BACKGROUND:One driving motivation in the development of point-of-care (POC) diagnostics is to conveniently and immediately provide information upon which healthcare decisions can be based, while the patient is on site. Ambient ionization mass spectrometry (MS) allows direct chemical analysis of unmodified and complex biological samples. This suite of ionization techniques was introduced a decade ago and now includes a number of techniques, all seeking to minimize or eliminate sample preparation. Such approaches provide new opportunities for POC diagnostics and rapid measurements of exogenous and endogenous molecules (e.g., drugs, proteins, hormones) in small volumes of biological samples, especially when coupled with miniature mass spectrometers.CONTENT: Ambient MS-based techniques are applied in diverse fields such as forensics, pharmaceutical development, reaction monitoring, and food analysis. Clinical applications of ambient MS are at an early stage but show promise for POC diagnostics. This review provides a brief overview of various ambient ionization techniques providing background, examples of applications, and the current state of translation to clinical practice. The primary focus is on paper spray (PS) ionization, which allows quantification of analytes in complex biofluids. Current developments in the miniaturization of mass spectrometers are discussed.

Paper spray (PS) is an ambient ionization technique applicable to ionizing analytes from untreated dried biofluid samples. In-field sample analysis could benefit from the capability to use a finger prick of blood to measure drugs in whole blood at low cost and in a short time. Some studies may require specialized blood collection devices that can be used in remote areas. In this study, four different dried blood spot (DBS) devices are used with PS sources and tested for rapid quantification of imatinib and N-desmethyl-imatinib. A triple quadrupole mass spectrometer allows analyte detection with high sensitivity. Analytical figures of merit for the four devices are compared, and it is concluded that several of the novel devices successfully deploy DBS with PS and yield similar results to traditional manual PS methods. Clinical samples collected in a remote location were analyzed as a proof of concept for in-field blood collection and subsequent rapid laboratory analysis. Graphical abstract Dried blood spot analyis by paper spray ionization MS/MS for in field sample collection.

MRM-profiling is a supervised method characterized by its simplicity, speed and the absence of chromatographic separation. It can be used to rapidly isolate discriminating molecules in healthy/disease conditions by tailored screening of signals associated with hundreds of molecules in complex samples.

We report an accelerated biomarker discovery workflow and results of sample screening by mass spectrometry based on multiple reaction monitoring (MRM). This methodology shows promising initial results for the currently unsolved challenge of Parkinson's disease (PD) laboratory diagnosis by biomarker screening. Small molecules present in cerebrospinal fluid (CSF) at low parts per million levels are monitored using specific transitions connecting ion pairs. A set of such transitions constitutes a multidimensional chemical profile used to distinguish and characterize different CSF samples using multivariate statistical methods.