Analyte Signal Intensity Research Articles

Unlocking the potential of 3D printed microfluidics for mass spectrometry analysis using liquid infused surfaces

Combining microfluidics with mass spectrometry (MS) analysis has great potential for enabling new analytical applications and simplifying existing MS workflows. The rapid development of 3D printing technology has enabled direct fabrication of microfluidic channels using consumer grade 3D printers, which holds great promise to facilitate the adoption of microfluidic devices by the MS community. However, photo polymerization-based 3D printed devices have an issue with chemical leeching, which can introduce contaminant molecules that may present as isobaric ions and/or severely suppress the ionization of target analytes when combined with MS analysis. Although extra cure and washing steps have alleviated the leeching issue, many such contaminant peaks can still show up in mass spectra. In this work, we report a simple surface modification strategy to isolate the chemical leachates from the channel solution thereby eliminating the contaminant peaks for MS analysis. The channel was prepared by fabricating a layer of polydimethylsiloxane graft followed by wetting the graft using silicone oil. The resulting liquid infused surface (LIS) showed significant reduction in contaminant peaks and improvement in the signal intensity of target analytes. The coating showed good stability after long-term usage (7 days) and long-term storage (∼6 months). Finally, the utility of the coating strategy was demonstrated by printing herringbone microfluidic mixers for studying fast reaction kinetics, which obtained comparable reaction rates to literature values. The effectiveness, simplicity, and stability of the present method will promote the adoption of 3D printed microdevices by the MS community.

Application of dispersive liquid–liquid extraction followed by rapid and direct mass spectrometry analysis to evaluate parabens in high salinity water sample

As an emerging marine pollutant, parabens have attracted more and more attention due to their widespread existence and potential toxicity in living organisms. In this work, a sensitive and accurate ultrasound-assisted liquid–liquid extraction (LLE) method, followed by a combination of nanoscale electrospray mass spectrometry detection technique, was proposed to determine the trace parabens in high salinity water sample. The method used only one organic solvent for the extraction and ionization of the target in simulated seawater samples. The extraction/ionization of salts is restrained due to their microsolubility or even insolubility in the extraction solvent (also spray solvent), which greatly enhanced the signal intensity of the target analytes and achieved desalination in the mass spectrometry. Several parameters that affect the extraction and ionization efficiencies were investigated. Under the optimal conditions (extraction solvent, 800 µL ethyl acetate; volume ratio of sample to organic phase, 6:1; extraction time, 7 min; nano-tube, a-nanotube; ionization voltage, 2.3 kV), the proposed method was effectively implemented for the detection of five parabens in different real water samples (seawater water and domestic water). The results showed that the limits of detection ranged between 0.21 and 1.11 ng mL−1. In addition, satisfactory accuracy and precision were obtained in real seawater samples for all parabens. This study demonstrated that the combination of LLE and nanoscale electrospray technology is suitable for detecting analytes in high salinity such as seawater.

Strategies for MALDI-MS method development to investigate different pharmaceutical drug modalities

High-throughput screening (HTS) is an ultra-high throughput tool that allows the identification of diverse, pharmaceutically active compounds in the early stages of drug discovery, by enabling chemists to screen reactions at micromole/nanomole scales. To eliminate the bottleneck arising from analysis of large libraries, Matrix Assisted Laser Desorption Ionization Mass Spectrometry (MALDI-MS) can be utilized as a compatible, ultra-fast, label-free, analysis tool. Upon integrating this technique with suitable liquid handling robots that can accurately spot matrices and analytes on a MALDI plate, chemical reactions can be screened at a sampling rate of <1 s per sample. While earlier efforts to improve MALDI-HTS applications were geared towards the development of automation and data processing tools, a systematic method development study across different drug modalities was needed to understand the contribution of different parameters such as MALDI matrices, choice of matrices, additives, and solvent composition, on MALDI-MS signal intensities of analytes. The current study will demonstrate the importance of initial MALDI-MS method development on small molecules, peptides, antibodies, and antibody drug conjugates. This study is designed as a starting point for MALDI-MS signal optimization, which can eventually lead to the development of effective MALDI-HTS methods for various modalities, thus paving the way for a wide range of applications, including but not limited to conformational analysis.

How does the order of sample analysis influence the matrix effect during LC-MS bioanalysis?

Mass spectrometry coupled with liquid chromatography is a valuable tool for drug development and personalised drug therapy. The matrix effect is caused by enhancing or suppressing the analyte signal intensity by the interfering compounds of biological fluids. The matrix effect may influence the reliability of the quantitative results. Thus, its evaluation is a critical part of bioanalytical method validation. Identified factors affecting the matrix effect are the physicochemical properties of the analyte, type of biological material, analytical conditions, the ion source construction and calculation method. The order of analysis of test samples (pure solutions and post-extraction spiked samples) is another factor possibly affecting quantifying the matrix effect variability between sources. Our primary goal was to find which experimental design – interleaved or set of blocks – is more sensitive to detect matrix effect variability. Additionally, to better understand the reason of variability, we evaluated the influence of chromatographic elution and the type of plasma (normal, lipemic or hemolyzed), co-elution, and carry-over of phospholipids. We used chemometric methods: Principal Component Analysis and Partial Least-Squares Discriminant Analysis. Although a comparable (but statistically different) matrix effect (%RSDMF) is observed using the interleaved and block schemes, for some compounds, the order of the samples strongly influences the results. The interleaved scheme was generally more sensitive in detecting the matrix effect than the block scheme. Thus, reporting the order of samples is needed to ensure the repeatability of experiments. Chemometrics suggests that lipemic samples analyzed in isocratic conditions are most prone to the matrix effect. Different compositions of matrix lots of the same type – especially lipemic – may influence method reliability. Thus, evaluating more than one source of lipemic and hemolyzed plasma is recommended.

Substrate-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry of Some Small Biomolecules Using TiO2-Nanotubes: The Effect of Nanotube Diameter and Salt Addition.

Substrate-assisted laser desorption/ionization (SALDI) is a kind of soft ionization method that is most suitable for the analysis of low molecular weight analytes when it is coupled with a time-of-flight mass spectrometer. Unlike the conventional matrix-assisted laser desorption/ionization, there is no interference in the SALDI with matrices for the low mass analyte peaks (m/z < 700). The focus of this work is to develop substrates based on nanomaterials to obtain higher sensitivity, better reproducibility, and easier preparation. The mass spectra of some small molecules (capecitabine, hemin, methadone, noscapine, oxycodone, thebaine, malathion, chlorpyrifos, ethion, permethrin, and phosalone) deposited on the TiO2-nanotube (TiO2-NTs) plate by the SALDI-TOF-MS technique are reported. The nanotubes are synthesized in different diameter sizes of nanotubes via the anodizing method. The intensity of the analyte peaks and the softness of ionization are optimized by varying the diameter of nanotubes and adding relevant alkali salts to the analytes. In addition, the reproducibility of the signal intensity of analytes is optimized by changing the surface hydrophilicity of the TiO2-NT plate.

Fast and simple analysis of the content of Zn, Mg, Ca, Na, and K in selected beverages widely consumed by athletes by flowing liquid cathode atmospheric pressure glow discharge optical emission spectrometry.

An atmospheric pressure glow discharge (APGD) system, generated between a flowing liquid cathode (FLC) and a gas (He) jet anode, was applied for the determination of Zn, Mg, Ca, Na, and K in selected beverages commonly chosen by athletes (namely Coca-Cola Zero, energy and vitamin drinks, pre-workout, branched-chain amino acids, almond drink, and whey protein) by optical emission spectrometry (OES). In some cases (i.e., Coca-Cola, energy drink, and almond drink), sugared and sugar-free versions of the beverages were analyzed with the purpose of establishing the impact of added sugar on the analyte signal intensities. The analysis was performed after a simplified sample preparation procedure, which involved only their dilution and acidification with HNO3 to a concentration of 0.2 mol L-1. To determine the most suitable conditions for performing the analysis, optimization of the crucial operating parameters and sample dilution was carried out. Under the compromise conditions, the instrumental detection limits (DLs) were established and found to be 21, 0.91, 20, 0.062, and 0.14 μg L-1 for Zn, Mg, Ca, Na, and K, respectively. Due to the relatively low detection limits, the analyte content could be determined for a fairly high dilution, being concurrently the same for all analytes, which further simplified the whole procedure. It was found that the vast majority of samples could be determined using external calibration with simple standard solutions. The standard addition technique used for calibration was only required for the determination of Mg in three samples. The analysis results were consistent (in the majority of cases the recovery values were in the range of 88-111%) with the values obtained for the reference method (inductively coupled plasma optical emission spectrometry, ICP-OES), which proved the reliability of the results obtained from the developed FLC-APGD-OES system.

Focusing Plasma Desorption/Ionization Mass Spectrometry.

A plasma-based source named focusing plasma desorption/ionization (FPDI) is described, which applies a high direct current voltage between a metal wire inside a polymeric hollow truncated cone and a piece of a one-sided coated conducting paper substrate. The conducting paper acts as both the counter electrode and the sample carrier. Upon the generation of a visible plasma beam, it would directly ionize the samples spotted on the conducting paper substrate or located around the plasma beam. The signal intensity of target analytes in mass spectrometric analysis is dependent highly on whether the conducting paper substrate is grounded or not, the type of conducting paper substrate, the inside diameter of the polymeric hollow truncated cone tip, the metal wire tip-to-polymer tip distance, the polymer tip-to-paper substrate distance, the applied voltage, and the helium flow rate. Based on the experimental observation, a plausible mechanism is proposed for the generation of the plasma beam from FPDI. Compared to the available low-temperature plasma, flowing atmospheric-pressure afterglow, and helium plasma ionization sources, FPDI has demonstrated higher sensitivity and better compatibility with commercial mass spectrometers without any extra power supplies. As a proof of concept, FPDI coupled with a mass spectrometer has also been applied for the discrimination of different brands of gasoline and determination of solid tablets and pesticides with limits of detection in the range of 2.2 to 30.7 ng mL-1.

Recent Achievements in Electrochemical and Optical Nucleic Acids Based Detection of Metal Ions.

Recently nucleic acids gained considerable attention as selective receptors of metal ions. This is because of the possibility of adjusting their sequences in new aptamers selection, as well as the convenience of elaborating new detection mechanisms. Such a flexibility allows for easy utilization of newly emerging nanomaterials for the development of detection devices. This, in turn, can significantly increase, e.g., analytical signal intensity, both optical and electrochemical, and the same can allow for obtaining exceptionally low detection limits and fast biosensor responses. All these properties, together with low power consumption, make nucleic acids biosensors perfect candidates as detection elements of fully automatic portable microfluidic devices. This review provides current progress in nucleic acids application in monitoring environmentally and clinically important metal ions in the electrochemical or optical manner. In addition, several examples of such biosensor applications in portable microfluidic devices are shown.

Laser Ablation Electrospray Ionization Achieves 5 μm Resolution Using a Microlensed Fiber.

A pulsed (10 Hz) infrared (IR) (1064 nm) laser is focused on a sample surface by means of a microlensed fiber. Analytes desorbed from the surface are captured by charged microdroplets before entering a mass spectrometer. By translating the sample surface, a chemical map is generated with a resolution of 5 μm, defined as the change from 20 to 80% of the analyte signal intensity. As a demonstration of the power of this new imaging technique, analytes from a parsnip root section are imaged and compared with that obtained from conventional laser ablation electrospray ionization mass spectrometry. The improvement in spatial resolution is about a factor of 20.

Triboionization in Discontinuous Atmospheric Pressure Inlet for a Miniature Ion Trap Mass Spectrometer.

Discontinuous atmospheric pressure interface (DAPI) consisting of a pinch valve, a silicone tube, and two metal capillaries has been widely used in miniature mass spectrometry. It is interesting that clear ion signals could be observed even when the extra ionization source was turned off. In-depth analysis suggested that this new ionization phenomenon known as triboionization is based on the surface friction on the inner surface of the silicone tube during the on/off of the pinch valve. In this study, triboionization in the DAPI of a miniature ion trap mass spectrometer was investigated. It was discovered that the signal intensity depended greatly on the material and the roughness of the silicone tube used in the DAPI. By rubbing the inner surface of the silicone tube, for example, the signal intensity can increase by nearly 20 times. Two connected pinch valves were developed to study the effects of the discharge pressure, the number, and the frequency of on/off of the pinch valve on triboionization, which were verified to have a large impact on the product ions. In addition, the humidity of the inner surface of the silicone tube impacted the signal intensity of product ions and the mass spectrum patterns, where the product ions were typically protonated ions. As the humidity increases, the signal intensity of analytes with high proton affinity increases accordingly. This triboionization source, which does not require heat, light, radiation, auxiliary gas, or solution, has been preliminarily proved to have potential for surface detection after continuous enrichment.

B1 inhomogeneity correction of RARE MRI at low SNR: Quantitative in vivo 19 F MRI of mouse neuroinflammation with a cryogenically-cooled transceive surface radiofrequency probe.

Low SNR in fluorine-19 (19 F) MRI benefits from cryogenically-cooled transceive surface RF probes (CRPs), but strong B1 inhomogeneities hinder quantification. Rapid acquisition with refocused echoes (RARE) is an SNR-efficient method for MRI of neuroinflammation with perfluorinated compounds but lacks an analytical signal intensity equation to retrospectively correct B1 inhomogeneity. Here, a workflow was proposed and validated to correct and quantify 19 F-MR signals from the inflamed mouse brain using a 19 F-CRP. In vivo 19 F-MR images were acquired in a neuroinflammation mouse model with a quadrature 19 F-CRP using an imaging setup including 3D-printed components to acquire co-localized anatomical and 19 F images. Model-based corrections were validated on a uniform 19 F phantom and in the neuroinflammatory model. Corrected 19 F-MR images were benchmarked against reference images and overlaid on in vivo 1 H-MR images. Computed concentration uncertainty maps using Monte Carlo simulations served as a measure of performance of the B1 corrections. Our study reports on the first quantitative in vivo 19 F-MR images of an inflamed mouse brain using a 19 F-CRP, including in vivo T1 calculations for 19 F-nanoparticles during pathology and B1 corrections for 19 F-signal quantification. Model-based corrections markedly improved 19 F-signal quantification from errors > 50% to < 10% in a uniform phantom (p < 0.001). Concentration uncertainty maps ex vivo and in vivo yielded uncertainties that were generally < 25%. Monte Carlo simulations prescribed SNR ≥ 10.1 to reduce uncertainties < 10%, and SNR ≥ 4.25 to achieve uncertainties < 25%. Our model-based correction method facilitated 19 F signal quantification in the inflamed mouse brain when using the SNR-boosting 19 F-CRP technology, paving the way for future low-SNR 19 F-MRI applications in vivo.

Capillary Electrophoresis-Mass Spectrometry with Multisegment Injection and In-Capillary Preconcentration for High-Throughput and Sensitive Determination of Therapeutic Decapeptide Triptorelin in Pharmaceutical and Biological Matrices.

A capillary electrophoresis–tandem mass spectrometry method with a multisegment injection and an in-capillary field-enhanced sample stacking for determination of therapeutic peptide triptorelin in pharmaceutical and biological matrices was developed. The CE separation conditions were optimized in order to obtain maximal separation efficiency, analytical signal intensity and stability, and minimal adsorption of the analyzed peptide onto the capillary wall (1 M formic acid—HFo, pH 1.88). The implementation of the field-enhanced sample injection into CE improved the value of limit of detection 50 times while the multisegment injection increased the sample throughput three times in comparison to a conventional CE approach. The proposed method was characterized by favorable performance parameters, such as linearity (r2 ≥ 0.99), limit of detection (5 ng mL−1 in water matrix, 25 ng mL−1 in plasma matrix), precision (relative standard deviation, 1.5–9.4% for intraday and 2.3–11.9% for interday reproducibility), or accuracy (relative errors in the range of 80–109%). The FDA-validated method was successfully applied to the analysis of triptorelin in the commercial drug Diphereline® 0.1 mg (powder for injection) and in spiked human plasma samples. Favorable performance parameters along with proven application potentialities indicate the usefulness of the proposed method for its routine use in drug quality control laboratories and for clinical analysis, such as determination of triptorelin levels in plasma (for pharmacokinetic study).

Implementation of an enclosed ionization interface for the analysis of liquid sample streams with direct analysis in real time mass spectrometry.

The development of an interface to analyze liquid sample streams with direct analysis in real time mass spectrometry (DART-MS) is of great interest for coupling various analytical techniques, using non-volatile salts, with MS. Therefore, we devised an enclosed ionization interface and a sample introduction system for the versatile analysis of liquid samples with DART-MS. The sample introduction system consists of a nebulizer, a spray chamber and a transfer line, while the confined ionization interface is created by implementing a cross-shaped housing between ion source outlet and mass spectrometer inlet. Methodical studies of the effects of various setup parameters on signal intensity and peak shape were conducted, while its diverse applicability was demonstrated by coupling with high-performance liquid chromatography (HPLC) for the analysis of alcohols, organic acids and furanic compounds. The confinement of the ionization interface results in a robust setup design with a well-defined ionization region for focusing of the sprayed sample mist. Thereby, an increase in analyte signal intensity by three orders of magnitude and improved signal stability and reproducibility were obtained in comparison with a similar open ionization interface configuration. Additionally, the successful quantification of alcohols could be demonstrated as well as the compatibility of the setup with HPLC gradient elution. A versatile setup design for the analysis of liquid sample streams with DART-MS was devised for monitoring reactions or hyphenating analytics with MS. The design minimizes interferences from the laboratory surroundings as well as allows for safe handling of hazardous and toxic chemicals, which renders it suitable for a broad range of applications.

Detection of fuel-oxidizer explosives utilizing portable capillary electrophoresis with wipe-based sampling.

Portable analytical instrumentation that can provide an alarm indication for the presence of explosives and related components is critical for the identification of explosives-based hazards and threats. Many explosives incident reports involve an inorganic oxidizer-fuel mixture which can include pyrotechnics, fireworks, flash powders, black powders, black powder substitutes, and improvised or homemade explosives. A portable CE instrument with targeted analysis of common inorganic oxidizer ions, for example, chlorate, perchlorate, and nitrate, was used here as a rapid detection platform. Unlike frequently used gas-phase separation and detection instrumentation such as ion mobility spectrometry (IMS), an automated liquid extraction mechanism is required for CE separation using acetate paper sample collection wipes. Target inorganic oxidizers were inkjet-printed onto sample wipes to investigate instrument response relative to the collected analyte spatial distribution. Overall, analyte signal intensities increased with off-center sample deposition due to improved sample extraction from wipes and no change in response was observed for varied array distributions across wipes. The system demonstrated sub 200ng detection limits for all target analytes, with further improvement when normalizing to an internal standard.

B1 inhomogeneity correction of RARE MRI with transceive surface radiofrequency probes

The use of surface radiofrequency (RF) coils is common practice to boost sensitivity in (pre)clinical MRI. The number of transceive surface RF coils is rapidly growing due to the surge in cryogenically cooled RF technology and ultrahigh-field MRI. Consequently, there is an increasing need for effective correction of the excitation field ( ) inhomogeneity inherent in these coils. Retrospective B1 correction permits quantitative MRI, but this usually requires a pulse sequence-specific analytical signal intensity (SI) equation. Such an equation is not available for fast spin-echo (Rapid Acquisition with Relaxation Enhancement, RARE) MRI. Here we present, test, and validate retrospective B1 correction methods for RARE. We implemented the commonly used sensitivity correction and developed an empirical model-based method and a hybrid combination of both. Tests and validations were performed with a cryogenically cooled RF probe and a single-loop RF coil. Accuracy of SI quantification and T1 contrast were evaluated after correction. The three described correction methods achieved dramatic improvements in B1 homogeneity and significantly improved SI quantification and T1 contrast, with mean SI errors reduced from >40% to >10% following correction in all cases. Upon correction, images of phantoms and mouse heads demonstrated homogeneity comparable to that of images acquired with a volume resonator. This was quantified by SI profile, SI ratio (error < 10%), and percentage of integral uniformity (PIU > 80% in vivo and ex vivo compared to PIU > 87% with the reference RF coil). This work demonstrates the efficacy of three B1 correction methods tailored for transceive surface RF probes and RAREMRI. The corrected images are suitable for quantification and show comparable results between the three methods, opening the way for T1 measurements and X-nuclei quantification using surface transceiver RF coils. This approach is applicable to other MR techniques for which no analytical SI exists.

Impact of matrix effects and ionization efficiency in non-quantitative untargeted metabolomics.

LC-MS-based untargeted metabolomics has become increasingly popular due to the vast amount of information gained in a single analysis. Many studies utilize metabolomics to profile metabolic changes in various representative biofluids, tissues, or other sample types. Most analyses are performed measuring changes in the metabolic pool of a single biological matrix due to an altered phenotype, such as disease versus normal. Measurements in such experiments are typically highly reproducible with little variation due to analytical and technological advancements in mass spectrometry. With the expanded application of metabolomics into various non-analytical scientific disciplines, the emergence of studies comparing the signal intensities of specific analytes across different biological matrices (e.g. plasma vs. urine) is becoming more common, but the matrix effect between sample types is often neglected. Additionally, the practice of comparing the signal intensities of different analytes and correlating to relative abundance is also increasingly prevalent, but the response ratio between analytes due to differences in ionization efficiency is not always accounted for in data analysis. This report serves to communicate and raise awareness of these two well-recognized issues to prevent improper data interpretation in the field of metabolomics. We demonstrate the impact of matrix effects and ionization efficiency with labeled analytical standards in human plasma, serum, and urine and describe how the direct comparison of non-quantitative signal intensities between biofluids, as well as between different analytes in the same biofluid, in untargeted metabolomics is inaccurate without proper response corrections. Human plasma, serum, and urine (n = 4 technical replicates per biofluid) were spiked with a panel of labeled internal standards all at identical concentrations, simultaneously extracted, and analyzed by UHPLC-HRMS. Signal intensities were compared for demonstration of the impact of matrix effects in untargeted metabolomics. A neat mixture of two co-eluting, structurally-similar labeled standards at the same concentration was also analyzed to demonstrate the effect of ionization efficiency on signal intensity. Despite being spiked at identical concentrations, labeled standards we examined in this study showed significant differences in their signal intensities between biofluids, as well as from each other in the same biofluid, due to matrix effects. Co-eluting standards were also found to yield significantly different signal intensities at identical concentrations due to differences in ionization efficiency. Due to the presence of matrix effects in untargeted, non-quantitative metabolomics, the signal intensity of any single analyte cannot be directly compared to the signal intensity of that same analyte (or any other analyte) between any two different matrices. Due to differences in ionization efficiency, the signal intensity of any single analyte cannot be directly compared to the signal intensity of any other analyte, even in the same matrix.

Dynamic Plasmonic Platform To Investigate the Correlation between Far-Field Optical Response and SERS Signal of Analytes.

The design of surface-enhanced Raman spectroscopy (SERS) platforms based on the coupling between plasmonic nanostructures and stimuli-responsive polymers has attracted considerable interest over the past decades for the detection of a wide range of analytes, including pollutants and biological molecules. However, the SERS intensity of analytes trapped inside smart hybrid nanoplatforms is subject to important fluctuations because of the spatial and spectral variation of the plasmonic near-field enhancement (i.e., its dependence with the distance to the nanoparticle surface and with the localized surface plasmon resonance). Such fluctuations may impair interpretation and quantification in sensing devices. In this paper, we investigate the influence of the plasmonic near-field profile upon the Raman signal intensity of analytes trapped inside thermoresponsive polymer-coated gold nanoarrays. For this, well-defined plasmonic arrays (nanosquares and nanocylinders) were modified by poly(N-isopropylacrylamide) (PNIPAM) brushes using surface-initiated atom-transfer radical polymerization. Molecular probes were trapped inside these Au@PNIPAM nanostructures by simple physisorption or by covalent grafting at the end of PNIPAM brushes, using click chemistry. The SERS spectra of molecular probes were studied along various heating/cooling cycles, demonstrating a strong correlation between SERS intensities and near-field spectral profile of underlying nanoparticles, as confirmed by simulations based on the finite difference time domain method. Thermoresponsive plasmonic devices thus provide an ideal dynamic SERS platform to investigate the influence of the near-field plasmonic profile upon the SERS response of analytes.

Study on carbon-induced signal enhancement in inductively coupled plasma mass spectrometry: an approach from the spatial distribution of analyte signal intensities

This study proposed a novel approach for quantifying carbon-induced signal enhancement in ICP-MS considering the spatial distribution of analyte signal intensities.

Ion formation in droplet-assisted ionization.

In droplet-assisted ionization (DAI), intact molecular ions are generated from molecules in aerosol droplets by passing the droplets through a temperature-controlled capillary inlet. Ion formation is explored through the effects of analyte mass flow, droplet solvent composition, and capillary temperature on ion signal intensity. A Waters SYNAPT G2-S is adapted for DAI by reconfiguring the inlet with a temperature-controlled capillary. Droplets are generated by atomization of a solution containing analyte and then sampled through the inlet. If desired, solvent can be removed from the droplets prior to analysis by sending the aerosol through a series of diffusion dryers. Size distributions of the dried aerosols allow the mass flow of analyte into the inlet to be determined. Analyte signal intensities are orders of magnitude higher from droplets containing a protic solvent (water) than an aprotic solvent (acetonitrile). The highest signal intensities for DAI are obtained with inlet temperatures above 500°C, though the optimum temperature is analyte dependent. At elevated temperatures, droplets are thought to undergo rapid solvent evaporation and bursting to produce ions. The lowest signal intensities are generally obtained in the 100-350°C range, where slow solvent evaporation is thought to inhibit ion formation. As the temperature decreases from 100°C down to 25°C, the signal intensity increases significantly. When 3-nitrobenzonitrile, a common matrix for solid-state matrix-assisted ionization (MAI), is added to droplets consisting of 50/50 v/v water and acetonitrile, the matrix enhances ion formation to produce a signal intensity comparable to DAI in 100% water. The results are consistent with other inlet ionization techniques, suggesting that similar ion formation mechanisms are operative. Optimized ion yields (the combined effects of ionization probability and ion transmission) for DAI are currently in the 10-5 to 10-6 range, which is sufficient for many aerosol applications.

Prussian blue nanoparticles based lateral flow assay for high sensitive determination of clenbuterol

Prussian blue nanoparticles (PBNPs), one kind of metal organic frameworks with the general formula of Fe4[Fe(CN)6]3·nH2O, are increasing attractive due to their excellent properties. Here, with PBNPs as labels, a PBNP-based competitive lateral flow assay (LFA) for efficient and sensitive detection of clenbuterol was developed. With unique control structure, PBNPs are quite larger than most of the commonly used labels, meaning much fewer antibodies are needed in the probe to produce clearly visible results, which will bring a more sensitive dose-response relation between the analyte concentration and signal intensity. Under optimal conditions, the PBNP-based LFA showed a great linear relationship over the range of 0.5–5 ng mL−1 for clenbuterol. The visual limit of detection was 1.0 ng mL−1, 5-fold improvement in sensitivity compared with that of the traditional gold nanoparticles based LFA. In our perception, our work opens new possibilities to choose metal organic frameworks as labeling matrices in immunoassays.