Nanometer resolution TEM sample manipulator for rotational and translational positioning

The design and fabrication process for a high performance manipulation stage for nanometer resolution TEM sample positioning over a 20 μm range is presented. A two level, planar stage is moved in three translational and three rotational directions by just two types of actuators; three horizontal and three vertical combdrives. The vertical combdrives are suspended by optimally designed torsion-beams, improving lateral stiffness by at least a factor of 50 compared to rectangular beams, hence minimizing the chance of electrostatic side pull-in

SUSMETRO : Impact Assessment Tools for Food Planning in Metropolitan Regions : IA tools and serious gaming in support of sustainability targets for food planning, nature conservation and recreation

By offering a series of decision support tools for stakeholders of metropolitan regions, SUSMETRO facilitates and enables evidence-based decision making by means of ‘serious gaming’. Making use of the Phase 1 thematic maps such as on agricultural competitiveness, nature conservation and recreational values, stakeholders can compare impacts of traditional versus innovative forms of agricultural production. The SUSMETRO Impact Assessment tool provides information on the expected effects of spatial planning with regard to the self-supportive capacities of the region (ecological footprint) and the share of recreational and nature conservation facilities (land use functions), offering cost-benefit calculations regarding the expected economic revenues. The whole process is embedded in a Landscape Character Assessment process and guided by Knowledge Brokerage procedures to strengthen the science-policy interface. In sum, the SUSMETRO approach allows a wide range of stakeholders to co-develop images for sustainable Metropolitan Agriculture

Design and modeling of a precision 6 DOF MEMS-based parallel kinematic TEM sample manipulator

A design for a 6 Degree-of-freedom precision MEMS-based manipulator for a TEM will is presented. The elastic mechanism is designed and modeled with the specific design considerations regarding kinematic constraint design and elastic energy storage. The typical relatively large deformations of elastic hinges in MEMS result in relatively large displacements and large rigid body rotations. For accurate analysis geometrically non-linear elasticity theory has been used. The drive stiffness has great influence on the longitudinal stiffness of leaf-springs. Leaf-springs used at a relatively low drive stiffness, as is usually the case in MEMS, can benefit from reinforcement, but only in certain cases. The stiffness and so the natural frequency decrease due to deflection of elastic elements in a system can be drastic. In the proposed hexapod design the maximum lowest natural frequency shift due to a displacement of 25 μm is only 10

MEMS based 6 degrees-of-freedom parallel kinematic precision micro manipulator

A design is presented for a 6 Degree-of-freedom parallel kinematic precision micro manipulator comprising 3 translations of 20 μm stroke, and three small correction rotation strokes of 5°. The elastic deformations of the manipulator have been optimized for minimal elastic energy storage at a large guiding stiffness. The parallel kinematics facilitates 6 electrostatic lateral comb-drive actuators to be made in-plane of the wafer, using a mechanism to direct the motion to out-of-plane to obtain 6 DOF. One single technology can be used to manufacture the actuators and mechanisms. The fabrication involves deep reactive ion etching with a back-etch release process, offering great design freedom, resulting in a compact design

MEMS 6 degrees of freedom parallel micro manipulator for TEM sample manipulation

Up till now MEMS actuators acted either only in-plane or only out-of plane restricting to 3 DOF manipulation. A design for a millimeter-sized manipulator with 6 degrees of freedom to manipulate a micron-sized substrate at nanometer resolution over strokes of 10 microns with a position stability better than 100 pm over a minute is presented as part of the Multi Axis Micro Stage (MAMS) project of IOP precision technology of SenterNovem. A secondary goal of the project is to generate principle solutions for manipulation and sensing in the micro domain. A parallel kinematic manipulator has been designed in MEMS processes to operate in a TEM environment. The parallel kinematics is used to convert in-plane motion to 6 DOF. For large angles the MEMS device is mounted on a second stage, which is designed with assembly like techniques. Currently the MEMS devices are being processed in the MESA+ clean room

A planar 3 dof sample manipulator for nano-scale characterization

We present the first monolithic manipulator for in-plane positioning in three degrees of freedom (DOF), based on a parallel flexure-mechanism. The manipulator stage is capable of translation in the x- and y-direction (maximum of ±9 μm) as well as rotation about the z-axis (maximum of ±2 degrees). A power-port based model has been developed to give insight in the systems behavior. The effect of anisotropy in the Young’s modulus of single crystalline silicon (SCS) on the flexure stiffness is modeled and matches the real system

Systematic metareview of prediction studies demonstrates stable trends in bias and low PROBAST inter-rater agreement

Objectives: To (1) explore trends of risk of bias (ROB) in prediction research over time following key methodological publications, using the Prediction model Risk Of Bias ASsessment Tool (PROBAST) and (2) assess the inter-rater agreement of the PROBAST.Study Design and Setting: PubMed and Web of Science were searched for reviews with extractable PROBAST scores on domain and signaling question (SQ) level. ROB trends were visually correlated with yearly citations of key publications. Inter-rater agreement was asResults: One hundred and thirty nine systematic reviews were included, of which 85 reviews (containing 2,477 single studies) on domain level and 54 reviews (containing 2,458 single studies) on SQ level. High ROB was prevalent, especially in the Analysis domain, and overall trends of ROB remained relatively stable over time. The inter-rater agreement was low, both on domain (Kappa 0.04-0.26) and SQ level (Kappa -0.14 to 0.49). Conclusion: Prediction model studies are at high ROB and time trends in ROB as assessed with the PROBAST remain relatively stable. These results might be explained by key publications having no influence on ROB or recency of key publications. Moreover, the trend may suffer from the low inter-rater agreement and ceiling effect of the PROBAST. The inter-rater agreement could potentially be improved by altering the PROBAST or providing training on how to apply the PROBAST.& COPY; 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Analysis and support of clinical decision makingDevelopment and application of statistical models for medical scientific researc

Towards personalized treatment of prostate cancer: PSMA I&T, a promising prostate-specific membrane antigen-targeted theranostic agent

Prostate-specific membrane antigen (PSMA) is a well-established target for nuclear imaging and therapy of prostate cancer (PCa). Radiolabeled small-molecule PSMA inhibitors are excellent candidates for PCa theranostics-they rapidly and efficiently localize in tumor lesions. However, high tracer uptake in kidneys and salivary glands are major concerns for therapeutic applications. Here, we present the preclinical application of PSMA I&T, a DOTAGA-chelated urea-based PSMA inhibitor, for SPECT/CT imaging and radionuclide therapy of PCa. 111In-PSMA I&T showed dose-dependent uptake in PSMA-expressing tumors, kidneys, spleen, adrenals, lungs and salivary glands. Coadministration of 2-(phosphonomethyl)pentane-1,5-dioic acid (2-PMPA) efficiently reduced PSMA-mediated renal uptake of 111In-PSMA I&T, with the highest tumor/kidney radioactivity ratios being obtained using a dose of 50 nmol 2-PMPA. SPECT/CT clearly visualized subcutaneous tumors and sub-millimeter intraperitoneal metastases; however, high renal and spleen uptake in control mice (no 2-PMPA) interfered with visualization of metastases in the vicinity of those organs. Coadministration of 2-PMPA increased the tumor-to-kidney absorbed dose ratio during 177Lu-PSMA I&T radionuclide therapy. Hence, at equivalent absorbed dose to the tumor (36 Gy), coinjection of 2-PMPA decreased absorbed dose to the kidneys from 30 Gy to 12 Gy. Mice injected with 177Lu-PSMA I&T only, showed signs of nephrotoxicity at 3 months after therapy, whereas mice injected with 177Lu-PSMA I&T + 2-PMPA did not. These data indicate that PSMA I&T is a promising theranostic tool for PCa. PSMA-specific uptake in kidneys can be successfully tackled using blocking agents such as 2-PMPA