This paper describes the development towards a miniaturized analytical system that can perform the major key functions of a flow cytometer. The development aims at diagnostic applications for cell counting and sorting with the ultimate goal of a low-cost portable instrument for point of care diagnosis. The present systems configuration consists of a disposable microfluidic device, that enables injection, single file cell flow through a miniaturized laser induced fluorescence detection system as well as sorting of identified samples. The microfluidic devices were fabricated by means of rapid prototyping technologies based on thick film photo-polymers. This paper reports various approaches on cell sorting and demonstrates sorting of single cells by means of an off-chip valve switching technique. The miniaturized fluorescence detection system employs active and passive micro-optical components, including semiconductor laser and ultra bright LED sources, highly sensitive avalanche photodiodes as well as micro-prism, holographic diffraction gratings and fibre optics for transmission and collection of light. Furthermore we demonstrate the feasibility of integrating solid-state components as part of an on-chip detection system.

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The performance of an 8 × 8 array of 6.0 × 6.0 mm2 (active area) SiPMs was evaluated for PET applications using crystal arrays with different pitch sizes (3.4 mm, 1.5 mm, 1.35 mm and 1.2 mm) and custom designed five-channel front-end readout electronics (four channels for position information and one channel for timing information). The total area of this SiPM array is 57.4 × 57.4 mm2, and the pitch size is 7.2 mm. It was fabricated using enhanced blue sensitivity SiPMs (MicroFB-60035-SMT) with peak spectral sensitivity at 420 nm. The performance of the SiPM array was characterized by measuring flood histogram decoding quality, energy resolution, timing resolution and saturation at several bias voltages (from 25.0 V to 30.0 V in 0.5 V intervals) and two different temperatures (5 °C and 20 °C). Results show that the best flood histogram was obtained at a bias voltage of 28.0 V and 5 °C and an array of polished LSO crystals with a pitch as small as 1.2 mm can be resolved. No saturation was observed up to a bias voltage of 29.5 V during the experiments, due to adequate light sharing between SiPMs. Energy resolution and timing resolution at 5 °C ranged from 12.7 ± 0.8% to 14.6 ± 1.4 % and 1.58 ± 0.13 ns to 2.50 ± 0.44 ns, for crystal array pitch sizes of 3.4 mm and 1.2 mm respectively. Superior flood histogram quality, energy resolution and timing resolution were obtained with larger crystal array pitch sizes and at lower temperature. Based on our findings, we conclude that this large-area SiPM array can serve as a suitable photodetector for high-resolution small-animal PET or dedicated human brain PET scanners.

This publication details CMOS foundry fabrication, reliability stress assessment, and packaged sensor test results obtained during qualification of the SensL B-Series silicon photomultiplier (SiPM). SiPM sensors with active-area dimensions of 1, 3, and 6 mm were fabricated and tested to provide a comprehensive review of SiPM performance highlighted by fast output rise times of 300 ps and photon detection efficiency of greater than 41%, combined with low afterpulsing and crosstalk. Measurements important for medical imaging positron emission tomography systems that rely on time-of-flight detectors were completed. Results with LSYO:Ce scintillation crystals of 3 × 3 × 20 mm 3 demonstrated a 225 AE 2-ps coincidence resolving time (CRT), and the fast output is shown to allow for simultaneous acquisition of CRT and energy resolution. The wafer level test results from ∼150 k 3-mm SiPM are shown to demonstrate a mean breakdown voltage value of 24.69 V with a standard deviation of 0.073 V. The SiPM output optical uniformity is shown to be AE10% at a single supply voltage of 29.5 V. Finally, reliability stress assessment to Joint Electron Device Engineering Council (JEDEC) industry standards is detailed and shown to have been completed with all SiPM passing. This is the first qualification and reliability stress assessment program run to industry standards that has been reported on SiPM.

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Purpose: The MatrixSL-9-30035-OEM (Matrix9) from SensL is a large-area silicon photomultiplier (SiPM) photodetector module consisting of a 3 × 3 array of 4 × 4 element SiPM arrays (total of 144 SiPM pixels) and incorporates SensL's front-end electronics board and coincidence board. Each SiPM pixel measures 3.16 × 3.16 mm 2 and the total size of the detector head is 47.8 × 46.3 mm 2 . Using 8 × 8 polished LSO/LYSO arrays (pitch 1.5 mm) the performance of this detector system (SiPM array and readout electronics) was evaluated with a view for its eventual use in small-animal positron emission tomography (PET). Methods: Measurements of noise, signal, signal-to-noise ratio, energy resolution, flood histogram quality, timing resolution, and array trigger error were obtained at different bias voltages (28.0-32.5 V in 0.5 V intervals) and at different temperatures (5• C degree steps) to find the optimal operating conditions. Results: The best measured signal-to-noise ratio and flood histogram quality for 511 keV gamma photons were obtained at a bias voltage of 30.0 V and a temperature of 5• C. The energy resolution and timing resolution under these conditions were 14.2% ± 0.1% and 4.2 ± 0.1 ns, respectively. The flood histograms show that all the crystals in the 1.5 mm pitch LSO array can be clearly identified and that smaller crystal pitches can also be resolved. Flood histogram quality was also calculated using different center of gravity based positioning algorithms. Improved and more robust results were achieved using the local 9 pixels for positioning along with an energy offset calibration. To evaluate the front-end detector readout, and multiplexing efficiency, an array trigger error metric is introduced and measured at different lower energy thresholds. Using a lower energy threshold greater than 150 keV effectively eliminates any mispositioning between SiPM arrays. Conclusions: In summary, the Matrix9 detector system can resolve high-resolution scintillator arrays common in small-animal PET with adequate energy resolution and timing resolution over a large detector area. The modular design of the Matrix9 detector allows it to be used as a building block for simple, low channel-count, yet high performance, small animal PET or PET/MRI systems. C 2015 American Association of Physicists in Medicine. [http://dx

We present the first results of the MINDVIEW project. An innovative imaging system for the human brain examination, allowing simultaneous acquisition of PET/MRI images, has been designed and constructed. It consists of a high sensitivity and high resolution PET scanner integrated in a novel, head-dedicated, radio frequency coil for a 3T MRI scanner. Preliminary measurements from the PET scanner show sensitivity 3 times higher than state-of-the-art PET systems that will allow safe repeated studies on the same patient. The achieved spatial resolution, close to 1 mm, will enable differentiation of relevant brain structures for schizophrenia. A cost-effective and simple method of radiopharmaceutical production from C-carbon monoxide and a mini-clean room has been demonstrated. It has been shown thatC-raclopride has higher binding potential in a new VAAT null mutant mouse model of schizophrenia compared to wild type control animals. A significant reduction in TSPO binding has been found in gray matter in a small sample of drug-naïve, first episode psychosis patients, suggesting a reduced number or an altered function of immune cells in brain at early stage schizophrenia.

In this work, we present a complete design implementation and characterization of an analog silicon photomultiplier (SiPM) with integrated time-to-digital converter (TDC). The combination of a photodetector together with on-chip readout circuitry in close proximity enables system-level advantages such as internal parasitic reduction for better singlephoton timing resolution (SPTR), but also overall simplicity and compactness. The system comprises a C-Series analog SiPM developed by SensL, a TDC, and a comparator. The design was implemented in 0.35µm CMOS technology. The proposed analog SiPM features 48% photon detection efficiency (PDE) at 420nm wavelength and +6.0V excess bias. Thanks to the small size of the electronics, the overall sensor fill factor is 75% and its sensitive area is 3×3mm 2. The SiPM fast output, which is a specialized terminal for fast timing output signals, has a parasitic capacitance of about 12pF. The TDC is a multi-path-gated ring oscillator with a 6-bit coarse counter and 9-bit phase detector. Post-layout simulation results indicate a 65ps LSB in typical corner with differential non-linearity (DNL) and integral non-linearity (INL) of ±0.55LSB and ±1LSB, respectively. The comparator is composed of two preamplifier stages followed by a complementary self-biased differential amplifier stage (CSDA), directly coupled to the fast output through a capacitor. Post-layout simulation indicates 48V/ns slew rate and a preamplifier stage bandwidth of ~1GHz. The comparator power consumption without the additional preamplifier stage is 198µW.