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We present an autonomous scanning droplet cell platform designed for on-demand alloy electrodeposition and real-time electrochemical characterization for investigating the corrosion-resistance properties of multicomponent alloys. Automation and machine learning are currently driving rapid innovation in high throughput and autonomous materials design and discovery. We present two alloy design case studies: one focusing on a multi-objective corrosion resistant alloy optimization, and a case study highlighting the complexity of the multimodal characterization needed to provide insight into the underlying structural and chemical factors that drive observed material behavior. This motivates a close coupling between autonomous research platforms and scientific machine learning methodology that blends mechanistic physical models and black box machine learning models. This emerging research area presents new opportunities to accelerate materials synthesis, evaluation, and hence discovery and design.

Thin-film continuous composition spreads of Fe-Co-O were fabricated by reactive cosputtering from elemental Fe and Co targets in reactive Ar/O2 atmosphere using deposition temperatures ranging from 300 to 700 °C. Fused silica and platinized Si/SiO2 strips were used as substrates. Ti and Ta were investigated as adhesion layer for Pt and the fabrication of the Fe-Co-O films. The thin-film composition spreads were characterized by high-throughput electron-dispersive X-ray spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, atomic force microscopy, scanning electron microscopy, and optical transmission spectroscopy. The Fe-content ranged from 28 to 72 at. %. The spinel phases Fe2CoO4 and FeCo2O4 could be synthesized and stabilized at all deposition temperatures with a continuous variation in spinel composition in between. The dependence of the film surface microstructure on the deposition temperature and the composition was mapped. Moreover, the band gap values, ranging from 2.41 eV for FeCo2O4 to 2.74 eV for Fe2CoO4, show a continuous variation with the composition.

Active learning—the field of machine learning (ML) dedicated to optimal experiment design—has played a part in science as far back as the 18th century when Laplace used it to guide his discovery of celestial mechanics. In this work, we focus a closed-loop, active learning-driven autonomous system on another major challenge, the discovery of advanced materials against the exceedingly complex synthesis-processes-structure-property landscape. We demonstrate an autonomous materials discovery methodology for functional inorganic compounds which allow scientists to fail smarter, learn faster, and spend less resources in their studies, while simultaneously improving trust in scientific results and machine learning tools. This robot science enables science-over-the-network, reducing the economic impact of scientists being physically separated from their labs. The real-time closed-loop, autonomous system for materials exploration and optimization (CAMEO) is implemented at the synchrotron beamline to accelerate the interconnected tasks of phase mapping and property optimization, with each cycle taking seconds to minutes. We also demonstrate an embodiment of human-machine interaction, where human-in-the-loop is called to play a contributing role within each cycle. This work has resulted in the discovery of a novel epitaxial nanocomposite phase-change memory material., Machine learning driven research holds big promise towards accelerating materials’ discovery. Here the authors demonstrate CAMEO, which integrates active learning Bayesian optimization with practical experiments execution, for the discovery of new phase- change materials using X-ray diffraction experiments.

Combinatorial synthesis and high-throughput characterization of a Ni-Ti-Co thin film materials library are reported for exploration of reversible martensitic transformation. The library was prepared by magnetron co-sputtering, annealed in vacuum at 500 °C without atmospheric exposure, and evaluated for shape memory behavior as an indicator of transformation. Composition, structure, and transformation behavior of the 177 pads in the library were characterized using high-throughput wavelength dispersive spectroscopy (WDS), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and four-point probe temperature-dependent resistance (R(T)) measurements. A new, expanded composition space having phase transformation with low thermal hysteresis and Co > 10 at. % is found. Unsupervised machine learning methods of hierarchical clustering were employed to streamline data processing of the large XRD and XPS data sets. Through cluster analysis of XRD data, we identified and mapped the constituent structural phases. Composition-structure-property maps for the ternary system are made to correlate the functional properties to the local microstructure and composition of the Ni-Ti-Co thin film library.

Ag–V–O thin-film materials libraries, with both composition (Ag22-77V23-78Ox) and thickness (123–714 nm) gradients were fabricated using combinatorial reactive magnetron co-sputtering aiming on establishing relations between composition, structure, and functional properties. As-deposited libraries were annealed in air at 300 °C for 10 h. High-throughput characterization methods of composition, structure and functional properties were used to identify photoelectrochemically active regions. The phases AgV6O15, Ag2V4O11, AgVO3, and Ag4V2O7 were observed throughout the composition gradient. The photoelectrochemical properties of Ag–V–O films are dependent on composition and morphology. An enhanced photocurrent density (~300–554 μA/cm2) was obtained at 30 to 45 at.% Ag along the thickness gradient. Thin films of these compositions show a nanowire morphology, which is an important factor for the enhancement of photoelectrochemical performance. The photoelectrochemically active regions were further investigated by high-throughput synchrotron-X-ray diffraction and transmission electron microscopy (Ag32V68Ox) which confirmed the presence of Ag2V4O11 as the dominating phase along with the minor phases AgV6O15 and AgVO3. This enhanced photoactive region shows bandgap values of ~2.30 eV for the direct and ~1.87 eV for the indirect bandgap energies. The porous nanostructured films improve charge transport and are hence of interest for photoelectrochemical water splitting.

To realize high specific capacity Li-metal batteries, a protection layer for the Li-metal anode is needed. We are carrying out combinatorial screening of Li-alloy thin films as the protection layer...

Interest in high entropy alloy thermoelectric materials is predicated on achieving ultralow lattice thermal conductivity $\kappa\sub{L}$ through large compositional disorder. However, here we show that for a given mechanism, such as mass contrast phonon scattering, $\kappa\sub{L}$ will be minimized along the binary alloy with the highest mass contrast, such that adding an intermediate-mass atom to increase atomic disorder can increase thermal conductivity. Only when each component adds an independent scattering mechanism (such as adding strain fluctuation to an existing mass fluctuation) is there a benefit. In addition, both charge carriers and heat-carrying phonons are known to experience scattering due to alloying effects, leading to a trade-off in thermoelectric performance. We apply analytic transport models, based on perturbation and effective medium theories, to predict how alloy scattering will affect the thermal and electronic transport across the full compositional range of several pseudo-ternary and pseudo-quaternary alloy systems. To do so, we demonstrate a multicomponent extension to both thermal and electronic binary alloy scattering models based on the virtual crystal approximation. Finally, we show that common functional forms used in computational thermodynamics can be applied to this problem to further generalize the scattering behavior that is modeled.

Thin-film continuous composition spreads of Fe-Co-O were fabricated by reactive cosputtering from elemental Fe and Co targets in reactive Ar/O

Thin films of two types of high-entropy oxides (HEOs) have been deposited on 76.2 mm Si wafers using combinatorial sputter deposition. In one type of the oxides, (MgZnMnCoNi) O(x), all the metals have a stable divalent oxidation state and similar cationic radii. In the second type of oxides, (CrFeMnCoNi) O(x), the metals are more diverse in the atomic radius and valence state, and have good solubility in their sub-binary and ternary oxide systems. The resulting HEO thin films were characterized using several high-throughput analytical techniques. The microstructure, composition, and electrical conductivity obtained on defined grid maps were obtained for the first time across large compositional ranges. The crystalline structure of the films was observed as a function of the metallic elements in the composition spreads, that is, the Mn and Zn in (MgZnMnCoNi) O(x) and Mn and Ni in (CrFeMnCoNi) O(x). The (MgZnMnCoNi) O(x) sample was observed to form two-phase structures, except single spinel structure was found in (MgZnMnCoNi) O(x) over a range of Mn > 12 at. % and Zn < 44 at. %, while (CrFeMnCoNi)O(x) was always observed to form two-phase structures. Composition-controlled crystalline structure is not only experimentally demonstrated but also supported by density function theory calculation.

On the basis of a set of machine learning predictions of glass formation in the Ni–Ti–Al system, we have undertaken a high-throughput experimental study of that system. We utilized rapid synthesis followed by high-throughput structural and electrochemical characterization. Using this dual-modality approach, we are able to better classify the amorphous portion of the library, which we found to be the portion with a full width at half maximum (fWhm) of >0.42 Å(−1) for the first sharp X-ray diffraction peak. Proper phase labeling is important for future machine learning efforts. We demonstrate that the fWhm and corrosion resistance are correlated but that, while chemistry still plays a role in corrosion resistance, a large fwhm, attributed to a glassy phase, is necessary for the highest corrosion resistance.

Ni based amorphous materials have great potential as hydrogen purification membranes. In the present work the melt spun (Ni0.6Nb0.4−yTay)100−xZrx with y=0, 0.1 and x=20, 30 was studied. The result of X-ray diffraction spectra of the ribbons showed an amorphous nature of the alloys. Heating these ribbons below T

Although there is significant interest in elucidating the role of placenta-derived exosomes (PdEs) during pregnancy, the exosomal profile in pregnancies complicated by gestational diabetes mellitus (GDM) remains to be established. The aim of this study was to compare the gestational-age profile of PdEs in maternal plasma of GDM with normal pregnancies and to determine the effect of exosomes on cytokine release from human umbilical vein endothelial cells. A prospective cohort of patients was sampled at three time points during pregnancy for each patient (i.e., 11–14, 22–24, and 32–36 weeks' gestation). A retrospective stratified study design was used to quantify exosomes present in maternal plasma of normal (n = 13) and GDM (n = 7) pregnancies. Gestational age and pregnancy status were identified as significant factors contributing to variation in plasma exosome concentration (ANOVA, P < 0.05). Post hoc analyses established that PdE concentration increased during gestation in both normal and GDM pregnancies; however, the increase was significantly greater in GDM (∼2.2-fold, ∼1.5-fold, and ∼1.8-fold greater at each gestational age compared with normal pregnancies). Exosomes isolated from GDM pregnancies significantly increased the release of proinflammatory cytokines from endothelial cells. Although the role of exosomes during GDM remains to be fully elucidated, exosome profiles may be of diagnostic utility for screening asymptomatic populations.

Thin-film material libraries in the ternary and quaternary metal oxide systems Fe-V-O, Cu-V-O, and Cu-Fe-V-O were synthesized using combinatorial reactive co-sputtering with subsequent annealing in air. Their compositional, structural, and functional properties were assessed using high-throughput characterization methods. Prior to the investigation of the quaternary system Cu-Fe-V-O, the compositions (Fe61V39)Ox and (Cu52V48)Ox with promising photoactivity were identified from their ternary subsystems Fe-V-O and Cu-V-O, respectively. Two Cu-Fe-V-O material libraries with (Cu29-72Fe4-27V22-57)Ox and (Cu11-55Fe27-73V12-34)Ox composition spread were investigated. Seven mixed ternary and quaternary phase regions were identified: I (α-Cu3FeV6O26/FeVO4), II (Cu5V2O10/FeVO4/α-Cu3Fe4V6O26), III (Cu5V2O10), IV (Cu5V2O10/FeVO4, V (FeVO4/γ-Cu2V2O7/α-Cu3Fe4V6O26), VI (β-Cu2V2O7/α-Cu3Fe4V6O26/FeVO4), and VII (β-Cu3Fe4V6O26/FeVO4). In the investigated composition range, two photoactive regions, (Cu53Fe7V40)Ox and (Cu45Fe21V34)Ox, were identified, exhibiting 103 μA/cm2 and 108 μA/cm2 photocurrent density for the oxygen evolution reaction at 1.63 V vs reversible hydrogen electrode, respectively. The highest photoactive region (Cu45Fe21V34)Ox comprises the dominant α-Cu3Fe4V6O24 phase and minor FeVO4 phase. This photoactive region corresponds to having an indirect bandgap of 1.87 eV and a direct bandgap of 2.58 eV with an incident photon-to-current efficiency of 30% at a wavelength of 310 nm.

Crystalline Pd/Pd-Ag membranes are widely used for hydrogen separation from CO2 and other gases in power generation applications. To substitute these high cost noble metal alloy membranes, the Ni-Nb-Zr amorphous alloys are being developed that exhibit relatively high permeability of hydrogen between 200–400 °C. Atom probe tomography (APT) experiments performed on these ribbons revealed nm-scale Nb-rich and Zr-rich regions (clusters) embedded in a ternary matrix, indicating phase separation within the Ni-Nb-Zr amorphous alloy. Density functional theory (DFT) simulations have predicted that these clusters are composed of icosahedral coordination polyhedra. The interatomic distances and correlation lengths of the short range order of these alloys were determined by neutron total scattering which match well with our DFT based molecular dynamics (DFT-MD) simulations.

Amorphous (Ni0.6Nb0.4)1-xZrx membranes were investigated by means of X-ray diffraction, thermogravimetry, differential thermal analysis and tensile modulus measurements. Crystallization occurs only above 673 K, and even after hydrogenation the membranes retain their mainly amorphous nature. However, after exposure to gaseous hydrogen, the temperature dependence of the tensile modulus, M, displays large variations. The modulus of the hydrogen reacted membrane is higher with respect to the pristine samples in the temperature range between 298 K and 423 K. Moreover, a sharp drop in M is observed upon heating to approximately 473 K, well below the glass transition temperature of these glasses. We propose that the changes in the moduli as a function of temperature on the hydrogenated samples are due to the formation of nanocrystalline phases of Zr hydrides in (Ni0.6Nb0.4)1-xZrx-H membanes.

Amorphous (Ni 0.6 Nb 0.4 ) 1−x Zr x membranes were investigated by means of X-ray diffraction, thermogravimetry, differential thermal analysis and tensile modulus measurements. Crystallization occurs only above 673 K, and even after hydrogenation the membranes retain their mainly amorphous nature. However, after exposure to gaseous hydrogen, the temperature dependence of the tensile modulus, M, displays large variations. The modulus of the hydrogen reacted membrane is higher with respect to the pristine samples in the temperature range between 298 K and 423 K. Moreover, a sharp drop in M is observed upon heating to approximately 473 K, well below the glass transition temperature of these glasses. We propose that the changes in the moduli as a function of temperature on the hydrogenated samples are due to the formation of nanocrystalline phases of Zr hydrides in (Ni 0.6 Nb 0.4 ) 1−x Zr x -H membanes.

Amorphous metallic membranes display promising properties for hydrogen purification up to an ultrapure grade (purity > 99.999%). The hydrogen permeability through amorphous membranes has been widely studied in the literature. In this work we focus on two additional properties, which should be considered before possible application of such materials: the propensity to crystallize at high temperatures should be avoided, as the crystallized membranes can become brittle; the hydrogen solubility should be high, as solubility and permeability are proportional. We investigate the crystallization process and the hydrogen solubility of some membranes based on Ni, Nb, and Zr metals, as a function of Zr content, and with the addition of Ta or B. The boron doping does not significantly affect the crystallization temperature and the thermal stability of the membrane. However, the hydrogen solubility for p ~7 bar is as high as H/M ~0.31 at T = 440 °C and H/M ~0.27 at T = 485 °C. Moreover, the membrane does not pulverize even after repeated thermal cycles and hydrogenation processes up to 485 °C and 7 bar, and it retains its initial shape.

Ni-Nb-Zr amorphous membranes, prepared by melt-spinning, show great potential for replacing crystalline Pd-based materials in the field of hydrogen purification to an ultrapure grade (>99.999%). In this study, we investigate the temperature evolution of the structure of an amorphous ribbon with the composition Ni32Nb28Zr30Cu10 (expressed in atom %) by means of XRD and DTA measurements. An abrupt structural expansion is induced between 240 and 300 °C by hydrogenation. This structural modification deeply modifies the hydrogen sorption properties of the membrane, which indeed shows a strong reduction of the hydrogen capacity above 270 °C.

Most of the global H2 production is derived from hydrocarbon-based fuels, and efficient H2/CO2 separation is necessary to deliver a high-purity H2 product. Hydrogen-selective alloy membranes are emerging as a viable alternative to traditional pressure swing adsorption processes as a means for H2/CO2 separation. These membranes can be formed from a wide range of alloys, and those based on Pd are the closest to commercial deployment. The high cost of Pd (USD *31,000 kg-1) is driving the development of less-expensive alternatives, including inexpensive amorphous (Ni60Nb40)100-xZrx alloys. Amorphous alloy membranes can be fabricated directly from the molten state into continuous ribbons via melt spinning and depending on the composition can exhibit relatively high hydrogen permeability between 473 and 673 K. Here we review recent developments in these low-cost membrane materials, especially with respect to permeation behavior, electrical transport properties, and understanding of local atomic order. To further understand the nature of these solids, atom probe tomography has been performed, revealing amorphous Nb-rich and Zr-rich clusters embedded in majority Ni matrix whose compositions deviated from the nominal overall composition of the membrane.

Inherent interindividual and intraindividual variation in the length of the menstrual cycle limits the accuracy of predicting days of peak fertility. To improve detection of days of peak fertility, a more detailed understanding of longitudinal changes in cervicovaginal fluid (CVF) biomarkers during the normal menstrual cycle is needed. The aim of this study, therefore, was to characterize longitudinal changes in CVF proteins during the menstrual cycle using a quantitative, data-independent acquisition mass spectrometry approach. Six serial samples were collected from women (n = 10) during the menstrual cycle. Samples were obtained at two time points for each phase of the cycle: early and late preovulatory, ovulatory, and postovulatory. Information-dependent acquisition (IDA) of mass spectra from all individual CVF samples was initially performed and identified 278 total proteins. Samples were then pooled by time of collection (n = 6 pools) and analyzed using IDA and information-independent acquisition (Sequential Windowed Acquisition of All Theoretical Mass Spectra [SWATH]). The IDA library generated contained 176 statistically significant protein identifications (P < 0.000158). The variation in the relative abundance of CVF proteins across the menstrual cycle was established by comparison with the SWATH profile against the IDA library. Using time-series, pooled samples obtained from 10 women, quantitative data were obtained by SWATH analysis for 43 CVF proteins. Of these proteins, 28 displayed significant variation in relative abundance during the menstrual cycle (assessed by ANOVA). Statistical significant changes in the relative expression of CVF proteins during preovulatory, ovulatory, and postovulatory phases of menstrual cycle were identified. The data obtained may be of utility not only in elucidating underlying physiological mechanisms but also as clinically useful biomarkers of fertility status.

Background: Of the 130 million babies born each year, 8 million die before their first birthday. A contributing factor in many of these deaths is poor pregnancy outcome as a result of complications of pregnancy. Preeclampsia (PE) and Gestational Diabetes Mellitus (GDM) are the common pregnancy complications that have no effective antenatal treatment other than steroid administration and timely delivery. Each occurs with an incidence of 5-10% and is responsible for the majority of obstetric and paediatric morbidity and mortality. These can permanently impact on lifelong health. Early detection of disease risk and onset is the first step in implementing efficacious treatment and improving patient outcome. In the context of antenatal screening, the objective is to identify biomarkers (e.g. proteins) that are informative of the risk of asymptomatic pregnant women subsequently developing complications of pregnancy. Recent studies highlight the putative utility of tissue-specific nanovesicles (i.e. exosomes) in the diagnosis of disease onset and treatment monitoring. It was hypothesized that presymptomatic women who subsequently develop pregnancy complications display altered exosome profile (i.e. concentration and/or protein content) at first trimester of pregnancy (i.e. 6-12 weeks). The general aim of this thesis was to identify blood-borne biomarkers (i.e. exosomes) that may be used at the first antenatal visit to identify presymptomatic women who are at risk of developing complications of pregnancy. Methods: A time-series experimental design was used to establish pregnancy-associated changes in maternal plasma exosome concentrations during first trimester. Serial samples of plasma were collected from normal healthy pregnant women (n=10) at 6, 7, 8, 9, 10, 11 and 12 weeks of gestation. Plasma samples from pregnant women at 11-14 weeks of gestation who developed preeclampsia (n=15) and gestational diabetes mellitus (n=7) were also collected. Exosomes were isolated by differential and buoyant density centrifugation and characterised by size distribution and morphology using nanoparticles tracking analysis (NTA; NanoSightt) and transmission electron microscopy (TEM) respectively. The total number of exosome vesicles and placenta-derived exosome vesicles were determined by quantifying immunoreactive exosomal CD63 and a placenta-specific marker (PLAP) by ELISA. Finally, the differentially expressed exosomal proteins and peptides were identified by Liquid Chromatography and Mass Spectrometry based approaches (LC-MS/MS). Statistical analysis was performed using the Graph Pad Prism software. Results: EM and NTA identified the presence of 50 - 120 nm spherical vesicles in maternal plasma as early as 6 weeks of pregnancy. The number of exosomes in maternal circulation increased significantly (ANOVA, p=0.002) with the progression of pregnancy (from 6 to 12 weeks). The concentration of placenta-derived exosomes in maternal plasma (i.e. PLAP+) increased progressively with gestational age, from 6 weeks 70.6 p 5.7 pg/ml to 12 weeks 117.5 p 13.4 pg/ml. Regression analysis shows that week is a factor that explains g70% of the observed variation in plasma exosomal PLAP concentration, total exosome number only explains 20%. The total number of exosome was 1.31e12 p 1.60e12 (mean p SD) during the first trimester in women who developed Gestational Diabetes Mellitus (GDM) in second trimester and 1.09e11 p 3.17e10 in women who developed Preeclampsia (PE). The statistical analysis showed that the total number of released exosomes in the first trimester of pregnancy complicated with GDM was three- fold higher than normal pregnancy and the concentration of the exosomes released from the placental cells was twofold compared to PLAP concentration in normal pregnancy. In addition, a significant (pl0.001) increase in the cumulative number of exosomes was observed during the first trimester of preeclamptic condition when compared with the first trimester normal pregnancy condition. Conclusion: This study presents longitudinal data on placental-derived exosomes in the first trimester of pregnancy, starting from as early as 6 weeks. Early detection of women at risk of pregnancy complications would provide opportunity to evaluate appropriate intervention strategies to limit acute adverse sequelae. The rationale for developing early pregnancy screening tests is not only for the management of the contemporaneous pregnancy but also to optimise lifelong and intergenerational health. If this can be achieved, it will provide an opportunity for early assessment of risk and the implementation of an alternative clinical management strategy to improve outcome for both the mother and the baby.

Inherent interindividual and intraindividual variation in the length of the menstrual cycle limits the accuracy of predicting days of peak fertility. To improve detection of days of peak fertility, a more detailed understanding of longitudinal changes in cervicovaginal fluid (CVF) biomarkers during the normal menstrual cycle is needed. The aim of this study, therefore, was to characterize longitudinal changes in CVF proteins during the menstrual cycle using a quantitative, data-independent acquisition mass spectrometry approach. Six serial samples were collected from women (n = 10) during the menstrual cycle. Samples were obtained at two time points for each phase of the cycle: early and late preovulatory, ovulatory, and postovulatory. Information-dependent acquisition (IDA) of mass spectra from all individual CVF samples was initially performed and identified 278 total proteins. Samples were then pooled by time of collection (n = 6 pools) and analyzed using IDA and information-independent acquisition (Sequential Windowed Acquisition of All Theoretical Mass Spectra [SWATH]). The IDA library generated contained 176 statistically significant protein identifications (P0.000158). The variation in the relative abundance of CVF proteins across the menstrual cycle was established by comparison with the SWATH profile against the IDA library. Using time-series, pooled samples obtained from 10 women, quantitative data were obtained by SWATH analysis for 43 CVF proteins. Of these proteins, 28 displayed significant variation in relative abundance during the menstrual cycle (assessed by ANOVA). Statistical significant changes in the relative expression of CVF proteins during preovulatory, ovulatory, and postovulatory phases of menstrual cycle were identified. The data obtained may be of utility not only in elucidating underlying physiological mechanisms but also as clinically useful biomarkers of fertility status.

Background Human placenta releases specific nanovesicles (i.e. exosomes) into the maternal circulation during pregnancy, however, the presence of placenta-derived exosomes in maternal blood during early pregnancy remains to be established. The aim of this study was to characterise gestational age related changes in the concentration of placenta-derived exosomes during the first trimester of pregnancy (i.e. from 6 to 12 weeks) in plasma from women with normal pregnancies. Methods A time-series experimental design was used to establish pregnancy-associated changes in maternal plasma exosome concentrations during the first trimester. A series of plasma were collected from normal healthy women (10 patients) at 6, 7, 8, 9, 10, 11 and 12 weeks of gestation (n = 70). We measured the stability of these vesicles by quantifying and observing their protein and miRNA contents after the freeze/thawing processes. Exosomes were isolated by differential and buoyant density centrifugation using a sucrose continuous gradient and characterised by their size distribution and morphology using the nanoparticles tracking analysis (NTA; Nanosight™) and electron microscopy (EM), respectively. The total number of exosomes and placenta-derived exosomes were determined by quantifying the immunoreactive exosomal marker, CD63 and a placenta-specific marker (Placental Alkaline Phosphatase PLAP). Results These nanoparticles are extraordinarily stable. There is no significant decline in their yield with the freeze/thawing processes or change in their EM morphology. NTA identified the presence of 50–150 nm spherical vesicles in maternal plasma as early as 6 weeks of pregnancy. The number of exosomes in maternal circulation increased significantly (ANOVA, p = 0.002) with the progression of pregnancy (from 6 to 12 weeks). The concentration of placenta-derived exosomes in maternal plasma (i.e. PLAP+) increased progressively with gestational age, from 6 weeks 70.6 ± 5.7 pg/ml to 12 weeks 117.5 ± 13.4 pg/ml. Regression analysis showed that weeks is a factor that explains for >70% of the observed variation in plasma exosomal PLAP concentration while the total exosome number only explains 20%. Conclusions During normal healthy pregnancy, the number of exosomes present in the maternal plasma increased significantly with gestational age across the first trimester of pregnancy. This study is a baseline that provides an ideal starting point for developing early detection method for women who subsequently develop pregnancy complications, clinically detected during the second trimester. Early detection of women at risk of pregnancy complications would provide an opportunity to develop and evaluate appropriate intervention strategies to limit acute adverse sequel.

Objectives: We have established that the release of placenta-derived exosomes (PdE) increases gradually during gestation in healthy normal pregnancies. The release and composition of exosomes from placentae of pregnancies complicated by GDM, however, remain to be fully elucidated. The aim of this study was to establish the gestational-age profile of PdE in maternal plasma of GDM pregnancies. Methods: Plasma samples were obtained from normal (n=20 per group) and GDM (n=7 per group) pregnancies in the first (FT 11-14 weeks), second (ST 22-24 weeks) and third (TT 32-36 weeks) trimester pregnancy. All samples were collected from Davila Clinic (Santiago, Chile). Exosomes were isolated from plasma by differential and buoyant density centrifugation. The total number of exosomes and PdE were determined by quantifying immunoreactive exosomal CD63 and placenta-specific marker (PLAP) by ELISA and fluorescence nanoparticle tracking analysis (NTA, NanoSight NS500). The PLAP/CD63 ratio (i.e. immunoractive PLAP content per exosome) was used as a measure of the contribution of PdE to total exosomes in maternal blood. Results: Variation in the concentration of PdE in maternal plasma was assessed by ANOVA with the variance partitioned between gestational age and pregnancy status (i.e. normal or GDM). Both gestational age and pregnancy status were identified as significant factors (ANOVA, p

Objectives: The concentration of microparticles is increased in the circulation of women with pre-eclampsia (PE). Failed extravillous trophoblast invasion is associated with early onset of PE. The aim of this study was to quantify the number of particles in plasma from pre-symptomatic women who subsequently developed preeclampsia and establish their effect on EVT migration. Methods: Plasma samples were obtained from normal (NP, n=20) and PE (n=15) pregnancies in the first (11-14 weeks) trimester from Davila Clinic (Santiago, Chile). The number of total particles (TP) and particles with diameter ranging between 30-150 nm (P30-150) were determined using a nanoparticle tracking analysis (NTA, NanoSight NS500). HTR-8/SVneo (EVT) were used as target cells to establish the effect of plasma (10% plasma in RPMI media) from NP and PE pregnancies on migration using a real-time imaging system (Incucyte™). RPMI media was used as control. In addition, plasma was subjected to sonication before exposure to EVT. Results: TP and P30-150 were significantly higher (p