles of Mg(OH)2 via hydrothermal methods, aiming to control its purity, particle size, and morphology by understanding its growth under non-uniform nucleation. Characterization of crystal morphology and structure was conducted through scanning electron microscopy and X-ray diffraction, while laser particle size detection assessed the secondary particle size distribution. The study focused on how MgO's hydrothermal process conditions influence Mg(OH)2 crystal growth, particularly through ion concentration and release rate adjustments to direct crystal growth facets. These adjustments shifted the dominant growth plane, enhancing the peak intensity ratio I001/I101 from 1.03 to 2.14, thereby reducing surface polarity and secondary aggregation of crystals. The study of the physicochemical properties of the same sample at different times revealed the pattern of crystal dissolution and recrystallization. A 2 h hydrothermal reaction notably altered the particle size distribution, with a decrease in particles sized 0.2~0.4 μm and an increase in those sized 0.4~0.6 μm, alongside new particles over 1 μm, indicating a shift toward uniformity through dissolution and recrystallization. Optimal conditions (6% magnesium oxide concentration, 160 °C, 2 h) led to the synthesis of highly dispersed, uniformly sized magnesium hydroxide, showcasing a simple, eco-friendly, and high-yield process.

High-yield and cost-effective biosynthesis process for producing antimicrobial peptide AA139

AA139, a variant of natural antimicrobial peptide (AMP) arenicin-3, displayed potent activity against multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria. Nevertheless, there were currently few reports on the bioprocess of AA139, and the yields were less than 5 mg/L. Additionally, it was difficult and expensive to prepare AA139 through chemical synthesis due to its complex structure. These factors have impeded the further research and following clinical application of AA139. Here, we reported a bioprocess for the preparation of AA139, which was expressed in Escherichia coli (E. coli) BL21 (DE3) intracellularly in a soluble form via SUMO (small ubiquitin-related modifier) fusion technology. Then, recombinant AA139 (rAA139, refer to AA139 obtained by recombinant expression in this study) was obtained through the simplified downstream process, which was rationally designed in accordance with the physicochemical characteristics. Subsequently, the expression level of the interest protein was increased by 54% after optimization of high cell density fermentation (HCDF). Finally, we obtained a yield of 56 mg of rAA139 from 1 L culture with a purity of 98%, which represented the highest reported yield of AA139 to date. Furthermore, various characterizations were conducted to confirm the molecular mass, disulfide bonds, and antimicrobial activity of rAA139.

Synthesis of salcaprozate sodium and its significance in enhancing pancreatic kininogenase absorption performance.

We conducted pharmacokinetic research wherein salcaprozate sodium (SNAC) was utilized as a penetration enhancer by incorporating it into pancreatic kininogenase (PK) to improve the bioavailability of pancreatic kininogenase enteric-coated tablets. We conducted invitro studies on PK using the Caco-2 cell model and quantified PK levels using the enzyme-linked immunosorbent assay (ELISA) method. We conducted methodological verification by blending SNAC and PK powders into enteric-coated capsules, and studied the pharmacokinetic characteristics. Based on the PK transport assay, the cumulative permeation rates of the test group that employed a SNAC to PK ratio of 32:1, 16:1, 8:1, 4:1, and 2:1 were 13.574%, 7.597%, 10.653%, 3.755%, and 2.523%, respectively. We conducted a uniformity test on the powder that contained a blend of SNAC and PK. The relative standard deviations (RSDs) for both the power containing SNAC and the power not containing SNAC were less than 10%. Based on the methodological verification, invivo pharmacokinetic study of PK met the experimental requirements. As indicated by the results of invivo pharmacokinetic research on rats, the test group (This group used SNAC) had a PK AUC0-12 h of 5679.747 ng/L*h and t1/2 of 4.569 h, while the control group (This group did not use SNAC) had a PK AUC0-12 h of 4639.665 ng/L*h and t1/2 of 3.13 h. This study has established a low-cost, environmentally friendly, and safe SNAC synthesis route with high process yield suitable for industrial production. SNAC demonstrates an absorption-enhancing effect on PK, and the optimal ratio of SNAC to PK is determined to be 32:1.

Reinforcement Fiber Production from Wheat Straw for Wastepaper-Based Packaging Using Steam Refining with Sodium Carbonate

Locally sourced agricultural residues are a promising feedstock for the production of reinforcement fibers for wastepaper-based packaging papers. An eco-friendly high yield process to generate fibers from wheat straw using high pressure steam and sodium carbonate is presented. The wheat straw was impregnated with up to 16% of sodium carbonate and steam treated for 10 min at temperatures from 148 °C to 203 °C. The pulps were characterized concerning their chemical composition and test sheets with 100% straw fibers and with 15% and 30% straw fibers blended with recycled pulp were prepared. Fiber yields ranged from 70% to 45%, wherein more severe treatment conditions contributed to increased paper strength but lower yields. At comparable fiber yields, treatments featuring a higher chemical input, coupled with lower treatment temperatures, resulted in improved paper strength. By blending recycled pulp with up to 30% of straw fibers with a beating degree of roughly 45 °SR, the burst, compression and tensile strength was enhanced by up to 66%, 74% and 59%, respectively. As the enhancement effect decreases with a high steam treatment intensity and a high proportion of wheat straw, a moderate treatment and limited use of wheat straw may be the best choice.

Sublimed C60 for efficient and repeatable perovskite-based solar cells

Thermally evaporated C60 is a near-ubiquitous electron transport layer in state-of-the-art p–i–n perovskite-based solar cells. As perovskite photovoltaic technologies are moving toward industrialization, batch-to-batch reproducibility of device performances becomes crucial. Here, we show that commercial as-received (99.75% pure) C60 source materials may coalesce during repeated thermal evaporation processes, jeopardizing such reproducibility. We find that the coalescence is due to oxygen present in the initial source powder and leads to the formation of deep states within the perovskite bandgap, resulting in a systematic decrease in solar cell performance. However, further purification (through sublimation) of the C60 to 99.95% before evaporation is found to hinder coalescence, with the associated solar cell performances being fully reproducible after repeated processing. We verify the universality of this behavior on perovskite/silicon tandem solar cells by demonstrating their open-circuit voltages and fill factors to remain at 1950 mV and 81% respectively, over eight repeated processes using the same sublimed C60 source material. Notably, one of these cells achieved a certified power conversion efficiency of 30.9%. These findings provide insights crucial for the advancement of perovskite photovoltaic technologies towards scaled production with high process yield.

Development of a three-stage process for high coal desulfurization and char yield

Efficient pyrolytic desulfurization with high char yield is a promising yet challenging approach for the cleaner utilization of abundant high-sulfur coal reserves. In this study, we have discovered that a single pyrolysis process under either oxidizing or reducing conditions cannot efficiently remove various sulfur forms while preserving a high char yield. To address this challenge, we propose a three-stage desulfurization process: a low-temperature oxidative pyrolysis (LTOP), a high-temperature reductive pyrolysis (HTRP), and a dry magnetic separation process. LTOP operates in a fluidized bed for only a few minutes to oxidize the diamagnetic pyrite particle surface to Fe2O3 while minimizing char losses. HTRP occurs in another fluidized bed for an appropriate duration to substantially remove organic sulfur while reducing Fe2O3 to highly magnetic Fe3O4 or Fe. Partially magnetized pyrite particles are then removed from the char through magnetic separation. When applied to anthracite coal with a total sulfur content of 4.99%, this process achieves nearly 100% desulfurization for pyritic sulfur and 74.81% for organic sulfur. Ultimately, it recovers 94.5% of the original coal excluding volatiles as char, with 91.6% being low-sulfur char.

Biotechnological lactic acid production from low-cost renewable sources via anaerobic microbial processes.

Lactic acid (LA) production from microbial fermentation using low-cost renewable sources has emerged as an attractive alternative to the use of petroleum-based products. This approach not only offers sustainable solutions for waste management but also enables the production of value-added products in an eco-friendly manner. However, to make this approach economically viable, optimizing the production process for high yield, productivity, and purity while minimizing costs is crucial. To address these challenges, various approaches have been proposed, including the use of neutralizing agents, high cell density cultures, co-cultures, fed-batch fermentation, and product removal strategies. Overall, this review underscores the potential of microbial fermentation for LA production as a sustainable and cost-effective solution to meet the growing demand for eco-friendly products. Further optimization of fermentation processes and the development of new microbial strains and fermentation techniques are key to advancing this approach. The production of LA through microbial fermentation presents a sustainable and eco-friendly solution to the increasing demand for eco-friendly products. With continued innovation, we can expect to see a significant reduction in the environmental impact of industrial processes, coupled with a more cost-effective and high-purity source of lactic acid for various industries.

Enhancement of dieckol extraction yield from Ecklonia cava through optimization of major variables in generally recognized as safe solvent-based process

Ecklonia cava (EC), an edible brown macroalga abundant in intertidal areas of East Asia (Korea, Japan, and China), contains high-value bioactive compounds such as dieckol, which has antifungal, anti-inflammatory, antitumor, and antihyperlipidemic activities. However, no studies have been reported on the utilization of EC as a biorefinery feedstock, and the design of a more economical and high-yield process is required for the utilization of dieckol for the human healthcare industry. In this study, we designed a bioprocess for the high-yield recovery of dieckol from EC in a generally recognized as safe (GRAS) solvent to facilitate its application in the food and healthcare industries. Preliminary studies identified ethanol as an efficient solvent with the highest dieckol extraction yield (2.9 mg/g biomass). In order to maximize the recovery of dieckol from EC, the major extraction variables (solvent concentration, reaction temperature, and reaction time) were optimized based on statistical methods. Based on the predictive model, the numerical optimization determined that the solution with the highest dieckol content per weight of extract (62.6 vol% ethanol concentration, 54.2°C temperature, 13.2 min) was the optimal extraction condition. Under the determined conditions, the dieckol yield from EC achieved 6.4 mg dieckol/g EC (95.5% agreement with the predicted value). The designed process offers several advantages, including improving the utilization feasibility of EC, utilizing GRAS solvents with potential human applications, short extraction time (13.2 min), maximized process yield, and the highest dieckol recovery compared to previous reports.

High-Yielding Process for the Synthesis of Hydroxychloroquine under Concentrated Conditions: Nucleophilic Amination of Chloropyridines Promoted by Dimethyl Sulfoxide or Catalyzed by 3,5-Bis(trifluoromethyl)phenol

High-Yielding Process for the Synthesis of Hydroxychloroquine under Concentrated Conditions: Nucleophilic Amination of Chloropyridines Promoted by Dimethyl Sulfoxide or Catalyzed by 3,5-Bis(trifluoromethyl)phenol

High -yield Fabrication of Thin Glass Interposers

Thin glass substrates with through vias (TGV) have excellent properties for a new generation of interposers. Glass has a large bulk resistance and low loss at high frequency (RF, mmWave). Physically, it is moisture insensitive, highly dimensionally stable, and has a thermal expansion coefficient that can be tailored to match silicon. The surface of as-received glass has roughness below 1 nm, like silicon wafers, and thus supports fine line/space patterning and advanced processes like damascene. A key focus of our current work involves metallizing thin glass interposers with TGVs, including both copper electroplating of TGVs and patterning of redistribution layers. We demonstrate void-free fill for vias ranging from in aspect ratio from 2:1 to 8:1, in a bottoms-up process like that used for through silicon vias. The vias are hermetic by helium leak detection, even after annealing in some cases to 450C. Since thin (≤ 200 micron) free-standing glass substrates are difficult to handle in current fabs, we discuss an advanced temporary bond approach using silicon or glass handles which enables high-yield processing. The bond is robust to temperatures exceeding 400 °C, and creates handle/glass stacks with total thickness variation (TTV) similar to that of a silicon wafer. The end result is a bonded pair that can be processed like a silicon wafer, with a simple mechanical debond to yield the processed thin glass. We discuss the bond and debond processes, showing the ability to control the bond strength. Data on the bonded glass stack resistance to various processing steps will also be shown.