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6698e118c9c6a5c07a97d651 | 4 | These systems produce the calcium aluminosilicate (CAS) glasses. "The glass-forming region for calcium aluminosilicate glasses has been determined" by . However, "the formation mechanism and crystallization process of glass phases are still unclear" . In their work, "the glass phase and the crystallized samples of the CaO-SiO2-Al2O3 system were characterized using X-ray diffraction, optical microscopy, scanning electron microscopy, energy-dispersive spectroscopy and Raman spectroscopy. … The results showed that the chemical composition significantly influences the crystallization of the CaO-SiO2-Al2O3 glass" . Decreasing the basicity and the mass ratio of CaO and SiO2, is favoring the crystallization of the glass phase; increasing the content of Al2O3 is inhibiting the crystallization of the glass phase . Actually, "among the materials available, CaO-Al2O3-SiO2 (CAS) is a predominant ternary glass-ceramic system" with great potential applications , and references therein). |
6698e118c9c6a5c07a97d651 | 5 | "Raman scattering is a weak phenomenon and that is sometimes the reason for being unable to acquire a Raman spectrum, particularly at a low concentration or with a limited amount of sample. However, the most frequent reason for not being able to acquire a Raman spectrum is because a strong fluorescent background and the detector noise generated by it overwhelms the Raman signal. Therefore, it should be self-evident that a Raman spectrometer is ideal for performing laser-excited photoluminescence" . Absorbing a photon, an electron is promoted to an excited level of energy. It can decay emitting a photon. This "emission process is called photoluminescence", since "the excited state was reached through the absorption of a photon … Photoluminescence occurs in many bulk materials that are direct band gap semiconductors and also because of impurities that absorb and emit light in an otherwise transparent medium" . |
6698e118c9c6a5c07a97d651 | 6 | As told also by , "fluorescence or laser-excited luminescence has always been considered troublesome in Raman spectroscopy, since they easily mask the much weaker Raman signals and degrade the quality of the spectra. People have developed several strategies to eliminate the bad influence of fluorescence, … but it is still difficult to obtain pure Raman spectra without fluorescence interference in many cases" (see references in Yu et al.). For lanthanide materials, the situation becomes even worse because most of the lanthanide ions are luminescent and abundant luminescence bands are commonly seen in Raman spectra of them, which makes the interpretation of such spectra sometimes rather difficult. However, see this problem from a different view, fluorescence signals generated in Raman spectroscopy sometimes can also be helpful, since they may provide useful additional information of the material" . The previous research made by Yu and coworkers "indicates that Raman spectroscopy is ultrasensitive to lanthanide luminescence and thus can be utilized for detecting trace lanthanide impurities" . In the article by Yu and coworkers, we find the Raman spectra of rare earth sesquioxides RE2O3 (RE=Eu, Gd, Dy, Ho, Er, Tm, Yb, Lu, Sc and Y). |
6698e118c9c6a5c07a97d651 | 7 | For Raman spectroscopy in general, as observed by Sadagov et al., 2020, "increasing employment of Raman spectroscopy for the qualitative and quantitative analyses of substances and materials requires to record accurate and device-independent Raman spectra. … To ensure the independence of the Raman spectra on the hardware, it is necessary to solve the following two problems", which are regarding the "calibration of the Raman spectrometer with respect to the wavenumber scale" and the calibration "with respect to the shape of the spectra, i.e., with respect to the relative intensities of the Raman peaks" . For what is regarding the special glass compositions, "the following requirements are imposed" by NIST: "(a) sufficiently strong fluorescence under the influence of laser radiation that excites Raman scattering, which is capable of ensuring Stokes shifts in the wavenumber range from 200 to 4000 cm -1 ; (b) photostability; and (c) low absorption at the wavelength of exciting radiation, which is required to prevent heating caused by laser radiation" . Sadagov and coworkers studied the "fluorescence calibration standards based on phosphate matrix glass activated with ions of rare-earth metals". |
6698e118c9c6a5c07a97d651 | 8 | As previously told, here we will consider the RRUFF Raman data of REO glass standards, which are courtesy of Elizabeth Cairns, University of Edinburgh. We consider the broad scans from 0 to 6000 cm -1 . "The area from 0 to about 1600 cm -1 is the so-called Raman "fingerprint zone". The spectral pattern of this area reflects a fingerprint enabling the identification of a material, just as a fingerprint enables the identification of a person. This is also the area in which most Raman signals of inorganic solids occur". Usually, spectra are recorded "only across fingerprint zone, … Fingerprint spectra are also typically background corrected. This means any slope generated by luminescence has been subtracted from the spectrum. Background correction prepares the data for the computer to find the peak locations and match them against a library containing spectra of known materials" (GemmoRaman, 2012). "The extended area from 0 to about 3000-6000 cm -1 (depending on spectrometer) is called a broad scan area. Broad scan contains both Raman fingerprint zone and an extended range for photoluminescence studies. The line between the zones is not very distinct. Photoluminescence reactions do occur at both areas and sometimes mix with or overwhelm any Raman signals. … For gemology it is advisable to pay attention to luminescence as much as Raman signals, because it often contains important information about chromophores (such Cr) and rare earth elements (REE)" (GemmoRaman, 2012). |
6698e118c9c6a5c07a97d651 | 9 | Here in the following, the Raman broad scan is given with a baseline adjustment. The spectrum is decomposed by means of Fityk software, where q-BWF functions are defined (see Appendix for details). Fig. : Raman broad scan RRUFF Glass-(Ce) R110075 (green) decomposed in q-BWF functions (red curves). The sum of these components is given in yellow. In fact, green data and yellow line are practically undistinguishable. |
6698e118c9c6a5c07a97d651 | 10 | Fig. : Four q-BWF components of the spectrum and the values of their q and xi parameters. Note that when the parameter q is close to 1, to have asymmetry, we need to strongly increase the parameter xi. Note also the white dots, they are representing the "center" of the function. In the case of q-BWF, such as for BWF, the "center" does not coincide with the maximum of the component. |
6698e118c9c6a5c07a97d651 | 11 | From the Figure , we can see that the band between 1700 and 2800 cm -1 is made of functions which are not Gaussians, besides being asymmetric. Let us compare the decompositions of this band in the case that, for the decomposition of the total spectrum, q-BWF functions or Gaussians are used. The comparison is proposed in the Fig. . As in the case of the Figure , let us consider the parameters of the two central bands. The result is given in the following Figure . |
6698e118c9c6a5c07a97d651 | 12 | All the spectra seen before Fig. In the Figure , we show the spectra seen before, with relative intensities (largest value equal to 1). We can note the presence of three regular luminescence patterns in the Raman broad scans. We have the set of patterns for R110075 (Ce), R110080 (Gd), R110078 (Sm). The peaks as in the Figs. 2 and 5 remember the patterns of ice/water systems ). Then we have the single R110083 (Ho). The third set of patterns is that of R110079 (Eu), R110085 (Tm), R110087 (Lu). |
6698e118c9c6a5c07a97d651 | 13 | To understand R110079 (Eu), let us consider . The researchers studied Eu2O3 doped 5ZnO-20Nb2O5-75TeO2 glasses. In this case, "Raman spectra show that Eu2O3 dopant induces the changes in the local structure of glasses. The higher the dopant concentration, the larger the nonlinear refractive n2 and the faster the temporal response. The Figure , and their intensity increase with the increasing Eu2O3 concentration". In our Figure , the large peak is at about 2480 cm -1 . In the Figure by Zhao et al., we can see also a peak at 4532.5 cm -1 . In our Figure , the peak is at about 4582 cm -1 . |
6698e118c9c6a5c07a97d651 | 14 | In Yu et al., 2014, it is told that for Eu2O3, "since Eu 3+ can effectively be excited by 532 nm laser, the spectrum collected with 532 nm excitation presents strong intrinsic luminescence of Eu 3+ , which totally masks the lowwavenumber Raman bands. Based on the well investigated energy levels of Eu 3+ , the luminescence band at 2500 cm -1 can be assigned to 5 D0→ |
63a5c10816e9a8e1bb3299c9 | 0 | Plastic pollution has been a growing issue to everyone and everywhere worldwide. The incorrect disposal of these materials and the damage caused by the incorrect disposal of plastic waste and their persistence in the environment has become a significant concern in the 21 st century. Remediation of plastic pollution has mainly focused on the cleanup and recycling of macroplastics, plastic pieces bigger than 5 mm, while the removal and recycling of smaller plastic pieces has received less attention. These small plastic pieces or particles of various shapes and sizes between 1 μm-5mm in diameter are called microplastics (MPs). They occur everywhere in the environment including air, drinking water, food, soil, and ocean. While microplastics as small as 1.6 μm have been detected in ocean water their uneven shapes suggest that fragmentation to yet smaller plastic particles is happening in the environment. Microplastics suspension in the world's ocean account for a greater amount of plastic pollution than the larger plastic items of marine debris. Based on previous scientific studies the mass of microplastics in the ocean is larger than that of macroplastics. |
63a5c10816e9a8e1bb3299c9 | 1 | Primary microplastics are plastic particles that are manufactured at a size less than 5 mm. Some primary microplastics are intentionally designed as microbeads for use in cosmetics, such as exfoliating hand cleansers and facial scrubs. These are also used in cleaning agents because of their mild abrasive action. Microfibers from textile industry are another significant source of primary microplastics. They are defined as synthetic fibers of polyester, nylon, acrylic, and other synthetic textiles of diameter less than 10μm, approximately 1/100 th of the diameter of a human hair. Textiles release high levels of microfibers during manufacturing and wet processing stages like bleaching, dyeing, and finishing. Laundering of textiles is one of the major sources of microfiber release. This is due to the mechanical motion from the washing machine that causes the cloth to wear and release microfibers into the washing water. Secondary microplastics are formed from the breakdown of larger plastic particles. This type of microplastics are usually generated by chemical, physical, biological, thermal, photic, and other exposure of larger plastic debris. For example, small debris produced by the abrasion of vehicle tires on road surfaces are a major source of secondary microplastics. Other sources are particles released due to deterioration of paints, road markings, and marine coatings. Due to the variety of products that degrade into secondary microplastics their composition is highly variable. For example, polyester, acrylic, and polypropylene fibers are the major types of microplastic pollution generated by the textile industry in form of microfibers. Microplastics released from tire wear typically consist of natural rubber, styrenebutadiene rubber, polybutadiene rubber, and butyl rubber. Both types of microplastics can also contain chemical additives such as plasticizers, flame retardants, etc. For example, the plasticizer phthalate and flame retardant polybrominated biphenyls are common additives that can cause harmful biological effects such as carcinogenicity or disruption of the endocrine system. Humans are constantly inhaling and ingesting microplastics through air, water and food. The prevalence of microplastics in the environment is exponentially expanding not only to the ocean but also to freshwater sources, agricultural soil, and the air. These microplastic/microfibers enter the ocean from sewer discharges and wastewater treatment plants and are often mistaken for food by sea creatures. Through the food chain they can make their way into the human body. Microplastics have also been reported in other food and beverages such as table salt, honey, tea bags, and beer. One study estimated that an average adult is consuming 2000 microplastics per year just through the consumption of salt. Microplastics have also been found in drinking water. The average concentrations reported were 94 MPs/L for bottled water and 32 MPs/L for tap water. Regarding the size, it is reported that over 90% of the microplastics found in bottled water correspond to particles smaller than 5 μm, which are smaller than the mean 960 μm reported for tap water This demonstrates that water treatment plants are not completely effective in eliminating microplastics. The growing concern on how microplastics can affect all forms of life and ecosystems, as well as their consequences towards human health, has gathered a rising scientific interest. Using CAS comprehensive human-curated scientific data, this paper explores the research trends of this growing field via the analysis of academic and patent literature from 2011-2021 to understand the general progress of the field, as well as the classes of materials and concepts driving research and innovation. As a subject-matter expert curated database, the CAS Content Collection is utilized here for quantitative analysis of publications against variables including time, country/region, research area, and substance details. We hope that this paper serves as a broad, informative overview of the themes driving the scientific literature towards this potentially life altering issue. |
63a5c10816e9a8e1bb3299c9 | 2 | The search query (Microplastic? or micro-plastic?) limited to publications from 2010 to 2022 resulted in a total of 10,000 documents from the CAS Content Collection. Though the retrieval of documents was larger than that of previous bibliometric studies , the decision was made to broaden the search formula to include microfibers and nanoplastics, to focus on sustainability, environment and health, and to exclude results containing specific words that caused false positives. |
63a5c10816e9a8e1bb3299c9 | 3 | The final query used was: (((microfiber? or microplastic? or micro-plastic? or nanoplastic?) and (pollu? or sustainab? or contamin? or health or "synthetic polymeric fiber" or dyes or waste or "synthetic fiber" or "eco-friendly" or toxicity or environment? or ingestion or "fast fashion" or textile or ecosystem or vector or wastewater or soil or remed? or blood or feces or fecal or "human body" or inflamm? or microbi? or recycl? or aquatic or metal or inhal? or indoor or freshwater or circular or seawater or marine or bioaccumul?)) not (fragrance or inhibitor or sensor or cof or "covalent organic framework" or spinning or electrospinning or surgery) and 2010-2022/py). This resulted in 12,653 documents of different types. After screening for only Journal and Patent publications and for publications between 2011 and 2021 (data from 2022 was incomplete and so was excluded), the final pool of documents used for the analysis in this manuscript totaled to 9,403 (7,789 academic journals and 1614 patents). |
63a5c10816e9a8e1bb3299c9 | 4 | The topic of microplastics has experienced a drastic surge in scientific publications in the last decade. Academic publications on this topic have seen an exponential growth starting in 2015 (Fig. ). The number of publications went from 81 in 2011 to 2811 in 2021. Patent publications on the other hand have not experienced such drastic growth. One can still observe an increase from 104 publications in 2015 to 283 in 2020 that does follow the publication trend of journals, with a slight decrease in 2021 (Fig. and Supporting Fig. ). |
63a5c10816e9a8e1bb3299c9 | 5 | The US comes in the second place in both types of publications with Biomass Energy Enhancements LLC being its top patent assignee and North Carolina State University having the highest number of journal publications (Supporting Table ). Interestingly, though the US is in 2 nd place, unexpectedly it is the UK company GE Healthcare UK Limited and the German organization Carl Freudenberg KG that come in 4 th and 5 th place respectively in number of patent publications. |
63a5c10816e9a8e1bb3299c9 | 6 | Another key observation is that academic institutions dominate both journal and patent publication; this suggests that the methods to prevent or remediate microplastic pollution have not translated into commercial applications. It is not atypical for newer topics to be identified and thoroughly explored first by academic institutions and research groups before becoming an interest to the private sector. However, the lack of industrial publications may also indicate that there is not sufficient technical development, or economic incentive to address microplastic pollution. The CAS Content Collection also records the substances used in each individual document. With this information, we are able to obtain the top registered substances in microplastic research (Fig. ). It is of no surprise that the top 5 substances are ethene homopolymer (polyethylene), polystyrene, 1-propene homopolymer (polypropylene), polyethylene terephthalate (PET), and polyvinyl chloride (PVC). These correlate to the standard polymer composition of studied microplastics in the environment. Cellulose, as a biobased polymer, appears at high frequency in these documents, mostly due to being used as a replacement of synthetic polymers in applications such as electronics, composites, applications in the biomedical field, sustainable biomaterials, textiles, and to remove microplastics from the environment, etc. Cellulose is also considered a microplastic in some studies, especially modified or regenerated cellulose in the form of rayon or cellophane particles. |
63a5c10816e9a8e1bb3299c9 | 7 | Analysis of the substance class distribution of the total number of substances recorded per year reveals several research trends (Fig. ). The rise in the recorded number of polymers also demonstrates the increase interest in studying this phenomenon. More interesting is the rise of organic/inorganic small molecules from 2017 onwards, in part due to interest in identifying and measuring small molecules and monomers released during plastic degradation. A general look into academic publications also shows the growing concern of pollutants from the environment and chemical additives used in manufacturing seeping into living organisms from microplastics, among other things. The elements class has also increased significantly in 2020 and 2021. For example, carbon (specifically activated carbon) is being studied for water treatment and purification, including the removal of microplastics. Other examples for the appearance of elemental carbon in literature includes the activation of carbon metabolism due to presence of microplastics in plants, methodology development to exclude carbon particles (ex: carbon black) when measuring microplastics, and how microplastics can affect the carbon cycle. The development of carbon-based catalysts derived from microplastics is also discussed in academic literature. The elements class is also increased due to the identification of microplastics as vectors for elements like As, Cd, Cr, Cu, Pb, Mn and Zn via the heavy metal absorption of the different polymers that are the main components of microplastics. |
63a5c10816e9a8e1bb3299c9 | 8 | From this high-level conceptual analysis, we see three main clusters of research interest: the green, blue, and red clusters. The green microplastic cluster shows other names associated with microplastics (plastics, nanoplastics), which reflects on the research into the role they play in environmental pollution (water pollution, environmental pollutants), and on the health concerns these can create via consumption by humans and animals (risk assessment, Homo sapiens, toxicity, bioaccumulation, fish). |
63a5c10816e9a8e1bb3299c9 | 9 | The red polyester cluster focuses mostly on the types of polymers that compose microplastics, especially those associated with microfibers and the textile industry (textiles, polyurethane, rayon). It also demonstrates research interest related to modification of these polymers (polyamides, fluoropolymers), textile preparations (nonwoven fabric), and other mitigation efforts (filtration, extraction, sand) to prevent the release of microplastics into the environment. |
63a5c10816e9a8e1bb3299c9 | 10 | The blue cluster focuses mostly on the properties of these particles, specifically of microfibers, like surface structure, particle size, absorption, etc. There is also the appearance of a small lavender cluster that emphasizes the main location of this type of pollution (seawater, seawater pollution), the waste generated (waste polymeric materials), and water treatment (wastewater treatment). Lastly, there is a very small yellow cluster that shows other affected areas of MP pollution (soil, soil pollution), with connections to different types of bacteria. This reflects the effect of microplastics on bacteria and the accumulation of bacteria on the surface of microplastics. 51 The presence of microplastics is widespread; because of the facility of measurement, their occurrence in water has been more comprehensively studied than in solid matrixes, but their presence in soil and air is also substantiated. The oceans were estimated to contain 490,000 tons of plastic in 2010. In native sea water, 400 particles of microplastics were found per 1000 L of water, while the concentration in the North Pacific Subtropical Gyre (Garbage Patch) of microplastics is approximately 33 per 1000 L of water (or 250 mg microplastics/m 3 ). 15-31% of the microplastics in the oceans were estimated to be primary microplastics, with 35% of them being textile fibers, 28% tire wear particles, and 2% derived from cosmetics. The remaining 69-85% of the microplastics are thus secondary microplastics, derived from fragmentation of larger plastic pieces. In shallow ocean water, microplastics were predominantly polyethylene and polypropylene, while in deeper water microplastics containing polyesters and acrylates were the most prevalent. Drinking water obtained from faucets contained 5500 particles per 1000 L. Bottled water contained anywhere from 10-6300 particles/L, with water from glass and reusable plastic containing the most plastic and the number of particles found dependent on the size of particles interrogated. Surface water in Germany contained 7 particles per 1000 L, while the Los Angeles River contained 12,000 1-5 mm plastic particles per 1000 L. Solids, particularly soils, sediments, and sewage sludge, are another source of microplastic contamination. On a Brazilian beach, 50-300 particles were found per square meter. In sediments, 6-4300 particles/kg were found, including 81/kg in an Indian shipbreaking yard and 4300/kg in Tasmanian sediments. Sewage sludge from North America and Europe is estimated to contribute 700,000 tons of microplastic waste per year. Compost in Germany contained 900 particles/kg. Agricultural films are estimated to add 150,000 tons of plastic to soils in China per year. Shellfish and other water-borne organisms act both as sinks for microplastics and sources of microplastics for the environment and the humans and animals that may eat them. Mussels contained 0-4600 particles per kilogram of wet mass, with Chinese mussels containing larger counts of particles than European mussels. . 70-5800 microplastic particles per kilogram of wet mass were found in bivalves and 340-11,000 in clams. Lugworms contained 1200 particles per kilogram , and Scottish lobsters contained 280-680 g of microplastic per lobster. Salt, sea salt, and other foods contain microplastics; Mediterranean sea salt contained 37 g of microplastics per kilogram and sea salt contains 46-680 particles/kg (with the larger counts corresponding to smaller microplastic particles with diameters < 100 m). Finally, the air can transport microplastics as well. From samples of plastic debris from the oceans or marine sediments, the most prevalent polymers found were polyethylene (33%), polypropylene (27%), polystyrene (17%), polyesters (10%), poly(vinyl chloride) (2%), and poly(ethylene terephthalate) (1%). An important issue to note is that analytical methods for characterizing and counting microplastic particles are imprecise. Different methods are suitable for different types of polymers, and most cannot accommodate high-throughput methods, making determining their incidence in the environment onerous or impossible. In addition, nanometer-scale microplastic particles are harder yet to count and quantify, making the presence of microplastics in the environment and correlation of their presence to biological and health effects difficult if not impossible. |
63a5c10816e9a8e1bb3299c9 | 11 | Given the ubiquity of microplastics in the environment, how much microplastic do people and other living things take in? Microplastics can be taken into organisms or generated internally by ingestion, inhalation, or skin exposure; once inside an organism, microplastics can be taken into cells by translocation, or by endocytosis. Dosage data on microplastics is limited. Mussels, for example, may contribute up to 5 g of microplastics per week to the diet of each shellfish consumer, while 1800-10,000 plastic microparticles per person may be consumed with seafood annually. In a year, a consumer may take in 160,000-1,000,000 microplastic particles from tap water and 533 g of microplastics from salt; the particles are predominantly polyethylene, polypropylene, and poly(ethylene terephthalate). Overall, 39,000-52,000 microplastic particles a year were estimated to be consumed per person with food, both from the food itself and from particles deposited from the air onto plates and silverware. Another estimate was that an average person ingests 14-714 mg of microplastics per day. Through simulation, it has been estimated that about 100,000 microplastic particles per person could be inhaled annually. While their use has been banned in many countries, up to 2.4 mg/d of microplastic particles in soap may be taken in through the skin. The amount of microplastic present in the food we eat, the water we drink, and in the air we breathe is important for understanding how much microplastic we take in, but microplastics taken into an organism may not be retained and thus may not be present to exert their biological effects. Knowing how microplastics are taken into and retained by tissues is thus critical for assessing their impact on human health. Microplastic particle entry may occur directly from the gastrointestinal (GI) tract, by endocytosis either through the lungs (with 78-200 m particles) or through Peyer's patches in the GI tract (patches of lymphoid cells in the small intestine which mediate the development of immune responses to ingested proteins), by phagocytosis through the lungs (for 1-3 m particles), or by persorption (kneading particles through gaps between epithelial cells). In mice, 28-50% of the 100 nm poly(lactate-glycolate) particles administered were taken up by mice from oral administration, while 0.01-7.5% of 1 m and 10 m particles were internalized (primarily through the Peyer's patches in their intestinal tracts). The size, surface functionalization, charge, and protein adsorption to microplastic particles are important in how the particles are retained or eliminated by organisms. Microplastics may be removed from organisms by transfer to bile, urine, exhalations, cerebrospinal fluid, and breast milk. In mussels, 10 m polystyrene nanoparticles entered circulation from the gut. When 200 g of starch particles were given to people, the particles were observed in a variety of body fluids, but only 0.002% of the particles were found in blood after 24 h. As noted in mice, the bioavailability of microplastics likely depends strongly on particle size. Microplastics may be removed from organisms by transfer to bile, urine, exhalations, cerebrospinal fluid, and breast milk. In mussels, 10 m polystyrene nanoparticles entered circulation from the gut. In mice, 28-50% of the 100 nm poly(lactate-glycolate) particles administered were taken up by mice from oral administration, while 0.01-7.5% of 1 m and 10 m particles were internalized (primarily through the Peyer's patches in their intestinal tracts). When 200 g of starch particles were given to people, the particles were observed in a variety of body fluids, but only 0.002% of the particles were found in blood after 24 h. As noted in mice, the bioavailability of microplastics likely depends strongly on particle size. |
63a5c10816e9a8e1bb3299c9 | 12 | Health effects of microplastics have been determined for many species because there is concern both about their health and about the effects of microplastic on individual organisms and on ecosystems. The effects of microplastics on the health of a variety of single-cell and multi-cellular organisms [, sponges, water fleas, and daphnids, nematodes, sea urchins, oysters, clams, invertebrates (crabs, the crustacean Hyatella azteca, snails, lugworms, and fish zebrafish(Danio rerio)) , European perch, Japanese medaka (Oryzias latipes), goby (Pomaschistus microps), and European sea bass (Dicentrarchus labrax)] have been studied. Many effects were noted, including reduced feeding and photosynthesis, intestinal damage and inflammation, changes in oxidative stress and stress-related genes, reduced reproduction, changes in intestinal bacteria (the intestinal microbiome), and inhibition of acetylcholinesterase (AChE). |
63a5c10816e9a8e1bb3299c9 | 13 | Mice are a common model organism for evaluating the health effects of potentially toxic or harmful agents in humans, and thus the effect of microplastics on them has been analyzed. In pooled data with zebrafish, intestinal bacteria were significantly perturbed in the presence of microplastics; populations of Chlamydia, Proteobacteria, and Firmicutes in the GI tract increased while the population of Bacteroides in the GI tract decreased. 5 m polystyrene particles at 1 mg/L concentrations in mice decreased intestinal mucus, perturbed the intestinal microbiome, and perturbed their livers (with decreased liver weight and altered gene expression and metabolic enzymes amounts). With larger doses (15 and 20/mg/kg/d polystyrene, greater than estimates of human doses of 14-700 mg/d), oxidative stress, GI inflammation, decreased intestinal mucus, and liver toxicity were observed, though the larger doses may make the results less applicable at ordinary levels of consumption. In addition, changes in the uterus, fibrosis, and altered gender ratio and metabolism in children were observed, indicating that microplastics may exert estrogenic effects. In addition, thyroid disruption was also observed. AChE enzyme inhibition and alterations in its gene expression were noted as well. The internal wear of implants containing plastics has been a known source of microplastic deposition in people and in other mammals such as dogs. The particles induce fibrin deposition and necrosis in the nearby joint areas, while macrophages take up the polymer. Particles were found in the aorta of a dog who had received an implant eighteen months earlier, indicating that sufficiently small microplastic particles can be transported throughout the organism. Polyethylene particles formed by implant wear in humans were taken up by macrophages and suppressed their ability to clear bacterial infections. The effect of the particles depends on their composition. Researchers used a simulated multicompartment digestive tract with human intestinal bacteria to characterize the effect of PET microplastic particles on humans. At doses of 166 mg/d, degradation of the PET particles was observed, and the colonic bacteria in each compartment were altered distinctly. PET degradation and biological effects of microplastics on the human intestinal microbiome are thus reasonably expected. In ground glass nodules (GGN) (lesions in human lungs), cotton, rayon, and microplastic fibers (>20 m) were found in a larger fraction of the lesions than in lung tissue. The incidence of microplastic-containing GGN correlated positively to age and to the detection of cancer. The microfibers were more degraded in GGN than in lung tissue; rougher fibers may either be more toxic or immunogenic themselves or may release toxic chemicals into the surrounding tissue. Finally, a recent article studied microplastics found in the feces of people with inflammatory bowel disease (IBD) (either Crohn's disease or ulcerative colitis) and without IBD. While most of the microplastics found were > 300 m, more of the smaller particles (< 30 m) were found in people with IBD than in people without IBD, with PET, PVC, and polyamide particles the most prevalent. The number of particles found in feces correlated positively with the severity of IBD, likely due to increased leakage through the gastrointestinal tract linings of IBD patients. |
63a5c10816e9a8e1bb3299c9 | 14 | Perturbation of the intestinal microbiome is seen consistently as an effect of microplastic exposure. Bacteria such as Firmicutes and Bacteroides species can live on and colonize microplastic particles, but their numbers may not be increased in the intestinal tract. In a study using colonic bacterial samples from two people in an artificial colon with three compartments to mimic the ascending, transverse, and descending colon, significant perturbations in bacterial prevalence were observed upon dosage with high concentrations of MP. The bacterial species most affected by MP depended upon the colonic compartment, though the effect of MP on each bacterial species was consistent throughout the artificial colon. Chlamydia, Desulfobacterota, Cloacabacillus, Synergisteles, and Bilophila species increased. α-Proteobacteria increased in the human colon model and other species , but in other species, their levels were reduced. Similarly, Firmicutes species levels increased in the human colon model and decreased in other organisms. β-Proteobacteria and Parabacteroides decreased in the human model, and Bacteroides levels decreased both in the human colon model and in zebrafish and mice. In mice, Coprococcus and Anaeroplasma increased while many other bacterial levels decreased in the presence of MP; the expression of metabolic and amino acid genes was substantially altered from their expression in the absence of microplastics. Given the importance of the microbiome in human health, microplastics may thus be able to alter the metabolism of many organisms, including humans. One active question from microplastic exposure is whether microplastics can concentrate and/or transport toxic compounds, including additives in plastic manufacture such as phthalates, unreacted monomers, and flame retardants such as polybrominated diaryl ethers (PBDE), and persistent organic pollutants (POP) such as DDT, pharmaceutical agents, or metals released into the environment. In algae, microplastics and copper exerted cooperative toxicity; in daphnids, microfibers and phenanthrene also showed cooperative toxicity. In mussels, the combination of 2-6 m polystyrene particles and fluoranthene exhibited significant toxicity, with GI inflammation, hemocyte impairment, and increased oxidative stress enzymes. Though fluoranthene partitioned selectively into the microparticles over water or algae, it was not transported out of the mussels' GI tracts. When pyrene, polystyrene and polyethylene were administered to mussels, pyrene was found in the GI tract and gills, while DNA strand breaks were found in hemocytes. In lugworms, polychlorinated biphenyl (PCB)-contaminated sediment and polystyrene microplastics were co-administered; the microplastics reduced feeding and increased PCB concentrations in lugworms. Lugworms treated with 5% PVC microplastics in sand in combination with nonylphenol, Triclosan, or PBDE-47 showed reduced feeding or phagocytosis and increased oxidative stress than in the absence of the particles; the particles increased concentrations of the added substances, and with Triclosan, 55% of the lugworms died. Goby fish given 1-5 m polystyrene microparticles with pyrene showed an increase in bile metabolites, decreased lipid metabolism, and inhibition of AChE. Interestingly, the goby fish showed delayed pyrene-induced mortality. In European sea bass, combinations of microplastics and mercury were evaluated; while low concentrations of microplastics did little, high concentrations of microplastics with or without mercury altered lipid metabolism in muscle, and both high microplastic concentrations (without mercury) and low concentrations of microplastics with mercury inhibited AChE. Another potential hazard microplastic particles may present is the ability to carry bacteria and viruses. Plastics are known to harbor bacterial biofilms; an earlier document showed that small plastic pieces immersed in seawater accreted biofilms. Amaral-Zettler et al. characterized the bacteria which colonized microplastics and found that they differed significantly from the bacteria in the waters where the plastics were found; the microplastic colonies were less diverse than free colonies but were less dominated by single species than were free colonies. UV exposure and aging of plastics increased the accretion of bacteria, likely by altering the surface potential and charge. Dinoflagellates, photosynthetic bacteria, and Vibrio species (though V. pseudohaemolytica and not V. cholerae) were found on microplastics. A recent article found that the Escherichia coli phage T4 adhered to polystyrene microplastic particles; as with bacteria, the adherence depended on surface functionalization and potential and increased with aging. T4 phages on polystyrene microplastics survived better than in culture and retained their infectivity. While viruses have not been shown to be carried by microplastics in the environment, and the corresponding survival and infectivity of pathogenic viruses are not known, the article suggests that viruses may also be carried on microplastics. In addition, the permeability of the intestinal tract to microplastics suggests that if intestinal viruses and bacteria colonize microplastics, they may provide a vector for intestinal diseases and may enhance their severity. |
63a5c10816e9a8e1bb3299c9 | 15 | Overall, there are some conclusions that may be made. The biological activity of microplastics depends on particle size, with smaller particles evincing larger effects. Refinement of analytical tools to detect and quantify smaller microplastic particles (nanoplastics) is thus important to clarify the exposures and effects of microplastics. From known observations, however, microplastics are ubiquitous, with water, salt, foods, soil, and even the air containing them (beyond occupational exposure). The shapes and surface functionalization of particles are likely important in determining protein and bacterial binding to microplastics, their uptake, and their toxicities. The uptake of microplastics is not completely defined, but uptake of smaller microplastics through the skin and by ingestion appears to be higher than the uptake of larger microplastics, and the shape (particles versus fibers) of microplastics is also likely to alter their retention. Microplastics appear to cause inflammation (particularly gut inflammation), reduced intestinal mucus, and perturbation of the intestinal microbiome; because of their size, microplastics are treated as foreign bodies rather than being detoxified as a chemical agent. They also alter lipid metabolism and inhibit acetylcholinesterase. Microplastics may act as estrogenic agents, either directly or through additives or substances present in the plastic particles. |
63a5c10816e9a8e1bb3299c9 | 16 | The ability of microplastics to concentrate or transport chemicals into organisms is not well specified. Bouwemeester et al. noted that the possible dosage of chemicals delivered by the expected microparticle intake is small, though the marginal addition of any amount of chemicals by this route may still harm health. While microplastics are known to adsorb chemicals from a variety of matrixes, their ability to deliver them is not yet known. Multiple studies indicate that microplastics amplify the toxicity of chemicals, but the mechanism by which they do so is not yet known. Microplastics may alter the partitioning of chemicals between organisms and the environment, or between various organ systems. Alternatively, oxidative stress perturbations may alter how effectively organisms can detoxify substances which would prolong their residence times and thus increase their biological effects. Inflammation may also damage the gastrointestinal tract, altering digestive processes and increasing the permeability of the intestinal tract, permitting higher amounts of toxic substances to enter circulation and to cause systemic effects. All of these are likely to act cooperatively with toxic compounds to harm the health of ecosystems and organisms, including people. |
63a5c10816e9a8e1bb3299c9 | 17 | Overall, there are likely negative health effects from microplastics, but their magnitudes and causes are not clear. Better understanding of the presence and size distribution of microplastics is necessary to clarify their dosages and effects. It is likely, however, that microplastics are harmful and that reducing their occurrence in the environment and their intake into living things would be beneficial. |
63a5c10816e9a8e1bb3299c9 | 18 | Removal of microplastics from the ocean and freshwater ecosystems is much more feasible than from the land or the atmosphere. Fortunately, the former is also of the greatest significance, since the vast majority of microplastic particles and microfibers reside in aquatic ecosystems, where they are believed to pose the greatest threat to the well-being of humans and animals. |
63a5c10816e9a8e1bb3299c9 | 19 | Efforts to directly remove existing microplastics from the waters have been, however, very limited, as reflected in the extremely low quantity of related literature. This is not surprising considering the sheer volume of water in the sea (even coastal areas), making it unrealistic to install any dedicated apparatus for microplastics removal. Nevertheless, some innovative solutions utilizing watercrafts have been proposed. Wartsila Water & Waste from Finland and Grimaldi Group from Italy have collaborated to develop modified sulfur scrubber for cargo ships by adding a microplastics-capturing filter. Microplastic particles can thereby be collected while the ship travels in the ocean. The device is reportedly capable of removing 76 particles from every cubic meter of water. A similar technique was proposed by Suzuki, where a filter is placed in the cooling water return line of a boat's outboard engine to collect microplastic particles. Researchers have also taken advantage of ships' ballast water to remove microplastics. Backflushed water is filtered through devices attached to the ballast water treatment system during deballasting to remove microplastics from water discharged back to the sea. Similarly, Mitsui O.S.K Lines demonstrated a centrifugal filtration system installed on a cargo ship's ballast system. Since the device was connected to the cooling water line, it is operational throughout the entire trip, rather than just at deballasting sites. |
63a5c10816e9a8e1bb3299c9 | 20 | The Ocean Cleanup from Netherlands developed plastic waste collecting systems ("Interceptors") capable of floating on water surface and collecting plastic debris, and have deployed prototypes in rivers as well as oceans. The devices are, however, not specifically designed for microplastics, although they are claimed to be effective for microplastics smaller than 0.5 cm. |
63a5c10816e9a8e1bb3299c9 | 21 | Another potential removal method involves mussels. Researchers from Plymouth Marine Laboratory found that a particular species of mussels, when fed with microplastics along with algae, can turn microplastics into feces pellets that float to water surface and are easy to collect. In one experiment, 300 mussels filtered about 250,000 microplastic particles in an hour. Extra steps, e.g. using watercrafts, would still be needed to collect the feces pellets, although the technique was claimed to be potentially applicable also to wastewater treatment plants, etc. |
63a5c10816e9a8e1bb3299c9 | 22 | Still, removing existing microplastics directly from waters is very difficult and would require unrealistically large amounts of time and effort, and related research is very sparse. Furthermore, the research and development efforts bring in little financial return and must rely on sponsorship or donations. In comparison, capturing microplastics before they enter water ecosystems is far more feasible. The most widely used methods are wastewater treatment plants (WWTP), which have been studied in large numbers of publications. WWTPs were not originally designed to capture microplastics; the facilities purify sewage water via a variety of physical, chemical and biological processes before discharging it to water ecosystems. WWTPs treat wastewater in a series of stages, referred to preliminary/primary (skimming, sedimentation, etc.) secondary (coagulation, flocculation, etc.) and sometimes tertiary (dissolved air flotation, rapid sand filtration, membrane bioreactors, etc.) treatments. WWTPs, especially those carrying out tertiary treatments, are typically found to be quite effective at removing microplastics (90% and above). Still, research efforts in further improving removal efficiency are ongoing. 107 Also, the removed microplastics in WWTPs end up in sewage sludge and will eventually go into the environment again. Separation of microplastics from sludge is difficult, yet their utilization through pyrolysis into hydrocarbon fuels has been studied. To get insights on the research interest in microplastics removal, the same pool of publications obtained as described in the Methods section were analyzed. Figure shows the numbers of publications involving various keywords related to microplastics removal: coagulation, filtration, floatation, flocculation, membrane bioreactor (MBR), and wastewater treatment plants (WWTP). It can be seen that the publication volumes featuring most of the keywords grew significantly since the mid-2010s, a trend very similar to that observed in the overall publication volume (Figure ). This suggests that researchers in the corresponding fields reacted quickly to growing concerns in microplastics, with removal-related research efforts increasing at a pace similar to that of microplastics research in general. Of all the keywords in Figure , "filtration" produced the largest number of documents. However, it is worth noting that filtration may have been used in many microplastics studies unrelated to removal, so the publication volume shown here is likely higher than that for actual removal studies; the same may be true for "WWTP". The document counts for "coagulation", "floatation", and "flocculation" are low, reflecting less interest in these basic removal techniques (often used in primary and secondary treatments in WWTPs). "MBR", on the other hand, produced many more documents, almost equaling those for "WWTP", suggesting the popularity of this newer, highly efficient removal method, which has been frequently used for tertiary treatments in WWTPs. Since microfibers lost from synthetic textiles during laundry make up the majority of microplastics in sewage water, and comprise an estimated 35% of primary microplastics, efforts to reduce their release will go a long way toward microplastics mitigation. Microfibers shed from textiles made from natural fibers such as cotton are less of a concern as they are generally biodegradable. In-drum accessories capable of capturing microfibers during laundry, such as laundry bags and laundry balls, as well as filters to catch microfibers from the effluent, are commercially available to consumers. Also, studies on reducing microfiber loss by reducing friction or improving the mechanical integrity of garments have been reported. Microplastics-related regulatory activities have taken place in the past few years in countries including the US, China, Canada, and some EU countries. Most laws and regulations involve the banning or restriction of cosmetics and drugs containing plastic microbeads, which are intentionally added into the products to facilitate scrubbing or exfoliating. These primary plastic particles are designed to be eventually rinsed down the drain into domestic sewage, thereby entering water ecosystems. Banning of cosmetic microbeads is a critical and straightforward step toward microplastics mitigation, but far from sufficient, since they constitute a mere 2% of primary microplastics. 109 Regulations concerning synthetic microfibers, which make up 35% of primary microplastics, has been nonexistent except a law in France requiring microfiber filters to be installed in new washing machines by 2025. Regulations targeting particles generated from tire wear, another major contribution to primary microplastics, are also rare, although EU lawmakers are considering setting standards on tire abrasion and durability. A regulation recently proposed by the California Department of Toxic Substances Control will require tire makers to seek alternatives to 6PPD, a commonly used antioxidant found to be directly related to the death of spawning coho salmon. This, as well as another regulation targeting zinc compounds in tires that will likely be proposed in 2023, will undoubtedly be critical pioneering efforts to control tire particles, although they are triggered by concerns over additives rather than the polymer matrices. |
63a5c10816e9a8e1bb3299c9 | 23 | An estimated 70-80% of all microplastics found in the oceans are secondary microplastics, i.e. those that are generated from natural degradation of discarded larger plastic products. These pollutants form over time in the environment and would find their way into water ecosystems without going through wastewater treatment plants. Stopping them from entering the environment, by regulating the manufacturing, use, and recycling of plastic products, is therefore a critical aspect of microplastics control. The good news is that the plastics crisis had raised awareness among administrations long before the term "microplastics" was introduced, and governments around the world have started taking encouraging actions in the past few years, especially against single-use plastic products. For example, a directive banning the production of single-use plastics such as straws, plates and polystyrene food containers took effect in EU in July 2021. The directive also mandates producer responsibility, requiring producers of food containers and lightweight bags, etc. to cover costs of managing wastes. In the US, eight states have banned single-use plastic bags, and numerous cities and municipalities have banned products such as plastic straws and expanded polystyrene cups and containers. No federal-level regulation about plastic waste exists yet; however, the sale of single-use plastic products in national parks and other public lands will be banned by 2032. The Canadian government also passed a regulation prohibiting single-use items such as checkout bags, cutlery, stir sticks and straws, to meet its zero plastic waste target by 2030. 121 Some US states and EU countries have managed to reduce plastic bag use by charging fees. In Portugal, for example, supermarket consumers have had to pay 0.08 euros per bag since 2015. As a result, the use of plastic bags in stores and supermarkets dropped by 90% in just one year. As with other environmental endeavors, a major challenge of microplastics removal efforts is the lack of profitability or financial resources. Apart from the remote possibility of utilizing collected microplastics as fuel, projects focusing on removing existing microplastics bring zero financial return and cannot survive without investments or donations. Thus, although regulatory and tax actions aiming at reducing the use of plastics and microplastics are rapidly growing, government support on removing microplastic particles or intercepting them before they enter the environment would also be desirable. This may include more financial assistance, regulations, as well as continuous efforts to raise public awareness on microplastics' harmfulness so that consumers are more willing to pay more, for cleaner water originating from wastewater treatment plants with specialized microplastics-removing equipment, for clothing less prone to microfiber shedding, for washing machines generating and release less microfibers, for more durable tires that shed less particles, and so on. However, the combat against microplastic pollution will require long-term dedication and concerted efforts among scientists, entrepreneurs, governments, and the public. |
63a5c10816e9a8e1bb3299c9 | 24 | The presence of microplastics in the environment has increased significantly over the past twenty years, driving concerns on what effects the particles have on human and animal health and the environment. Journal and patent publications in the CAS Content Collection have increased significantly in that period; while both the number of publications and the rate of increase of journal publications has risen over the last twenty years, patent publications regarding microplastics peaked in 2020 and have decreased since. |
63a5c10816e9a8e1bb3299c9 | 25 | Microplastics have attracted little commercial interest; academic institutions dominate both journal and patent publications. The occurrence of microfibers and the toxicity of microplastics or their contaminants are important interests in microplastic publications. Microplastics are likely harmful in the environment, the magnitude of hazard is not clear. Toxic substances and microplastics likely have cooperative toxic effects, but it isn't known whether transport of toxic substances by microplastics the cause is. Better analytical methods to detect and quantify the presence of smaller microplastic particles is necessary to assess both the prevalence and effects of microplastics and the effectiveness of removal technologies. Methods for microplastic removal are focused on membrane-based removal efforts during wastewater treatment, though they will likely need to be optimized to be compatible with current wastewater treatment methods and with the recovery of other resources from wastewater. Financial benefits do not currently exist for microplastic removal technologies, and while removal of microplastics may be an effective remedy in certain circumstances, prevention of their formation and occurrence is more likely to decrease microplastic prevalence in the environment. Macroplastic pollution will likely need to be reduced to reduce microplastic pollution, and reduction of both will almost certainly require government incentives, regulations, and actions. As noted above, eliminating microplastic pollution will require collaboration between businesses, scientists, governments, and the public. |
67b7566ffa469535b92db0eb | 0 | Assisted reproductive technology (ART) encompasses a broad spectrum of medical techniques designed to aid individuals and couples in overcoming infertility challenges, enabling the conception of a child. As infertility affects approximately 10-15% of couples worldwide, ART is a critical component of modern healthcare. Since its start with the birth of the first in vitro fertilization (IVF) baby in 1978 , ART has evolved significantly, incorporating groundbreaking scientific and technological advancements. These developments have transformed the field of reproductive medicine, offering innovative solutions for diverse reproductive issues and expanding possibilities for parenthood. |
67b7566ffa469535b92db0eb | 1 | ART procedures typically involve the handling of eggs, sperm, and embryos to achieve fertilization and implantation. Techniques such as IVF and cryopreservation are now standard practices in fertility clinics worldwide. In recent years, emerging technologies like artificial intelligence (AI), genetic testing, and stem cell research have further refined ART, enhancing its success rates while addressing ethical and social implications. Furthermore, experimental innovations like in vitro gametogenesis (IVG) hold the promise of providing gametes for individuals who are unable to produce their own, potentially revolutionizing reproductive options for individuals with infertility. Noteworthy, ART is a rapidly advancing field, but the application of certain novel and emerging technologies in humans is still highly experimental, tightly regulated, and surrounded by various ethical and legal challenges. They rely heavily on animal models, which offer valuable insights into reproductive biology and the effects of various ART interventions. In this report, we explore data from the CAS Content Collection , the largest human-curated repository of scientific information, to outline the research progress in ART. We analyze the publication landscape to offer perspective into the latest advancements, to identify key emerging concepts and challenges associated with ART. We review the most discussed and emerging concepts and assess the strategies to improve ART. By exploring its scientific basis, clinical applications, and societal impact, the report aims to provide a comprehensive understanding of how ART continues to shape the future of reproductive healthcare. The merit of the article stems from the extensive, wide-ranging coverage of the most up-to-date scientific information, allowing extensive breadth of landscape analysis and in-depth insights. |
67b7566ffa469535b92db0eb | 2 | Our search in the CAS Content Collection for ART-related documents retrieved over 50,000 scientific publications (mostly journal articles and patents) for the period 2000-2024. The number of related documents has consistently grown over the last two decades, more than tripling in that time (Figure ). Reflecting the early success of in vitro fertilization, form the 1980 the number of ART-related research has exhibited exponential growth (Figure , inset). Figure summarizes the top patent offices with the most ART-associated patents. The World Intellectual Property Organization (WIPO) and the China patent office are the notable leaders. We surveyed the substance data extracted from the CAS REGISTRY 17 regarding the types of substance classes commonly associated with ART. Our analysis indicates that proteins/peptides/nucleic acids and small molecules are most commonly associated with ART (Figure ). In patents, proteins/peptides/nucleic acids represent ~60%, and in journals ~86% of publications. Small molecules are the second largest group, with 12% in journals and ~40% in patents (Figure ). |
67b7566ffa469535b92db0eb | 3 | Efforts to overcome infertility have a long history, from the first documented case of artificial insemination in 1790 by John Hunter in England , through the discovery of the hormonal control of ovulation that laid the groundwork for ovarian stimulation in ART , and the introduction of cryopreservation techniques for sperm in the 1950s, further with the development of in vitro techniques to study fertilization in mammals , as well as the research on ovarian stimulation and egg retrieval in the 1960s. The first pregnancy achieved through in vitro human fertilization of a human oocyte was reported in 1973 although it ended in miscarriage. It was not until 1978 that the first successful IVF pregnancy and live birth occurred , with the IVF becoming mainstream in the 1980s. Currently, the traditional methods of ART involve established and widely used techniques that have formed the foundation of infertility treatments (Figure ). These methods primarily focus on the manipulation of eggs, sperm, or embryos to enhance the chances of conception. |
67b7566ffa469535b92db0eb | 4 | In vitro fertilization (IVF) is the most well-known ART procedure. It involves is a process of fertilization, in which an egg is combined with sperm in vitro. IVF includes the steps of ovarian stimulation using fertility drugs to produce multiple eggs, retrieval of mature eggs through a minor surgical procedure, fertilization of eggs with sperm in a laboratory dish, and transfer of resulting embryos into the uterus. Currently fully integrated into clinical practice, it is successfully applied in tubal factor infertility, endometriosis, male factor infertility, and unexplained infertility. IVF is now a cornerstone of human fertility treatment, enabling millions of births worldwide. Success rates vary by age, with the highest success rates (30-40% per cycle) for women under 35. Rates decline significantly after age 40. Artificial insemination is a medical procedure in which sperm is introduced into a woman's reproductive tract to facilitate fertilization and pregnancy. A sperm sample is collected, washed and concentrated to isolate healthy sperm, then placed directly into the uterus (intrauterine insemination, IUI) or cervix (intracervical insemination, ICI) during ovulation. It is mainly applied in cases of mild male infertility, unexplained infertility, or cervical mucus issues. It is simpler and less invasive than IVF. Success rates are typically 10-20% per cycle, depending on factors like age and sperm quality. Gamete intrafallopian transfer (GIFT) is a procedure that helps women conceive by placing eggs and sperm directly into the fallopian tubes. Eggs and sperm are collected and mixed before being placed into the fallopian tube via laparoscopy, allowing fertilization to occur naturally in the body. Used when one fallopian tube is functioning and there are no significant sperm issues. Requires a surgical procedure and general anesthesia. In contrast to IVF, which places fertilized eggs directly into the uterus, the GIFT technique allowed the eggs to fertilize and develop in the fallopian tube, and then find their way to the uterus for implantation. It is less commonly used today due to advances in IVF. Zygote intrafallopian transfer (ZIFT) is similar to IVF, but the fertilized egg (zygote) is transferred into the fallopian tube instead of the uterus. It is applied for patients with infertility but healthy fallopian tubes. Allows the zygote to develop in the natural environment of the fallopian tube. Combines the benefits of IVF and GIFT, but is less common now. Cryopreservation (fertility preservation) involves freezing and storing reproductive cells, such as eggs, sperm, or embryos, for future use. Cryopreservation is now a routine procedure for embryos and sperm, and is becoming more common for oocytes. It is applied for fertility preservation, e.g., for cancer patients undergoing chemotherapy or radiation, with excess embryos from IVF, or delaying childbearing for personal or professional reasons. Vitrification (rapid freezing) has significantly improved outcomes compared to slow freezing. Success rates depend on the age at which eggs or sperm are frozen. Long-term storage costs can be significant. Egg donation and sperm donation can help people have children when they are not able to produce healthy eggs or sperm on their own. Eggs or sperm are donated by a third party and used in ART procedures like IVF or intrauterine insemination to achieve pregnancy. Applied for individuals unable to produce viable gametes, such as women with premature ovarian failure or poor egg quality or men with no viable sperm. Widely used by older women, same-sex couples, or single parents. Donors are screened for medical and genetic conditions. Legal and ethical issues around donor anonymity and parental rights vary by country. Surrogacy involves a woman carrying and giving birth to a child for another person or couple using their embryos (gestational surrogacy) or her own egg (traditional surrogacy). While in traditional surrogacy the surrogate's egg is fertilized with sperm (via IUI or IVF), making her the biological mother, in gestational surrogacy the surrogate carries an embryo created through IVF using the intended parents' or donors' eggs and sperm, so she has no genetic link to the child. Applied for individuals with uterine issues or medical conditions preventing pregnancy, also for same-sex male couples or single men. Surrogacy laws vary widely by country and region. Advantages of the traditional ART methods described above include: (i) proven track record including decades of successful use and refinement; (ii) customizationcan be tailored to specific infertility causes; (iii) wide availability, offered by most fertility clinics worldwide. Traditional ART methods remain the backbone of modern infertility treatment, with ongoing advancements improving success rates and patient experiences. Still, traditional ART methods, while groundbreaking and beneficial for many, do have some shortcomings such as high costs, emotional and physical stress, lower success rates with age, risk of multiple births, health risks including ovarian hyperstimulation syndrome, as well as certain ethical and legal Issues. |
67b7566ffa469535b92db0eb | 5 | For embryo selection, AI algorithms analyze embryo images to assess their quality and potential for successful implantation. These algorithms use: (i) time-lapse imaging: AI monitors embryo development over time, evaluating factors such as morphology, cell division patterns, and dynamics; (ii) morphokinetic data: algorithms predict the likelihood of an embryo developing into a viable pregnancy by identifying subtle features not visible to the human eye. AI also helps improve sperm selection by: (i) sperm motility analysis, identifying the most motile and morphologically normal sperm; (ii) DNA integrity checks, assessing DNA fragmentation levels in sperm to select the healthiest candidates. Machine learning models analyze multiple data points to predict the success rate of IVF, including patient history (age, hormonal levels, lifestyle factors), clinical data (ovarian reserve markers, endometrial receptivity), as well as embryo quality metrics. AI can optimize ovarian stimulation protocols by personalizing medication dosages based on patient-specific responses, and predicting ovarian response to stimulation, reducing the risk of ovarian hyperstimulation syndrome (OHSS). AI-driven automation streamlines processes in ART labs, including monitoring and controlling incubator conditions, standardizing embryo grading to minimize human error, and managing cryopreservation protocols. AI leverages large datasets from clinics and research studies to identify trends and factors influencing ART success and improve treatment protocols by recognizing patterns in patient and embryo data. |
67b7566ffa469535b92db0eb | 6 | IVG represents a groundbreaking advancement in the field of ART offering new possibilities for addressing infertility, understanding human reproduction, and exploring genetic disorders. IVG is an experimental technology that enables the creation of sperm or eggs from somatic cells, such as skin or blood cells. IVG involves the differentiation of pluripotent stem cells (PSCs), such as embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs), into gametes. This process mimics the natural progression of gametogenesis, where primordial germ cells develop into mature gametes through intricate molecular and cellular pathways. Researchers have successfully produced functional gametes in animal models, such as mice, leading to healthy offspring. In 2024, scientists at Kyoto University created precursors to human gametes from induced pluripotent stem cells (iPSCs). While IVG has been successfully demonstrated in animal models, translating these techniques to human systems remains a work in progress due to the complexity of human gametogenesis and important ethical concerns. Potential uses of IVG include: providing gametes for individuals unable to produce viable eggs or sperm; enabling same-sex couples to have genetically related children; as well as addressing infertility due to age or medical conditions. IVG can be used to study early embryonic development and genetic diseases in controlled environments. There are ethical concerns regarding embryo creation and manipulation -it might lead to ethical dilemmas about creating and discarding large numbers of embryos, etc. Safety and efficacy need extensive validation before clinical application. One of the primary safety concern regarding germline editing is the lack of sufficient data on long-term consequences and potential off-target effects. There is a growing emphasis on involving the public in discussions about the ethical, legal, and social implications of genetic material editing. |
67b7566ffa469535b92db0eb | 7 | Stem cell-based therapies have emerged as a promising avenue in the ART, leveraging the regenerative and differentiation potential of stem cells to enhance reproductive outcomes. It is paving the way for advanced reproductive treatments. The application of stem cell-based therapies in ART relies on their ability to: (i) differentiate into reproductive cell typesfor example, inducing embryonic stem cells or induced pluripotent stem cells to form oocytes or sperm; (ii) secrete growth factorsstem cells release paracrine signals that enhance tissue repair and cellular function; (iii) integrate into host tissuestransplanted stem cells can integrate into reproductive tissues, contributing to structural and functional recovery. |
67b7566ffa469535b92db0eb | 8 | In the context of ART, stem cells hold potential in several key areas: Age-related decline in ovarian reserve is a major cause of infertility. Mesenchymal stem cells and bone marrow-derived stem cells have shown promise in regenerating ovarian tissue, improving folliculogenesis, and restoring hormonal balance. Stem cell transplantation has demonstrated potential in restoring spermatogenesis in individuals with azoospermia or other forms of male infertility. Spermatogonial stem cells (SSCs) can be harvested, cultured, and reintroduced into the testes to reinitiate sperm production. Conditions such as Asherman's syndrome and thin endometrium pose significant challenges for successful implantation. Endometrial stem cells (ESCs) and MSCs have been explored to regenerate and enhance endometrial receptivity. |
67b7566ffa469535b92db0eb | 9 | One of the most significant trends in ART is the integration of advanced genetic screening techniques. Preimplantation genetic testing (PGT) has become increasingly sophisticated, allowing for the detection of chromosomal abnormalities and single-gene disorders in embryos before implantation. PGT-A (aneuploidy screening) technique screens for chromosomal abnormalities, which are a leading cause of implantation failure and miscarriage. Advances in nextgeneration sequencing (NGS) have improved the accuracy and efficiency of PGT-A, leading to higher success rates in IVF cycles. PGT-M (monogenic disorders) is used to identify embryos carrying specific genetic mutations, enabling couples with hereditary conditions to have healthy offspring. The development of CRISPR-Cas9 and other gene-editing tools has further enhanced the potential for correcting genetic defects at the embryonic stage. PGT-SR (structural rearrangements) form of testing is designed for individuals with chromosomal translocations or inversions, helping to identify embryos with balanced chromosomal structures. These advancements not only improve the likelihood of a successful pregnancy but also reduce the risk of passing on genetic disorders, offering a more personalized approach to reproductive medicine. |
67b7566ffa469535b92db0eb | 10 | With advancements in genetic technologies, particularly gene editing, the landscape of ART is evolving to address not only infertility but also the prevention of genetic diseases. Gene editing in ART holds the promise of reducing heritable disorders, improving embryo selection, and enhancing reproductive success rates. It allows precise editing of genes in embryos, eggs, or sperm. The CRISPR-Cas9 system is the most prominent tool in gene editing , enabling precise modifications in the genome. By targeting specific DNA sequences, CRISPR-Cas9 can add, delete, or alter genes, making it a valuable technology in addressing inherited genetic disorders in embryos created via in vitro fertilization (IVF). Gene editing can correct mutations in embryos associated with hereditary diseases such as cystic fibrosis, sickle cell anemia, and Huntington's disease, preventing their transmission to future generations. Another line of application of gene editing in ART is for enhancement of embryo selectiongenetic screening combined with editing can improve embryo quality by selecting embryos with the highest potential for successful implantation and development. Gene editing can help also addressing infertilityit may help identify and correct genetic causes of infertility, such as chromosomal abnormalities or mutations affecting gamete function. |
67b7566ffa469535b92db0eb | 11 | The technique is controversial due to the potential for "designer babies" and unintended consequences. Moreover, editing one gene could have unforeseen effects on other genes or biological processes, potentially causing harm. Currently gene editing is banned for reproductive purposes in many countries. Research is ongoing, but clinical use for reproductive purposes remains highly regulated. One of the major safety concern regarding gene editing is the lack of sufficient data on long-term consequences and possible off-target effects. Unintended mutations could have serious consequences for individuals and future generations making it crucial to fully understand the potential long-term effects before clinical application. Even highly precise gene editing tools like CRISPR can sometimes make edits at unintended locations in the genome ("off-target effects"), which could lead to unforeseen health complications. Regulatory agencies are increasingly engaging with the scientific community to establish frameworks for the safe and ethical use of gene-editing technologies. There is a rising urgency on involving the public in debates regarding the ethical, legal, and social implications of gene editing. |
67b7566ffa469535b92db0eb | 12 | Mitochondrial replacement therapy (MRT), also known as mitochondrial donation, is a technique that aims to prevent the transmission of mitochondrial DNA (mtDNA) disorders from mother to child. This involves replacing defective mitochondria in an egg or embryo with healthy mitochondria from a donor, preventing mitochondrial diseases in offspring. Thus, MRT has been used to create embryos with genetic material from three individuals: the mother, the father, and a mitochondrial donor (so called "three-parent babies"). MRT raises ethical concerns related to genetic modification and the long-term effects on future generations. MRT is particularly beneficial for women with mitochondrial disorders who wish to have genetically related children. The technology is currently regulated differently across countries, with some permitting its use under strict guidelines and others banning it outright. Gene editing and MRT technologies are compared in Table . Intracytoplasmic sperm injection (ICSI) is an ART procedure that involves injecting live sperm directly into the cytoplasm of a mature egg using a micromanipulation tool. The fertilized egg is then cultured and transferred as in IVF It represents a refinement of IVF and is the most common and successful treatment for male infertility caused by sperm issues, such as low sperm count, poor motility, or abnormal morphology, or when previous IVF attempts have failed. Success rates are similar to IVF, but ICSI can significantly improve fertilization rates in cases of male infertility. 107 |
67b7566ffa469535b92db0eb | 13 | Improved embryo culture systems: There are many ways to improve embryo culture systems in ART. These include new culture platform design creating better microenvironment for embryos, new media formulations including antioxidants to reduce oxidative damage and improve blastocyst development, perfusion-based systems using dynamic media flow instead of static culture. Advances in time-lapse imaging and monitoring 108, 109 , and optimized culture media 110 allow continuous monitoring of embryo development, enabling better selection for transfer and increasing implantation rates. |
67b7566ffa469535b92db0eb | 14 | Next-generation sequencing (NGS) is a genomic testing technology that is used in ART to screen embryos for genetic defects. Preimplantation genetic testing (PGT) using NGS helps identify genetic abnormalities in embryos. It can identify euploidy, aneuploidy, and chromosomal mosaicism. Using PGT enhances the likelihood of healthy pregnancies while minimizing the risk of genetic disorders. Cryopreservation enhancements: Cryopreservation techniques in ART have improved in several ways, including vitrification -a rapid freezing process that prevents ice crystal formation, improving survival rates of frozen gametes and embryos, coupled with improved and optimized cryoprotectants, vapor tanks storing tissue in the vapor phase of nitrogen instead of immersing it in liquid nitrogen, offering better survival rates for frozen eggs, sperm, and embryos, increasing ART success rates. Fertility preservation innovations: Techniques such as ovarian tissue cryopreservation and artificial ovary development are advancing, benefiting individuals facing fertilityimpacting medical treatments. Ovarian rejuvenation technique is used to stimulate the ovaries to produce new eggs, particularly in women with diminished ovarian reserve or premature ovarian failure. It may include injecting platelet-rich plasma (PRP) into the ovaries to stimulate tissue repair and egg production, or stem cells to regenerate ovarian tissue. The technique is still experimental, with mixed results in early studies. |
67b7566ffa469535b92db0eb | 15 | Non-invasive and automated technologies: (i) Time-lapse imaging -continuous monitoring of embryos without the need for manual handling improves embryo selection and reduces stress on the embryos; (ii) Automated IVF systems: robotics and automation are being integrated into laboratories to improve the efficiency and consistency of processes like fertilization and embryo transfer; (iii) Non-invasive genetic testing: techniques to assess the genetic health of embryos using culture media, rather than invasive biopsy, are being developed to minimize risks. Artificial wombs: Research into ectogenesis, or artificial womb technology, aims to support the development of embryos outside the human body. Such technology is providing solutions for individuals unable to carry pregnancies due to medical or anatomical reasons, and advancing neonatal care by supporting extremely premature infants. 121, 122 |
67b7566ffa469535b92db0eb | 16 | AI is being used to enhance embryo selection and optimize culture conditions, leading to improved success rates. Machine learning helps identify patterns in embryo development and patient responses, enabling more personalized treatment plans. Indeed, notable improvements were observed in the accuracy of diagnosing and predicting successful outcomes in fertility treatments. AI-driven models provided more precise forecasts of the optimal timing for clinical interventions such as egg retrieval and embryo transfer, which are critical to the success of ART cycles. In vitro gametogenesis offers several potential advantages, including: enabling reproduction for individuals with impaired fertility due to lack of functional sperm or eggs, allowing same-sex couples to have genetically related offspring, providing greater control over genetic selection through embryo screening, and potentially reducing the physical burden on women by eliminating the need for ovarian stimulation during egg retrieval; however, this technology is still in early stages and raises ethical concerns regarding genetic manipulation and potential misuse. IVG has shown promise in animal models, including creating offspring with biological contributions from same-sex parents. |
67b7566ffa469535b92db0eb | 17 | Stem cell-based therapies in ART offer potential advantages like improving ovarian reserve function, stimulating follicle development, repairing damaged reproductive tissues, and potentially generating new germ cells, potentially providing hope for individuals struggling with infertility due to conditions like premature ovarian failure or low sperm count, by leveraging the unique ability of stem cells to proliferate and differentiate into specialized cell types. They represent a cutting-edge approach to address infertility and enhance reproductive health. These therapies leverage the regenerative potential of stem cells to create gametes, repair reproductive tissues, and improve ART outcomes. Gene therapies in ART offer the potential to prevent genetic diseases in future generations by allowing for the identification and correction of genetic mutations in embryos, potentially leading to healthier babies with a reduced risk of inheriting genetic disorders, while also providing more options for couples facing infertility due to genetic issues; however, ethical concerns and the need for further research remain significant challenges. Although in early stages, gene editing is being explored to address infertility caused by genetic mutations. This could also potentially correct genetic issues in embryos before implantation. Currently, gene editing in humans, particularly germline editing (which affects eggs, sperm, or embryos and can be passed on to future generations), is heavily restricted or banned in many countries due to ethical, safety, and societal concerns. Indeed, changes made to germline cells are heritable, meaning they affect future generations. This raises ethical questions about consent, as future generations cannot consent to these modifications. There are fears that gene editing could be used for non-therapeutic enhancements (e.g., selecting for intelligence, appearance, or athletic ability), leading to societal inequality and eugenics-like practices. Also, some groups argue that altering human DNA is "playing God" or interferes with natural processes. There are also safety concerns that current gene-editing technologies, like CRISPR-Cas9, are not 100% precise and can cause unintended mutations, which could lead to cancer or other health issues. Editing one gene could have unforeseen effects on other genes or biological processes, potentially causing harm. Furthermore, there is no global agreement on how gene editing should be regulated, leading to a patchwork of laws and guidelines. Access to gene-editing technologies could exacerbate existing inequalities, with only wealthy individuals or countries benefiting. |
67b7566ffa469535b92db0eb | 18 | The ban on germline editing in humans remains largely in place globally, with most countries prioritizing caution and ethical considerations. However, the rapid pace of technological advancement and the potential for misuse have highlighted the need for stronger international cooperation and oversight. While somatic cell editing continues to advance and show promise for treating diseases, the debate over germline editing is far from settled, with ongoing discussions about its ethical, social, and scientific implications. |
67b7566ffa469535b92db0eb | 19 | ART in animals has been applied (i) in agriculture and livestock production, to improve genetic traits, such as milk yield, growth rate, and disease resistance, enhancing productivity and sustainability in livestock industries; (ii) in conservation biology, to address challenges in endangered species conservation by preserving genetic material, supporting captive breeding, and combating inbreeding depression; (iii) cross-species surrogacy has emerged as a strategy to sustain populations of species with critically low numbers. It has been applied also in companion animal breeding, to supports breeding programs for pets, particularly for rare or exotic species, ensuring genetic health and diversity. |
67b7566ffa469535b92db0eb | 20 | The development and optimization of the assisted reproductive technologies rely heavily on animal models, which offer valuable insights into reproductive biology and the effects of various ART interventions. Animal models are indispensable in ART research due to their biological and physiological similarities to humans and their role in studying species-specific reproductive processes. Moreover, animal models provide a controlled environment to study the mechanisms of reproduction, test new technologies, and assess the safety and efficacy of ART interventions. Thus, animals enable repeated experiments, ensuring consistent data collection; animal research minimizes direct experimentation on humans in the initial stages of ART development; certain animal species closely resemble human reproductive physiology, making them ideal for translational research; models help optimize ART for wildlife and livestock with unique reproductive traits. Furthermore, animal models allow for iterative refinement of techniques, provide insights into developmental biology and long-term effects, and enable high throughput testing of interventions. The development and application of ART in humans and model animals follow parallel tracks, with most techniques undergoing extensive testing in animals before being adapted for human use. |
67b7566ffa469535b92db0eb | 21 | Common animal models in ART research include: (i) rodents (mice and rats)due to their short reproductive cycles, ease of genetic manipulation, and low cost; (ii) livestock (cattle, sheep, and goats) -contributing to both agricultural efficiency and wildlife conservation by adapting techniques for endangered species; (iii) non-human primates -the closest models to humans in reproductive biology; (iv) zebrafish -a unique model for early embryogenesis due to their external fertilization and transparent embryos; and (v) wildlife models -supporting global conservation efforts by enhancing genetic diversity and population recovery. Techniques applied to animal models vs. humans are compared in Table . |
67b7566ffa469535b92db0eb | 22 | Although the application of particular ART in humans is still highly experimental, tightly regulated, and surrounded by ethical and legal challenges, certain ART methods are already widely available. While established techniques such as in vitro fertilization (IVF), cryopreservation, egg and sperm donation, and surrogacy are widely used to address infertility and help individuals or couples conceive, emerging technologies are expanding the boundaries of what is possible. Some examples include: (i) time-lapse imaging -advanced embryo monitoring systems improving the selection of viable embryos for transfer; (ii) preimplantation genetic testing screening embryos for chromosomal abnormalities or inherited conditions, reducing the risk of miscarriage and genetic disorders; (iii) in-vitro maturation enables immature eggs to mature outside the body, providing an alternative for patients who cannot undergo traditional stimulation protocols; (iv) laser-assisted hatching technique helps embryos implant by softening the protective shell (zona pellucida), which can sometimes hinder implantation in older women or those using frozen embryos; (v) AI is enhancing embryo selection, predicting treatment outcomes, and customizing patient protocols; machine learning models analyze patient data to predict the probability of successful pregnancy, tailoring treatment protocols accordingly. Success rates for ART vary based on factors like age, the cause of infertility, and the type of procedure. Advanced techniques like genetic testing and AI are helping to improve outcomes. Notable recent patents ART-related patents in CAS Content Collection grow not only in numbers but also in formulation and methodology diversity. Summarized in Table are notable recent patents related to ART, illustrating their diversity. |
67b7566ffa469535b92db0eb | 23 | While ART hold immense promise, they come with certain challenges and ethical concerns. Ensuring the health of both parents and offspring is paramount. Therefore, safety and efficacy need extensive validation before clinical application. Embryo-related ethics: Creating more embryos than needed raises concerns about what happens to unused embryos. Some view the disposal of embryos as ethically problematic, particularly in cultures or religions that ascribe moral status to embryos. Preimplantation genetic testing allows the selection of embryos free from genetic disorders but raises concerns about eugenics and the potential for "designer babies". |
67b7566ffa469535b92db0eb | 24 | Parental and child rights: Use of donors (egg, sperm) and surrogates introduces legal and emotional complexities regarding parental rights and the child's right to know their genetic origins. Using gametes or embryos from deceased individuals raises questions about consent and the welfare of the resulting child. Societal biases and legal hurdles may affect the access of same-sex couples or single individuals to ART. Genetic and technological ethics: Technologies like CRISPR used in ART raise concerns about unintended consequences, heritable changes, and societal implications of altering human genetics. The creation of gametes from stem cells and the development of artificial wombs challenge traditional views of reproduction and may blur ethical boundaries. |
67b7566ffa469535b92db0eb | 25 | Social and cultural implications: ART commercialization may lead to exploitation, particularly of egg donors and surrogates, in countries with less regulatory oversight. ART can reinforce inequalities, as wealthier individuals have greater access to advanced treatments. Widespread use of ART could influence societal norms regarding family size, age of parenting, and population demographics. |
67b7566ffa469535b92db0eb | 26 | Legal and regulatory issues: ART practices and laws vary widely across countries, leading to ethical inconsistencies. People traveling to countries with more lenient ART laws may exploit loopholes, complicating ethical oversight and enforcement. Use of AI and genetic data in ART raises concerns about patient confidentiality and potential misuse of sensitive information. |
67b7566ffa469535b92db0eb | 27 | The World Health Organization (WHO) has called for a global registry of human gene-editing research and stricter oversight. The UNESCO International Bioethics Committee has recommended a moratorium on germline editing. In the United States germline editing is not explicitly banned but is heavily restricted. Federal funds cannot be used for germline editing research, and the FDA is prohibited from approving clinical trials involving heritable genetic modifications. Many European countries have laws prohibiting germline editing. The Oviedo Convention explicitly bans heritable genome editing. In China, after the controversial case of He Jiankui (who created the first gene-edited babies in 2018), China introduced stricter regulations and penalties for unauthorized gene-editing experiments. The UK allows gene editing in embryos for research purposes but prohibits implantation of edited embryos. In 2023, the UK approved CRISPR-based therapies for treating blood disorders like sickle cell anemia and beta-thalassemia, marking a significant step forward for somatic gene editing. The International Summit on Human Genome Editing continues to debate the ethical and scientific implications of germline editing, with many experts calling for a cautious approach. Australia maintains a ban on germline editing, with strict penalties for violations. However, in 2023, the Australian government began reviewing its gene-editing laws to potentially allow somatic cell editing for therapeutic purposes. 167 |
67b7566ffa469535b92db0eb | 28 | ART is rapidly evolving, with research focused on improving safety, success rates, and accessibility. Future trends involve: (i) tailoring treatments to individual genetic profiles through personalized medicine approach; (ii) improving embryo selection and predicting outcomes via AI integration and automation; (iii) expanded accessibility by developing lower-cost methods to reach underserved populations; as well as (iv) exploring the long-term health of ART-conceived children and refining techniques like artificial gametes. |
67b7566ffa469535b92db0eb | 29 | Emerging technologies in ART are pushing the boundaries of reproductive medicine, offering hope to individuals facing infertility while raising profound ethical and societal questions. From AI-driven embryo selection to in vitro gametogenesis and gene editing, these advancements promise to redefine parenthood. However, translating these innovations into clinical practice requires careful consideration of safety, accessibility, and ethical implications to ensure equitable and responsible use. Once an ART innovation proves successful in animal models, it progresses to clinical trials in humans, beginning with small, carefully monitored studies. Innovations like time-lapse imaging, laser-assisted hatching, and AI-driven embryo selection have all transitioned from theory or animal-based research to human use after rigorous validation. |
6263af30bdc9c2a677dfcd74 | 0 | Precise assembly of molecular chromophores assisted by proteins as scaffolds plays an important role in natural light-harvesting complexes in photosynthetic organisms such as plants and bacteria. Specifically, the intricate supramolecular organization of chromophores (e.g. chlorophyll dyes) on protein scaffolds leads to shift of light absorption to longer wavelengths, a characteristic phenomenon of J-aggregation, and promotes the efficient energy transfer at different size and time scales. Such J-aggregation has also been observed in a series of synthetic molecular chromophores, such as amphiphilic cyanine dyes in aqueous solution, as well as derivatives of perylene bisimides, porphyrins, 8, 9 chlorophylls, phthalocyanines, BODYPI, squaraines, and hydroazaacene dicarboximide . In addition, J-aggregates were also observed in the self-assembly of synthetic bacteriochlorins attached to peptides as a type of biohybrid light-harvesting systems. We have previously reported the aggregation behavior in a coilplate-coil molecule of pyrrolopyrrole cyanine (PPcy) derivative in the co-precipitation with a polymeric surfactant in a mixture of tetrahydrofuran and water. The flash precipitation of PPcy in water resulted in the formation of both H-and J-aggregates together with some monomers. Nevertheless, the effects of chemical structures and molecular weights of synthetic polymers as scaffolds on Jaggregation coupling of molecular chromophores remain poorly understood. Studies to address these issues are important to realize a rational molecular design of synthetic chromophore/polymer complexes for applications such as artificial photosynthesis and biomedical applications. |
6263af30bdc9c2a677dfcd74 | 1 | Herein, we report a series of polyester-tethered molecular chromophores by controllable polymerization from the two ends of a pyrrolopyrrole cyanine (PPcy) derivative as the initiator (Scheme 1, S1a). The chemical structures and chain-lengths of the polyesters play a critical role in fine-tuning the excitonic coupling among PPcy chromophores within colloidal nanoparticles in water. Moreover, we present a new type of thermo-switchable near-infrared (NIR) emission caused by the reversible transformation between monomeric (M) and J-aggregate states of the fluorophores. We further demonstrate the potential of these thermosensitive materials for applications such as tumor imaging and the high efficiency of phototherapy. |
6263af30bdc9c2a677dfcd74 | 2 | We first synthesized a series of polymers (denoted as PPCx, where x represents the number-average degree of polymerization of PCL on each side) by grafting biodegradable polycaprolactone (PCL) from a hydroxyl-bearing PPcy initiator (P0) via ring-opening polymerization (Scheme S1). The resulting polymers were characterized by nuclear magnetic resonance (NMR) spectroscopy (Figure ), gel permeation chromatography (GPC) and differential scanning calorimetry (DSC) (Figure & S4). As the number-average degree of polymerization (x) increased from 5 to 20, the melting temperature (Tm) of PPC polymers gradually rose from 30.5 to 44.3 o C. Tm remained nearly constant at 54.8 o C in the PPC25-179, which was close to that of blank PCL37 (51.8 o C) without PPcy units (Figure ). Colloidal nanoparticles (NPs) composed of these PPCx (1 mg/mL) were prepared in aqueous media by the typical nanoprecipitation method using PCL37-b-POEGMA60 as a surfactant. The average diameter of these NPs is approximately 45~65 nm, as measured by dynamic light scattering (DLS) and transmission electron microscopy (TEM) (Figure ). |
6263af30bdc9c2a677dfcd74 | 3 | The optical properties of the PPCx NPs were then characterized. First, the UV-VIS-NIR absorption spectrum of PPC5 NPs exhibit an intense and sharp J-aggregation band (denoted as J-band) with a maximum absorption wavelength (λmax,abs) of 788 nm and a full width of half maximum (FWHM) of 46 nm (Figure ). The steady-state fluorescence (FL) emission spectrum of PPC5 J-aggregate showed a monomodal peak at 810 nm (λmax,em) and a FWHM of 35 nm, and a FL quantum yield (Φ) (0.65%) 6.5-fold higher than that of the NPs composed of physically blended hydroxyl-bearing PPcy initiator (P0) and PCL (Figure & S2, Table ). With the increase of the numberaverage degree of polymerization (x) from 5 to 25, the J-band in the absorption spectra was gradually attenuated, accompanied with the enhanced absorbance of monomeric PPcy (M-band, Figure ). In the FL emission spectra, an approximate 10 nm blue shift of λmax,em was observed with the increase of x from 5 to 20. |
6263af30bdc9c2a677dfcd74 | 4 | Meanwhile, compared to the relatively low Φ (0.65%) of PPC5, Φ of PPC10, PPC15 and PPC20 were improved to 3.8% ~ 4.6% (Table ). The FL quantum yield is further improved to 8% for PPC79 NPs and 24% for PPC194 NPs. Such enhancement of Φ with an increase of PCL chain length could be attributed to the suppression of homo resonance energy transfer (HRET) due to the increased distance among J-aggregates. This hypothesis was further confirmed by the dynamic fluorescence results (Figure ), where FL lifetime of PPC5 (0.50 ns) is significantly shorter than those of PPC10~25 (1.14~1.94 ns, λem = 800 nm). Moreover, the FL lifetime of PPC79 (0.77 ns, λem = 760 nm) is much shorter than that of PPC194 (2.05 ns, λem = 760 nm), while the excitation wavelength was maintained as same as 635 nm. (Table ) The lifetimes of PPC5 and PPD2 NPs (where PCL is replaced with polydecalactone for PPD2) were measured to be 0.50 and 0.59 ns, respectively, which were lower than those of other PPCx NPs (Figure ). PPC25 also showed a dominant J-resonance emission despite only a small proportion of J-aggregates in the NPs, which could be attributed to the intra-particle Fӧrster resonance energy transfer (FRET) from monomeric state to J-aggregates. At x = 79 and 194, the J-band completely disappeared and the M-band turned dominant in the absorption spectra. The fluorescence images acquired by In Vivo Imaging System (IVIS) clearly show the strongest fluorescence of PPC5-25 NPs at 820 nm, compared to the brightest emission of PPC79-194 NPs at 760 nm (Figure ). A systematic summary of the optical properties of all the PPCx NPs is presented in Table . |
6263af30bdc9c2a677dfcd74 | 5 | To confirm the important role of the covalent bonding between PCL and PPcy in the precipitation-induced J-aggregation, we conducted a control experiment by encapsulating physically blended P0 and PCL37 with PCL37-b-POEGMA60 into NPs in water. The feed ratio between P0 and PCL37 is approximately 1:3.3 (by mass), consistent with the theoretical molecular weight ratio between P0 and PCL block in PPC20. A typical absorption feature of the dimeric and monomeric state of PPcy and a blueish green color of dispersion were observed. In contrast to PPC5 NPs, the NPs composed of P0 physically blended with blank PCL37 displayed the typical H-aggregate and monomeric bands (denoted as H-and M-band, respectively) with λmax,abs at 688 and 748 nm, respectively (Figure ), and weak fluorescence (Figure ). These results suggest that the covalent bonding between PPcy and PCL is crucial in the formation of J-aggregates in the colloidal NPs. |
6263af30bdc9c2a677dfcd74 | 6 | To investigate the influence of the polymer structure on the optical properties of tethered PPcy, we synthesized another group of polyesters, denoted as PPLz (z represents the degree of polymerization of PLLA on each side of PPcy), by grafting poly (L-lactic acid) (PLLA) from P0 via a similar synthetic scheme of ring-opening polymerization (ROP) (Scheme S1). In contrast to the J-band as observed in PPCx NPs, characteristic H-band appeared in the absorption spectra of PPLz NPs (Figure ). These H-aggregate NPs showed weak to none fluorescence, a typical feature of Haggregation. With the decrease of z from 22 to 10, the absorbance of H-band was gradually enhanced. Similar feature of the absorption spectrum can be observed in an amorphous isomer of PPL10, i.e. poly(D,L-lactic acid) (denoted as PP(DL)L10) (Figure ). While the ARTICLE Please do not adjust margins Please do not adjust margins a Fluorescence decays at 760 nm or 800 nm upon the laser excitation of 635 nm. b Fluorescence quantum yields (Φ) of NPs solution were measured by the standard method using PPcy in chloroform (Φ = 0.69, which was determined by using indocyanine green (ICG) as the standard. mechanism of the different aggregate structures favorable for PPC and PPL remains unclear and warrants further study, it was also observed in some donor-acceptor merocyanine dyes that subtle change of the substituent groups resulted in dramatically different aggregating states (i.e. H-and J-aggregates) in spin-coated thin films on quartz substrates. We were curious whether the formation of J-aggregation of fluorophores for PPC is due to the semicrystalline behavior of PCL. To verify the hypothesis, the amorphous biodegradable polymer polydecalactone (PDL) was chosen to replace PCL to afford PPDy. Due to the limited reactivity of ɛ-decalactone (DL) in ROP, only PPD2 and PPD6 with low degree of polymerization of PDL were obtained. One can see that both PPD2 and PPD6 NPs showed sharp J-bands in their absorption spectra (Figure ). Interestingly, the absorption spectrum of PPD6 NPs with an intense J-band at 785 nm and a shoulder peak at 735 nm is quite similar to that of PPC15, although the chain length of PDL in PPD6 is almost 3-fold shorter than that of PCL in PPC15. These results suggest that PDL with amorphous nature can also induce the J-aggregation of PPcy fluorophores. |
6263af30bdc9c2a677dfcd74 | 7 | To explore the effect of different surfactants on PPcy aggregation, we used PEG45-b-PCL105, PEG114-b-PCL53, and PEG66-b-PLA43, in comparison with POEGMA60-b-PCL37, to encapsulate PPC20 aggregates in water. The results are presented in Figure . One can see that, with the same load (50% by weight) of PPC20, the dispersions stabilized with PEG114-b-PCL53 or POEGMA60-b-PCL37 remained transparent, in contrast to the obvious turbidity of the dispersions stabilized with PEG45-b-PCL105 or PEG66-b-PLA43, respectively. The dispersions remained turbid for the latter two surfactants even when the load of PPC20 decreased to 33% by weight (Figure ). Such turbidity is also reflected from the light scattering effect in the low-wavelength region of the UV-VIS-NIR absorption spectra. These results suggest the larger loading |
6263af30bdc9c2a677dfcd74 | 8 | To characterize the thermoresponsive properties of the NPs as described above, we first applied thermal treatment to PPC15 NPs which were heated from 25 o C. Upon heating, the intensity of the Jabsorption band at 789 nm decreased until disappearance at 55 o C, accompanied by the enhanced absorbance of the M-band at 740 nm (Figure ). After cooling down and maintaining at 25 o C for 30 min, the J-absorption band was recovered nearly completely (Figure ). The continuous attenuation of J-band with gradual increase of temperature (Figure & 4h) can be attributed to the heatinginduced decrease of Flory-Huggins interaction parameter χ, i.e. the incompatibility between PCL and chromophore. In addition, the increased vibrational and/or translational mobility of both fluorophores and polymers upon heating may also facilitate the dissociation of J-aggregates and even order-to-disorder transition within NPs. We further measured the absorption spectra over 5 heating-cooling cycles and found similarly periodic variations of the absorbance at 677, 740 and 789 nm, respectively, indicating the good reversibility of J-to-M transition (Figure ). |
6263af30bdc9c2a677dfcd74 | 9 | Moreover, little change of the average diameter (56 nm) of NPs (Figure ) was observed by DLS after the heating process, suggesting good colloidal stability and integrity of the NPs. In the emission spectra of PPC15 NPs at 55 o C, the fluorescence (FL) intensity at 806 nm became 10-fold lower than the initial FL intensity at 25 o C. Notably, a full recovery of FL intensity was also observed after cooling down, further supported by the IVIS images (Figure ). The dramatic attenuation of emission at 55 o C may be due to the reabsorption phenomena of monomers confined in NPs. Similar phenomenon of enhanced FL intensity was also observed in Jaggregates of other molecular fluorophores, 4 resembling nature's strategy of circumventing concentration quenching in photosynthetic light-harvesting systems. Please do not adjust margins Please do not adjust margins |
6263af30bdc9c2a677dfcd74 | 10 | We observed similar reversibility in the thermally induced J-to-M transformation for PPC25, PPC20, PPC10 and PPD6 NPs (Figure & Figure ). Nevertheless, the critical annealing temperature (Tc) required to complete the J-to-M transition is higher for the PPCx NPs with shorter PCL chains. Specifically, Tc of PPC25, PPC20, PPC15 and PPC10 NPs increases in the order of 45, 53, 55, 65 o C, respectively. In addition, the J-band of PPC5 NPs remains stable even at 70 o C (Figure ). Similarly, no spectral change was observed for PPD2 NPs and NPs composed of P0/PCL37 physical blend when being heated up to 70 o C (Figure ). Moreover, some extent of H-to-M transformation was observed for PPL10 NPs upon heating at 70 o C (Figure ). Nevertheless, PPL10 NPs remained almost nonfluorescent before and after heating. These results indicate that both the composition and the chain length of the tethering polymers could affect the phase temperature of the NPs, which was further studied by X-ray scattering spectroscopy in the following section. |
6263af30bdc9c2a677dfcd74 | 11 | To investigate the relationship between the optical properties and the phase separation of PPCx in solid states, we prepared thin films by drop-casting polymer solution (1 mg/mL in tetrahydrofuran) on glass substrates, followed by drying of the films under ambient condition. First, J-band was observed in the absorption spectra of PPC15 film. At 70 o C, J-band disappeared completely (Figure ). Subsequent cooling down to 25 o C enabled recovery of the J-band. The IVIS images of PPC15 films showed the highest FL intensity at 820 nm (Figure ). At 70 o C, the strongest FL was observed at 780 nm. With temperature decreased to 25 o C, the maximal FL intensity was observed at 820 nm again (Figure ). |
6263af30bdc9c2a677dfcd74 | 12 | Figure shows the patterns of small-angle x-ray scattering (SAXS) from PPCx films at room temperature. The SAXS profile of PPC5 film at 25 o C shows multiple sharp peaks in the region of q = 0.05-0.40 Å -1 (Figure ). The scattering pattern most resembles that of multiple continuous cubic phases as revealed in the phase separation of BAB-type block copolymers. The SAXS profiles of both PPC10 and PPC15 films show three diffraction peaks at q = 0.15, 0.23 and 0.26 Å - 1 with a characteristic ratio of 1: √2: √3 (Figure & S15a), suggesting presence of body-centered cubic (BCC) phase separation. In contrast to PPC5, PPC10 and PPC15, the SAXS diffraction patterns of PPC25, PPC79, and PPC194 all appear similar to that of blank PCL. (Figure ) The disappearance of the diffraction peaks at q = 0.15, 0.23 and 0.26 Å -1 when x 25 suggests the domination of PCL phase and minimal phase separation between PPcy and PCL. These SAXS results suggest that shorter chain length of PCL leads to enhanced phase separation between PCL and PPcy in PPCx films. |
6263af30bdc9c2a677dfcd74 | 13 | Figure shows the wide-angle x-ray scattering (WAXS) profiles of PPCx in comparison to blank PCL37 films at room temperature. One can see multiple diffraction peaks with maximal scattering intensities at q = 1.52 and 1.68 Å -1 , indexed as ( ) and ( ) intrinsic to a orthorhombic phase of crystalline PCL, in blank PCL37 and all the PPCx films except x = 5 or 10. The WAXS profile of PPC10 films shows obvious reduced intensities of the characteristic diffraction peaks of PCL, and emergence of two relatively broad peaks around q = 0.8 and 3.6 Å -1 , respectively. Nevertheless, these two peaks, together with other characteristic peaks of crystalline PCL, all disappear in the WAXS profile of PPC5 films, with only a broad halo remaining in the region of q = 1.0-4.0 Å -1 . |
6263af30bdc9c2a677dfcd74 | 14 | We further monitored the evolution of phase transition of PPC15, PPC10, and PPC5 films by both SAXS and WAXS in situ during the heating-cooling process. Figure shows the SAXS pattern of PPC15 film in a heating-cooling cycle from 30 to 55 o C and backwards. Figure shows little change of diffraction peaks at q = 0.15, 0.23 and 0.26 Å -1 during the increase of the temperature from 30 to 50 ℃. But all the three peaks disappeared when the film was heated to 55 o C. After being cooled down to 30 o C, the SAXS pattern recovered. |
6263af30bdc9c2a677dfcd74 | 15 | Compared to PPC15, PPC10 film exhibited a similar temperaturedependent variation in SAXS profiles (Figure ), but slightly higher thermal stability of the phase separation. The SAXS patterns, corresponding to BCC phase, of PPC10 film at 45 and 55 o C are essentially similar to that at 30 o C. The three diffraction peaks at q = 0.15,0.23 and 0.26 Å -1 disappeared after the film was further heated to 65 o C. (Figure ) The WAXS profiles of PPC10 films at different temperatures (Figure ) show that the intensity of the multiple scattering spikes corresponding to lamellae of crystalline PCL became obviously weaker at 45 o C and completely disappeared at 55 and 65 o C at which the polymer completely melted. |
6263af30bdc9c2a677dfcd74 | 16 | Considering the relatively high fluorescence quantum yields (Table ) at the same mass concentration (1 mg/mL), we chose PPC15 and PPC20 NPs to evaluate their performance for fluorescence imaging in Please do not adjust margins Please do not adjust margins vivo (Figure ). Both of two NPs showed low cytotoxicity (Figure ) and excellent blood compatibility in vitro (Figure ). For fluorescence imaging in vivo, an aliquot of PPC15 and PPC20 NPs with a dose of 25 μg/g was intravenously injected via tail vein to a mouse bearing a xenografted tumour model of 4T1 or HepG2. |
6263af30bdc9c2a677dfcd74 | 17 | The fluorescence intensity of mice injected with PPC15 or PPC20 NPs displayed similar evolution within 12 hours. (Figure ). After 12 hours of administration, the ex vivo imaging results showed that the dependence of the mean fluorescence intensity at different band-pass wavelengths at tumors and livers was consistent with the fluorescence spectra of both NPs in water, suggesting the presence of J-aggregation in both PPC15 and PPC20 NPs under the physiological condition of mice in vivo (Figure & S9m, Figure ). |
6263af30bdc9c2a677dfcd74 | 18 | Additionally, no noticeable histopathological abnormalities were found in livers, kidneys and spleens (Figure ). To assess the pharmacokinetics of PPC15 and PPC20 NPs, the same dose of NPs was injected into mice, from which the blood samples were collected and imaged at serval time points (Figure ). Blood circulation half-time of PPC15 and PPC20 NPs were both 4.5 hours. |
6263af30bdc9c2a677dfcd74 | 19 | Due to the relatively weak fluorescence and high fraction of PPcy, PPD2 and PPC5 NPs are more suitable for photoacoustic (PA) imaging and photothermal therapy (Figure , S27 & S28). The photothermal efficiency of PPC10, PPC5 and PPD2 NPs was examined by NIR laser irradiation at 808 nm with a power density of 2 W/cm 2 for 15 min. The temperature of PPD2 NPs (0.1 mg/mL) increased to 60 o C and maintained constant. In contrast to the photothermal behavior of PPD2 NPs, the temperature of PPC5 and PPC10 NPs slightly decreased after reach of the maximum (53.4 and 50.8 o C, respectively), which could be due to the photothermally reduced absorbance at 808 nm of PPC5 and PPC10 NPs (Figure ). |
6263af30bdc9c2a677dfcd74 | 20 | We further characterized the temperature-dependence of the PA spectra of PPC10, PPC15, and PPD2 NPs as temperature-responsive PA probes for potential bioimaging applications (Figure ). The PA spectrum of PPC15 NPs shows two peaks at 710 and 770 nm, corresponding to monomeric and J-aggregate states, respectively (Figure ). Upon heating at 45 o C for 10 mins, the intensity of the PA signal at 770 nm decreased by 3.5-fold due to the disappearance of J-band. Similar results were obtained with PPC10 NPs. In contrast, PPD2 NPs exhibit no change in PA signal upon heating under the Given the fact that the photoacoustic contrast of chromophores is proportional to their photothermal conversion efficiency, PPD2 NPs, due to their relatively high photothermal conversion efficiency as described above, were chosen for in vivo photoacoustic imaging of tumor models under pulsed laser excitation at 770 nm. The PA intensity at 770 nm at tumor site was monitored at different time points after administration of PPD2 NPs (Figure ). A weak PA signal in the tumor region was observed at 0 h (i.e., immediately after the tail-vein injection of the NPs) and enhanced obviously at 12 h, indicating that NPs gradually accumulated in the tumor (Figure ). |
6263af30bdc9c2a677dfcd74 | 21 | For the photothermal therapy of the tumor model (HepG2), an 808-nm laser with a power density of 2 W/cm 2 was used to irradiate the tumors in xenografted tumor-bearing mice once at 12 h after tailvein injection (dose of 6.7 μg/g) of the NPs. The status of the tumor after the laser irradiation was monitored by IVIS imaging system every two days (up to 10 days). Immediately after the laser irradiation for 10 min, some parts of the tumor in the PPD2-treated mice turned dark brown. Interestingly, the fluorescence of the PPD2 NPs disappeared in the tumor region after the laser irradiation. After 2 days, the tumor region developed eschars and turned black in the whole tumour region (Figure ). No obvious change was observed after 4 days, except for some slight recovery of the fluorescence in the tumour region. Some shrinkage of the tumor was observed after 8 days and 10 days, respectively. Similar results, except for some recurrence of the tumor of some mice, were observed in the group Please do not adjust margins Please do not adjust margins of mice treated with PPC5 NPs and the laser irradiation under the same condition as described above. (Figure ) The comparison suggests that the phototherapeutic effect of PPC5 NPs is not as good as that of PPD2 ones, which is consistent with the superior photothermal effect of the latter as shown in Figure . In contrast to the obvious phototherapeutic effect of PPD2 and PPC5 NPs, the control group of mice treated with PBS and the laser irradiation under the same condition did not show any phototherapeutic effect at all, and obvious growth of the tumor was observed over 10 days (Figure ). In addition, negligible changes were observed in the time dependence of body weight of mice (Figure ), suggesting the good biocompatibility of these NPs. |
6263af30bdc9c2a677dfcd74 | 22 | We have presented synthesis, optical properties and biomedical applications of a series of polyester-tethered fluorophores of pyrrolopyrrole cyanine (PPcy) derivatives and their colloidal nanoparticles dispersed in water. We found that both the chemical composition and chain length of polyesters affect the intermolecular aggregation among PPcy fluorophores and the optical properties of the nanoparticles. Relatively short chains of polycaprolactone or polydecalactone tethered from PPcy promote the formation of Jaggregates when co-precipitating in water in the presence of amphiphilic block copolymers (e.g., PCL37-b-POEGMA60) as the stabilizer. Such J-aggregation could be precisely tuned by variation of the polymer chain lengths. In contrast, non-fluorescent Haggregation was observed in poly(lactide)-tethered PPcy while the other conditions were kept similar to those PPcy tethered by polycaprolactone. Both J-and H-aggregates of PPcy confined in the colloidal nanoparticles thermoresponsive and reversible aggregate-to-monomer transitions. The enhanced fluorescence intensity of such J-aggregating nanoparticles vs. the monomers under the same concentration resembles nature's strategy of circumventing concentration quenching in photosynthetic lightharvesting systems. Moreover, these polyester-tethered PPcy nanoparticles are broadly useful in biomedical applications, such as NIR fluorescence or photoacoustic imaging and phototherapy of tumor models in animals. |
65fc0a5166c138172975afd1 | 0 | Magnesium and its alloys are attractive and promising materials for the aerospace, automotive, and medical industries due to their low density, excellent formability, non-toxicity, and damping properties . However, unlike aluminum and titanium, Mg alloys are characterized by a low corrosion resistance due to their high reactivity and the absence of a stable passive oxide layer . At present, the main ways of tailoring mechanical and corrosion properties of magnesium alloys are alloying, surface modification, as well as the use of corrosion inhibitors . |
65fc0a5166c138172975afd1 | 1 | The main groups of Mg alloys used in industry are Mg-Al-Zn, Mg-Ca, and Mg-REEs (rareearth elements) alloys . The AZ-series Mg-Al-Zn alloys account for more than 90% of currently used magnesium alloys . Alloying with aluminum makes it possible to increase the strength, hardness, casting properties, and corrosion resistance of magnesium alloys . The microstructure of such alloys is a solid solution of aluminum and β-phase (Mg17Al12) in Mg, the presence of which increases the corrosion potential and reduces its corrosion rate. |
65fc0a5166c138172975afd1 | 2 | Among them, magnesium-lithium (Mg-Li) alloys are the lightest metal engineering materials . According to the binary phase diagram of the Mg-Li system , alloying of magnesium with lithium improves the ductility of the alloy due to the transformation of the crystal structure from a hexagonal close-packed (hcp) with a lithium content of less than 5.7 wt.% (α-phase is a solid solution of lithium in magnesium) to body-centered cubic (bcc) with a Li content of more than 11.3 wt.% (β-phase, a solid solution of magnesium in lithium). In turn, magnesium alloys containing 5.7-11.3 wt.% of Li have both hcp and bcc crystal structures . Due to the simultaneous presence of the α-and β-phases, such magnesium alloys are characterized by medium strength and high ductility . This difference in the microstructure of the alloys has a significant influence on the corrosion rate of Mg-Li alloys. Xu et al. and Li et al. reported that Mg-Li alloys containing high amounts of Li (above 10.3 wt.%) have superior corrosion resistance due to the formation of a protective lithium carbonate surface film upon bcc Mg-Li matrix. However, Zhao et al. for Mg-4Li and Mg-12Li alloys reported opposite corrosion behavior and increased corrosion rates. |
65fc0a5166c138172975afd1 | 3 | The effect of Li concentration on the corrosion resistance of Mg alloys, additionally containing other alloying elements is not so straightforward . Common Mg alloys have various types of intermetallic particles (IMPs) in their microstructure, most of them being cathodic relative to the alloy matrix . The corrosion rate of Mg-Li alloys with low Li content is comparable to that of traditional Mg alloys without Li . The addition of a high amount of Li causes the formation of new types of Li-rich IMPs, commonly Mg-Li and Al-Li types , |
65fc0a5166c138172975afd1 | 4 | intensifying local galvanic corrosion of such alloys . An increase in the volume fraction of the Li-containing IMPs promotes filiform corrosion along the grain boundaries and inside the β-Li phase . An increase in the corrosion rate with increasing amounts of Li was reported for Mg-Al-Li, Mg-Zn-Li, Mg-Li-Al-Zn-Y, Mg-Li-Ca, and Mg-Al-Li-Zn alloys . |
65fc0a5166c138172975afd1 | 5 | However, the aspect of the corrosion inhibition of such alloys still requires deeper studies and understanding. It is known that Li salts can be used as effective corrosion inhibitors for Mg alloys due to the formation of a surface Li2CO3 film , while the knowledge on the use of other inhibitors for corrosion protection of Mg-Li alloys is very limited. Nevertheless, the implementation of an effective inhibitor can significantly improve the corrosion resistance of Mg-Li alloys and extend their applications. |
65fc0a5166c138172975afd1 | 6 | There are numerous potential corrosion inhibitors for magnesium alloys, which can be categorized as organic and inorganic inhibitors . The latter usually act as precipitation-type inhibitors and their effectiveness is strongly related to the microstructure of a Mg alloy, since the inhibition is usually based on retarding the cathodic activity of IMPs. In our previous works , we have shown that inorganic oxidizing anions, such as permanganates and molybdates, are effective inhibitors for the corrosion protection of AZ31 and WE43 alloys. In the case of the AZ31 alloy, the inhibition mechanism is based on the formation of a surface oxide layer suppressing the cathodic activity of IMPs and the anodic activity of the Mg matrix. Therefore, the implementation of such inhibitors can potentially decrease the negative impact of Li-rich IMPs on the corrosion resistance of Mg-Li alloys. |
65fc0a5166c138172975afd1 | 7 | Recently, special attention has been paid to the examination of the surface film formation and mapping of the Li distribution in Mg-Li alloys, which is a challenging but essential task for understanding the origin of corrosion resistance in this class of Mg alloys . On the other hand, the accurate examination of corrosion processes of Mg alloys, especially by electrochemical techniques, is still important. For this, a combination of classical electrochemical techniques and hydrogen evolution monitoring is usually applied . In our recent studies we have proposed a new approach to implement multisine dynamic electrochemical impedance spectroscopy (g-DEIS) monitoring as an expedient method to examine the kinetics of the nonstationary corrosion process of Mg alloys. We believe that this technique also can be effectively used to monitor the inhibition effectiveness of corrosion inhibitors towards Mg alloys , as was previously done for Al alloys . To our best knowledge, no attempt to examine the corrosion protection of Mg alloys containing Li by soluble molybdates has been described in the literature. Moreover, the correlation of the inhibition mechanism with the amount of Li and, consequently, the microstructure of these alloys still requires a better fundamental understanding. |
65fc0a5166c138172975afd1 | 8 | The aim of the present study was to elucidate the inhibition efficiency of molybdate ions towards the AZ31-xLi (x = 4, 8, 12) Mg alloys depending on the amount of the molybdate inhibitor in the corrosive medium and Li in the AZ31 Mg alloy. To do so, a set of classical electrochemical techniques, coupled with g-DEIS monitoring and spectroscopic surface analyses, has been used and the inhibition mechanism of AZ31-xLi (x = 4, 8, 12) Mg alloys by soluble molybdates has been proposed. A detailed examination of corrosion processes and inhibition efficiency of molybdates towards the AZ31 alloy without Li addition has been reported in our previous publication . Therefore, this alloy is not examined in the present contribution, and data from cab be used as a reference. |
65fc0a5166c138172975afd1 | 9 | Magnesium alloys AZ31-xLi (x = 4, 8, 12) examined in this study were obtained by a casting method. The target elemental composition of the alloys was as that of the AZ31 alloy with the addition of 4, 8, or 12 wt.% of Li. Metals used for the process were purchased from Sigma Aldrich. The process was carried out in a Balzers VSG 02 single-chamber vacuum induction melting furnace at a temperature of 650°C, and a pressure of 600 Torr (8 × 10 4 Pa) in the argon atmosphere. Obtained billets were then cut into samples with sizes ca. 20 mm × 20 mm × 5 mm. Before experiments, the samples were mechanically ground up to P4000 grit emery paper in 99% ethanol. After grinding, the samples were ultrasonically cleaned for 5 min in a Skymen JP-008 bath. |
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