Self-aspiration sampling design for rapid analyses of volatile organic compounds based on atmospheric pressure chemical ionization/photoionization combined ionization source mass spectrometry.

Development of combined mass spectrometry ionization sources has enabled expansion of the application and scope of mass spectrometry. A novel hybrid ionization system combining vacuum ultraviolet (VUV) and atmospheric pressure chemical ionization (APCI) was constructed. Gaseous samples were self-aspirated into an ionization zone through a capillary by negative pressure, generated by high-speed airflow based on the Venturi effect. Compared with APCI mode alone, the signal-to-noise ratio (S/N) in APCI/VUV mode was increased by about 276-times. To increase the ionization efficiency further, correlated experimental conditions were optimized. Four types of volatile organic compounds (VOCs) were tested to evaluate the performance of the APCI/VUV ion source. Excellent linearity and limit of detection were achieved for compounds in mixed solutions. Quantitative analyses of four VOCs (toluene, cyclohexanone, styrene and ethylbenzene) using APCI/VUV-MS were done, and the relative standard deviations (RSDs) were 1.57%, 6.30%, 4.49% and 8.21%, respectively, indicating that the APCI/VUV ionization source had excellent reproducibility. Our results demonstrated that the developed method was promising for analyzing VOCs as well as being rapid, simple, and easy to operate.

Pharmacokinetic and pharmacodynamic studies of nicotine in rat brain: a simultaneous investigation of nicotine metabolites and the release of neurotransmitters in vivo.

Introduction: The body's ability to metabolize nicotine and the disposition of nicotine in the brain are important determinants of its exposure. Limited knowledge about the near real-time changes of neurochemicals during the brain nicotine metabolic process hinders the recognition of its multiple neuropharmacological effects. Methods: An online microdialysis coupled with UHPLC-HRMS/MS method for the in vivo multi-analysis of nicotine metabolites and several neurotransmitters in rat brain was developed. Whether the systemic modulation of metabolic enzyme CYP2B would modulate nicotine pharmacokinetics and local neurochemical effects was further investigated. Results: The dynamic profiles of over 10 nicotine metabolites and neurotransmitters were simultaneously obtained after a single injection of nicotine (2 mg·kg-1, i.p.) using the new method. Proadifen pretreatment (50 mg·kg-1·d-1, i.p., 4 days) caused significant inhibition of brain CYP2B1 activity. When exposed to nicotine, the brain C max of nicotine was 1.26 times higher and the levels of nicotine metabolites, nornicotine, and nicotine-N-oxide, were decreased by 85.3% and 34.4% in proadifen-pretreated rats. The higher level of brain nicotine induced a greater release of dopamine, serotonin, glutamate, and γ-amino-butyric acid in the nucleus accumbens. The concentrations of nicotine and dopamine were positively correlated, and the average levels of γ-amino-butyric acid and serotonin were 2.7 and 1.2 times higher, respectively, under the inhibition of nicotine metabolism. Discussion: These results demonstrated that inhibiting nicotine metabolism in rats can enhance the residence of brain nicotine and its local neurotransmitter effects. The metabolic activity of nicotine under different physiological conditions could regulate nicotine's bioavailability and its resulting pharmacology.

Rapid and sensitive determination of free fatty acids based on in-source microdroplet-driven derivatization coupled with high-resolution mass spectrometry.

Accurate and sensitive measurements of free fatty acids (FFAs) in biological samples are valuable for diagnosing and prognosing diseases. In this study, an in-source microdroplet derivation strategy combined with high-resolution mass spectrometry was developed to analyze FFAs in lipid extracts of biological samples directly. FFAs were rapidly derivated with 2-picolylamine (PA) in the microdroplet which is derived by electrospray. With the proposed method, twelve typical FFAs were determined reliably with high sensitivity and acceptable linearities (R2 ≥ 0.94). The LODs and LOQs for the twelve FFAs were 9-76 pg mL-1 and 30-253 pg mL-1, respectively. The developed method was applied to analyze the alteration of FFAs in liver and kidney samples of rats induced by perfluorooctane sulfonate (PFOS) exposure. The good results demonstrate that the established analysis technique is dependable and has promising applications in detecting FFAs associated with complex biological samples.

A core-molecule-shell Au@PATP@Ag nanorod for nicotine detection based on surface-enhanced Raman scattering technology.

Nicotine is an addictive substance often found in tobacco and cigarette smoke and excessive exposure to it can cause various diseases. Herein, core-molecule-shell gold/4-aminothiophenol/silver nanorods (Au@PATP@Ag NRs) were prepared for quantitative detection of nicotine by using surface-enhanced Raman scattering (SERS) technology. The obtained Au@PATP@Ag NRs showed an outstanding SERS effect due to the plasticity of their morphology and the bimetallic synergistic effect between the excellent stability of Au and the highly enhanced effect of Ag. The Au@PATP@Ag NRs substrate exhibited an extremely high enhancement factor (EF) of 2.17 × 107. In addition, in-situ synthesized PATP was used as an internal standard to correct signal fluctuation and improve the reliability of quantitative nicotine detection. A wide linear dynamic range from 10-8 to 10-3 M was obtained and an ultra-low limit of detection (LOD) was about 3.12 × 10-9 M, which was superior to most of previously reported methods. This work has also been used for determining nicotine content in cigarettes and simulated environmental tobacco smoke by using a portable device. These results indicated that the developed SERS method had many potential applications in the quantitative determination of nicotine in real tobacco samples.

Molecular mechanisms of caramel-like odorant-olfactory receptor interactions based on a computational chemistry approach.

Molecular mechanisms of caramel-like odorant-olfactory receptor interactions were investigated based on molecular docking and molecular dynamics simulations. The transmembrane regions TM-3, TM-5 and TM-6 of receptors were main contributors of amino acid residues in the docking. Molecular docking results showed that hydrogen bonding and pi-pi stacking were the key forces for the stabilization of caramel-like odorants. The binding energies were positively correlated with the molecular weight of caramel-like odorants. Residues Asn155 (84%, OR2W1), Asn206 (86%, OR8D1), Ser155 (77%, OR8D1), Asp179 (87%, OR5M3), Val182 (84%, OR2J2) and Tyr260 (94%, OR2J2) with high frequencies played an important role in the complexes formation. Odorants 4-hydroxy-5-methylfuran-3(2H)-one (16#) and methylglyoxal (128#) were screened by molecular field-based similarity analysis, which tended to bind to the receptors OR1G1 and OR52H1 respectively, resulting a caramel-like aroma perception. The obtained results are useful for better understanding the perception of caramel-like odorants and their high-throughput screening.

Ru(II)-modified metal organic framework as excellent electrochemiluminescence emitter for ultrasensitive nicotine detection.

The sensitive and selective nicotine detection in cigarette is necessary due to the cigarette addiction problem and the neurotoxicity of nicotine on human body. In this study, a novel electrochemiluminescence (ECL) emitter with excellent performance was prepared for nicotine analysis, by combining Zr-based metal organic framework (Zr-MOF) and branched polyethylenimine (BPEI)-coated Ru(dcbpy)32+ through electrostatic interaction. Ru(dcbpy)32+ integrated by Zr-MOF could be catalyzed by the reaction intermediates SO4•-, produced from the co-reactant S2O82-, resulting in a significant increase in ECL response. Interestingly, SO4•- with strong oxidizing ability could preferentially oxidize nicotine, leading to ECL quenching. The constructed ECL sensor based on the Ru-BPEI@Zr-MOF/S2O82- system displayed ultrasensitive determination of nicotine with a lower detection limit of 1.9 × 10-12 M (S/N = 3), which is three orders lower than previously reported ECL results and 4-5 orders lower than that of other types of method. This method puts forward a new approach for building efficient ECL system with greatly improved ECL sensitivity for nicotine detection.

Untargeted Metabolomics Using UHPLC-HRMS Reveals Metabolic Changes of Fresh-Cut Potato during Browning Process.

Surface browning plays a major role in the quality loss of fresh-cut potatoes. Untargeted metabolomics were used to understand the metabolic changes of fresh-cut potato during the browning process. Their metabolites were profiled by ultra-high performance liquid chromatography coupled with high resolution mass spectrometry (UHPLC-HRMS). Data processing and metabolite annotation were completed by Compound Discoverer 3.3 software. Statistical analysis was applied to screen the key metabolites correlating with browning process. Fifteen key metabolites responsible for the browning process were putatively identified. Moreover, after analysis of the metabolic causes of glutamic acid, linolenic acid, glutathione, adenine, 12-OPDA and AMP, we found that the browning process of fresh-cut potatoes was related to the structural dissociation of the membrane, oxidation and reduction reaction and energy shortage. This work provides a reference for further investigation into the mechanism of browning in fresh-cut products.

Vanillin-Catalyzed highly sensitive luminol chemiluminescence and its application in food detection.

Among various chemiluminescence (CL) systems, luminol-H2O2 system is used extensively due to its cheapness and sensitivity. Herein, 4-hydroxy-3-methoxybenzaldehyde, known as vanillin, was firstly found to be able to catalyze H2O2 very efficiently to produce •OH and O2•-, which can be used to enhance the CL of luminol-H2O2 as Co+. In alkaline aqueous solution, vanillin catalyzed the dissociation of H2O2 into active •OH and O2•- radicals and accelerated luminol-H2O2 reaction to emit strong CL signal. Combining the stabilizing function of ß-CD, CL intensity of luminol-H2O2 was enhanced further. Thus, dual-signal amplification of luminol-H2O2 chemiluminescence based on the catalyzing function of vanillin and the stabilizing function of ß-CD was proposed and its mechanism was explored deeply in the manuscript. Interestingly, vanillin is a highly prized flavor compound broadly used as food additive, however, the excessive intake of vanillin is harmful to human and thus the determination of vanillin is very important. On the basis of the luminol-ß-CD-H2O2/vanillin reaction, a low-cost, rapid and simple CL sensor has been established to detect vanillin. The sensor was able to detect vanillin in the range of 1.0 µM âˆ¼ 75 µM with a detection limit of 0.89 µM (S/N = 3). It can also be used for CL imaging detection with satisfactory results.

Detection of ß-amyloid peptide aggregates by quartz crystal microbalance based on dual-aptamer assisted signal amplification.

ß-amyloid peptide (Aß) aggregates are regarded as a typical neuropathology hallmark for the diagnosis of Alzheimer's disease (AD). Aß40 aggregates include soluble oligomers (Aß40O) and insoluble fibrils (Aß40F). Both of them can simultaneously bind to two different kinds of its aptamer (Apt1 and Apt2). As a mass-sensitive sensing platform, quartz crystal microbalance (QCM) converts changes in mass on the Au chip surface into frequency shift. Here, a dual-aptamer assisted Aß40 aggregates assay was developed. Taking Aß40O detection as an example, Apt2 was modified on the surface of Au chip by Au-S bond. Subsequently, the solution consisted of Aß40O and gold nanoparticles-Apt1 (AuNPs-Apt1) were injected into the QCM chamber. As a result, Aß40O was specifically recognized and captured by Apt2. AuNPs-Apt1 were also combined on the surface of the Au chip because Aß40O can simultaneously bind to Apt1. Then, a significant frequency shift occurred because of the large weight of AuNPs. Similarly, this procedure can be used to detect Aß40F. This QCM biosensor was able to detect Aß40O with a range of 0.2-10 pM with a detection limit of 0.11 pM, while the linear range for Aß40F was 0.1-10 pM with a detection limit of 0.02 pM. This QCM biosensor was simple and highly sensitive, which provided a new method for Aß40 aggregates detection.

Characterization of Traditional Chinese Sesame Oil by Using Headspace Solid-Phase Microextraction/Gas Chromatography-Mass Spectrometry, Electronic Nose, Sensory Evaluation, and RapidOxy.

Xiao Mo Xiang You (XMXY) is a traditional Chinese sesame oil variety that is obtained through a hot water flotation process. This unique process gives the oil a unique aroma, health benefits, and excellent product stability. Although XMXY is always the most expensive among all the sesame oil varieties, it is usually used as a flavoring in many traditional Chinese daily food products and is increasingly popular. In order to reveal the characteristics of the oil, the volatile components, sensory evaluation, and oxidation stability of five XMXY samples were, respectively, analyzed by using headspace solid-phase microextraction/gas chromatography−mass spectrometry, an electronic nose, sensory evaluation, and RapidOxy. Comparisons and multidimensional statistical analysis were also carried out to distinguish XMXY from roasted sesame oil (RSO) and cold-pressed sesame oil (CSO) samples. In total, 69 volatiles were identified from XMXY, RSO, and CSO samples. Some compounds possessed high odor activity value (OAV > 1) in XMXY, including heterocyclic compounds, phenols, and sulfur-containing compounds. Additionally, they were also the main volatile components that distinguish XMXY from RSO and CSO. Roasted and nutty aromas were the dominant aroma attributes of XMXY. XMXY had better flavor intensity and oxidation stability than the other two sesame oil samples. These results are very valuable for the quality control and product identification of traditional Chinese sesame oil.

Correction: Quartz crystal microbalance for telomerase sensing based on gold nanoparticle induced signal amplification.

Correction for 'Quartz crystal microbalance for telomerase sensing based on gold nanoparticle induced signal amplification' by Haitang Yang et al., Chem. Commun., 2019, 55, 5994-5997, DOI: .

Quartz Crystal Microbalance Detection of Poly(ADP-ribose) Polymerase-1 Based on Gold Nanorods Signal Amplification.

Recent findings have thrust poly(ADP-ribose) polymerase-1 (PARP-1) into the limelight as a potential biomarker and chemotherapeutic target for cancer. Thus, a sensitive method for detection of PARP-1 is necessary for early diagnosis of cancer and drug development. However, the poor electrochemical and optical activity of PARP-1 and its product poly(ADP-ribose) (PAR) prompted researchers to develop more methods. Here, we developed an efficient method for the determination of PARP-1 by using quartz crystal microbalance (QCM) because it is mass-sensitive. Once activated by the specific DNA, PARP-1 cleaves nicotinamideadenine dinucleotide (NAD+) into nicotinamide and ADP-ribose to synthesize a hyperbranched poly(ADP-ribose) polymer. Although QCM is mass-sensitive, it is not sensitive enough to discern PAR effectively. So, positively charged cetyltrimethylammonium bromide (CTAB)-coated gold nanorods (GNRs) were introduced to increase the frequency change significantly because of the strong electrostatic interaction between them with negatively charged PAR. PARP-1 ranging from 0.06 to 3 nM can be facilely detected with a low detection limit of 0.04 nM. The strategy has been used to evaluate PARP-1 inhibitors and to detect PARP-1 activity in real cancer cells lysate with satisfactory results, indicating that it was a promising candidate for clinical diagnosis and drug screening in the future.

Quartz crystal microbalance for telomerase sensing based on gold nanoparticle induced signal amplification.

A novel circulating-flow quartz crystal microbalance (QCM) biosensing method has been established to detect telomerase. Oligonucleotide-functionalized gold nanoparticles (GNPs-cDNA) have been used to amplify the frequency change, which enable this QCM to be a sensitive biosensor for telomerase activity detection. The detection limit was as low as 37 cells per mL. The assay platform exhibited excellent selectivity.

Direct Analysis of Carbonyl Compounds by Mass Spectrometry with Double-Region Atmospheric Pressure Chemical Ionization.

Direct analysis of highly reactive volatile species such as the aliphatic aldehydes as vital biomarkers remains a great challenge due to difficulties in the sample pretreatment. To address such a challenge, we herein report the development of a novel double-region atmospheric pressure chemical ionization mass spectrometry (DRAPCI-MS) method. The DRAPCI source implements a separated structural design that uses a focus electrode to divide the discharge and ionization region to reduce sample fragmentation in the ionization process. Counterflow introduction (CFI) configuration was adopted in the DRAPCI source to reduce background noise, while ion transmission efficiency was optimized through simulating the voltage of the focus electrode and the ion trajectory of the ion source. The limits of detection (LODs) of four carbonyl compounds cyclohexanone, hexanal, heptanal, and octanal by DRAPCI-MS were between 0.1 and 3 µg·m-3, approximately two to eight times lower than those by atmospheric pressure chemical ionization mass spectrometry. Additionally, the DRAPCI-MS method carried out effective in situ analyses of the volatile components in expired milk and the exhaled breath of smokers, demonstrating the DRAPCI-MS as a practical tool to analyze complex mixtures. The DRAPCI-MS method provides a rapid, sensitive, and high-throughput technique in the real-time analysis of gaseous small-molecule compounds.

Nicotine Pharmacokinetics in Rat Brain and Blood by Simultaneous Microdialysis, Stable-Isotope Labeling, and UHPLC-HRMS: Determination of Nicotine Metabolites.

The disposition and metabolism of nicotine in the brain is an important determinant of its exposure. We have developed a novel method for the dynamic determination of nicotine and its metabolites in rat brain and blood by simultaneous microdialysis sampling, stable-isotope labeling, and ultra high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) assaying. Microdialysis probes were inserted into both the right striatum and jugular vein of Sprague-Dawley rats. The collections of dialystes after nicotine intraperitoneal injection were analyzed by the optimized UHPLC-HRMS. Nicotine-pyridyl- d4 was used as a metabolic tracer, and several stably labeled isotopes were applied to calibrate the in vivo recoveries of retrodialysis. The quadrupole-Orbitrap HRMS provided reliable characterization of the nicotine derivatives with less than 3.5 ppm mass measurement accuracy. Good precision and accuracy were obtained for different analytes within the predefined limits of acceptability and the range of the standard curve. Nicotine and its 11 metabolites were identified in most microdialysis samples from the blood and brain tissue samples. Besides cotinine as the main metabolic product of nicotine, trans-3'-hydroxy-cotinine, nicotine- N-oxide, and norcotinine were proven to be the second most abundant metabolites. The other seven nicotine products, including 4-oxo-4-(3-pyridyl)-butanoic acid, 4-hydroxy-4-(3-pyridyl)-butanoic acid, cotinine- N-oxide, nicotine- N-glucuronide, cotinine- N-glucuronide, and trans-3'- hydroxy-cotinine- O-glucuronide, which have not been determined previously in animal brain, were present in minor amounts. The pharmacokinetic profile of nicotine metabolites indicated that the metabolic characteristic of nicotine in the brain was relatively different from that in the blood. The present work would provide comprehensive evidence for clarifying the differences between nicotine metabolism in the brain and peripheral system.

DNA tetraplexes-based toehold activation for controllable DNA strand displacement reactions.

Most of the dynamic DNA devices are rationally constructed by utilizing toehold-mediated DNA strand displacement reactions. However, such approaches have been mainly limited to the operation with double-stranded hybridization and lack the versatility of DNA scaffold responses for additional levels of controlling DNA strand displacement reactions. Herein, we propose a toehold activation strategy based on the DNA tetraplex (G-quadruplex or i-motif), where the toehold domain is designed by attaching a complementary single-stranded segment (CS) to a G-rich/C-rich segment. Modulating G-quartet/C·C(+) numbers and/or the CS lengths can easily tune the strand displacement kinetics. This scheme allows fine control of DNA strand displacement rates over 2 orders of magnitude by adjusting the concentration of various environmental stimuli. This strategy expands the rule set of designing dynamic DNA devices and will be useful in building diverse environmental stimuli-fuelled molecular devices.

Assembly of DNA-functionalized gold nanoparticles on electrospun nanofibers as a fluorescent sensor for nucleic acids.

A facile approach was developed to assemble DNA-functionalized gold nanoparticles on the electrospun nanofibers. This novel nanocomposite was successfully applied to constructing a highly sensitive and selective fluorescent sensor for nucleic acids.

A reusable quartz crystal microbalance biosensor for highly specific detection of single-base DNA mutation.

A reusable quartz crystal microbalance (QCM) biosensor based on the toehold-mediated strand displacement reaction (SDR) is first developed for highly specific detection of single-base DNA mutation. N5, N¹°-methylenetetrahydrofolate reductase (MTHFR) gene C677T mutation is chosen as a model to investigate the performance of the constructed biosensor. The capture DNA immobilized on the gold electrode surface of QCM hybridizes with the conjugate of biotinylated reporter DNA and streptavidin (abbreviated to reporter probe) to form the recognition layer. A toehold domain in the reporter DNA is specifically designed to bind the complementary mutant DNA and trigger the SDR, eventually resulting in the release of the complex of reporter probe and mutant DNA from the gold surface, and then the recognition layer is mildly regenerated by subsequently injecting the reporter probe again. The fabricated biosensor shows good repeatability for the mutant DNA, as more than 87% signal intensity of the sensor remained after six repetitive measurements. A linear range of 1-75 nM is achieved with a detection limit of 0.8 nM at room temperature. This biosensor also affords remarkable specificity to the mutant DNA against its wild-type DNA with a discrimination factor of 33. The potential of applying this biosensor in screening real samples is confirmed by spiked HeLa cells lysate with a recovery of 108%. The proposed sensing strategy provides a simple and universal solution for repetitive and highly specific detection of single-base DNA mutation.

Highly selective detection of single-nucleotide polymorphisms using a quartz crystal microbalance biosensor based on the toehold-mediated strand displacement reaction.

Toehold-mediated strand displacement reaction (SDR) is first introduced to develop a simple quartz crystal microbalance (QCM) biosensor without an enzyme or label at normal temperature for highly selective and sensitive detection of single-nucleotide polymorphism (SNP) in the p53 tumor suppressor gene. A hairpin capture probe with an external toehold is designed and immobilized on the gold electrode surface of QCM. A successive SDR is initiated by the target sequence hybridization with the toehold domain and ends with the unfolding of the capture probe. Finally, the open-loop capture probe hybridizes with the streptavidin-coupled reporter probe as an efficient mass amplifier to enhance the QCM signal. The proposed biosensor displays remarkable specificity to target the p53 gene fragment against single-base mutant sequences (e.g., the largest discrimination factor is 63 to C-C mismatch) and high sensitivity with the detection limit of 0.3 nM at 20 °C. As the crucial component of the fabricated biosensor for providing the high discrimination capability, the design rationale of the capture probe is further verified by fluorescence sensing and atomic force microscopy imaging. Additionally, a recovery of 84.1% is obtained when detecting the target sequence in spiked HeLa cells lysate, demonstrating the feasibility of employing this biosensor in detecting SNPs in biological samples.

A self-assembled DNA nanostructure-amplified quartz crystal microbalance with dissipation biosensing platform for nucleic acids.

A self-assembled DNA nanostructure as an efficient signal amplifier was introduced to create a simple and label-free quartz crystal microbalance with dissipation monitoring (QCM-D) biosensing platform for highly sensitive and selective detection of nucleic acids.