Pekka Östman

Poly(dimethylsiloxane) electrospray devices fabricated with diamond-like carbon–poly(dimethylsiloxane) coated SU-8 masters

This study presents coupling of a poly(dimethylsiloxane) (PDMS) micro-chip with electrospray ionization-mass spectrometry (ESI-MS). Stable electrospray is generated directly from a PDMS micro-channel without pressure assistance. Hydrophobic PDMS aids the formation of a small Taylor cone in the ESI process and facilitates straightforward and low-cost batch production of the ESI-MS chips. PDMS chips were replicated with masters fabricated from SU-8 negative photoresist. A novel coating, an amorphous diamond-like carbon-poly(dimethylsiloxane) hybrid, deposited on the masters by the filtered pulsed plasma arc discharge technique, improved significantly the lifetime of the masters in PDMS replications. PDMS chip fabrication conditions were observed to affect the amount of background peaks in the MS spectra. With an optimized fabrication process (PDMS curing agent/silicone elastomer base ratio of 1/8 (w/w), curing at 70 degree C for 48 h) low background spectra were recorded for the analytes. The performance of PDMS devices was examined in the ESI-MS analysis of some pharmaceutical compounds and amino acids.

Matrix effect in the analysis of drugs of abuse from urine with desorption atmospheric pressure photoionization-mass spectrometry (DAPPI-MS) and desorption electrospray ionization-mass spectrometry (DESI-MS).

We have studied the matrix effect within direct analysis of benzodiazepines and opioids from urine with desorption electrospray ionization-mass spectrometry (DESI-MS) and desorption atmospheric pressure photoionization-mass spectrometry (DAPPI-MS). The urine matrix was found to affect the ionization mechanism of the opioids in DAPPI-MS favoring proton transfer over charge exchange reaction. The sensitivity for the drugs in solvent matrix was at the same level with DESI-MS and DAPPI-MS (LODs 0.05-6 μg mL(-1)) but the decrease in sensitivity due to the urine matrix was higher with DESI (typically 20-160-fold) than with DAPPI (typically 2-15-fold) indicating better matrix tolerance of DAPPI over DESI. Also in MS/MS mode, DAPPI provided better sensitivity than DESI for the drugs in urine. The feasibility of DAPPI-MS/MS was then studied in screening the same drugs from five authentic, forensic post mortem urine samples. A reference measurement with gas chromatography-mass spectrometry (GC-MS) (including pretreatment) revealed 16 findings from the samples, whereas with DAPPI-MS/MS after sample pretreatment, 15 findings were made. Sample pretreatment was found necessary, since only eight findings were made from the same samples untreated.

Preparation of porous n-type silicon sample plates for desorption/ionization on silicon mass spectrometry (DIOS-MS)

This study focuses on porous silicon (pSi) fabrication methods and properties for desorption ionization on silicon mass spectrometry (DIOS-MS). PSi was prepared using electrochemical etching of n-type silicon in HF-ethanol solution. Porous areas were defined by a double-sided illumination arrangement: front-side porous areas were masked by a stencil mask, eliminating the need for standard photolithography, and backside illumination was used for the backside ohmic contact. Backside illumination improved the uniformity of the porosified areas. Porosification conditions, surface derivatizations and storage conditions were explored to optimize pSi area, pore size and pore depth. Chemical derivatization of the pSi surfaces improved the DIOS-MS performance providing better ionization efficiency and signal stability with lower laser energy. Droplet spreading and drying patterns on pSi were also examined. Pore sizes of 50-200 nm were found to be optimal for droplet evaporation and pore filling with the sample liquid, as measured by DIOS efficiency. With DIOS, significantly better detection sensitivity was obtained (e.g. 150 fmol for midazolam) than with desorption ionization from a standard MALDI steel plate without matrix addition (30 pmol for midazolam). Also the noise that disturbs the detection of low-molecular weight compounds at m/z < 500 with MALDI could be clearly reduced with DIOS. Low background MS spectra and good detection sensitivity at the 100-150 fmol level for pharmaceutical compounds were achieved with DIOS-MS.

Capillary liquid chromatography-microchip atmospheric pressure chemical ionization-mass spectrometry

A miniaturized nebulizer chip for capillary liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (capillary LC-microchip APCI-MS) is presented. The APCI chip consists of two wafers, a silicon wafer and a Pyrex glass wafer. The silicon wafer has a DRIE etched through-wafer nebulizer gas inlet, an edge capillary insertion channel, a stopper, a vaporizer channel and a nozzle. The platinum heater electrode and pads for electrical connection were patterned on to the Pyrex glass wafer. The two wafers were joined by anodic bonding, creating a microchip version of an APCI-source. The sample inlet capillary from an LC column is directly connected to the vaporizer channel of the APCI chip. The etched nozzle in the microchip forms a narrow sample plume, which is ionized by an external corona needle, and the formed ions are analyzed by a mass spectrometer. The nebulizer chip enables for the first time the use of low flow rate separation techniques with APCI-MS. The performance of capillary LC-microchip APCI-MS was tested with selected neurosteroids. The capillary LC-microchip APCI-MS provides quantitative repeatability and good linearity. The limits of detection (LOD) with a signal-to-noise ratio (S/N) of 3 in MS/MS mode for the selected neurosteroids were 20-1000 fmol (10-500 nmol l(-1)). LODs (S/N = 3) with commercial macro APCI with the same compounds using the same MS were about 10 times higher. Fast heat transfer allows the use of the optimized temperature for each compound during an LC run. The microchip APCI-source provides a convenient and easy method to combine capillary LC to any API-MS equipped with an APCI source. The advantages and potentials of the microchip APCI also make it a very attractive interface in microfluidic APCI-MS.

A Microfabricated Nebulizer for Liquid Vaporization in Chemical Analysis

A miniaturized nebulizer chip for vaporization of liquid samples for mass spectrometry has been designed, fabricated, and characterized for fluidic and thermal performance. Silicon/glass chip has a liquid sample channel placed centrally between symmetric nebulizer gas channels. The liquid sample is nebulized and vaporised by an integrated platinum heater. The vaporized sample exits through an etched nozzle, and is ionized by an external corona needle. The ions are analysed by a mass spectrometer. The chip has been fabricated in both anisotropically wet etched and DRIE versions in silicon, with an anodically bonded Pyrex glass cover plate. Three different fluidic inlet designs are presented, with both through-wafer and edge insert versions. The shape of the erupting gas jet has been visualized by infrared thermography by using a low-diffusivity imaging screen and high heat capacity helium as a test gas. Dimensions of the jets thermal footprint on the screen show that the jet is very narrow and confined, and this is confirmed in mass spectrometry results. This confined jet supplies the sample to the ionization region near corona tip, enabling efficient use of very small sample amounts and submicroliter flows.1591

Measuring insulin in human vitreous humour using LC‐MS/MS

Besides its particular importance as a widely used therapeutic agent, insulin (and its synthetic derivatives) has been suspected, purported, and proven to be a lethal weapon in numerous cases of attempted or successful homicide and suicide. In addition to blood and urine as common matrices for clinical diagnosis and post-mortem analysis, vitreous humour has gained considerable attention in autopsy and follow-up investigations due to its ability to provide valuable information on cause and time of death. However, post-mortem insulin analyses using such specimens have been rare due to the limited penetration of peptide hormones into the vitreous body, and immunoassays were exclusively employed in those studies. In the present communication, the determination of insulin(s) from vitreous humour by means of immunopurification combined with ultrahigh performance liquid chromatography--high resolution/high accuracy (tandem) mass spectrometry is reported. Exploiting the constantly increasing sensitivity and robustness of modern mass-spectrometry-based instruments, the option to identify insulin in post-mortem vitreous samples is demonstrated with a specimen collected from a non-diabetic victim who died from an insulin overdose. This communication represents the first successful mass-spectrometry-based analysis of post-mortem material related to an insulin poisoning case.

Application of electrospray ionization product ion spectra for identification with atmospheric pressure matrix-assisted laser desorption/ionization mass spectrometry - a case study with seized drugs.

Product ion spectra obtained with liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI/MS/MS) were applied to the identification of seized drug samples from atmospheric pressure matrix-assisted laser desorption/ionization product ion spectra (AP-MALDI-MS/MS spectra). Data acquisition was performed in the information-dependent acquisition (IDA) mode, and the substance identification was based on a spectral library previously created with LC-ESI/MS/MS using protonated molecules as precursor ions. A total of 39 seized drug samples were analyzed with both AP-MALDI and LC-ESI techniques using the same triple-quadrupole instrument (AB Sciex 4000QTRAP). The study shows that ESI-MS/MS spectra can be directly utilized in AP-MALDI-MS/MS measurements as the average fit and purity score percentages with AP-MALDI were 90% and 85%, respectively, being similar to or even better than those obtained with the reference LC/ESI-MS/MS method. This fact enables the possibility to use large ESI spectral libraries, not only to ESI analyses but also to analyses with other ionization techniques which produce protonated molecules as the base peak. The data obtained shows that spectral library search works also for analytical techniques which produce multi-component mass spectra, such as AP-MALDI, unless isobaric compounds are encountered. The spectral library search was successfully applied to rapid identification of confiscated drugs by AP-MALDI-IDA-MS/MS.

Modified Porous Silicon Surfaces as DIOS-MS Sample Plates

This study presents a novel porous silicon (pSi) fabrication method for the matrix-free desorption/ionization on silicon mass spectrometry (DIOS-MS). The fabrication conditions and surface treatments of pSi on DIOS-MS performance are explored. Utilization of pSi sample plates in the analysis of low molecular weight pharmaceutical compounds is shown.

PDMS electrospray devices fabricated by PDMS-diamond-coated SU-8 masters

This study presents a new design for chip-based electrospray ionization mass spectrometry (ESI-MS), in which ESI is generated by direct spraying from a polydimethylsiloxane (PDMS) micro-channel electrokinetically without pressure assistance. PDMS devices were fabricated using SU-8-masters, which were coated with amorphous PDMS-diamond hybrid to increase their life-time. The presented technique allows rapid and low-cost batch-production of the ESI-MS chips.