A machine learning approach for early prediction of gestational diabetes mellitus using elemental contents in fingernails.

The aim of this pilot study was to predict the risk of gestational diabetes mellitus (GDM) by the elemental content in fingernails and urine with machine learning analysis. Sixty seven pregnant women (34 control and 33 GDM patient) were included. Fingernails and urine were collected in the first and second trimesters, respectively. The concentrations of elements were determined by inductively coupled plasma-mass spectrometry. Logistic regression model was applied to estimate the adjusted odd ratios and 95% confidence intervals. The predictive performances of multiple machine learning algorithms were evaluated, and an ensemble model was built to predict the risk for GDM based on the elemental contents in the fingernails. Beryllium, selenium, tin and copper were positively associated with the risk of GDM while nickel and mercury showed opposite result. The trained ensemble model showed larger area under curve (AUC) of receiver operating characteristic curve (0.81) using fingernail Ni, Cu and Se concentrations. The model was validated by external data set with AUC = 0.71. In summary, the results of the present study highlight the potential of fingernails, as an alternative sample, together with machine learning in human biomonitoring studies.

Suppression of spectral interference in dual-elemental analysis of single particles using triple quadrupole ICP-MS.

Single particle-inductively coupled plasma-mass spectrometry (SP-ICP-MS) was used in the analysis of single particles/cells. Although quadrupole mass analyzers are widely used, the long settling time restricts measurement to single elements in individual particles. Recently, dual-elemental analysis has successfully been developed with the assistance of oxygen gas in the collision cell. This simple approach greatly expands the capability of quadrupole-based ICP-MS. In this study, we adopted bandpass mode in the first quadrupole (Q1) to improve the limit of detection of single particles against spectral interference. A model was developed to explain the rationale behind the selection of quadrupole voltages. The quadrupole voltages were optimized systematically so that the mass bandwidth of Q1 allowed the transmission of two target analytes while the interference species were rejected. As a result, the signal from the polyatomic interference was reduced by 98% with no significant change in the analyte signal. The bandpass mode was further applied to accurately determine the isotope ratio of 109Ag/107Ag in 80-nm Ag nanoparticles, as well as the Ag content in AgSn alloy particles, under the polyatomic interference of 91Zr16O originating from dissolved ions and particles. This technique was further applied to the determination of two Yb isotopes in algal cells with interference from Gd. Results indicate that this approach has great potential for assessing single particles and biological cells in the presence of severe interference from imaging agents, drugs, or biological fluids.

An integrated ICP-MS-based analytical approach to fractionate and characterize ionic and nanoparticulate Ce species.

Cerium dioxide nanoparticles (CeO2 NPs) are widely used in various fields, leading to concern about their effect on human health. When conducting in vivo investigations of CeO2 NPs, the challenge is to fractionate ionic Ce and CeO2 NPs and to characterize CeO2 NPs without changing their properties/state. To meet this challenge, we developed an integrated inductively coupled plasma-mass spectrometry (ICP-MS)-based analytical approach in which ultrafiltration is used to fractionate ionic and nanoparticulate Ce species while CeO2 NPs are characterized by single particle-ICP-MS (sp-ICP-MS). We used this technique to compare the effects of two sample pretreatment methods, alkaline and enzymatic pretreatments, on ionic Ce and CeO2 NPs. Results showed that enzymatic pretreatment was more efficient in extracting ionic Ce or CeO2 NPs from animal tissues. Moreover, results further showed that the properties/states of all ionic and nanoparticulate Ce species were well preserved. The rates of recovery of both species were over 85%; the size distribution of CeO2 NPs was comparable to that of original NPs. We then applied this analytical approach, including the enzymatic pretreatment and ICP-MS-based analytical techniques, to investigate the bioaccumulation and biotransformation of CeO2 NPs in mice. It was found that the thymus acts as a "holding station" in CeO2 NP translocation in vivo. CeO2 NP biotransformation was reported to be organ-specific. This is the first study to evaluate the impact of enzymatic and alkaline pretreatment on Ce species, namely ionic Ce and CeO2 NPs. This integrated ICP-MS-based analytical approach enables us to conduct in vivo biotransformation investigations of CeO2 NPs.

Dual-elemental analysis of single particles using quadrupole-based inductively coupled plasma-mass spectrometry.

Single-particle inductively coupled plasma-mass spectrometry (SP-ICP-MS) is used for elemental analysis of single particles and biological cells. Time-of-flight (TOF) mass analyzers are widely used for multiple element analysis of individual particles. Owing to the sequential nature of the mass analyzer, quadrupole-based ICP-MS generally gives poor analytical performance when more than one element are being monitored. In this study, we present the first accurate and precise dual-mass measurement of individual particles using quadrupole-based ICP-MS, with the assistance of oxygen collision gas. Simultaneous measurement of the intensity of 107Ag and 109Ag of Ag nanoparticles (AgNP) showed particle recovery of 100% and Pearson correlation coefficient of 0.97, indicating proper sampling of all particles in the ICP. This technique gives good measurement precision (RSD <8%) and high accuracy in size measurement (error <3%). This technique was further applied to determine the elemental content and isotope ratios of particles and to study cell viability after Cisplatin staining. The results are comparable to that of existing TOF and multi-collector ICP-MS, indicating that quadrupole-based ICP-MS can be a cost-effective alternative for simultaneous measurement of two isotopes. Acquisition with longer integration time and shorter settling time is also proposed to further improve the sensitivity and number of isotopes monitored. This study will potentially open up more possibilities of using quadrupole based ICP-MS in biomedical research as quantification of multi-elements in single cells is far more informative. Other possible applications include classification of cancer subtypes according to the abundance of several biomarkers, as well as elemental bio-imaging of transcripts and proteins in tissues by laser ablation.

Current applications and future perspectives on elemental analysis of non-invasive samples for human biomonitoring.

Humans are continuously exposed to numerous environmental pollutants including potentially toxic elements. Essential elements play an important role in human health. Abnormal elemental levels in the body, in different forms that existed, have been reported to be correlated with different diseases and environmental exposure. Blood is the conventional biological sample used in human biomonitoring. However, blood samples can only reflect short-term exposure and require invasive sampling, which poses infection risk to individuals. In recent years, the number of research evaluating the effectiveness of non-invasive samples (hair, nails, urine, meconium, breast milk, placenta, cord blood, saliva and teeth) for human biomonitoring is increasing. These samples can be collected easily and provide extra information in addition to blood analysis. Yet, the correlation between the elemental concentration in non-invasive samples and in blood is not well established, which hinders the application of those samples in routine human biomonitoring. This review aims at providing a fundamental overview of analytical methods of non-invasive samples in human biomonitoring. The content covers the sample collection and pretreatment, sample preparation and instrumental analysis. The technical discussions are separated into solution analysis and solid analysis. In the last section, the authors highlight some of the perspectives on the future of elemental analysis in human biomonitoring.

Integration of sub-organ quantitative imaging LA-ICP-MS and fractionation reveals differences in translocation and transformation of CeO2 and Ce3+ in mice.

Information on the risk of exposure to cerium oxide (CeO2) nanoparticles (NPs) is limited. To assess risk, we must know where and how such NPs are distributed to the body after exposure, both short- and long-term. In this work, an integrated approach of quantitative LA-ICP-MS bioimaging and fractionation was employed to study the translocation and transformation of CeO2 and Ce3+ in mouse spleen and liver. The complementary information retrieved by the two techniques above on the accumulation of Ce and dissolution/aggregation were found consistent. In brief, a detailed fine scanning of a region of interest in the organ was performed after fast-screening at low spatial resolution. In the spleen, after short-term high-dose exposure, CeO2 NPs was found mainly in the marginal zone and caused an up-regulation of Zn in the white pulp. After long-term low-dose exposure, CeO2 was found in the marginal zone and white pulp. In the liver, CeO2 NPs were mainly distributed in the Kupffer cells and lobule periphery. The high spatial resolution LA maps of H&E-stained liver sections allowed imaging close to cell level; this enabled an estimation of Ce content in Kupffer cells. Furthermore, fractionation by ultrafiltration was also employed to differentiate the ionic and NP species in the organs. This fractionation showed aggregation of Ce ions in spleen, supporting the LA-ICP-MS results. Transmission electron microscopy revealed that long-term CeO2 exposure triggered an immune response to infection in the spleen and confirmed the differential deposition of Ce in the marginal zone. The integrated analyses based on ICP-MS together with histology and TEM investigation suggests that long-term low doses of CeO2 NPs may cause toxicity in the liver and impair functions of the immune system.

Quantifying silver nanoparticle association and elemental content in single cells using dual mass mode in quadrupole-based inductively coupled plasma-mass spectrometry.

In this study, a method of simultaneous dual mass detection for single cell analysis by quadrupole-based ICP-MS (ICP-QMS) is proposed. The method shows potential for use in quantitative investigations of nanoparticle association and elemental composition of cells. Dual mass detection had been attempted in the analysis of two-element core-shell nanoparticles and in isotope dilution analysis. In this method the detector switches between two selected masses during the analysis. Dual mass mode eliminates the discrepancies in signal that can occur due to sample instability or fluctuation in sample uptake when two masses are analysed sequentially by conventional single cell analysis (SP mode). Preliminary tests showed that using an Mg spike as marker of cells in dual mass mode was feasible for the quantification of cells. The method showed good linearity and a reproducible detection rate, and the results were comparable to the SP mode. The approach was then employed with algal cells exposed to silver nanoparticles (AgNP), to study on the Ag-associated cells and AgNP by monitoring the Ag and Mg signal in one analytical run. Finally, Mg and Mn were detected, and then quantified using the same approach to evaluate the elemental composition and correlation between different elements of the exposed cells. It is believed that this dual mass approach can extend the capability of ICP-QMS for multi-elemental detection at the single cell level, representing an enormous potential for size characterization, quantification and elemental composition evaluation in single cell (particle) analysis.