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Metformin (MET) and sitagliptin (STG) are widely used as the first-line and long-term oral hypoglycemic agents for managing type 2 diabetes mellitus (T2DM). However, the current lack of convenient and rapid measurement methods poses a challenge for individualized management. This study developed a point-of-care (POC) assay method utilizing a miniature mass spectrometer, enabling rapid and accurate quantification of MET and STG concentrations in human blood and urine. By combining the miniature mass spectrometer with paper spray ionization, this method simplifies the process into three to four steps, requires minimal amounts of bodily fluids (50 μL of blood and 2 μL of urine), and is able to obtain quantification results within approximately 2 min. Stable isotope-labeled internal standards were employed to enhance the accuracy and stability of measurement. The MS/MS responses exhibited good linear relationship with concentration, with relative standard deviations (RSDs) below 25%. It has the potential to provide immediate treatment feedback and decision support for patients and healthcare professionals in clinical practice. [ABSTRACT FROM AUTHOR]

A new method was proposed for point-of-care testing (POCT) of immunosuppressants in blood using thin-layer paper spray ionization and a miniature mass spectrometer. The aluminum thin-layer plate was used as paper spray substrate, and cut into an equilateral triangle. Aliquots of 10 μL blood sample were loaded on the aluminum thin-layer plate, and then 20 μL methanol was dropped as elution/spray solvent. The tip of the triangular plate was placed 1.0 cm in front of the discontinuous atmospheric pressure interface (DAPI) of the miniature mass spectrometer. When the spray voltage was applied, the sample was eluted from the triangular plate and formed paper spray ionization at the tip. Coupled with the miniature mass spectrometer, five immunosuppressants were detected under negative ion mode. The precursor ions ［M-H］- of tacrolimus, sirolimus, everolimus, ciclosporin A, and mycophenolic acid are m/z 802.6, 912.6, 957.1, 1 200.8, 319.1, and product ions are m/z 560.2 and 604.3, m/z 590.3 and 321.2, m/z 590.3 and 365.2, m/z 1 088.8, m/z 287.4 and 275.1, respectively. Based on the observed signal-to-noise ratio (S/N) of the most intense tandem mass spectrometry (MS/MS) fragment peaks and using the S/N=3 and 10 as the criteria, the limits of detection (LODs) and quantitation (LOQs) are estimated to be 0.5-5 mg/L and 1-10 mg/L, respectively. The internal standard method was used for quantitative analysis, and indapamide was used as the internal standard compound. Sufficient linearity for each analyte is obtained with the correlation coefficients (r) greater than 0.99. The proposed method displays good recoveries in the range of 91.0%-114.3% with the relative standard deviations (RSDs) less than 8.4%. Moreover, the developed method was used for the analysis of blood samples, which spiked with tacrolimus, sirolimus, everolimus, cyclosporine A and mycophenolic acid at the concentration of 100 mg/L. The analytical results demonstrated the consistency between the proposed method and the traditional liquid chromatography-mass spectrometry (LC-MS) method. The entire analysis procedure can be completed within 1 min. The proposed method is simple, fast, accurate, efficient, and suitable for POCT of immunosuppressants in blood.

The development and application of ambient ionization and miniature mass spectrometry have become the current research hotpot, which is capable of rapid, sensitive, on-site and real-time analysis of samples without complex sample pretreatment. In this study, a rapid on-site method using dielectric barrier discharge ionization (DBDI) and a miniature mass spectrometer was developed for the screening of prohibited substances in spray cosmetics. Helium gas was used as the discharge gas and 1 mm thick quartz glass was used as the dielectric barrier in a custom-made DBDI ion source. The two brass electrodes were 10 mm apart, both mounted outside the quartz glass. The inner diameter of the glass tube at the gas inlet and outlet was 1 mm. When the experiment was carried out, the DBDI ion source was placed 3 cm in front of the discontinuous atmospheric pressure interface (DAPI) of the miniature mass spectrometer. The spray cosmetic sample was placed 8 cm directly above the plasma beam generated by the DBDI. Without any sample pretreatment, once the sample spray valve was pressed, the sample microdroplets generated in the vertical direction collided with the plasma beam generated in the horizontal direction. In the region between the DBDI and the miniature mass spectrometer, the target substances were ionized by energy and charge transfer with the plasma beam, and then detected by the miniature mass spectrometer. The helium flow rate was set at an optimum value of 220 mL/min by a gas mass flow controller. Coupled with the miniature mass spectrometer, four prohibited colorants in disposable hair dye spray and four prohibited fragrances in spray lotion were screened. Based on the observed signal-to-noise ratio (S/N) of the most intense MS/MS fragment peaks and using S/N=3 as a criterion, the limits of detection (LODs) were estimated between 10 and 50 μg/kg for the eight prohibited substances. The entire analysis procedure could be completed within 1 min. The simplified analytical protocol can effectively solve the disadvantages of traditional analytical methods that are cumbersome and time-consuming. The proposed method is simple, rapid, sensitive, efficient, and suitable for rapid on-site screening of prohibited substances in spray cosmetics.

A new method was proposed for point-of-care testing (POCT) of immunosuppressants in blood using thin-layer paper spray ionization and a miniature mass spectrometer. The aluminum thin-layer plate was used as paper spray substrate, and cut into an equilateral triangle. Aliquots of 10 μL blood sample were loaded on the aluminum thin-layer plate, and then 20 μL methanol was dropped as elution/spray solvent. The tip of the triangular plate was placed 1.0 cm in front of the discontinuous atmospheric pressure interface (DAPI) of the miniature mass spectrometer. When the spray voltage was applied, the sample was eluted from the triangular plate and formed paper spray ionization at the tip. Coupled with the miniature mass spectrometer, five immunosuppressants were detected under negative ion mode. The precursor ions ［M-H］- of tacrolimus, sirolimus, everolimus, ciclosporin A, and mycophenolic acid are m/z 802.6, 912.6, 957.1, 1 200.8, 319.1, and product ions are m/z 560.2 and 604.3, m/z 590.3 and 321.2, m/z 590.3 and 365.2, m/z 1 088.8, m/z 287.4 and 275.1, respectively. Based on the observed signal-to-noise ratio (S/N) of the most intense tandem mass spectrometry (MS/MS) fragment peaks and using the S/N=3 and 10 as the criteria, the limits of detection (LODs) and quantitation (LOQs) are estimated to be 0.5-5 mg/L and 1-10 mg/L, respectively. The internal standard method was used for quantitative analysis, and indapamide was used as the internal standard compound. Sufficient linearity for each analyte is obtained with the correlation coefficients (r) greater than 0.99. The proposed method displays good recoveries in the range of 91.0%-114.3% with the relative standard deviations (RSDs) less than 8.4%. Moreover, the developed method was used for the analysis of blood samples, which spiked with tacrolimus, sirolimus, everolimus, cyclosporine A and mycophenolic acid at the concentration of 100 mg/L. The analytical results demonstrated the consistency between the proposed method and the traditional liquid chromatography-mass spectrometry (LC-MS) method. The entire analysis procedure can be completed within 1 min. The proposed method is simple, fast, accurate, efficient, and suitable for POCT of immunosuppressants in blood. [ABSTRACT FROM AUTHOR]

The automation of traditional Chinese medicine (TCM) pharmaceuticals has driven the development of process analysis from offline to online. Most of common online process analytical technologies are based on spectroscopy, making the identification and quantification of specific ingredients still a challenge. Herein, we developed a quality control (QC) system for monitoring TCM pharmaceuticals based on paper spray ionization miniature mass spectrometry (mini-MS). It enabled real-time online qualitative and quantitative detection of target ingredients in herbal extracts using mini-MS without chromatographic separation for the first time. Dynamic changes of alkaloids in Aconiti Lateralis Radix Praeparata (Fuzi) during decoction were used as examples, and the scientific principle of Fuzi compatibility was also investigated. Finally, the system was verified to work stably at the hourly level for pilot-scale extraction. This mini-MS based online analytical system is expected to be further developed for QC applications in a wider range of pharmaceutical processes.

The development and application of ambient ionization and miniature mass spectrometry have become the current research hotpot, which is capable of rapid, sensitive, on-site and real-time analysis of samples without complex sample pretreatment. In this study, a rapid on-site method using dielectric barrier discharge ionization (DBDI) and a miniature mass spectrometer was developed for the screening of prohibited substances in spray cosmetics. Helium gas was used as the discharge gas and 1 mm thick quartz glass was used as the dielectric barrier in a custom-made DBDI ion source. The two brass electrodes were 10 mm apart, both mounted outside the quartz glass. The inner diameter of the glass tube at the gas inlet and outlet was 1 mm. When the experiment was carried out, the DBDI ion source was placed 3 cm in front of the discontinuous atmospheric pressure interface (DAPI) of the miniature mass spectrometer. The spray cosmetic sample was placed 8 cm directly above the plasma beam generated by the DBDI. Without any sample pretreatment, once the sample spray valve was pressed, the sample microdroplets generated in the vertical direction collided with the plasma beam generated in the horizontal direction. In the region between the DBDI and the miniature mass spectrometer, the target substances were ionized by energy and charge transfer with the plasma beam, and then detected by the miniature mass spectrometer. The helium flow rate was set at an optimum value of 220 mL/min by a gas mass flow controller. Coupled with the miniature mass spectrometer, four prohibited colorants in disposable hair dye spray and four prohibited fragrances in spray lotion were screened. Based on the observed signal-to-noise ratio (S/N) of the most intense MS/MS fragment peaks and using S/N=3 as a criterion, the limits of detection (LODs) were estimated between 10 and 50 μg/kg for the eight prohibited substances. The entire analysis procedure could be completed within 1 min. The simplified analytical protocol can effectively solve the disadvantages of traditional analytical methods that are cumbersome and time-consuming. The proposed method is simple, rapid, sensitive, efficient, and suitable for rapid on-site screening of prohibited substances in spray cosmetics. [ABSTRACT FROM AUTHOR]

The automation of traditional Chinese medicine (TCM) pharmaceuticals has driven the development of process analysis from offline to online. Most of common online process analytical technologies are based on spectroscopy, making the identification and quantification of specific ingredients still a challenge. Herein, we developed a quality control (QC) system for monitoring TCM pharmaceuticals based on paper spray ionization miniature mass spectrometry (mini-MS). It enabled real-time online qualitative and quantitative detection of target ingredients in herbal extracts using mini-MS without chromatographic separation for the first time. Dynamic changes of alkaloids in Aconiti Lateralis Radix Praeparata (Fuzi) during decoction were used as examples, and the scientific principle of Fuzi compatibility was also investigated. Finally, the system was verified to work stably at the hourly level for pilot-scale extraction. This mini-MS based online analytical system is expected to be further developed for QC applications in a wider range of pharmaceutical processes. [Display omitted] • The PSI-mini-MS has been developed as a PAT for online quality monitoring of TCM pharmaceuticals. • PSI-mini-MS allows real-time monitoring of TCM pharmaceutical processes without LC separation. • PSI-mini-MS enables identification and quantification of target ingredients in TCM extracts. • Changes of Fuzi alkaloids during decoction monitored by PSI-mini-MS were used as examples. • The scientific principle of Fuzi compatibility was demonstrated by PSI-mini-MS online analysis. [ABSTRACT FROM AUTHOR]

Dalbergia odorifera T. Chen (Dalbergiae Odoriferae Lignum, DOL), renowned for its therapeutic applications in traditional Chinese medicine and its value in crafting luxury items, faces challenges due to the slow heartwood formation process and subsequent market adulteration. The proliferation of counterfeit products necessitates reliable methods for rapid, on-site authentication. This study aims to establish a rapid, green, and on-site method to identify the authenticity of DOL. A comprehensive analysis was conducted on 10 batches of DOL samples sourced from diverse locations, utilizing a miniature mass spectrometer (mini MS) equipped with a paper capillary spray (PCS) technique. Multivariate statistical approaches were employed to classify the samples and pinpoint chemical markers indicative of authenticity. Subsequent MS-guided separation and thin-layer chromatography (TLC) verified the markers' validity and assessed the greenness profile by Analytical Eco-scale (AES), Green Analytical Procedure Index (GAPI), and Analytical GREEnness (AGREE). A total of 10 batches of DOL samples detected by PCS-mini MS were classified into authentic and counterfeit, by unsupervised cluster analysis. Sativanone (m/z 301.1, VIP=6.0, p=0.000001) and 3′-O-methylviolanone (m/z 331.1, VIP=3.2, p=0.000382) were regarded as the chemical markers for the rapid identification of DOL. The results of the TLC method were consistent with this method, and the new method is greener. The application of mini MS for on-site authentication of DOL via specific chemical markers offers significant advantages, including operational simplicity, high efficiency, greenness, and accuracy. The deployment of this strategy promises to facilitate the effective regulation of DOL, ensuring authenticity and quality. [Display omitted] • The chemical markers of DOL were revealed, providing a basis for identification. • An on-site identification method of DOL based on PCS-mini MS was developed. • Multiple green indicators were used to evaluate the method, to reflect the greenness. [ABSTRACT FROM AUTHOR]

Selective removal of alkali metal cations from mixed cation multiply-charged peptide ions is demonstrated here using gas-phase ion/ion reactions with a series of weakly coordinating anions (WCAs), including hexafluorophosphate (PF6 (-)), tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (BARF), tetrakis(pentafluorophenyl)borate (TPPB), and carborane (CHB11Cl11 (-)). In all cases, a long-lived complex is generated by dication/anion condensation followed by ion activation to compare proton transfer with alkali ion transfer from the peptide to the anion. The carborane anion was the only anion studied to undergo dissociation exclusively through loss of the metallated anion, regardless of the studied metal adduct. All other anions studied yield varying abundances of protonated and metallated peptide depending on the peptide sequence and the metal identity. Density functional theory calculations suggest that for the WCAs studied, metal ion transfer is most strongly favored thermodynamically, which is consistent with the experimental results. The carborane anion is demonstrated to be a robust reagent for the selective removal of alkali metal cations from peptide cations with mixtures of excess protons and metal cations.

The development and application of ambient ionization and miniature mass spectrometry have become the current research hotspot, capable of rapid, sensitive, on-site, and real-time analysis of samples without complicated sample pretreatment. In this study, a rapid, on-site method was developed for the screening of hazardous substances in infant toiletries using ambient ionization and miniature mass spectrometry. Without time-consuming sample pretreatment, the liquid contained in baby wipes was drawn and then dropped onto a Grade 3MM triangle paper substrate. A metal mini-alligator clip was used to hold the triangular piece of paper with its tip about 1 cm in front of the inlet of a miniature mass spectrometer. Aliquots of 10 μL methanol containing 0.3% formic acid was used as spray solvent and dropped onto the paper substrate. A spray voltage of 3.0 kV was applied, and then charged droplets were emitted from the paper tip, leading to the acquisition of the MS/MS spectra in positive ion mode. Based on the observed signal-to-noise ratio (S/N) of the most intense MS/MS fragment peaks and using S/N=3 as a criterion, the limits of detection (LODs) of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one were estimated to be 50 and 20 μg/kg, respectively. Other infant toiletry samples, including toothpaste, baby bottle and dish liquid, and nappy cream, were analyzed by extraction nano-electrospray ionization (nanoESI). A borosilicate glass capillary (1.5 mm×0.86 mm×5 cm) with a pulled tip was prepared using a P-1000 micropipette puller. The samples spiked with the analytes, such as toothpaste spiked with diethylene glycol and salicylic acid, baby bottle and dish liquid spiked with atranol and lyral, and nappy cream spiked with propylparaben and butylparaben, were gently picked up using a metal wire probe, and then inserted into the pulled capillary, which had been prefilled with 10 μL of spray solvents. The capillary was placed in front of the inlet of the miniature mass spectrometer. A high voltage of 3.0 kV in positive ion mode or -2.5 kV in negative ion mode was applied via the metal wire, producing the spray for immediate nanoESI analysis. The LODs were estimated to be between 10 and 50 μg/kg for the eight hazardous substances. Coupling with miniature mass spectrometry, the entire analysis could be completed in less than 1 min. The simplified analytical procedures effectively solve the disadvantages of traditional analytical methods that are cumbersome and time-consuming. The proposed method is simple, rapid, sensitive, efficient, and suitable for rapid, on-site screening of hazardous substances in infant toiletries. [ABSTRACT FROM AUTHOR]

The present study reports on a streamlined analytical platform for rapid, straightforward, and on-site sample analysis using a miniature mass spectrometer with adequate tandem mass spectrometry (MS/MS) capability. An "all-in-one" workflow is developed combining accelerated air-assisted in-syringe extraction, sorbent-packed membrane clean-up, and needle spray ionization with an in-house built syringe assembly. A custom-made metal needle with a sharp, thin, and conical tip of micrometer-scale served as an integral component of the syringe assembly. This needle was capable of both aspirating a high-speed airflow for a highly efficient in-syringe extraction and performing stable electrospray for direct miniature mass spectrometry analysis. As a proof-of-concept demonstration, the developed protocol was implemented for the identification of 40 adulterated cosmetic ingredients and validated in terms of sensitivity, linearity, matrix effect, and recovery. A custom expandable mass spectral library was established in-house for smart suspect screening. Compound search and identification were conducted following a two-stage strategy using the full-scan MS and MS/MS data. The methodology demonstrates excellent potential for outside-the-laboratory chemical analysis by reducing the high time and labor costs associated with traditional sample preparation and chromatographic separation procedures, which would meet product quality and safety inspection requirements for on-site compliance check and regulatory enforcement at the testing sites such as supermarkets, department stores, wholesale markets, and roadside stalls. Image 1 • A streamlined analytical platform was established for rapid on-site sample analysis using a miniature mass spectrometer. • An "all-in-one" workflow combined sample extraction, clean-up, and ionization with a syringe assembly built in-house. • A pulled micrometer-scale needle enabled a high-speed airflow to be aspirated for highly efficient in-syringe extraction. • A custom expandable mass spectral library was established for smart suspect screening. [ABSTRACT FROM AUTHOR]

Military, public safety and emergency rescue have put forward an urgent need for the technology of on-site, real-time, accurate and rapid detection. Ambient ionization mass spectrometry can directly analyze sample on-site, and it has characteristics of simplicity, fast, no sample preparation and can be used to analyze gaseous, liquid and solid sample. The research development of ambient ionization technology was summarized in this paper. In the section of laser desorption/ionization source, the research development and application of four ionization source were introduced, including electrospray assisted laser desorption ionization, laser ablation electrospray ionization, laser-induced acoustic desorption electrospray ionization and plasma-assisted laser desorption ionization. In the content of plasma ionization source, the low temperature plasma (LTP) probe was introduced. The protein and peptide could be detected using paper-based analytical devices (PADs) coupled with LTP. In order to solve the floating potential problem in the plasma, the symmetrical or T-shape DBDI was researched. The miniatured LTP was researched aiming to decrease the high voltage in the plasma. In the electrospray ionization source part, the paper spray and syringe spray ionization were introduced, such as detecting some medicines and bacteria. The application of ambient ionization technology in the detection of chemical warfare agents, biology and explosives was introduced. In the part of chemical warfare agents (CWAs) detection, the microhollow cathode discharge plasma ionization source, and the plasma ionization source coupled with mass spectrometry in the lab and the Mini 105 to analyze highly toxic nerve agents (G-series, V-series) and blistering warfare agents and the stimulants were introduced. On the basis of plasma-PADs, gold nanoparticles-enhanced ion-transmission mass spectrometry for highly sensitive detection of CWAs was introduced. In the biology detection content, membrane electrospray ionization source coupled with miniature mass spectrometry was used to analyze biomarker in the body fluid, and the ambient laser desorption coupled with rapid evaporative ionization mass spectrometry was researched to improve lipid-based microbial species level identification. The atmospheric pressure MALDI and DESI FT-ICR in the application of mass spectrometry imaging of single cell and biological tissue were introduced. In the explosive detection section, aerodynamic assisted thermo desorption-corona discharge ionization and dynamic liquid/solid friction assisted desorption-LTP ionization sources in the application of detecting TNT, C4 were introduced. In addition, the testing of repeatability and constancy of DESI-MS with reference samples were introduced. In the last, the problems and future perspectives of ambient ionization mass spectrometry were discussed. Ambient ionization mass spectrometry is expected to provide new research ideas in the area of on-site, real-time, online, in-situ measurements. [ABSTRACT FROM AUTHOR]

Knowledge of the isocitrate dehydrogenase (IDH) mutation status of glioma patients could provide insights for decision-making during brain surgery. However, pathology is not able to provide such information intraoperatively. Here we describe the first application of a miniature mass spectrometer (MS) to the determination of IDH mutation status in gliomas intraoperatively. The instrumentation was modified to be compatible with use in the operating room. Tandem MS was performed on the oncometabolite, 2-hydroxyglutarate, and a reference metabolite, glutamate, which is not involved in the IDH mutation. Ratios of fragment ion intensities were measured to calculate an IDH mutation score, which was used to differentiate IDH mutant and wild-type tissues. The results of analyzing 25 biopsies from 13 patients indicate that reliable determination of IDH mutation status was achieved (p = 0.0001, using the Kruskal-Wallis non-parametric test). With its small footprint and low power consumption and noise level, this application of miniature mass spectrometers represents a simple and cost-effective platform for an important intraoperative measurement. [ABSTRACT FROM AUTHOR]

Current miniature mass spectrometers mainly focus on the analyses of organic and small biological molecules. In this study, we explored the possibility of developing high resolution miniature ion trap mass spectrometers for whole protein analysis. Theoretical derivation, GPU assisted ion trajectory simulation, and initial experiments on home‐developed "brick" mass spectrometer were carried out. Results show that ion‐neutral collisions have smaller damping effect on large protein ions, and a higher buffer gas pressure should be applied during ion trap operations for protein ions. As a result, higher pressure ion trap operation not only benefits instrument miniaturization, but also improves mass resolution of protein ions. Dynamic mass scan rate and generation of low charge state protein ions are also found to be helpful in terms of improving mass resolutions. Theory and conclusions found in this work are also applicable in the development of benchtop mass spectrometers. [ABSTRACT FROM AUTHOR]

A better understanding of nanoelectrospray ionization (nano‐ESI) would be beneficial in further improving the performances of nano‐ESI. In this work, the pulsed high‐voltage (HV) nano‐ESI has been electrically modeled and then systematically characterized by both voltage‐current and mass spectrometry measurements. First, the equivalent resistance of a nano‐ESI source changes with respect to both emitter tip diameter and the HV applied. Increased voltage could improve both spray current and ionization efficiency of the pulsed HV nano‐ESI. Compared with conventional DC HV method, a pulsed HV has less heating effect on the capillary tip and thus allowing the application of a much higher voltage onto a nano‐ESI source. As a result, a pulsed HV nano‐ESI could further boost the ionization efficiency of nano‐ESI by employing even higher voltages than conventional DC nano‐ESI sources. [ABSTRACT FROM AUTHOR]

The increasing variability of the illicit drug market has imposed serious health risks for people who use drugs (PWUD), particularly due to the increasing co-occurrence of opioids and etizolam (or other benzodiazepines) in some jurisdictions. A miniature mass spectrometer (MS) equipped with paper capillary spray ionization was evaluated for its ability to quantify fentanyl, fluorofentanyl, carfentanil, and etizolam in illicit drug samples. Prior to testing actual drug samples, inter- and intra-day reproducibility, calibration linearity, and analytical sensitivity were assessed. The development of a continuous spray solvent delivery system improved MS/MS quantitation by prolonging ionization stability. A simple, rapid and quantitative tandem mass spectrometry method was developed and employed for the analysis of real-world illicit drug samples provided by PWUD at a harm reduction site in Victoria, British Columbia, Canada. Limits of detection ranged from 0.001 to 0.24% w/w of illicit analyte in the original solid drug samples. Target analytes were detected and quantified via the miniature MS system for samples where conventional on-site drug checking technologies were not always effective. These promising results demonstrate the potential role for miniature mass spectrometer systems for on-site drug checking services that can be both sensitive to trace, toxic levels as well as adaptable/selective for new drug threats as they appear in the illicit drug supply. [Display omitted] • The increased variability of the illicit drug market has imposed serious health risks for people who use drugs (PWUD). • A rapid & quantitative miniature MS method was developed and employed for the analysis of real-world illicit drug samples. • Target analytes were quantified via miniature MS, where other on-site drug checking technologies were not always effective. • Miniature MS systems for on-site drug checking services are sensitive, adaptable and selective for new drug threats. [ABSTRACT FROM AUTHOR]

Miniaturizing instruments for spectroscopic applications requires the designer to confront a tradeoff between instrument resolution and instrument throughput [and associated signal-to-background-ratio (SBR)]. This work demonstrates a solution to this tradeoff in sector mass spectrometry by the first application of one-dimensional (1D) spatially coded apertures, similar to those previously demonstrated in optics. This was accomplished by replacing the input slit of a simple 90° magnetic sector mass spectrometer with a specifically designed coded aperture, deriving the corresponding forward mathematical model and spectral reconstruction algorithm, and then utilizing the resulting system to measure and reconstruct the mass spectra of argon, acetone, and ethanol. We expect the application of coded apertures to sector instrument designs will lead to miniature mass spectrometers that maintain the high performance of larger instruments, enabling field detection of trace chemicals and point-of-use mass spectrometry. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

In mass spectrometer design, there has been a historic belief that there exists a fundamental trade-off between instrument size, throughput, and resolution. When miniaturizing a traditional system, performance loss in either resolution or throughput would be expected. However, in optical spectroscopy, both one-dimensional (1D) and two-dimensional (2D) aperture coding have been used for many years to break a similar trade-off. To provide a viable path to miniaturization for harsh environment field applications, we are investigating similar concepts in sector mass spectrometry. Recently, we demonstrated the viability of 1D aperture coding and here we provide a first investigation of 2D coding. In coded optical spectroscopy, 2D coding is preferred because of increased measurement diversity for improved conditioning and robustness of the result. To investigate its viability in mass spectrometry, analytes of argon, acetone, and ethanol were detected using a custom 90-degree magnetic sector mass spectrometer incorporating 2D coded apertures. We developed a mathematical forward model and reconstruction algorithm to successfully reconstruct the mass spectra from the 2D spatially coded ion positions. This 2D coding enabled a 3.5× throughput increase with minimal decrease in resolution. Several challenges were overcome in the mass spectrometer design to enable this coding, including the need for large uniform ion flux, a wide gap magnetic sector that maintains field uniformity, and a high resolution 2D detection system for ion imaging. Furthermore, micro-fabricated 2D coded apertures incorporating support structures were developed to provide a viable design that allowed ion transmission through the open elements of the code. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

In recent years, mass spectrometry (MS) is increasingly attracting interests for clinical applications, which also calls for technical innovations to make a transfer of MS from conventional analytical laboratories to clinics. The system design and analysis procedure should be friendly for novice users and appliable for on-site clinical diagnosis. In addition, the analysis result should be auto-interpreted and reported in formats much simpler than mass spectra. This motivates new ideas for developments in all the aspects of MS. In this review, we report recent advances of direct sampling ionization and miniature MS system, which have been developed targeting clinical and even point-of-care analysis. We also discuss the trend of the development and provide perspective on the technical challenges raised by diseases such as coronavirus SARS-CoV-2. • Technical innovations are highly desired to make a transfer of MS from conventional analytical laboratories to clinics. • Ambient ionization enables direct MS analysis of biological samples and facilitates the transfer of MS to non-expert users. • Miniature MS system enables on-site MS analysis for clinical and POC diagnostics. • MS shows promising solutions to the challenge of pandemic diseases, such as SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Proteomics by mass spectrometry (MS) allows for the identification of amino acid/peptide sequences in complex mixtures. Peptide analysis and quantitation enables screening of protein biomarkers and targeted protein biomarker analysis for clinical applications. Whereas miniature mass spectrometers have primarily demonstrated point-of-care analyses with simple procedures aiming at drugs and lipids, it would be interesting to explore their potential in analyzing proteins and peptides. In this work, we adapted a miniature MS instrument for peptide analysis. A mass range as wide as 100-2000 m / z was achieved for obtaining peptide spectra using this instrument with dual linear ion traps. MS 2 and MS 3 can be performed to analyze a wide range of peptides. The parameters of pressure, electric potentials, and solution conditions were optimized to analyze peptides with molecular weights between 900 and 1800 Da. The amino acid sequences were identified using both beam-type and in-trap collision-induced dissociation, and the results were comparable to those obtained by a commercial quadrupole time-of-flight mass spectrometer. With product ion monitoring scan mode, peptide quantitation was performed with a limit of detection of 20 nM achieved for the Met peptide. The method developed has also been applied to the analysis of the trypsin-digested cell lysate of SKBR3 cells with a low expression level of the Met gene.