A three dimensional semiconductor device includes a first die; and a second die overlaying the first die, wherein said first die comprises signals are selectively coupleable to the second die using Through Silicon Vias.

A wafer includes a group of tiles of programmable logic formed thereon, wherein each tile comprises a micro control unit (MCU) communicating with adjacent MCUs, and wherein each MCU is controlled in a predetermined order of priority by adjacent MCUs; and dice lines on the wafer to separate the group into one or more end-devices.

A semiconductor device comprising first layer comprising multiplicity of first transistors and, second layer comprising multiplicity of second transistors and, at least one function constructed by the first transistors are structure so it could be replaced by a function constructed by the second transistors.

A three dimensional semiconductor device is described with two transistor layers overlaid. The first transistor layer comprises a plurality of flip-flops each having an input and an output, wherein the inputs are selectively coupleable to the second transistor layer.

I propose to pursue two emerging Force Microscopy techniques that allow measuring structural properties below the surface of the specimen. Whereas Force Microscopy (most commonly known under the name AFM) is usually limited to measuring the surface topography and surface properties of a specimen, I will demonstrate that Force Microscopy can achieve true 3D images of the structure of the cell nucleus. In Ultrasound Force Microscopy, an ultrasound wave is launched from below towards the surface of the specimen. After the sound waves interact with structures beneath the surface of the specimen, the local variations in the amplitude and phase shift of the ultrasonic surface motion is collected by the Force Microscopy tip. Previously, measured 2D maps of the surface response have shown that the surface response is sensitive to structures below the surface. In this project I will employ miniature AFM cantilevers and nanotube tips that I have already developed in my lab. This will allow me to quickly acquire many such 2D maps at a much wider range of ultrasound frequencies and from these 2D maps calculate the full 3D structure below the surface. I expect this technique to have a resolving power better than 10 nm in three dimensions as far as 2 microns below the surface. In parallel I will introduce a major improvement to a technique based on Nuclear Magnetic Resonance (NMR). Magnetic Resonance Force Microscopy measures the interaction of a rotating nuclear spin in the field gradient of a magnetic Force Microscopy tip. However, these forces are so small that they pose an enormous challenge. Miniature cantilevers and nanotube tips, in combination with additional innovations in the detection of the cantilever motion, can overcome this problem. I expect to be able to measure the combined signal of 100 proton spins or fewer, which will allow me to measure proton densities with a resolution of 5 nm, but possibly even with atomic resolution.

The main scientific objective of the project is to enhance the understanding of the fundamental principles for controlling electron transfer reactions between nanoparticles (NPs), carbon nanotubes (CNTs), their assemblies confined into three-dimensional (3D) microscale networks, conductive nano/-microporous silicone (NMPSi) chips and different bioelements, such as glucose oxidising and oxygen reducing enzymes. The technological objective of the project is to construct potentially implantable microscale self-contained wireless biodevices working in different biomatrices, e.g. blood, plasma, saliva. Novel biodevices will be constructed by combination of glucose and oxygen sensitive biosensors powered by biofuel cells, all made from 3D nanobiostructured materials and operated by wireless microtransmitter/transducer system. To produce 3D microscale devices with superior characteristics mathematical modelling of their performance will be compared against experimentally determined parameters. Nanowiring of appropriate redox enzymes with NPs, CNTs, proper surface modifications, and use of Os and Ru redox complexes, are chosen as a major direction to solve main obstacles in the area of bioelectronics, i.e. poor electronic communication between the biocomponents and the electronic elements along with insufficient operational stability. The 3D structure of nanobiodevices will provide very high efficiency and stability along with their miniaturisation for successful application in biomedicine and health care. The developed, wireless self-contained and potentially implantable, 3D nanobiostructure-based devices will be used to improve quality of life and increase safety in case of widely occurring chronic diseases. Moreover, in the long-term, 3D nanobiostructure-based elements will be essential for constructing devices to be used for neuron/nerve stimulations and compensation of human disabilities.

Background: Osteoarthritis (OA) is a common musculoskeletal disease occurring worldwide. Despite extensive research, etiology of OA is still poorly understood. Histopathological grading (HPG) of 2D tissue sections is the gold standard reference method for determination of OA stage. However, traditional 2D-HPG is destructive and based only on subjective visual evaluation. These limitations induce bias to clinical in vitro OA diagnostics and basic research that both rely strongly on HPG. Objectives: 1) To establish and validate the very first 3D-HPG of OA based on cutting-edge nano/micro-CT (Computed Tomography) technologies in vitro; 2) To use the established method to clarify the beginning phases of OA; and 3) To validate 3D-HPG of OA for in vivo use. Methods: Several hundreds of human osteochondral samples from patients undergoing total knee arthroplasty will be collected. The samples will be imaged in vitro with nano/micro-CT and clinical high-end extremity CT devices using specific contrast-agents to quantify tissue constituents and structure in 3D in large volume. From this information, a novel 3D-HPG is developed with statistical classification algorithms. Finally, the developed novel 3D-HPG of OA will be applied clinically in vivo. Significance: This is the very first study to establish 3D-HPG of OA pathology in vitro and in vivo. Furthermore, the developed technique hugely improves the understanding of the beginning phases of OA. Ultimately, the study will contribute for improving OA patients' quality of life by slowing the disease progression, and for providing powerful tools to develop new OA therapies.

Bacterial infection into host cells is an important and highly active field of research. Understanding the interactions and the distribution of the host-cell scaffolding protein network during bacterial entry poses a major challenge. The molecular architecture of actin comet tails, filamentous structures assembled by internalized bacteria to move inside the host-cell cytoplasm and from cell-to-cell, remains unknown. Cryo-electron tomography (cryo-ET) is the most advanced method for visualizing the architecture of hydrated cells at a resolution better than 5 nm. Cryo-ET will be used to visualize the three dimensional (3D) cytoskeleton reorganization directly in eukaryotic cells infected by Listeria. Measurements will be performed at cryo-temperatures, on vitrified cell samples preserved in a close-to-life state. Specimen thickness limitations will be overcome by the use of the focused ion beam (FIB) micro-machining method, to obtain 500 nm thick samples as required for the collection of good data. Cryo-ET will be combined with correlative cryo-fluorescence microscopy, to localize the scaffolding components recruited during Listeria uptake and motility: host-cell actin, septin and clathrin. We expect to achieve nanometer resolution maps of the cell area of interest. The distribution and the ultrastructure of the cytoskeletal scaffold at Listeria entry and of Listeria actin comet tails will be provided. The work will provide unprecedented insight into cytoskeleton architecture during bacterial pathogenesis. The applicant obtained her PhD at a structural biology institute in France. Joining the Baumeister laboratory in Germany, and collaborating with the Cossart group, will allow her to address new challenging questions on the structural organisation of the cell, at unprecedented resolution. The acquired combination of skills at a world-class level will contribute significantly to her professional maturity, and to increase the competitiveness of European science.

Understanding structure-property relationships across lengthscales is key to the design of functional and structural materials and devices. Moreover, the complexity of modern devices extends to three dimensions and as such 3D characterization is required across those lengthscales to provide a complete understanding and enable improvement in the material's physical and chemical behaviour. 3D imaging and analysis from the atomic scale through to granular microstructure is proposed through the development of electron tomography using (S)TEM, and 'dual beam' SEM-FIB, techniques offering complementary approaches to 3D imaging across lengthscales stretching over 5 orders of magnitude. We propose to extend tomography to include novel methods to determine atom positions in 3D with approaches incorporating new reconstruction algorithms, image processing and complementary nano-diffraction techniques. At the nanoscale, true 3D nano-metrology of morphology and composition is a key objective of the project, minimizing reconstruction and visualization artefacts. Mapping strain and optical properties in 3D are ambitious and exciting challenges that will yield new information at the nanoscale. Using the SEM-FIB, 3D 'mesoscale' structures will be revealed: morphology, crystallography and composition can be mapped simultaneously, with ~5nm resolution and over volumes too large to tackle by (S)TEM and too small for most x-ray techniques. In parallel, we will apply 3D imaging to a wide variety of key materials including heterogeneous catalysts, aerospace alloys, biomaterials, photovoltaic materials, and novel semiconductors. We will collaborate with many departments in Cambridge and institutes worldwide. The personnel on the proposal will cover all aspects of the tomography proposed using high-end TEMs, including an aberration-corrected Titan, and a Helios dual beam. Importantly, a postdoc is dedicated to developing new algorithms for reconstruction, image and spectral processing.

The applications for nanoparticles (NPs) in medicine have rapidly increased in recent years; some examples are drug delivery, medical imaging, in vitro biosensors and cancer treatment. Typically, the biological assessment of NPs is carried out first in vitro (in a 2D petri dish) and then in small animals in vivo (3D). This whole process is costly and time consuming; similarly to that is required for the drug development, 11-15 years and $500 to $800 million to reach the market. An intermediate step between (2D) in vitro and (3D) in vivo assays could provide relevant information, decreasing the total cost of the biological assessment. 3D in vitro assays mimic biologically relevant tissues in an economical and rapid manner; although, current 3D in vitro methods entail complex engineering steps. 3DinvitroNPC focuses on a simple and innovative strategy to create 3D in vitro cell cultures using sheets of porous materials and embedding living cells and NPs within those materials. 3D cell cultures require a material non-toxic for cells and highly porous to allow cells to grow within its microstructure. This project explores aerogels of biomaterials to create 3D in vitro novel scaffolds that are biodegradable and transparent. Combinations of cells and NPs in the 3D in vitro constructs permits the assessment of viability and functionality of NPs in relevant biological environments which is critical for using NPs in medical applications. Gold NPs and FexOy-NPs will be assessed, the first as model NPs and the latter as magnetic label of cells. FexOy-NPs internalized by cells, magnetically label the cells. Localization of magnetic cells using a magnet placed outside the body is a recently developed medical method non-invasive for tissue recovery after cerebral ischemia. For this purpose, the platform of 3DinvitroNPC will evaluate magnetic cells within the on-purpose developed 3D cell scaffolds.