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Accurate simulations of various physical processes on digital computers requires huge computing performance, therefore accelerating these scientific and engineering applications has a great importance. Density of programmable logic devices doubles in every 18 months according to Moore's Law. On the recent devices around one hundred double precision floating-point adders and multipliers can be implemented. In the paper an FPGA based framework is described to efficiently utilize this huge computing power to accelerate simulation of complex physical spatiotemporal phenomena. Simulating complicated geometries requires unstructured spatial discretization which results in irregular memory access patterns severely limiting computing performance. Data locality is improved by mesh node renumbering technique which results in predictable memory access pattern. Additionally storing a small window of node data in the on-chip memory of the FPGA can increase data reuse and decrease memory bandwidth requirements. Generation of the floating-point data path and control structure of the arithmetic unit containing dozens of operators is a very challenging task when the goal is high operating frequency. Long and high fanout control lines and improper placement can severely affect computing performance. In the paper an automatic data path generation and partitioning algorithm is presented to eliminate long delays and aid placement of the circuit. Efficiency and use of the framework is described by a case study solving the Euler equations on an unstructured mesh using finite volume technique. On the currently available largest FPGA the generated architecture contains three processing elements working in parallel providing 90 times speedup compared to a high performance microprocessor core.

Laser Ablation Electrospray Ionization is a recent development in mass spectrometry imaging. It has been shown that lipids and small metabolites can be imaged in various samples such as plant material, tissue sections or bacterial colonies without anysample pre-treatment. Further, laser ablation electrospray ionization has been shown to produce multiply charged protein ions from liquids or solid surfaces. This presents a means to address one of the biggest challenges in mass spectrometry imaging; the identification of proteins directly from biological tissue surfaces. Such identification is hindered by the lack of multiply charged proteins in common MALDI ion sources and the difficulty of performing tandem MS on such large, singly charged ions. We present here top-down identification of intact proteins from tissue with a LAESI ion source combined with a hybrid ion-trap FT-ICR mass spectrometer. The performance of the system was first tested with a standard protein with ECD and IRMPD fragmentation to prove the viability of LAESI FT-ICR for top-down proteomics. Finally, the imaging of a tissue section was performed, where a number of intact proteins were measured and the hemoglobin {\alpha} chain was identified directly from tissue using collision-induced dissociation and infrared multiphoton dissociation fragmentation.

In-vacuum active pixel detectors enable high sensitivity, highly parallel time- and space-resolved detection of ions from complex surfaces. For the first time, a Timepix detector assembly was combined with a Secondary Ion Mass Spectrometer for microscope mode SIMS imaging. Time resolved images from various benchmark samples demonstrate the imaging capabilities of the detector system. The main advantages of the active pixel detector are the higher signal-to-noise ratio and parallel acquisition of arrival time and position. Microscope mode SIMS imaging of biomolecules is demonstrated from tissue sections with the Timepix detector.

Microscope mode imaging for secondary ion mass spectrometry is a technique with the promise of simultaneous high spatial resolution and high speed imaging of biomolecules from complex surfaces. Technological developments such as new position-sensitive detectors, in combination with polyatomic primary ion sources, are required to exploit the full potential of microscope mode mass spectrometry imaging, i.e. to efficiently push the limits of ultra-high spatial resolution, sample throughput and sensitivity. In this work, a C60 primary source is combined with a commercial mass microscope for microscope mode secondary ion mass spectrometry imaging. The detector setup is a pixelated detector from the Medipix/Timepix family with high-voltage post-acceleration capabilities. The mass spectral and imaging performance of the system is tested with various benchmark samples and thin tissue sections. We show that the high secondary ion yield (with respect to traditional monatomic primary ion sources) of the C60 primary ion source and the increased sensitivity of the high voltage detector setup improve microscope mode secondary ion mass spectrometry imaging. The analysis time and the signal-to-noise ratio are improved compared to other microscope mode imaging systems, all at high spatial resolution. We have demonstrated the unique capabilities of a C60 ion microscope with a Timepix detector for high spatial resolution microscope mode secondary ion mass spectrometry imaging.

Osteoarthritis (OA) is a pathology that ultimately causes joint destruction. The cartilage is one of the principal affected tissues. Alterations in the lipid mediators and an imbalance in the metabolism of cells that form the cartilage (chondrocytes) have been described as contributors to the OA development. In this study, we have studied the distribution of lipids and chemical elements in healthy and OA human cartilage. Time of flight-secondary ion mass spectrometry (TOF-SIMS) allows us to study the spatial distribution of molecules at a high resolution on a tissue section. TOF-SIMS revealed a specific peak profile that distinguishes healthy from OA cartilages. The spatial distribution of cholesterol-related peaks exhibited a remarkable difference between healthy and OA cartilages. A distinctive colocalization of cholesterol and other lipids in the superficial area of the cartilage was found. A higher intensity of oleic acid and other fatty acids in the OA cartilages exhibited a similar localization. On the other hand, CN(-) was observed with a higher intensity in the healthy samples. Finally, we observed an accumulation of calcium and phosphate ions exclusively in areas surrounding the chondrocyte in OA tissues. To our knowledge, this is the first time that TOF-SIMS revealed combined changes in the molecular distribution in the OA human cartilage.

Biological tissue imaging by secondary ion mass spectrometry has seen rapid development with the commercial availability of polyatomic primary ion sources. Endogenous lipids and other small bio-molecules can now be routinely mapped on the sub-micrometer scale. Such experiments are typically performed on time-of-flight mass spectrometers for high sensitivity and high repetition rate imaging. However, such mass analyzers lack the mass resolving power to ensure separation of isobaric ions and the mass accuracy for elemental formula assignment based on exact mass measurement. We have recently reported a secondary ion mass spectrometer with the combination of a C60 primary ion gun with a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) for high mass resolving power, high mass measurement accuracy and tandem mass spectrometry capabilities. In this work, high specificity and high sensitivity secondary ion FT-ICR MS was applied to chemical imaging of biological tissue. An entire rat brain tissue was measured with 150 um spatial resolution (75 um primary ion spot size) with mass resolving power (m/{\Delta}m50%) of 67,500 (at m/z 750) and root-mean-square measurement accuracy less than two parts-per-million for intact phospholipids, small molecules and fragments. For the first time, ultra-high mass resolving power SIMS has been demonstrated, with m/{\Delta}m50% > 3,000,000. Higher spatial resolution capabilities of the platform were tested at a spatial resolution of 20 um. The results represent order of magnitude improvements in mass resolving power and mass measurement accuracy for SIMS imaging and the promise of the platform for ultra-high mass resolving power and high spatial resolution imaging.