Μm Pixel Size Research Articles

Inclusion of a GaAs detector model in the Photon Counting Toolkit software for the study of breast imaging systems.

We present an upgraded version of the Photon Counting Toolkit (PcTK), a freely available by request MATLAB tool for the simulation of semiconductor-based photon counting detectors (PCD), which has been extended and validated to account for gallium arsenide (GaAs)-based PCD(s). The modified PcTK version was validated by performing simulations and acquiring experimental data for three different cases. The LAMBDA 60 K module planar detector (X-Spectrum GmbH, Germany) based on the Medipix3 ASIC technology was used in all cases. This detector has a 500-μm thick GaAs sensor and a 256 × 256-pixel array with 55 μm pixel size. The first validation was a comparison between simulated and measured spectra from a 109Cd radionuclide source. In the second validation study, experimental measurements and simulations of mammography spectra were generated to observe the performance of the GaAs version of the PcTK with polychromatic radiation used in conventional x-ray imaging systems. The third validation study used single event analysis to validate the spatio-energetic model of the extended PcTK version. Overall, the software provided a good agreement between simulated and experimental data, validating the accuracy of the GaAs model. The software could be an attractive tool for accurate simulation of breast imaging modalities relying on photon counting detectors and therefore could assist in their characterization and optimization.

29‐4: Higher External Quantum Efficiency with Lower Current Density Injection of <10 μm Pixel Size Arrays for Display Application

In this paper, the gallium nitride (GaN) based Micro‐LED was fabricated based on a self‐aligned process with hydroxide treatment and ALD passivation from 100 μm down to 3 μm. The different current spreading performance was characterized based on the series resistance analysis. Then the size‐dependent carrier concentration profile was demonstrated via the capacitancevoltage measurement, identifying the various carrier injection behavior by different size. Finally, the external quantum efficiency and luminance versus current density dependence for array device and the single device was compared, revealing a higher efficiency at lower current density for array device, which is favorable for display application.

Visualization of the Distribution of PFOS and PFHxS in Concrete by DESI MSI

Firefighting training grounds (FTGs) may serve as a potential secondary source for the release of per- and polyfluoroalkyl substances (PFAS) due to historic use of aqueous film-forming foams (AFFFs). Understanding the heterogenicity and vertical distribution of PFAS in AFFF-impacted concrete is important for risk management and potential remediation. This study assessed whether desorption electrospray ionization mass spectrometry imaging (DESI MSI) can be used to analyze PFAS in a concrete core from an AFFF-impacted FTG to provide the vertical distribution of PFAS. PFOS and PFHxS were detected and observed to be distributed in the core mapped by DESI MSI in a manner consistent with data obtained using a conventional method of drilling samples along the depth of a concrete core (i.e., core sidewall drilling) followed by extraction into methanol and analysis by liquid chromatography mass spectrometry. Visualization by DESI MSI provided the mass distribution in greater detail at a resolution of 30–200 μm pixel size. DESI can provide location mapping at PFAS concentrations of >2.7 pg/mm2 (PFHxS) and 3.6 pg/mm2 (PFOS) with a spatial resolution much greater than that of the previously used core sidewall drilling method.

3.3: Higher External Quantum Efficiency with Lower Current Density Injection of <10 μm Pixel Size Arrays for Display Application

In this paper, the gallium nitride (GaN) based Micro‐LED was fabricated based on a self‐aligned process with hydroxide treatment and ALD passivation from 100 μm down to 3 μm. The different current spreading performance was characterized based on the series resistance analysis. Then the size‐dependent carrier concentration profile was demonstrated via the capacitancevoltage measurement, identifying the various carrier injection behavior by different size. Finally, the external quantum efficiency and luminance versus current density dependence for array device and the single device was compared, revealing a higher efficiency at lower current density for array device, which is favorable for display application.

Characterisation of hepatic lipid signature distributed across the liver zonation using mass spectrometry imaging

Background & AimsLipid metabolism plays an important role in liver pathophysiology. The liver lobule asymmetrically distributes oxygen and nutrition, resulting in heterogeneous metabolic functions. Periportal and pericentral hepatocytes have different metabolic functions, which lead to generating liver zonation. We developed spatial metabolic imaging using desorption electrospray ionisation mass spectrometry to investigate lipid distribution across liver zonation with high reproducibility and accuracy. MethodsFresh frozen livers from healthy mice with control diet were analysed using desorption electrospray ionisation mass spectrometry imaging. Imaging was performed at 50 μm × 50 μm pixel size. Regions of interest (ROIs) were manually created by co-registering with histological data to determine the spatial hepatic lipids across liver zonation. The ROIs were confirmed by double immunofluorescence. The mass list of specific ROIs was automatically created, and univariate and multivariate statistical analysis were performed to identify statistically significant lipids across liver zonation. ResultsA wide range of lipid species was identified, including fatty acids, phospholipids, triacylglycerols, diacylglycerols, ceramides, and sphingolipids. We characterised hepatic lipid signatures in three different liver zones (periportal zone, midzone, and pericentral zone) and validated the reproducibility of our method for measuring a wide range of lipids. Fatty acids were predominantly detected in the periportal region, whereas phospholipids were distributed in both the periportal and pericentral zones. Interestingly, phosphatidylinositols, PI(36:2), PI(36:3), PI(36:4), PI(38:5), and PI(40:6) were located predominantly in the midzone (zone 2). Triacylglycerols and diacylglycerols were detected mainly in the pericentral region. De novo triacylglycerol biosynthesis appeared to be the most influenced pathway across the three zones. ConclusionsThe ability to accurately assess zone-specific hepatic lipid distribution in the liver could lead to a better understanding of lipid metabolism during the progression of liver disease. Impact and ImplicationsZone-specific hepatic lipid metabolism could play an important role in lipid homoeostasis during disease progression. Herein, we defined the zone-specific references of hepatic lipid species in the three liver zones using molecular imaging. The de novo triacylglycerol biosynthesis was highlighted as the most influenced pathway across the three zones.

Semiempirical criterion for eliminating wraparound artifacts in single-grid-based phase-contrast X-ray imaging

Single-grid-based phase-contrast X-ray imaging (SG-PCXI) is a non-interferometric method for the simultaneous retrieval of absorption, phase-contrast (differential), and dark-field images from a single exposure with a common X-ray grid using a spatial harmonic imaging (SHI) technique. However, the retrieved images are often distorted by the wraparound artifacts that are caused by the spectral overlap of adjacent harmonic peaks in the Fourier domain, resulting in the degradation of image quality. In this study, a semiempirical criterion required for eliminating wraparound artifacts in SG-PCXI was established by considering two constraints: one to resolve periodic grid strips by the system resolution to use the SHI technique, and the other to ensure that the spectral contents of adjacent harmonic peaks are separated (not overlapped) to the greatest possible extent during data processing. Further, we assumed that the system resolution can be experimentally determined as the spatial frequency at a 10% modulation transfer function. To verify the efficacy of the semiempirical criterion, we conducted an experiment using a table-top setup, which primarily comprised a microfocus X-ray source with a 20 μm focal spot size, X-ray grids with strip densities of 150, 200, and 254 lines/inch, and a CMOS flat-panel detector with a 49.5 μm pixel size. The experimental measurements of the wraparound artifacts in our system setup were in good agreement with the semiempirical criterion over the entire range of test conditions, thus verifying its efficacy for SG-PCXI. Accordingly, the semiempirical criterion established in this study will be useful for designing a wraparound artifact-free system layout in SG-PCXI.

Focus on lasers, imaging, microscopy, and nanoscience

Focus on lasers, imaging, microscopy, and nanoscience

A tomographic microscopy-compatible Langendorff system for the dynamic structural characterization of the cardiac cycle.

Cardiac architecture has been extensively investigated ex vivo using a broad spectrum of imaging techniques. Nevertheless, the heart is a dynamic system and the structural mechanisms governing the cardiac cycle can only be unveiled when investigating it as such. This work presents the customization of an isolated, perfused heart system compatible with synchrotron-based X-ray phase contrast imaging (X-PCI). Thanks to the capabilities of the developed setup, it was possible to visualize a beating isolated, perfused rat heart for the very first time in 4D at an unprecedented 2.75 μm pixel size (10.6 μm spatial resolution), and 1 ms temporal resolution. The customized setup allows high-spatial resolution studies of heart architecture along the cardiac cycle and has thus the potential to serve as a tool for the characterization of the structural dynamics of the heart, including the effects of drugs and other substances able to modify the cardiac cycle.

Hopping Light Vat Photopolymerization for Multiscale Fabrication.

3D objects with features spanning from microscale to macroscale have various applications. However, the fabrication of such objects presents challenges to additive manufacturing (AM) due to the tradeoffs among manufacturable feature resolution, maximum build area, and printing speed. This paper presents a projection-based AM process called hopping light vat photopolymerization (HL-VPP) to address this critical barrier. The key idea of HL-VPP is to synchronize linear scanning projection with a galvo mirror's rotation. The projector moves continuously at a constant speed while periodically rotating a one-axis galvo mirror to compensate for the projector's linear movement so synchronized hopping motion can be achieved. By this means, HL-VPP can simultaneously achieve large-area (over 200mm), fast-speed (scanning speed of 13.5mm s-1 ), and high-resolution (10µm pixel size) fabrication. The distinguishing characteristic of HL-VPP is that it allows for hundreds of times lower refresh rates without motion blur. Thus, HL-VPP decouples the fabrication efficiency limit imposed by the refresh rate and will enable super-fast curing in the future. This work will significantly advance VPP's use in applications that require macroscale part size with microscale features. The process has been verified by fabricating multiple multiscale objects, including microgrids and biomimetic structures.

Novel, Green, and Scalable Aqueous Synthesis of Yellow–Green Emitting Cs3Cu2Cl5 Scintillator and its Application in High‐Resolution TFT Panel for X‐Ray Imaging Detector

AbstractCopper‐based metal halide scintillators have received increasing attention due to their high light yield and nontoxicity. However, the synthetic methods are still not feasible for actual commercialization for the difficulty in scaling up and the absence of green chemical footprint. Herein, we report a new, simple, aqueous synthetic method for the mass production of highly purified and crystallized Cs3Cu2Cl5 powder by a room‐temperature reaction between a saturated aqueous solution of CsCl and a saturated hydrochloric acid solution of CuCl. The product exhibits a photoluminence peak centering at 527 nm (FWHM = 106.7 nm) and a quantum yield (PLQY) of 97%. A prototype X‐ray imaging detector is fabricated by coupling a large area scintillation screen prepared by blade coating of Cs3Cu2Cl5 powder and a commercial thin‐film transistor (TFT) panel (16 cm × 13 cm, 125 µm pixel size) with readout circuit. The device exhibits a high spatial resolution of 4 lp mm−1, exceeding the theoretical limit of the TFT panel, and an excellent dynamic imaging ability. In short, this work demonstrates an efficient novel synthetic method of Cs3Cu2Cl5 and its application as X‐ray imaging device, providing an applicable solution for its future commercialization.

Molecular Networking and On-Tissue Chemical Derivatization for Enhanced Identification and Visualization of Steroid Glycosides by MALDI Mass Spectrometry Imaging.

Spatial metabolomics describes the spatially resolved analysis of interconnected pathways, biochemical reactions, and transport processes of small molecules in the spatial context of tissues and cells. However, a broad range of metabolite classes (e.g., steroids) show low intrinsic ionization efficiencies in mass spectrometry imaging (MSI) experiments, thus restricting the spatial characterization of metabolic networks. Additionally, decomposing complex metabolite networks into chemical compound classes and molecular annotations remains a major bottleneck due to the absence of repository-scaled databases. Here, we describe a multimodal mass-spectrometry-based method combining computational metabolome mining tools and high-resolution on-tissue chemical derivatization (OTCD) MSI for the spatially resolved analysis of metabolic networks at the low micrometer scale. Applied to plant toxin sequestration in Danaus plexippus as a model system, we first utilized liquid chromatography (LC)-MS-based molecular networking in combination with artificial intelligence (AI)-driven chemical characterization to facilitate the structural elucidation and molecular identification of 32 different steroidal glycosides for the host-plant Asclepias curassavica. These comprehensive metabolite annotations guided the subsequent matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) analysis of cardiac-glycoside sequestration in D. plexippus. We developed a spatial-context-preserving OTCD protocol, which improved cardiac glycoside ion yields by at least 1 order of magnitude compared to results with untreated samples. To illustrate the potential of this method, we visualized previously inaccessible (sub)cellular distributions (2 and 5 μm pixel size) of steroidal glycosides in D. plexippus, thereby providing a novel insight into the sequestration of toxic metabolites and guiding future metabolomics research of other complex sample systems.

38.2: Invited Paper: Enabling High Resolution Photopatternable Quantum Dot Downconverters

Quantum Dot downconverters can provide a scalable solution to tri‐color high‐resolution microLED and OLED displays by converting monochrome displays using photopatternable red and green QDs. Using internal measurements collected at NanoPattern Technologies, Inc. we model and discuss the practical wall plug efficiencies for downconverted InGaN blue microLED displays. In the range of 5 μm pixel sizes, using uncorrected 65 % film PLQY, the downconverted InGaN red emitter achieves a comparable external quantum efficiency compared to a direct red emitting AlInGaP when compared at practical current densities for microLED drivers.

53.1: Invited Paper: Process optimization of passive matrix GaN Micro‐LED displays

A passive matrix (PM) blue Micro light‐emitting diode (LED) device with 300 μm pixel size and 7/10/15/20/30/50/100 μm luminous area is designed. The 1 μm thick insulating layer composed of SiO2 is grown in four steps, which improves the quality of the insulating layer and reduces the risk of electrical leakage. The thick metal is used as the p lines and the n lines. The non‐conductive GaN is left as the structure underneath the p lines to alleviate the breakage of the p lines to improve the reliability of the device. The optimized technology is used to fabricate the micro‐display, and the optical and electrical characterization is carried out. Besides, we realize the character display. With no additional manufacturing process, this work will contribute to the implementation of highly reliable PM Micro‐LED display technology.

Photovoltaic implant simulator reveals resolution limits in subretinal prosthesis

Objective. PRIMA, the photovoltaic subretinal prosthesis, restores central vision in patients blinded by atrophic age-related macular degeneration (AMD), with a resolution closely matching the 100 µm pixel size of the implant. Improvement in resolution requires smaller pixels, but the resultant electric field may not provide sufficient stimulation strength in the inner nuclear layer (INL) or may lead to excessive crosstalk between neighboring electrodes, resulting in low contrast stimulation patterns. We study the approaches to electric field shaping in the retina for prosthetic vision with higher resolution and improved contrast. Approach. We present a new computational framework, Retinal Prosthesis Simulator (RPSim), that efficiently computes the electric field in the retina generated by a photovoltaic implant with thousands of electrodes. Leveraging the PRIMA clinical results as a benchmark, we use RPSim to predict the stimulus strength and contrast of the electric field in the retina with various pixel designs and stimulation patterns. Main results. We demonstrate that by utilizing monopolar pixels as both anodes and cathodes to suppress crosstalk, most patients may achieve resolution no worse than 48 µm. Closer proximity between the electrodes and the INL, achieved with pillar electrodes, enhances the stimulus strength and contrast and may enable 24 µm resolution with 20 µm pixels, at least in some patients. Significance. A resolution of 24 µm on the retina corresponds to a visual acuity of 20/100, which is over 4 times higher than the current best prosthetic acuity of 20/438, promising a significant improvement of central vision for many AMD patients.

Characterization of Silicon Photomultipliers (SiPMs) for Space Exploration

Silicon Photomultipliers (SiPMs) are the devices, which along with scintillation detectors can be used for the radiation measurements. We are developing instruments using scintillation detector and SiPM arrays for the measurements of high-energy X-rays and charged particles. These instruments are being developed for the future space exploration programs. Here, we report the work carried out for the characterization of SiPM and its response in the hardened environments. Results from two different experiments are presented. In the first experiment: electrical characterizations of SiPMs from two manufacturers i.e. SensL (now Onsemi) and Ketek have been carried out. Three different pixel sizes 20 μm, 35 μm and 50 μm of MicroC series from SensL and 50 μm pixel size of PM3350 series of Ketek have been tested. In order to see ‘device – to - device’ variations, three SiPMs of each pixel size are used in the experiment i.e. total twelve SiPMs have been characterized for the breakdown voltage, quenching resistor and their temperature dependences. Variations in the gain and microcell recovery time due to temperature are also estimated. In the second experiment: one of the SiPM models (SensL make 35 μm pixel size) has been subjected to various environmental tests mimicking the space conditions. Matching of pre and post I-V measurements for each tests confirms that performance of the device is not degraded and hence selected model of SiPM can be explored for the future space instrumentation.

Monte Carlo modelling of pixel clusters in Timepix detectors using the MCNP code

The track structure of the signal measured by the semiconductor pixel detector Timepix3 was modelled in the Monte Carlo MCNP® code. A detailed model at the pixel-level (256 × 256 pixels, 55 × 55 µm2 pixel size) was developed and used to generate and store clusters of adjacent hit pixels observed in the measured data because of particle energy deposition path, charge sharing, and drift processes. An analytical model of charge sharing effect and the detector energy resolution was applied to the simulated data. The method will help the user sort the measured clusters and distinguish radiation components of mixed fields by determining the response of Timepix3 detector to particular particle types, energies, and incidence angles that cannot be measured separately.

Monolithic pixel sensor with 25 µm × 35 µm pixel size and high time resolution implemented in 180 nm technology

A monolithic pixel sensor with small collection electrode and partially depleted sensor diode named HVMAPS25 has been implemented in the 180 nm technology of TSI semiconductors. The pixel size is 25 µm × 35 µm. The pixel electronics contains a fast and low power charge sensitive amplifier, a comparator, a threshold tuning DAC and a digital block that measures the arrival time of the hit with 10 bit resolution and the signal amplitude (time over threshold) with 6 bit resolution. A deep p-well has been used for isolation of the pixel electronics from the sensor substrate. The building blocks of the chip, simulations and the measurement results will be presented.

Characterization of a 30 µm pixel size CLIP-based 3D printer and its enhancement through dynamic printing optimization.

Resolving microscopic and complex 3D polymeric structures while maintaining high print speeds in additive manufacturing has been challenging. To achieve print precision at micrometer length scales for polymeric materials, most 3D printing technologies utilize the serial voxel printing approach that has a relatively slow print speed. Here, a 30-µm-resolution continuous liquid interface production (CLIP)-based 3D printing system for printing polymeric microstructures is described. This technology combines the high-resolution from projection microstereolithography and the fast print speed from CLIP, thereby achieving micrometer print resolution at x103 times faster than other high-resolution 3D printing technologies. Print resolutions in both lateral and vertical directions were characterized, and the printability of minimum 30 µm features in 2D and 3D has been demonstrated. Through dynamic printing optimization, a method that varies the print parameters (e.g. exposure time, UV intensity, and dark time) for each print layer, overhanging struts at various thicknesses spanning 1 order of magnitude (25 µm - 200 µm) in a single print are resolvable. Taken together, this work illustrates that the micro-CLIP 3D printing technology, in combination with dynamic printing optimization, has the high resolution needed to enable manufacturing of exquisitely detailed and gradient 3D structures, such as terraced microneedle arrays and micro-lattice structures, while maintaining high print speeds.

Automated multicolor mesoscopic imaging for the 3-dimensional reconstruction of fluorescent biomarker distribution in large tissue specimens.

Research in translational medicine often requires high-resolution characterization techniques to visualize or quantify the fluorescent probes. For example, drug delivery systems contain fluorescent molecules enabling in vitro and in vivo tracing to determine biodistribution or plasma disappearance. Albeit fluorescence imaging systems with sufficient resolution exist, the sample preparation is typically too complex to image a whole organism of the size of a mouse. This article established a mesoscopic imaging technique utilizing a commercially available cryo-microtome and an in-house built episcopic imaging add-on to perform imaging during serial sectioning. Here we demonstrate that our automated red, green, blue (RGB) and fluorescence mesoscope can generate sequential block-face and 3-dimensional anatomical images at variable thickness with high quality of 6 µm × 6 µm pixel size. In addition, this mesoscope features a numerical aperture of 0.10 and a field-of-view of up to 21.6 mm × 27 mm × 25 mm (width, height, depth).

Characterization of low light performance of a complementary metal-oxide semiconductor sensor for ultraviolet astronomical applications

Complementary metal-oxide semiconductor (CMOS) detectors offer many advantages over charge-coupled devices (CCDs) for optical and ultraviolet (UV) astronomical applications, especially in space where high radiation tolerance is required. However, astronomical instruments are most often designed for low light-level observations demanding low dark current and read noise, good linearity, and high dynamic range, characteristics that have not been widely demonstrated for CMOS imagers. We report the performance, over temperatures from 140 to 240 K, of a radiation hardened SRI 4k × 2k back-side illuminated CMOS image sensor with surface treatments that make it highly sensitive in blue and UV bands. After suppressing emission from glow sites resulting from defects in the engineering grade device examined, a 0.077 me − / s dark current floor is reached at 160 K, rising to 1 me − / s at 184 K, rivaling that of the best CCDs. We examine the trade-off between readout speed and read noise, finding that 1.43 e − median read noise is achieved using line-wise digital correlated double sampling at 700 kpix / s / ch corresponding to a 1.5 s readout time. The 15 ke − well capacity in high gain mode extends to 120 ke − in dual gain mode. Continued collection of photogenerated charge during readout enables a further dynamic range extension beyond 106 e − effective well capacity with only 1% loss of exposure efficiency by combining short and long exposures. A quadratic fit to correct for non-linearity reduces gain correction residuals from 1.5% to 0.2% in low gain mode and to 0.4% in high gain mode. Cross-talk to adjacent pixels is only 0.4% vertically, 0.6% horizontally, and 0.1% diagonally. These characteristics plus the relatively large (10 μm) pixel size, quasi 4-side buttability, electronic shutter, and sub-array readout make this sensor an excellent choice for wide field astronomical imaging in space, even at far-UV wavelengths where sky background is very low.