Portable Instrumentation for Ambient Ionization and Miniature Mass Spectrometers.

We critically evaluate the current status of portable mass spectrometry (pMS), particularly where this aligns with ambient ionization. Assessing the field of pMS can be quite subjective, especially in relation to the portable aspects of design, deployment, and operation. In this review, we discuss what it means to be portable and introduce a set of criteria by which pMS and ambient ionization sources can be assessed. Moreover, we consider the recent literature in terms of the most popular and significant advances in portable instrumentation for ambient ionization and miniature mass spectrometers. Finally, emerging trends and exciting future prospects are discussed and some recommendations are offered.

Charge inversion under plasma-nanodroplet reaction conditions excludes Fischer esterification for unsaturated fatty acids: a chemical approach for type II isobaric overlap.

Direct infusion ionization methods provide the highest throughput strategy for mass spectrometry (MS) analysis of low-volume samples. But the trade-off includes matrix effects, which can significantly reduce analytical performance. Herein, we present a novel chemical approach to tackle a special type of matrix effect, namely type II isobaric overlap. We focus on detailed investigation of a nanodroplet-based esterification chemistry for differentiating isotopologue [M + 2] signal due to unsaturated fatty acid (FA) from the monoisotopic signal from a saturated FA. The method developed involves the online fusion of nonthermal plasma with charged nanodroplets, enabling selective esterification of saturated FAs. We discovered that unsaturated FAs undergo spontaneous intramolecular reaction via a novel mechanism based on a carbocation intermediate to afford a protonated lactone moiety (resonance stabilized cyclic carbonium ion), whose mass is the same as the original protonated unsaturated FA. Therefore, the monoisotopic signal from any saturated FA can be selectively shifted away from the mass-to-charge position where the isobaric interference occurs to enable effective characterization by MS. The mechanism governing the spontaneous intramolecular reactions for unsaturated FAs was validated with DFT calculations, experimentation with standards, and isotope labeling. This novel insight achieved via the ultrafast plasma-nanodroplet reaction environment provides a potentially useful synthetic pathway to achieve catalyst-free lactone preparation. Analytically, we believe the performance of direct infusion MS can be greatly enhanced by combining our approach with prior sample enrichment steps for applications in biomedicine and food safety. Also, combination with portable mass spectrometers can improve the efficiency of field studies since front-end separation is not possible under such conditions.

Development and Clinical Validation of a Hook Effect-Based Lateral Flow Immunoassay Sensor for Cerebrospinal Fluid Leak Detection.

BACKGROUND AND OBJECTIVES: Rapid detection of cerebrospinal fluid (CSF) leaks is vital for patient recovery after spinal surgery. However, distinguishing CSF-specific transferrin (TF) from serum TF using lateral flow immunoassays (LFI) is challenging due to their structural similarities. This study aims to develop a novel point-of-care diagnostic assay for precise CSF leak detection by quantifying total TF in both CSF and serum. METHODS: Capitalizing on the substantial 100-fold difference in TF concentrations between CSF and serum, we designed a diagnostic platform based on the well-known "hook effect" resulting from excessive analyte presence. Clinical samples from 37 patients were meticulously tested using the novel LFI sensor, alongside immunofixation as a reference standard. RESULTS: The hook effect-based LFI sensor exhibited outstanding performance, successfully discriminating positive clinical CSF samples from negative ones with remarkable statistical significance (positive vs negative t -test; P = 1.36E-05). This novel sensor achieved an impressive 100% sensitivity and 100% specificity in CSF leak detection, demonstrating its robust diagnostic capabilities. CONCLUSION: In conclusion, our study introduces a rapid, highly specific, and sensitive point-of-care test for CSF leak detection, harnessing the distinctive TF concentration profile in CSF compared with serum. This novel hook effect-based LFI sensor holds great promise for improving patient outcomes in the context of spinal surgery and postsurgical recovery. Its ease of use and reliability make it a valuable tool in clinical practice, ensuring timely and accurate CSF leak detection to enhance patient care.

Rapid differentiation of cystic fibrosis-related bacteria via reagentless atmospheric pressure photoionisation mass spectrometry.

Breath analysis is an area of significant interest in medical research as it allows for non-invasive sampling with exceptional potential for disease monitoring and diagnosis. Volatile organic compounds (VOCs) found in breath can offer critical insight into a person's lifestyle and/or disease/health state. To this end, the development of a rapid, sensitive, cost-effective and potentially portable method for the detection of key compounds in breath would mark a significant advancement. Herein, we have designed, built and tested a novel reagent-less atmospheric pressure photoionisation (APPI) source, coupled with mass spectrometry (MS), utilising a bespoke bias electrode within a custom 3D printed sampling chamber for direct analysis of VOCs. Optimal APPI-MS conditions were identified, including bias voltage, cone voltage and vaporisation temperature. Calibration curves were produced for ethanol, acetone, 2-butanone, ethyl acetate and eucalyptol, yielding R2 > 0.99 and limits of detection < 10 pg. As a pre-clinical proof of concept, this method was applied to bacterial headspace samples of Escherichia coli (EC), Pseudomonas aeruginosa (PSA) and Staphylococcus aureus (SA) collected in 1 L Tedlar bags. In particular, PSA and SA are commonly associated with lung infection in cystic fibrosis patients. The headspace samples were classified using principal component analysis with 86.9% of the total variance across the first three components and yielding 100% classification in a blind-sample study. All experiments conducted with the novel APPI arrangement were carried out directly in real-time with low-resolution MS, which opens up exciting possibilities in the future for on-site (e.g., in the clinic) analysis with a portable system.