Low Levels Of Metals Research Articles

Alterations in Zinc, Copper, and Iron Levels in the Retina and Brain of Alzheimer's Disease Patients and the APP/PS1 Mouse Model.

Transition metals like copper, iron, and zinc are vital for normal central nervous system function and are also linked to neurodegeneration, particularly in the onset and progression of Alzheimer's disease (AD). Their alterations in AD, identified prior to amyloid plaque aggregation, offer a unique target for staging pre-amyloid AD. However, analysing their levels in the brain is extremely challenging, necessitating the development of alternative approaches. Here, we utilised laser ablation-inductively coupled plasma-mass spectrometry and solution nebulisation-inductively coupled plasma-mass spectrometry to quantitatively measure Cu, Fe, and Zn concentrations in the retina and hippocampus samples obtained from human donors (i.e., AD and healthy controls), and in the APP/PS1 mouse model of AD, and Wild Type controls, aged 9 and 18 months. Our findings revealed significantly elevated Cu, Fe, and Zn levels in the retina (*p < 0.05, **p < 0.01, ***p < 0.001) and hippocampus (*p < 0.05, *p < 0.05, *p < 0.05) of human AD samples compared to healthy controls. Conversely, APP/PS1 mouse models exhibited notably lower metal levels in the same regions compared to WT mice, Cu, Fe, and Zn levels in the retina (**p < 0.01, *p < 0.05, *p < 0.05) and hippocampus (**p < 0.01, **p < 0.01, *p < 0.05). The contrasting metal profiles in human and mouse samples, yet similar patterns within each species' retina and brain, suggest the retina mirrors cerebral metal dyshomeostasis in AD. Our findings lay the groundwork for staging pre-AD pathophysiology through assessment of transition metal levels in the retina.

Recent Developments in Low Temperature Wafer Level Metal Bonding for Heterogenous Integration

Abstract An overview of various low-temperature (&lt;200°C) wafer bonding processes using metal interlayers is presented. Such processes are very attractive for novel applications in 3D heterogenous packaging as the allow for simultaneous formation of electrical interconnects, as well as hermetic encapsulation of various sensors and microelectromechanical systems-based devices. Metal wafer bonding is a generic category of processes consisting of various sub-categories, each one defined by the different principles governing the process. One can differentiate between eutectic wafer bonding (a eutectic alloy is formed as bonding layer during the process by liquid-solid interdiffusion), intermetallic wafer bonding (an intermetallic alloy is formed as bonding layer during the process by solid-liquid interdiffusion, a process known also as solid liquid intermetallic diffusion transient liquid phase, and metal thermo-compression wafer bonding. Different critical/gating parameters were investigated and their impact for generally reducing processing temperatures for the different metal bonding systems was studied.

Chemical Durability And Mechanical Properties Of Cementitious Matrices Containing Ashes Obtained After Combustion Of Waste From Moukondo Landfill In Brazzaville, Republic Of Congo.

The regular burning of solid waste in the open air and on the ground is commonplace in the Republic of Congo. Burning waste produces pollutants and ashes that can be hazardous to the soil and surrounding waters. Inadequate management of the ash generated by the open burning of household waste results in site pollution, particularly heavy metal contamination (Pb, Ni, Cr, Cu, Zn...). The aim of this study is to develop cementitious matrices containing burnt ashes that are sufficiently effective to retain the heavy metals contained in these ashes in their structure. To this end, in order to assess the chemical durability of these cementitious matrices, we carried out static leaching tests at pH=4 and 7 at 25°C in distilled water on the raw ashes firstly, and then on the 24 cementitious matrices synthesized with different ash/cement/lime ratios. The mechanical durability of the cementitious matrices was assessed using flexural and compressive strength tests. The leaching results obtained demonstrated the effective immobilization of heavy metals in cementitious matrices, whose leachates contain very low levels of heavy metals compared with those of raw ash. Flexural and compressive strength tests showed an improvement in strength from 25°C to 60°C. Several cementitious matrices doped with waste ashes show flexural strengths higher than the recommended standard for flexural strength EN1339 (5 MPa) and compressive strength X31-211 (1 MPa) after 28 days curing at 60°C

A different application of the Aliquat® 336 loaded poly(vinylidene fluoride-co-hexafluoropropylene) based electrospun nanofibers disks for the preconcentration followed by flame atomic absorption spectrometry detection of low-level Bi(III)

It is the first report on the potential of electrospun nanofiber disks inserted in a filtration apparatus as a preconcentration strategy for the analysis of low-level metals. The nanofibers included 60 wt% of poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) and 40 wt% of ionic liquid Aliquat® 336. The electrospinning process was done by applying a voltage of 16 kV, an injection rate of 1 mL h−1, and 10 cm distance of the needle tip location from the drum collector. A circular piece of the prepared nanofiber disks was placed in a filtration apparatus, and 200 mL solution containing 1 mg of Bi(III) adjusted to 0.5 mol/L of hydrochloric acid was transmitted from inside the nanofiber disk by controlling the flowrate (3.3 mL s−1). The adsorbed Bi(III) was eluted by 10 mL of 0.2 mol/L solution of ethylendiaminetetraacetic acid and ammonium hydroxide mixture, and then was analyzed by flame atomic absorption spectrometry. The introduced technique (nanofiber disks-based solid phase extraction) can be used in the bismuth concentration range of 4–2000 µg/L, with a limit of detection 1.2 µg/L. The determined inter- and intra-day relative standard deviations (3 days and n = 7) for a solution of 100 µg/L of bismuth were 1.1 % and 2.4 %, respectively. The method offers a preconcentration factor of 200-fold. The fabricated nanofiber disks were used at least in 7 consecutive preconcentration experiments. The proposed method was selective towards Bi(III) and can be used satisfactory for its determination in real samples.

Temporal shifts in sources and composition of particulate metals in an environmental justice community: Impacts of continued emission reductions, COVID-19, and wildfires

In this study, we evaluated trends in the composition and source contributions of ambient particulate metals, many of which are toxic air contaminants, in Paramount, California. Paramount is an environmental justice community disproportionately impacted by air pollution from multiple emission sources near sensitive receptors. Concentrations of ambient metals bound to total suspended particulates (TSP) were measured hourly using a Xact 625 ambient metal monitor between 2017 and 2020. The Positive Matrix Factorization (PMF) model identified traffic, industry, and soil dust as major contributors. Results showed that contributions of traffic and soil dust noticeably declined during the COVID-19 lockdown period (March–April 2020) due to reduced human activities but reverted to normal levels within a few months. Industry-related factors, however, dropped significantly during this period and remained low throughout the year. Contributions from industry-related sources in Paramount began declining even before 2020, despite no similar trend in regional levels, implying local emission reductions. These reductions resulted from tariffs, decreased demand, regulatory actions by the South Coast Air Quality Management District, and voluntary controls by local facilities. Consequently, Paramount is experiencing drastically lower levels of metals (up to 80%, depending on the metal and source) from metal-processing facilities and related sources. Moreover, we observed markedly elevated concentrations of several metals (e.g., Ba, Ca, Mn, K, etc.) during the unprecedented September 2020 wildfires that engulfed much of the western US, adding to the limited body of studies on this phenomenon and emphasizing the considerable impact of massive wildfires on ambient levels of particulate metals.

Urinary metals and their associations with DNA oxidative damage among e-waste recycling workers in Hong Kong

Recycling electronic waste (e-waste) poses risks of metal exposure, potentially leading to health impairments. However, no previous study has focused on this issue in Hong Kong. Therefore, from June 2021 to September 2022, this study collected urine samples from 101 e-waste workers and 100 office workers in Hong Kong to compare their urinary levels of metals using ICP-MS. Among the 15 included metals (with detection rates above the 70 % threshold), eight showed significantly higher urinary concentrations (unit: μg/g creatinine) in e-waste workers compared to office workers: Li (25.09 vs. 33.36), Mn (1.78 vs. 4.15), Ni (2.10 vs. 2.77), Cu (5.81 vs. 9.23), Zn (404.35 vs. 431.52), Sr (151.33 vs. 186.26), Tl (0.35 vs. 0.43), and Pb (0.69 vs. 1.16). E-waste workers in Hong Kong generally exhibited lower metal levels than those in developing regions but higher than their counterparts in developed areas. The urine level of 8-hydroxy-2-deoxyguanosine (8-OHdG) was determined by HPLC-MS/MS, and no significant difference was found between the two groups. Multiple linear regression models revealed no significant association between individual metal and urinary 8-OHdG concentrations. However, the metal mixture was identified to marginally elevate the 8-OHdG concentrations (1.12, 95 %CI: 0.04, 2.19) by quantile g‑computation models, with Mn and Cd playing significant roles in such effect. In conclusion, while the metal levels among Hong Kong e-waste workers compared favorably with their counterparts in other regions, their levels were higher than those of local office workers. This underscores the need for policymakers to prioritize attention to this unique industry.

Heavy metal spatial distribution, source analysis, and ecological risks in the central hilly area of Hainan Island, China: results from a high-density soil survey.

The presence of heavy metals in soil has gained considerable attention due to their potential risks to ecosystems and human health. In this study, a thorough soil investigation was performed in the hilly region of central Hainan, which was formerly regarded as an area with the highest ecological environmental quality. A total of 7094 soil samples were systematically collected with high density over a large area. Simultaneously, a detailed investigation was conducted on the surrounding environment of each sampling point, including environmental factors such as soil, land use and crop types. The soil samples were analysed for heavy metals, pH, organic matter, and other parameters. The soil heavy metal pollution level, ecological risk and health risk were evaluated using the geo-accumulation index and the potential ecological risk index. The findings showed that the average contents of the heavy metals As, Cd, Cr, Cu, Hg, Ni, Pb and Zn in the soil were 1.68, 0.042, 24.2, 6.49, 0.0319, 7.06, 29.6 and 49.8mg·kg-1 respectively. Except for Hg, the mean values of the other heavy metals were either lower than or similar to the background values of Hainan. Also, only a few localised areas showed contamination by heavy metals. The primary sources of heavy metals, identified by a positive matrix factorisation model, could be categorised into four types: natural sources related to the soil formation process from acidic intrusive rocks (such as granite); natural sources primarily influenced by atmospheric deposition; anthropogenic sources associated with agricultural activities; and natural sources related to the soil formation process from middle-mafic intrusive rocks and black shales. The correlation analysis and variance analysis findings suggested that the content of heavy metals in the soil was primarily associated with the parent rock. The study area generally had low heavy metal levels and was not significantly polluted. However, agricultural activities still affected the enrichment of heavy metals. Therefore, it is imperative to remain vigilant about the ecological risks linked to soil heavy metals while continuing land development and expanding agricultural activities in the future. These findings indicate that conducting high-density soil surveys can enhance our understanding of regional soil heavy metals and enable reliable recommendations for agricultural planning. Whether in areas with low pollution risk or potential pollution risk, it is recommended that high-density soil surveys be conducted provide scientific guidance for further agricultural development.

Exposure to low levels of heavy metals and chronic kidney disease in the US population: A cross sectional study.

Exposure to heavy metals (cadmium, mercury, and lead) has been linked with adverse health outcomes, especially their nephrotoxic effects at high levels of exposure. We conducted a replication study to examine the association of low-level heavy metal exposure and chronic kidney disease (CKD) using a larger NHANES data set compared to previous studies. The large cross-sectional study comprised 5,175 CKD cases out of 55677 participants aged 20-85 years from the 1999-2020 National Health and Nutrition Examination Survey [NHANES]. Logistic regression analysis was applied to estimate the associations between CKD and heavy metals [Cd, Pb, Hg] measured as categorical variables after adjusting with age, race, gender, socioeconomic status, hypertension, diabetes mellitus and blood cotinine level as smoking status. Compared to the lowest quartile of blood Cd, exposures to the 2nd, 3rd and 4th quartiles of blood Cd were statistically significantly associated with higher odds of CKD after adjustment for blood Pb and Hg, with OR = 1.79, [95% CI; 1.55-2.07, p<0.0001], OR = 2.17, [95% CI; 1.88-2.51, p<0.0001] and OR = 1.52, [95% CI; 1.30-1.76, p<0.0001] respectively. The 2nd, 3rd and 4th quartiles of blood Cd remained statistically significantly associated with higher odds of CKD after adjustment for blood cotinine level, with OR = 2.06, [95% CI; 1.80-2.36, p<0.0001], OR = 3.18, [95% CI; 2.79-3.63, p<0.0001] and OR = 5.54, [95% CI; 4.82-6.37, p<0.0001] respectively. Exposure to blood Pb was statistically significantly associated with higher odds of CKD in the 2nd, 3rd and 4th quartile groups, after adjustment for all co-variates (ag, gender, race, socio-economic status, hypertension, diabetes mellitus, blood cadmium, mercury, and cotinine levels) in all the four models. Blood Hg level was statistically significantly associated with lower odds of CKD in the 2nd quartile group in model 2, 3rd quartile group in model 1, 2 and 3, and the 4th quartile group in all the four models. Our findings showed that low blood levels of Cd and Pb were associated with higher odds of CKD while low blood levels of Hg were associated with lower odds of CKD in the US adult population. However, temporal association cannot be determined as it is a cross sectional study.

Biostimulation of sulfate reduction for in-situ metal(loid) precipitation at an industrial site in Flanders, Belgium

A 30-month pilot study was conducted to evaluate the potential of in-situ metal(loid) removal through biostimulation of sulfate-reducing processes. The study took place at an industrial site in Flanders, Belgium, known for metal(loid) contamination in soil and groundwater. Biostimulation involved two incorporations of an organic substrate (emulsified vegetable oil) as electron donor and potassium bicarbonate to raise the pH of the groundwater by 1–1.5 units. The study focused on the most impacted permeable fine sand aquifer (8–9 m below groundwater level) confined by layers of non-permeable clay. The fine sands exhibited initially oxic conditions (50–200 mV), an acidic pH of 4.5 and sulfate concentrations ranging from 600 to 800 mg/L. At the central monitoring well, anoxic conditions (−200 to −400 mV) and a pH of 5.9 established shortly after the second substrate and reagent injection. Over the course of 12 months, there was a significant decrease in the concentration of arsenic (from 2500 to 12 μg/L), nickel (from 360 to <2 μg/L), zinc (from 78,000 to <2 μg/L), and sulfate (from 930 to 450 mg/L). Low levels of metal(loid)s were still present after 34 months (end of study). Mineralogical analysis indicated that the precipitates formed were amorphous in nature. Evidence for biologically driven metal(loid) precipitation was provided by compound specific stable isotope analysis of sulfate. In addition, changes in microbial populations were assessed using next-generation sequencing, revealing stimulation of native sulfate-reducing bacteria. These results highlight the potential of biostimulation for long-term in situ metal(loid) plume treatment/containment.

The effects of air plasma and argon cluster ion cleaning on quartz and calcite surfaces – Implications for rock-water-gas wettability

Wettability is a crucial factor controlling fluid transport and distribution in reservoir rocks. A significant discrepancy of reported contact angles for air plasma cleaned calcite-water-gas systems are evident from the literature. This work focuses on finding possible explanations for these discrepancies by studying the effect of two surface cleaning methods on the surface chemistry, which was utilized by employing XPS and TOF-SIMS analysis. Observed chemical changes were then discussed in relation to wettability. The two methods are i) air plasma cleaning, and ii) argon cluster ion cleaning. Air plasma cleaning exhibits a degree of reactivity towards the surface. The two surface cleaning methods are very similar in regard to efficiency. Air plasma cleaning of calcite surfaces resulted in an accumulation of low levels of metal oxides/hydroxyls. It was found that both quartz and calcite remain intact after surface cleaning, that is, neither of the cleaning processes degrade the material. It is suggested that the discrepancies in reported contact angle values is a combined effect of several factors, such as different degrees of i) surface roughness, ii) unavoidable adventitiously adsorbed hydrocarbons on the sample surfaces, and iii) non-native bulk components such as metal oxide/hydroxyls and biomarker material.

Ligated Pd-Catalyzed Aminations of Aryl/Heteroaryl Halides with Aliphatic Amines under Sustainable Aqueous Micellar Conditions.

Sustainable technology for constructing Pd-catalyzed C-N bonds involving aliphatic amines is reported. A catalytic system that relies on low levels of recyclable precious metal, a known and commercially available ligand, and a recyclable aqueous medium are combined, leading to a newly developed procedure. This new technology can be used in ocean water with equal effectiveness. Applications involving highly challenging reaction partners constituting late-stage functionalization are documented, as is a short but efficient synthesis of the drug naftopidil. Comparisons with existing aminations highlight the many advances being offered.

Evaluation of Metals in Printed Wiring Boards of Selected Discarded Mobile Phones in Nigeria

Obsolete mobile phones form a major component of the e-waste stream. The Printed wiring boards (PWBs) of mobile phones are packed with economic and toxic metals. Regulatory bodies such as Restriction of Hazardous Substances (RoHS) directives regulate the amount of these toxic metals in electrical and electronic equipment. This study is aimed at evaluating selected critical metals present in PWBs of three popular brands of discarded mobile phones used in Nigeria to understudy the behaviour of original equipment manufacturers (OEMs) regarding toxicity, economic potentials, and level of compliance with international initiatives by regulatory bodies to reduce the level of toxic metals in electronic equipment. PWBs obtained from 60 discarded mobile phones of 3 popular mobile phone brands used in Nigeria were chopped into smaller particles, extracted according to EPA 3050B method, and analysed using the Inductive Coupled Plasma-Optical Emission Spectrometry technique. It was observed that Mn, Fe, Zn, and Cu, had the highest concentration range across all brands studied. Notable toxic metals such as Pb, Cd, Cr, and As have mean and standard deviation values of 0.43±0.38 mg/kg, 0.62±0.160 mg/kg, 5.16±1.06 mg/kg, and 84.97±13.83 mg/kg respectively. Economic metals: Cu, Ag, and Au had mean and standard deviation values of 80.37±16.89 mg/kg, 2.12±0.43 mg/kg, and 0.95±0.19 mg/kg respectively. Results from the study indicate that PWBs of mobile phones are a perfect secondary source of a large variety of metals vital for the recycling industry. Also, the low levels of toxic metals suggest that some OEMs are already adopting the 'design-for-environment' option. Therefore, PWBs studied seem eco-friendly; however, need to be handled with care as there are still some toxic metals of concern not determined in this study.

Occurrence and Consumer Health Risk Assessment of Heavy Metals in Frozen Demersal Fish and Cephalopod Products from Benoa Port, Bali Province

Introduction: Heavy metal pollution has become an important environmental issue today. This study was aimed to identify the heavy metals of the two fishing products namely demersal fish and cephalopods landed at Benoa Port, Bali Province and their health risk effects on consumers. Methods: Demersal fish and cephalopod products were obtained from local fishermen at Benoa port. Atomic Absorption Spectrophotometry (AAS) was used to specify the (Pb, Cd, and Hg) in 34 fish fillet products weighing an average of 500 grams each. Statistical software was used to conduct an analysis of the collected data, while THQ, TTHQ, and TCR were calculated and compared with USEPA regulations. Results and Discussion: The results of this research showed that the content of heavy metals in demersal fish and cephalopod products was lower than the levels suggested by official agencies in a number of countries. In populations of various ages, the target Hazard Quotient (THQ) for the heavy metal was less than 1. At this point, the Total THQ result did not imply any risk to human health from ingestion of these two fishery products. When these two products were ingested, the target cancer risk (TCR) did not represent a cancer risk. Conclusion: The outcomes of this study showed that the bioaccumulation levels of both fishery products with low levels of heavy metals are safe for human consumption.

Green and sustainable practices for an energy plant cultivation on naturally contaminated versus spiked soils. The impact of ageing soil pollution in the circular economy framework

Silybum marianum L. Gaertn. or milk thistle is an energy-produced weed that has been shown to be tolerant of heavy metal-contaminated soils. In the present study, its cultivation was studied in soils laboratory-spiked (artificial) with Cu and Zn solutions. Meanwhile, plant growing on naturally contaminated soils of Mediterranean regions, both urban and rural, was investigated. The metal concentrations spiked in artificial polluted soils were estimated to be roughly equivalent to those in naturally contaminated soils. Plants grown in artificially contaminated soils incorporated the metal added to the soils more rapidly and in higher proportions. The contamination of soil samples was carried out using different chemical reagents, salts containing the metals with oxidation number II, highlighting the fact that the reagent containing the metal is crucial regarding artificial soil pollution. Statistically significant differences were observed between the individual pollution patterns, as far as plant metals uptake concern. It was also found that the aged, contaminated soils transfer lower levels of metals to the plants. Therefore, aging or weathering of contamination alters toxicity levels in the soil environment by determining transport and uptake into the soil-to-plant system. Eventually, from the present research, it emerged the fact that in urban soils that have aged perennial pollution, the uptake of metals by plants is probably lower than in rural ones. Furthermore, with proper management, it is possible to grow plants, with low nutrient requirements, in urban soils by adopting smart, green and eco-friendly techniques, enhancing sustainable cultivation in the framework of circular economy.

Urine manganese, cadmium, lead, arsenic, and selenium among autism spectrum disorder children in Kuala Lumpur.

The development of autism spectrum disorder (ASD) may stem from exposure to environmental pollutants such as heavy metals. The primary objective of this study is to determine the role of heavy metals of concern such as manganese (Mn), cadmium (Cd), lead (Pb), arsenic (As), and essential trace element selenium (Se) among ASD children in Kuala Lumpur, Malaysia. A total of 155 preschoolers in Kuala Lumpur between the ages 3 to 6 participated in an unmatched case-control study, comprising ASD children (n=81) recruited from an early intervention program for autism, and 74 children without autism who were recruited from public preschools. Urine samples were collected at home, delivered to the study site, and transported to the environmental lab within 24 hours. Inductively coupled plasma mass spectrometry (ICP-MS) was applied to measure the concentration of heavy metals in the samples. Data were analysed using bivariate statistical tests (Chi-square and T-test) and logistic regression models. This study demonstrated that Cd, Pb, and As urine levels were significantly greater in children without autism relative to those affected with ASD (p<0.05). No significant difference was in the levels of Se (p=0.659) and Mn (p=0.875) between children with ASD and the control group. The majority of children in both groups have urine As, Pb, and Cd values lower than 15.1 µg/dL, 1.0 µg/dL, and 1.0 µg/dL, respectively which are the minimal risk values for noncarcinogenic detrimental human health effect due to the heavy metal's exposure . Factors associated with having an ASD child included being a firstborn, male, and higher parental education levels (adjusted odds ratios (aOR) > 1, p<0.05). Preschoolers in this study demonstrated low levels of heavy metals in their urine samples, which was relatively lower in ASD children compared to the healthy matched controls. These findings may arise from the diminished capacity to excrete heavy metals, especially among ASD children, thereby causing further accumulation of heavy metals in the body. These findings, including the factors associated with having an ASD child, may be considered by healthcare professionals involved in child development care, for early ASD detection. Further assessment of heavy metals among ASD children in the country and interventional studies to develop effective methods of addressing exposure to heavy metals will be beneficial for future reference.

Estimation of Trace and Toxic Metals from Cannabis Sativa Plant in District, Kech Baluchistan, Pakistan

Background: Cannabis sativa, a plant indigenous to the Kech district in Baluchistan, Pakistan, is traditionally used for medicinal purposes. Understanding its trace and toxic metal content is crucial for evaluating its safety and therapeutic potential. Objective: The primary aim of this study is to estimate the levels of trace and toxic metals in various parts of Cannabis sativa plants grown in the Kech district and assess the potential health risks associated with their consumption. Methods: The leaves, stems, and roots of Cannabis sativa were analyzed for metals including Iron (Fe), Copper (Cu), Zinc (Zn), Potassium (K), Magnesium (Mg), Calcium (Ca), Sodium (Na), Cadmium (Cd), Lead (Pb), and Nickel (Co). Flame Atomic Absorption Spectroscopy was employed to quantify the metal content. Results: The plant exhibited high levels of Fe (20.34 ppm in leaves), Zn (24.14 ppm in leaves), Ca (9.29 ppm in leaves), Cu (14.40 ppm in leaves), K (10.56 ppm in leaves), Mg (13.47 ppm in leaves), and Na (12.25 ppm in leaves). Conversely, lower concentrations of Cd (0.65 ppm in leaves), Co (2.29 ppm in leaves), As (0.53 ppm in leaves), and Pb (1.60 ppm in leaves) were detected. The leaves contained higher concentrations of these metals compared to the stems and roots. Conclusion: The presence of beneficial trace metals like Fe, Cu, Zn, and Ca in significant amounts suggests Cannabis sativa's potential for treating diseases related to deficiencies of these metals. However, the low levels of toxic metals indicate minimal health risks, affirming its safety for medicinal use.

(Invited) Ru Selective Metal Deposition for Hybrid Metallization in Nano-Interconnect Applications

The connection of semiconductor devices happens through metal interconnects at the back end of line (BeOL) in integrated circuits. The BeOL consists of multiple metal levels that are vertically connected through small contact holes, or so-called vias. Especially at the lower metal levels, the vias are becoming much smaller in critical dimension, which increases their resistance significantly while more of these vias are needed to make the more complex connections in future device architectures. For these reasons, the vias resistance is becoming the dominating part of the total resistance of the stack and may become the limiting factor in keeping resistance-capacitance delay under control.In this work, the metal-on-metal area selective metal deposition is studied to make low resistive vias. The via is first prefilled with the Ru before performing the Cu metallization of the remainder of the vias and wires. Ru is chosen as the preferred metal [1] because it can be used without a metal barrier (it does not electromigrate) and this provides a large resistance benefit as compared to the Cu metallization which needs a TaN barrier combined with a Co liner. The combination of the different metals for the via (here Ru) and the metallization of wires (here Cu), is called a hybrid metallization scheme.We will discuss the challenges for the Ru selective deposition on the metal (growth area) towards different dielectrics as the non-growth area. The selectivity studies to optimize the Ru chemical vapour deposition (CVD) recipe and surface treatments are performed on blanket level (non-patterned wafers). A small molecule inhibitor dimethylamino-trimethylsilane (DMA-TMS) is used to passivate the dielectric surface which makes the dielectrics less reactive towards the Ru deposition improving thereby the selectivity of the CVD process (see also Fig.a).[2] We demonstrate that the growth rate and selectivity of Ru ASD depend on the CVD process conditions (type of co-reactant and process temperature) and the type of nanopattern (line spaces or via holes).[3]The most selective Ru process found with the line-space pattern (45/45nm line-space width) was also tested in nanoscale patterns with via holes of ~10.5nm.[4] It was found that the Ru growth rates in the patterned structures are enhanced as compared to the blanket substrates. The CVD Ru growth rates are ~ 1.3x higher in line-space nanopatterns as compared to flat metal substrates, and up to 3x higher in the small contact holes.[4] The growth enhancement of the CVD process is beneficial for the technological implementation of the process. The results show that the growth rate and the selectivity are different from the behavior on blankets and are also pattern dependent, which is consistent with a growth mechanism that is based on diffusion in addition to adsorption.[2] Therefore, the metal-on-metal selective deposition process may need to be optimized and adjusted to the patterned structure used in the interconnect application.[1] D. Gall et al, J. Appl. Phys. 2016, 119, p.085101.[2] F. Grillo and J. Soethoudt et al, Chem. Mater. 2020, 32, 22, 9560–9572.[3] A. Kumar Mandal et al, “Ruthenium Area-Selective Deposition for Nano-interconnect Structures: Process and nanopattern dependent selectivity and growth rate” Manuscript in submission 2023.[4] M.H. van der Veen et al, Proc. of the IITC 2021, S7-2.. Figure 1

Recent Developments in Low Temperature Wafer Level Metal Bonding for Heterogenous Integration

The low temperature metal bonding processes (<200°C) are attractive methods for novel applications in 3D packaging with simultaneous formation of electrical interconnections and hermetic encapsulation for microelectromechanical systems.Metal wafer bonding is a generic category of processes consisting of various sub-categories, each one defined by the different principles governing the process. One can differentiate between eutectic wafer bonding (a eutectic bonding layer is formed during process by liquid-solid interdiffusion), intermetallic bonding (an intermetallic alloy is formed as bonding layer during the process by solid-liquid interdiffusion, process known also as Solid Liquid Intermetallic Diffusion – SLID or Transient Liquid Phase – TLP), and metal thermo-compression (TC) wafer bonding.The bonding temperature range for the two types of processes showing liquid interface is relatively narrow (<10-20°C) while for metal TC the bonding temperature range is quite broad (~200°). This important parameter is differentiating the focus in studying the processes: for the low temperature eutectic and SLID/TLP the focus is primarily on the development of new materials systems and secondary on process optimization, while for metal TC the focus is equally shared between metal layers optimization (e.g. fabrication method, oxide management) and process optimization.The SLID bonding process studies were focusing on the Cu–In–Sn, Au–In and Bi–In material systems. It was demonstrated that electrical interconnections can be fabricated at bonding temperatures as low as 150°C by taking advantage of the Cu–In–Sn ternary system. The low processing temperatures allow for bonding of temperature sensitive materials and of materials with dissimilar thermo-mechanical properties by thermally induced stress management. Microstructural characterization confirmed the high bonding quality with low amount of defects in interconnections composed of a layered Cu / intermetallic / Cu structure, with a single-phase intermetallic Cu6(Sn,In)5 phase. Moreover, the mechanical testing shows that the bonds have tensile strength above 30 MPa.Au–In SLID bonding can be performed at temperatures slightly higher than the In melting temperature of 156°C. Successful bonds were demonstrated at 180°C. The resulting intermetallic bonding layer has a remelting temperature >450°C and a high shear strength above 30 MPa both at room temperature and 300°C.Another system studied was Au–In–Bi, utilizing the low eutectic point of In–Bi (72oC). Bonds at temperatures of 90 °C were proven. However, in order to consume the various In–Bi intermetallics with low melting temperatures (T< 110 oC), a bonding temperature higher than 110 oC should be used for a reliable result. We have demonstrated such SLID bonds at 115 oC, with a bond line consisting of Au / Au–In IMCs / Au, with Bi inclusions. All these materials have melting temperatures > 271 oC, with the bonding layer being stable at 450 oC if Bi does not form continuous structures.The study of metal TC bonding is reporting recent developments on the optimization of Cu-Cu and Al-Al wafer bonding. To decrease the bonding temperature of Cu-Cu TC bonding, Cu layers fabrication and oxide management are essential. By using certain surface pre-treatment methods such as plasma and self-assembled monolayer (SAM), Cu-Cu low temperature bonding was investigated. Various plasma concentrations were used to investigate the influence of plasma composition on bond strength.Further investigations were performed on the impact of different morphological Cu-properties and their effects on the bonding yield. The comparison of the interdiffusion behavior of layers deposited using different methods (e.g. physical vapor deposition - PVD Cu vs. electroplated - ECD Cu), as well as different surface preparation methods is being reported here. Different surface treatments like in-situ and ex-situ oxide management, as well as pre-bond CMP processes were tested in combination with the respective deposition methods. By combining the most effective sample and process parameters, the necessary bonding temperature for a successful Cu-Cu TC bonding could be reduced to temperatures of 175°C. The successful interdiffusion behavior at such low temperatures was confirmed by cross section TEM measurements.Apart from Cu, Aluminum is widely used material, due to its good electrical conductivity and compatibility with CMOS processes. Aluminum has a very stable native oxide and therefore high temperature and pressure are necessary to generate a successful Al-Al bond at wafer-level. The low temperature Al-Al TC bonding using a thin Palladium passivation layer at 350°C is reported here. The thermo-compression bonding was performed on both blank and patterned wafers.This work is reviewing recent achievements in the reduction of metal wafer bonding process temperature to less than 200°C based on the mechanical, structural and electrical characterization of the metal bonding layers.

Transcriptomic and behavioral analyses reveal unique target tissues and molecular pathways associated with embryonic exposure to low level glyphosate and metal mixtures in zebrafish

Investigation of developmental molecular events following exposure to environmentally relevant agrochemical mixtures is critical to predicting their potential long-term ecological and human health risks. Here, we sought to uncover transcriptomic changes during zebrafish (Danio rerio) embryonic development following exposure to glyphosate and co-exposure to metals. Glyphosate is widely used globally with an allowable drinking water limit of 700 ppb. We examined effects of glyphosate (10 ppb) alone and when co-exposed to a metal mixture containing low levels of arsenic (4 ppb), lead (5 ppb), cadmium (2 ppb), and vanadium (15 ppb). This mixture was derived based on behavioral and morphological toxicity findings and environmentally relevant concentrations found in agricultural regions where glyphosate and metals are ubiquitously present. Gene expression patterns coupled to a single-cell transcriptomic dataset revealed that developmental exposure (28–72 h post fertilization) to glyphosate dysregulates expression of developmental genes specific to the central nervous system. Subsequent studies indicated significant suppression of larval zebrafish movement with 10 ppb glyphosate exposure. Studies with glyphosate + metals mixture and metals mixture alone showed unique developmental transcriptomic patterns and behavioral changes compared to glyphosate exposure alone. However, some outcomes (e.g., changes in expression of genes involved in epigenetic regulation and extracellular matrix patterning) were common across all three exposures compared to the control. Notably, glyphosate + metals co-exposure distinctly suppresses lysosomal transcripts and targets renal developmental genes. While further studies are required to uncover the precise nature of the interactions between glyphosate and metals, our study shows that glyphosate at very low levels is a behavioral and neurotoxicant that changes when metals are present. Given this herbicide affects distinctive physiological processes, including renal development and lysosomal dysregulation when co-exposed with metals, we conclude that environmental cation levels should be considered in glyphosate toxicity and risk assessment.

PerPsych: An iPadOS-based open-source neuropsychological software for time perception assessment

Time perception is an important aspect of cognitive function that can be affected by mental illness and brain disease. Neuropsychological tests often assess time perception using computer displays, but smartphone or tablet software may offer some advantages. In this study, we present PerPsych, an open-source, iPadOS-based neuropsychological tool for testing time perception. PerPsych has the following features:•It is designed natively for iPadOS, using the low-level Metal interface to access the graphics processing unit for high-timing performance.•It allows researchers to conduct studies on time perception in individuals with cognitive impairment using a simple and user-friendly interface.•It supports various experimental paradigms and parameters for measuring time perception, such as duration estimation, production, and reproduction.