BACKGROUND:Psoriasis is a chronic, immune-mediated inflammatory skin disease. Screening skin metabolites could unravel the pathophysiology of psoriasis and provide new diagnostic approaches. Due to the lack of suitable methodologies for collecting scarce amounts of skin excretions, the psoriatic skin metabolome has not been extensively studied.

Ambient ionization mass spectrometry (AIMS) has grown into a group of emerging analytical techniques that allow rapid, real-time, high-throughput, in situ, and in vivo analysis in many scientific fields including biomedicine, pharmaceuticals, and forensic sciences. While dozens of AIMS techniques have been introduced over the past two decades, their broad commercial and industrial use is still restricted by multiple challenges. In this Perspective, we discuss the most relevant technical challenges facing AIMS, i.e., reproducibility, quantitative ability, molecular coverage, sensitivity, and data complexity, and scientists' recent attempts to overcome these hurdles. Furthermore, we present future directions of AIMS from our perspective, including the necessity that efforts should be made to unravel blind biomolecules in routine analysis, the construction of a data depository for AIMS users, the full automation of pipelines for prospect integration in a robotic laboratory, the movement toward on-site tests, and the expansion of outreach to motivate government officials in policymaking. We anticipate that, with progress in these critical but immature areas, AIMS technology will keep evolving to become a more robust and user-friendly set of technologies and, consequently, be translated into everyday life practice.

Metabolites excreted by skin have a huge potential as disease biomarkers. However, due to the shortage of convenient sampling/analysis methods, the analysis of sweat has not become very popular in the clinical setting (pilocarpine iontophoresis being a prominent exception). In this report, a facile method for sampling and rapid chemical profiling of skin metabolites excreted with sweat is proposed. Metabolites released by skin (primarily the constituents of sweat) are collected into hydrogel (agarose) micropatches. Subsequently, they are extracted in an online analytical setup incorporating nanospray desorption electrospray ionization and an ion trap mass spectrometer. In a series of reference measurements, using bulk sampling and electrospray ionization mass spectrometry, various low-molecular-weight metabolites are detected in the micropatches exposed to skin. The sampling time is as short as 10 min, while the desorption time is 2 min. Technical precision of micropatch analysis varies within the range of 3-42%, depending on the sample and the method of data treatment; the best technical precision (≤10%) has been achieved while using an isotopically labeled internal standard. The limits of detection range from 7 to 278 pmol. Differences in the quantities of extracted metabolites are observed for the samples obtained from healthy individuals (intersubject variabilities: 30-89%; n = 9), which suggests that this method may have the potential to become a semiquantitative assay in clinical analysis and forensics.

Cholesterol is an important lipid molecule in cell membranes and lipoproteins. Cholesterol is also a precursors of steroid hormones, bile acids, and vitamin D. Abnormal levels of cholesterol or its precursors have been observed in various human diseases, such as heart diseases, stroke, type II diabetes, brain diseases and many others. Therefore, accurate quantification of cholesterol is important for individuals who are at increased risk for these diseases. Multiple analytical methods have been developed for analysis of cholesterol, including classical chemical methods, enzymatic assays, gas chromatography (GC), liquid chromatography (LC), and mass spectrometry (MS). Strategy known as ambient ionization mass spectrometry (AIMS), operating at atmospheric pressure, with only minimal sample pretreatments for real time, in situ , and rapid interrogation of the sample has also been employed for quantification of cholesterol. In this review, we summarize the most prevalent methods for cholesterol quantification in biological samples and foods. Nevertheless, we highlight several new technologies, such as AIMS, used as alternative methods to measure cholesterol that are potentially next-generation platforms. Representative examples of molecular imaging of cholesterol in tissue sections are also included in this review article.

Paper spray ionization has been used as a fast sampling/ionization method for the direct mass spectrometric analysis of biological samples at ambient conditions. Here, we demonstrated that by utilizing paper spray ionization-mass spectrometry (PSI-MS) coupled with field asymmetric waveform ion mobility spectrometry (FAIMS), predictive metabolic and lipidomic profiles of routine breast core needle biopsies could be obtained effectively. By the combination of machine learning algorithms and pathological examination reports, we developed a classification model, which has an overall accuracy of 87.5% for an instantaneous differentiation between cancerous and noncancerous breast tissues utilizing metabolic and lipidomic profiles. Our results suggested that paper spray ionization-ion mobility spectrometry-mass spectrometry (PSI-IMS-MS) is a powerful approach for rapid breast cancer diagnosis based on altered metabolic and lipidomic profiles.

Background Psoriasis is an inflammatory skin disease causing multisystem effects. Introduction of biologic drugs has led to promising results in treatment of this disease. Here, we carry out time-dependent profiling of psoriasis-related putative metabolic biomarkers. Methods Skin excretion specimens were collected from 17 patients with psoriasis treated with biologics for 7 months. Blood specimens were obtained from the same patients at intervals of 1–3 months. A hydrogel micropatch sampling technique was implemented to collect lesional (L) and nonlesional (NL) skin specimens. The collected skin and blood specimens were analyzed by mass spectrometric methods. Results The metabolites present on L skin—in particular, choline, and citrulline—showed greater dynamics, corresponding to the resolution of psoriasis than the metabolites present in NL skin or blood. Choline levels in L skin and blood correlated positively, while citrulline correlated negatively with the severity of individual psoriasis plaques and general disease severity, respectively. Nevertheless, the correlations between the metabolite levels in blood and general disease severity were weaker than those between the metabolite levels on L skin and severity of individual plaques. The changes of these skin metabolites were more prominent in the responders to the treatment than in the nonresponders. Conclusions The results support the feasibility of characterizing dynamic changes in psoriatic skin metabolic profiles with the hydrogel micropatch probes and mass spectrometric tests. The study represents one of few attempts to explore relationships between skin and blood metabolite concentrations. However, practical use of the methodology in close clinical monitoring is yet to be demonstrated.

Sampling the skin surface is a convenient way to obtain biological specimens bearing clinically relevant information. Hydrogel micropatches enable noninvasive collection of skin excretion specimens, which can subsequently be subjected to rapid mass spectrometric analysis providing insights into the skin metabolome.

Micropatch-arrayed pads (MAPAs) are presented as a facile and sensitive sampling method for spatial profiling of topical agents adsorbed on the surface of skin. MAPAs are 28 × 28 mm sized pieces of polytetrafluoroethylene containing plurality of cavities filled with agarose hydrogel. They are affixed onto skin for 10 min with the purpose to collect drugs applied topically. Polar compounds are absorbed by the hydrogel micropatches. The probes are subsequently scanned by an automated nanospray desorption electrospray ionization mass spectrometry system operated in the tapping dual-polarity mode. When the liquid junction gets into contact with every micropatch, polar compounds absorbed in the hydrogel matrix are desorbed and transferred to the ion source. A 3D-printed interface prevents evaporation of hydrogel micropatches assuring good reproducibility and sensitivity. MAPAs have been applied to follow dispersion of topical drugs applied to human skin in vivo and to porcine skin ex vivo, in the form of self-adhesive patches. Spatiotemporal characteristics of the drug dispersion process have been revealed using this non-invasive test. Differences between drug dispersion in vivo and ex vivo could be observed. We envision that MAPAs can be used to investigate spatiotemporal kinetics of various topical agents utilized in medical treatment.