Plasma Mass Spectrometry Detection Research Articles

Retraction Note: Inductively coupled plasma-mass spectrometry (ICP-MS) detection of trace metal contents of children cosmetics

Retraction Note: Inductively coupled plasma-mass spectrometry (ICP-MS) detection of trace metal contents of children cosmetics

Green and Mild Fabrication of Magnetic Poly(trithiocyanuric acid) Polymers for Rapid and Selective Separation of Mercury(II) Ions in Aqueous Samples.

The removal and detection of highly toxic mercury(II) ions (Hg2+) in water used daily is essential for human health and monitoring environmental pollution. Efficient porous organic polymers (POPs) can provide a strong adsorption capacity toward heavy metal ions, although the complex synthetic process and inconvenient phase separation steps limit their application. Hence, a combination of POPs and magnetic nanomaterials was proposed and a new magnetic porous organic polymer adsorbent was fabricated by a green and mild redox reaction in the aqueous phase with trithiocyanuric acid (TA) and its sodium salts acting as reductive monomers and iodine acting as an oxidant. In the preparation steps, no additional harmful organic solvent is required and the byproducts of sodium iodine are generally considered to be non-toxic. The resulting magnetic poly(trithiocyanuric acid) polymers (MPTAPs) are highly porous, have large surface areas, are rich in sulfhydryl groups and show easy magnetic separation ability. The experimental results show that MPTAPs exhibit good adsorption affinity toward Hg2+ with high selectivity, rapid adsorption kinetics (10 min), a large adsorption capacity (211 mg g-1) and wide adsorption applicability under various pH environments (pH 2~8). Additionally, MPTAPs can be reused for up to 10 cycles, and the magnetic separation step of MPTAPs is fast and convenient, reducing energy consumption compared to centrifugation and filtration steps required for non-magnetic adsorbents. These results demonstrate the promising capability of MPTAPs as superior adsorbents for effective adsorption and separation of Hg2+. Based on this, the prepared MPTAPs were adopted as magnetic solid-phase extraction (MSPE) materials for isolation of trace Hg2+ from aqueous samples. Under optimized conditions, the extraction and quantification of trace Hg2+ in water samples were accomplished using inductively coupled plasma mass spectrometry (ICP-MS) detection after MSPE procedures. The proposed MPTAPs-based MSPE-ICP-MS method is efficient, rapid, sensitive and selective for the determination of trace Hg2+, and was successfully employed for the accurate analysis of trace Hg2+ in tap water, wastewater, lake water and river water samples.

Blood pressure and renal function responses in workers exposed to lead for up to six years

Abstract Background Lead is a widespread environmental toxicant. However, there is currently no consensus whether low-level lead exposure raises blood pressure (BP) or induces kidney dysfunction. Purpose The Study for Promotion of Health in Recycling Lead (SPHERL) assessed the BP and renal function (RF) responses for up to six years in the workers without previous occupational lead exposure. Methods BP was the average of 5 consecutive readings and the estimated glomerular filtration rate was derived from serum creatinine (eGFRcrt) and cystatin C (eGFRcys). Blood lead (BL) was measured by inductively coupled plasma mass spectrometry (detection limit 0.5 mg/dL). The statistical methods included multivariable-adjusted mixed models and interval-censored Cox regression analysis. Results The 234 workers analyzed were on average 28.5 years old and included 91.9% men. The baseline BL concentration was 4.35 µg/dL and increased 3.17-fold over follow-up (median: 2.03 years; range: 0.92-6.45 years). The changes in BP and RF were not significantly correlated with the follow-up-to-baseline BL ratio (p≥0.51 and p≥0.18, respectively). The fully-adjusted changes in systolic/diastolic BP associated with a doubling of BL were -0.25/-0.12 mm Hg (CI: -0.94 to 0.44/-0.66 to 0.42 mm Hg). Accordingly, the incidence of stage-1 or -2 hypertension was not associated with the BL change (p≥0.063). Similarly, the changes in eGFRcrt and eGFRcys associated with a 3-fold BL increment were not significant, amounting to -0.70 mL/min/1.73 m2(CI: -1.70 to 0.30 mL/min/1.73 m2) and -1.06 ml/min/1.73 m2 (-2.16 to 0.03 mL/min/1.73 m2). Conclusion The BP and RF responses to an over 3-fold BL increment were small and not significant confirming the safety of modern lead-handing facilities operating under current safety rules.Figure 1Figure 2

Enzymatic reaction and competitive prereduction enable label-free and separation-free inductively coupled plasma mass spectrometry detection of leukemia cells

The enzyme terminal deoxynucleotidyl transferase (TdT) exhibits significant activity in various leukemia cells, including human acute lymphoblastic leukemia cells (CCRF). It demonstrates substantial potential as a diagnostic biomarker for acute lymphoblastic leukemia (ALL). Herein, a highly sensitive method for the homogeneous quantification of TdT and CCRF cells, without the need for labeling or separation, was established based on inductively coupled plasma mass spectrometry (ICP-MS). The simple sensor relied on the TdT-induced polymerization process, lengthening the DNA strand and producing large amounts of the by-product phosphates of pyrophosphate (PPi). The PPi formed complexes with Cu²⁺, altering its morphology in homogeneous systems. The remaining Cu²⁺ competed with Hg²⁺ in consuming ascorbic acid (AA) through the pre-reduction of Hg²⁺, affecting the ICP-MS signal of Hg²⁺. Under optimal conditions, this approach exhibited excellent specificity and ultrahigh sensitivity, with limits of detection (LODs) as low as 0.05 U/L for TdT and 5 cells/mL for CCRF cells, respectively. The proposed method offers significant advantages, including high sensitivity and precision, operation at room temperature without the involvement of proteases, and the ability to accurately quantify in complex biological matrices. Consequently, the proposed method shows great promise as a valuable tool for TdT-related biological research and leukemia diagnosis.

Main nutritional components of food herbs in mountainous areas of Guizhou Province

To investigate the nutritional content of edible medicinal materials in mountainous areas of Guizhou Province and compare the comprehensive nutritional value of different varieties. A total of 15 kinds of edible herbs were collected from Guizhou Province. According to the national standard, direct drying method, Kjeldahl nitrogen determination method, Soxhlet extraction method, high performance liquid chromatography, inductively coupled plasma mass spectrometry and other detection method were used to determine the content of general nutrients, fat soluble vitamins, minerals and ash. According to the weight ranking of nutritional indexes in principal component analysis and membership function analysis, the quality of 9 kinds of food and drug substances and 6 kinds of Chinese medicinal materials were evaluated and ranked. The eigenvalues of the first 4 principal components were greater than 1, and the cumulative contribution rate was 82.32%. Compared with membership function analysis, the top 5 in comprehensive evaluation were Eucommia, Epimedium and honeysuckle, all of which were food and drug substances. The contents of calcium(851.69 mg/100 g), phosphorus(270.22 mg/100 g) and potassium(1446.48 mg/100 g) were the highest. The contents of carotene(21 963.87 μg/100 g) and vitamin E(57.82 mg/100 g) were the highest in the fat-soluble vitamins of Herbimedium. The contents of various indexes of honeysuckle were relatively high. Food and pharmaceutical substances have both medicinal value and nutritional value, and the overall nutritional benefit is higher than that of Chinese medicinal materials.

A novel zwitterionic magnetic nanocomposite developed for non-invasive speciation analysis of inorganic chromium

3-(2-Aminoethylamino)propyltriethoxysilane and carboxyethylsilanetriol sodium salt were grafted on silica-coated Fe3O4 nanoparticles via sol-gel process to prepare novel amine- and carboxyl-bifunctionalized magnetic nanocomposites (SMNPs-(NH2 + COOH)). After well characterized, this doubly functionalized material was used as magnetic solid-phase extraction (MSPE) adsorbent to separate and enrich inorganic chromium species followed by inductively coupled plasma-mass spectrometry detection. The optimization of MSPE operation parameters including pH was conducted. It is reasonably elucidated that the adsorption mechanisms of zwitterionic SMNPs-(NH2 + COOH) towards chromium species are electrostatic and/or coordination interactions. Cr(VI) and Cr(III) can be adsorbed around pH 3.0 and around 10.0 respectively with strong anti-interference ability not only from other co-existing ions but also from the two labile species each other, and eluted by dilute nitric acid solution. With a 15-fold enrichment factor, the limits of detection of Cr(VI) and Cr(III) were 0.008 and 0.009 μg L−1, respectively, profiting from the maximum adsorption capacities of 7.52 and 6.11 mg g−1. The just one magnetic extraction matrix based speciation scheme possesses excellent convenience and friendliness to Cr(VI) and Cr(III) without any oxidation or reduction prior to capture of these two species. This protocol has been successfully applied to the speciation analysis of inorganic chromium in real-world environmental water samples.

BLOOD PRESSURE AND RENAL FUNCTION RESPONSES IN WORKERS EXPOSED TO LEAD FOR UP TO SIX YEARS

Objective: As the contemporary environmental lead exposure is comparable to the pre-industry levels in developed countries, whether lead exposure still contributes to the hypertension and renal impairment is controversial. We aimed to assess the association between blood pressure, renal function and lead exposure at contemporary low level in a longitudinal occupational cohort. Design and method: The Study for Promotion of Health in Recycling Lead assessed the blood pressure (BP) including the incidence of hypertension and renal function (RF) responses for up to six years in the workers without previous occupational exposure. BP averaged by 5 consecutive readings and the estimated glomerular filtration rate (eGFR) derived from serum creatinine and cystatin C (eGFRcrt and eGFRcys). Blood lead (BL) was measured by inductively coupled plasma mass spectrometry (detection limit 0.5 mg/dL). The statistical methods included multivariable-adjusted mixed models and interval-censored Cox regression analysis. Results: The 234 workers analysed were on average 28.5 years old and included 91.9% men. The baseline BL concentration was 4.35 microgram/dL and increased 3.17-fold over follow-up (median: 2.03 years; range: 0.92-6.45 years). The changes in BP and RF were not significantly correlated with the follow-up-to-baseline BL ratio (p >= 0.51 and p >= 0.18, respectively). The fully-adjusted changes in systolic/diastolic BP associated with a doubling of BL were -0.25/-0.12 mm Hg (CI: -0.94 to 0.44/-0.66 to 0.42 mm Hg). Accordingly, the incidence of stage-1 or stage-2 hypertension was not associated with the BL change (p >= 0.063). Similarly, the changes in eGFRcrt and eGFRcys associated with a 2 fold BL increment were not significant, amounting to -0.70 mL/min/1.73 m2 (CI: -1.70 to 0.30 mL/min/1.73 m2) and 1.06 ml/min/1.73 m2 (-2.16 to 0.03 mL/min/1.73 m2). Conclusions: The BP and RF responses to an over 3-fold BL increment were small and not significant confirming the safety of modern lead-handing facilities operating under current safety rules.

Study on determination methods and analysis of micronutrients in take-away meals

To comprehensively analyze the trace nutrient contents in take-away meals, the simultaneous detection method of common vitamins in take-away meals were explored based on the samples' matrix, and the content of trace nutrients in take-away meals was analyzed combined with inductively coupled plasma-mass spectrometry(ICP-MS) detection of common elements. Fifty-seven take-away meals were collected randomly and analyzed. Vitamins were determined by high performance liquid chromatography-ultraviolet detector tandem fluorescence detector after pretreatment of samples including enzymatic digestion, hydrolysis and extraction. The separation was performed on a C_(18) column(250 mm×4.6 mm, 5 μm) with ion-pair acid reagents as the mobile phase for water-soluble vitamins and methanol for fat-soluble vitamins. Vitamin B_1, vitamin B_2, nicotinic acid, nicotinamide and vitamin A were detected by ultraviolet detector(UVD), while vitamin B_6 and E by fluorescence detector(FLD). Elemental analysis of calcium, magnesium, sodium, potassium, zinc, selenium and copper in the take-away meals was carried out according to GB 5009.268-2016 by ICP-MS to comprehensively evaluate the contents of micronutrients. Through optimization of chromatography and sample pretreatment conditions, the sensitivity of the established detection method can meet the needs of micronutrient evaluation with the detection limits and quantification limits of vitamins in the range of 0.002-0.098 mg/100 g and 0.007-0.327 mg/100 g, respectively. Good precision was obtained(<10%). The spiked recovery rates were 80.5%-103.8%(n=6). The result showed that the contents of micronutrients in take-away meals were generally low. The detection rates of vitamins ranged from 21.1% to 98.2%. The proposed method is simple and sensitive, and the contents of vitamins and elements determined were low in the collected take-away meals.

RETRACTED ARTICLE: Inductively coupled plasma-mass spectrometry (ICP-MS) detection of trace metal contents of children cosmetics

Consumption of cosmetic products in daily life in order to improve skin quality or appearance is becoming quite common. Over time, it may expose consumers to skin problems and effects caused by the absorption of chemical elements. Clean cosmetic production is important for our health. However, heavy metals can be found as impurities in raw materials or as by-products of the cosmetic production process. Women's ingestion and exposure to organic and inorganic contaminants in cosmetics through dermal absorption, due to reasons such as personal habits and characteristics of the living environment, may contribute to carcinogenic risks following daily dietary exposure. NCS ZC 81002b (Human Hair) was performed as a certified reference material in method validation. This work was conducted to evaluate element concentrations of selected elements (Al, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Hg, Cd and Pb) in 3 different brands of children's cosmetic products such as bright and colorful 22 eye shadows (7 different colour) 4 lipsticks (3 different colour) and 4 nail polishes (3 different colour) used by children in Turkey. The sample solutions were analyzed with the inductively coupled plasma mass spectrometry (ICP-MS) technique after the microwave digestion system. Consequently, the highest concentration of Al used as pigment was found in the eye shadow, lipstick and nail polish samples for the 3 brands, while the Se concentrations were the lowest in lipstick samples. The results of As, Cd, Hg, Pb, which are restricted or banned for use in cosmetic products in most countries, are below the limits set by the Food and Drug Administration (FDA) and Health Canada Product Safety Laboratory (PSL).

CCQM-K160: platinum group elements in automotive catalyst

Main textThe platinum group elements (PGEs) play an important role in reducing emissions from automotive vehicles through their use in catalytic convertors but also for catalysis in the pharmaceutical industry. The immense economic value of platinum (Pt), palladium (Pd) and rhodium (Rh) highlights the importance of highly accurate measurements. Therefore, there is a need for National Metrology Institutes (NMIs) and Designated Institutes (DIs) to demonstrate measurement capability in this space.A pilot comparison (CCQM-P63) for precious metals in automotive catalyst took place in 2006, but with a limited number of institutes participating. Furthermore, this study was performed over 17 years ago. Therefore, there was a need to maintain existing capability and demonstrate new capability in a key comparison, in order to claim calibration and measurement capability claims (CMCs). With the core capability matrix, this study falls into the "Difficult to dissolve metals/metal oxides" which will support CMC categories 8 (Metal and metal alloys), 9 (Advanced materials) and 14 (Other materials).Eleven NMIs and DIs participated in the Key Comparison CCQM-K160 Platinum Group Elements in Automotive Catalyst. Participants were requested to evaluate the mass fractions of Pt, Pd and Rh in mg/kg in an unused autocatalyst material (cordierite ceramic base). The Key Comparison Reference Values (KCRVs) and Degrees of Equivalence (DoEs) were calculated utilising the NIST Decision Tree for the measurands. The participants utilised a number of sample preparation and analytical methods including hot plate digestion, microwave digestion and sodium fusion, followed by either atomic absorption spectroscopy (AAS), inductively coupled plasma optical emission spectroscopy (ICP-OES) or inductively coupled plasma mass spectrometry (ICP-MS) detection. Several calibration techniques were used, namely external calibration, standard addition, isotope dilution mass spectrometry (IDMS) and an exact matching procedure. Additionally, one participant employed instrumental neutron activation analysis (INAA) with k0 standardisation which is a direct solid analysis method. The majority of participants claimed traceability to NIST primary calibrants or their own CRMs. Furthermore, several matrix CRMs were included or spiked samples for quality control. All institutes were required to determine the dry mass fraction using the stipulated protocol.The NIST decision tree was implemented for the calculation of the KCRVs and DoEs. The participant results overall showed good agreement with the KCRV, despite the variety of dissolution procedures and measurement techniques for this highly complex matrix and challenging measurands. Successful participation in CCQM-K160 demonstrated measurement capabilities for the determination of mass fraction of Pt, Pd and Rh in the mg/kg range and will support broad scope CMC claims for a wide range of challenging matrices.To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database https://www.bipm.org/kcdb/.The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

A Cascaded Phase-Transfer Microfluidic Chip with Magnetic Probe for High-Activity Sorting, Purification, Release, and Detection of Circulating Tumor Cells.

Microfluidic chips have emerged as a promising tool for sorting and enriching circulating tumor cells (CTCs) in blood, while the efficacy and purity of CTC sorting greatly depend on chip design. Herein, a novel cascaded phase-transfer microfluidic chip was developed for high-efficiency sorting, purification, release, and detection of MCF-7 cells (as a model CTC) in blood samples. MCF-7 cells were specifically captured by EpCAM aptamer-modified magnetic beads and then introduced into the designed cascaded phase-transfer microfluidic chip that consisted of three functional regions (sorting, purification, and release zone). In the sorting zone, the MCF-7 cells moved toward the inner wall of the channel and entered the purification zone for primary separation from white blood cells; in the purification zone, the MCF-7 cells were transferred to the phosphate-buffered saline flow under the interaction of Dean forces and central magnetic force, achieving high purification of MCF-7 cells from blood samples; in the release zone, MCF-7 cells were further transferred into the nuclease solution and fixed in groove by the strong magnetic force and hydrodynamic force, and the continuously flowing nuclease solution cleaved the aptamer on the trapped MCF-7 cells, causing gentle release of MCF-7 cells for subsequent inductively coupled plasma mass spectrometry (ICP-MS) detection or further cultivation. By measurement of the endogenous element Zn in the cells using ICP-MS for cell counting, an average cell recovery of 84% for MCF-7 cells was obtained in spiked blood samples. The developed method was applied in the analysis of real blood samples from healthy people and breast cancer patients, and CTCs were successfully detected in all tested patient samples (16/16). Additionally, the removal of the magnetic probes on the cell surface significantly improved cell viability up to 99.3%. Therefore, the developed cascaded phase-transfer microfluidic chip ICP-MS system possessed high integration for CTCs analysis with high cell viability, cell recovery, and purity, showing great advantages in early clinical cancer diagnosis.

Interlaboratory comparison of centrifugal ultrafiltration with ICP-MS detection in a first-step towards methods to screen for nanomaterial release during certification of drinking water contact materials

A key requirement for evaluating the safety of nano-enabled water treatment devices is measuring concentrations of insoluble nanomaterials released from devices into water that may be ingested by consumers. Therefore, there is a need for simple technique that uses commonly available commercial laboratory techniques to discriminate between nanoparticles and dissolved by-products of the nanomaterial (e.g., ionic metals). Such capabilities would enable screening for particulate or dissolved metals released into water from nanomaterial-containing drinking water contact materials (e.g., paint coatings) or devices (e.g., filters). This multi-laboratory study sought to investigate the use of relatively inexpensive centrifugal ultrafilters to separate nanoparticulate from ionic metal in combination with inductively-coupled plasma mass spectrometry (ICP-MS) detection. The accuracy, precision, and reproducibility for the proposed method were assessed using mixtures of nanoparticulate and ionic gold (Au) in a standard and widely utilized model water matrix (NSF International Standard 53/61). Concentrations for both ionic and nanoparticulate gold based upon measurements of Au mass in the initial solutions and Au permeating the centrifugal ultrafilters. Results across different solution compositions and different participating labs showed that ionic and nanoparticulate Au could be consistently discriminated with ppb concentrations typically resulting in <10 % error. A mass balance was not achieved because nanoparticles were retained on membranes embedded in plastic holders inside the centrifuge tubes, and the entire apparatus could not be acid and/or microwave digested. This was a minor limitation considering the ultrafiltration method is a screening tool, and gold concentration in the permeate indicates the presence of ionic metal rather than nanoforms. With further development, this approach could prove to be an effective tool in screening for nanomaterial release from water-system or device materials as part of third-party certification processes of drinking water compatible products.

Blood pressure and renal function responses in workers exposed to lead for up to six years.

The Study for Promotion of Health in Recycling Lead (SPHERL) assessed the blood pressure (BP) and renal function (RF) responses for up to 6 years in the workers without previous occupational lead exposure. BP was the average of five consecutive readings and the estimated glomerular filtration rate was derived from serum creatinine (eGFRcrt) and cystatin C (eGFRcys). Blood lead (BL) was measured by inductively coupled plasma mass spectrometry (detection limit 0.5 μg/dL). The statistical methods included multivariable-adjusted mixed models and interval-censored Cox regression analysis. The 234 workers analyzed were on average 28.5 years old and included 91.9% men. The baseline BL concentration was 4.35 μg/dL and increased 3.17-fold over follow-up (median: 2.03 years; range: 0.92-6.45 years). The changes in BP and RF were not significantly correlated with the follow-up-to-baseline BL ratio (p ≥ .51 and p ≥ .18, respectively). The fully-adjusted changes in systolic/diastolic BP associated with a doubling of BL were -0.25/-0.12mm Hg (CI: -0.94 to 0.44/-0.66 to 0.42mm Hg). Accordingly, the incidence of stage-1 or -2 hypertension was not associated with the BL change (p ≥ .063). Similarly, the changes in eGFRcrt and eGFRcys associated with a 3-fold BL increment were not significant, amounting to -0.70mL/min/1.73 m2 (CI: -1.70 to 0.30mL/min/1.73 m2 ) and -1.06mL/min/1.73 m2 (-2.16 to 0.03mL/min/1.73 m2 ). In conclusion, the BP and RF responses to an over 3-fold BL increment were small and not significant confirming the safety of modern lead-handing facilities operating under current safety rules.

Molecular epidemiology

Abstract Environmental exposures increase risk for multiple diseases, including dementia. The modern expansion of industrialization and the combustion of fossil fuels, coupled with extensive application of chemical fertilizers in farming, have led to an increase in the levels of toxic elements in the air, water and food. A key part of this work is to identify biological signatures associated with toxic element exposure, such as arsenic, and its effects on chronic disease conditions. This presentation will showcase a worked example illustrating how arsenic exposure will be assessed in urine samples. iAs, MMA, DMA and AsB will be analysed in urine by ion chromatography interfaced with inductively coupled plasma-mass spectrometry detection (ICP-MS) in Prof. Andy Meharg's lab, Queens's University, Belfast. DNAm data will be processed through Rnbeads 2.0. A principal-component analysis (PCA) was then used to identify technical variability (batch effect) in DNAm data. After removing batch effect, Clean DNAm data will be used in linear regression models to determine CpG loci associated with arsenic exposure.

Covalent organic frameworks based hierarchical porous hybrid monolithic capillary: Synthesis, characterization, and applications in trace metals analysis

The preparation of hierarchical porous monolithic column with high covalent organic frameworks (COF) loading and micropores accessibility is challenging due to the easy aggregability and sedimentation of COFs. Herein, a novel strategy based on high internal phase emulsion (HIPE) polymerization was proposed for preparing COF hybrid capillary monolithic column with hierarchical porosity. COFs with different frameworks including imine COFs (COF-OMe, COF-F and COF-SH), triazine COF (CTF-1) and boron-based COF (COF-5) were selected to investigate the universality of the preparation strategy. The presence of COF in the monolithic capillary was confirmed by scanning electron microscope, X-ray diffraction and fourier transform infrared spectroscopy. Nitrogen adsorption/desorption experiments and thermogravimetric analysis showed that the prepared COF hybrid monolithic capillary exhibited high COF loading (e.g., 28.7% for COF-SH) and accessibility (e.g., 98.5% for COF-SH), mainly due to the thin walls of void-window structures originated from polymerization of HIPE. The successful preparation of water-stable COF-F, COF-OMe, COF-SH and CTF-1 hybrid monolithic columns demonstrated the proposed synthesis strategy is universal to water-stable COF without tedious optimization of dispersion system, effectively avoiding the sedimentation of COF in pre-polymerization solution. Then, the sulfhydryl-modified COF hybrid polymer (poly(COF-SH-HIPE)) monolithic column was evaluated for the extraction of heavy metal ions, and a method based on poly(COF-SH-HIPE) monolithic capillary microextraction on-line coupled with inductively coupled plasma mass spectrometry detection was developed for analysis of trace Cd, Hg and Pb in human fluid samples.

All-in-One Microfluidic Chip for Online Labeling, Separating, and Focusing Rare Circulating Tumor Cells from Blood Samples Followed by Inductively Coupled Plasma Mass Spectrometry Detection.

Circulating tumor cell (CTC) detection is essential for early cancer diagnosis and evaluating treatment efficacy. Despite the growing interest in isolating CTCs and further quantifying surface biomarkers at the single-cell level, highly efficient separation of rare CTCs from massive blood cells is still a big challenge. Here, we developed an all-in-one microfluidic chip system for the immunolabeling, magnetic separation, and focusing of HepG2 cells (as a CTC model) and online combined it with single cell-inductively coupled plasma mass spectrometry (SC-ICP-MS) for quantitative analysis of the asialoglycoprotein receptor (ASGPR) on single HepG2 cells. Lanthanide-labeled anti-ASGPR monoclonal antibody and antiepithelial cell adhesion molecule-modified magnetic beads were prepared as signal and magnetic probes, respectively. Target cells were highly efficiently labeled with signal and magnetic probes in the mixing zone of the microfluidic chip and then focused and sorted in the separation zone by specific magnetic separation techniques to avoid matrix contamination. The average cell recovery of HepG2 cells was derived to be 94.1 ± 5.7% with high separation efficiency and purity. The sorted cells with signal probes were detected for enumeration and quantification of ASGPR on their surface by SC-ICP-MS. The developed method showed good specificity and high sensitivity, detecting an average of (1.0 ± 0.2) × 105 ASGPR molecules per cell surface. This method can be used for absolute quantitative analysis of ASGPR on the surface of single hepatocellular carcinoma cells in real-world samples, providing a highly efficient analytical platform for studying targeted drug delivery in cancer therapy.

Metal mixture and osteoporosis risk: Insights from plasma metabolite profiling

The pathophysiology of osteoporosis (OP) is influenced by exposure to nonessential harmful metals and insufficient or excessive intake of necessary metals. Investigating multiple plasma metals, metabolites, and OP risk among older adults may reveal novel clues of underlying mechanisms for metal toxicity on bone mass. A total of 294 adults ≥ 55 years from Wuhan communities were included. Plasma concentrations of 23 metals and metabolites were measured via inductively coupled plasma-mass spectrometry and global metabolite detection. To investigate the relationships between plasma metals, OP risk, and OP-related metabolites, three different statistical techniques were used: generalized linear regression model, two-way orthogonal partial least-squares analysis (O2PLS), and weighted quantile sum (WQS). The mean ages were 66.82 and 66.21 years in OP (n = 115) and non-OP (n = 179) groups, respectively. Of all 2999 metabolites detected, 111 differential between-group members were observed. The OP risk decreased by 58.5% (OR=0.415, 95% CI: 0.237, 0.727) per quartile increment in the WQS index indicative of metal mixture exposure. Consistency remained for bone mineral density (BMD) measurements. The O2PLS model identified the top five OP-related metabolites, namely, DG(18:2_22:6), 3-phenoxybenzoic acid, TG(16:1_16:1_22:6), TG(16:0_16:0_20:4), and TG(14:1_18:2_18:3), contributing most to the joint covariation between the metal mixture and metabolites. Significant correlations between each of them and the metal mixture were found using WQS regression. Furthermore, the five metabolites mediated the associations of the metal mixtures, BMD, and OP risk. Our findings shed additional light on the mediation functions of plasma metabolites in the connection between multiple metal co-exposure and OP pathogenesis and offer new insights into the probable mechanisms underpinning the bone effects of the metal mixture.

DNA tetrahedron-based CRISPR bioassay for treble-self-amplified and multiplex HPV-DNA detection with elemental tagging.

Sensitive quantification of multiple analytes of interest is of great significance for clinical diagnosis. CRISPR Cas platforms offer a strategy for improving the specificity, sensitivity, and speed of nucleic acid-based diagnostics, while their multiplex analysis capability is still limited and challenging. Herein, we develop a novel DNA Tetrahedron (DTN)-supported biosensor based on the spatially separated CRISPR Cas self-amplification strategy and multiple-metal-nanoparticle tagging coupled with inductively coupled plasma mass spectrometry (ICP-MS) detection to improve the sensitivity and feasibility of the platform for multiplex detection of HPV-DNA (HPV-16, HPV-18 and HPV-52). Given target DNA induces robust trans-cleavage activity of the Cas12a/crRNA duplex, and the surrounding corresponding single-stranded DNA (ssDNA) linker are cleaved into short fragments that are unable to bond metal-nanoparticle probes (197Au, 107Ag, 195Pt) onto DTN modified magnetic beads probe (MBs-DTN), resulting in obvious ICP-MS signal change. Of note, compared with ssDNA functionalized MBs, a higher Signal-to-Noise Ratio was obtained by using MBs-DTN in our system, further amplifying the signal by regulating probes on the surface of MBs. As expected, the HPV-DNA could be detected with detection limits as low as 218fM and be multiplexed assayed at one test with high accuracy and specificity by this proposed strategy. Furthermore, we demonstrated that the HPV-DNA in cervical swab samples could be detected, showing high consistency with DNA sequencing results. We believe that this work provides a promising option in designing CRISPR based multiplex detection system for high sensitivity, good specificity, and clinical molecular diagnostics.

Evaluation of Cd2+ stress on Synechocystis sp. PCC6803 based on single-cell elemental accumulation and algal toxicological response

With the development of single cell analysis techniques, the concept of precision toxicology has been proposed in recent years. Due to the heterogeneity of cells, we need to perform toxicological assessments on individual cells. Microalgae, one kind of important primary producers, play as a major pathway by which heavy metals enter the food chain and thus accumulate/transfer to higher trophic levels. Herein, the biosorption of Cd (Ex-Cd) and bioaccumulation of Cd (In-Cd) for Synechocystis sp. PCC 6803 were investigated by online 3D droplet microfluidic device combined with inductively coupled plasma mass spectrometry detection. Meanwhile, the algal toxicological responses of the algae cell to Cd2+ exposure under different concentration (50, 100, and 150 μg L − 1) and time (15 min, 24, 48 and 96 h) were studied. Combining single-cell analysis with toxicological indicators, the toxicity mechanism of Cd2+to algal was discussed. The single cell analysis results revealed heterogeneity in cellular uptake of Cd2+. The proportion of Cd-containing cells and Cd content in single algal cells all reached the maximum at 24 h. The uptake of Cd2+ occurred within 15 min under all tested exposure concentrations and a large part of Cd2+ were adsorbed on the algal cells surface. The Pearson correlation analysis showed that cell density, chlorophyll a and carotenoids were significantly negatively correlated with Cd accumulation, whereas ROS level and SOD activity were significantly positively correlated with Cd accumulation. It suggested that Cd2+accumulated intracellular would show toxic effects on the algal cells and oxidative stress is the main mechanism of Cd toxicity to algal cells. This work promotes our understanding of the toxicological responses of microalgae under Cd stress at single cells level.

Ultrasensitive determination of β-conglutin food allergen by means an aptamer assay based on inductively coupled plasma mass spectrometry detection

The overall objective of this work is the evaluation of different competitive aptamer assays based on inductively coupled plasma mass spectrometry (ICP-MS) detection for the determination of β-conglutin (food protein allergen from lupin) in flour samples. To this end, two competitive aptamer assay schemes were developed using either thiolated aptamers chemisorbed onto gold nanoparticles (AuNPs) or biotinylated aptamers linked to streptavidin-AuNPs. The influence of ICP-MS detection mode (i.e., conventional vs single particle) on assay performance was explored. In the case of the thiolated aptamer, the limit of detection (LoD) obtained using the single particle mode was improved 2-fold as compared to the LoD provided by the conventional mode. With regards to the biotinylated aptamer, the use of the conventional mode provided a 5-fold improvement of LoD as compared to that obtained for the single particle one. Using the optimized conditions, the best LoD of 2 pM was obtained with the biotinylated aptamer operating with conventional ICP-MS detection. When compared to previous reports using the same aptamer in a competitive assay, the developed method significantly improved the LoD by at least an order of magnitude. Different flour samples containing lupin were successfully analyzed according to European Conformity guidelines for the analysis of food contaminants.