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The ability to replace organs and tissues on demand could save or improve millions of lives each year globally and create public health benefits on par with curing cancer. Unmet needs for organ and tissue preservation place enormous logistical limitations on transplantation, regenerative medicine, drug discovery, and a variety of rapidly advancing areas spanning biomedicine. A growing coalition of researchers, clinicians, advocacy organizations, academic institutions, and other stakeholders has assembled to address the unmet need for preservation advances, outlining remaining challenges and identifying areas of underinvestment and untapped opportunities. Meanwhile, recent discoveries provide proofs of principle for breakthroughs in a family of research areas surrounding biopreservation. These developments indicate that a new paradigm, integrating multiple existing preservation approaches and new technologies that have flourished in the past 10 years, could transform preservation research. Capitalizing on these opportunities will require engagement across many research areas and stakeholder groups. A coordinated effort is needed to expedite preservation advances that can transform several areas of medicine and medical science. more...

The combination of complementary techniques for materials analysis can play a key role in both art conservation and academic research. Nowadays, the correlation of x‐ray fluorescence (XRF) with hyperspectral reflectance imaging in the visible and infrared region has become a valuable tool for palette identification, painting techniques studies and for the diagnostic support dedicated to restoration and conservation. Moreover, both techniques enable researchers to reveal fascinating underpaintings, "pentimenti", or even preparatory drawings offering new details on the creative process of the artist. This background has been a strong motivation for the development of a new multimodal tool for art and conservation: IRIS. IRIS is a mobile and reconfigurable scanner designed to address a wide range of demanding application, exploiting the opportunities given by simultaneous MA‐XRF and hyperspectral reflectance scanning in the visible‐near‐infrared (VNIR) and short‐wave‐infrared (SWIR) range from 400 to 2500 nm. The system has been designed for in‐situ, fast and non‐invasive scanning of the sample without compromising spectral resolution and high throughput performance. The scanner acquires co‐registered XRF/VNIR‐SWIR data, thus allowing the user to obtain the maximum profit from their possible correlated information: the two techniques can provide enhanced or complementary information on the same spot of analysis with minimum effort in terms of data processing and no need for spatial alignment. In the present work, the qualitative and quantitative performance of IRIS are explored, together with the presentation of in‐lab analysis on reference samples and a brief insight on a real case‐study. [ABSTRACT FROM AUTHOR] more...

This paper describes the working principle, the design, and the characterization of a three-axis frequency-modulated MEMS accelerometer, in which the differential frequency readout is performed through a novel time-switched approach. The proposed methodology is based on a double sampling of the oscillation frequency of a single resonator, consecutively biased in two different configurations in time. This technique enables to avoid offset thermal drift contributions typical of differential resonant accelerometers based on two distinct resonators with unavoidable mismatch in the temperature coefficient of frequency (TCf). Alternatively, a residual TCf offset drift component can be tuned to counterbalance other drift sources (e.g., stress-related), allowing a complete cancellation of the zero-g-offset (ZGO) thermal drift. Experiments on various samples report repeatable sub- $50~\mu \text{g}$ /K thermal drift without post-acquisition corrections, with a full-scale higher than $32~g$ at a $100~\mu \text{g}/\sqrt {\text {Hz}}$ consumer-grade resolution. [2018-0089] [ABSTRACT FROM AUTHOR] more...

This paper reports the developments toward an integrated, tri-axial, frequency-modulated, consumer-grade, and microelectromechanical system (MEMS) gyroscope. A custom low-power (160 μA), low-phase-noise integrated circuit is designed specifically for frequency-modulated operation. Both yaw- and pitch-rate sensing systems are demonstrated by coupling the circuit with two novel micromachined structures fabricated with a 24- μm-thick industrial process. In operation, both gyroscopes show a repeatable and stable scale factor, with less than 0.55% of part-to-part variability, obtained with no any calibration, and 35 ppm/ ^\circ C of variability over a 25–70  ^\circ C temperature range. [ABSTRACT FROM PUBLISHER] more...

This paper presents the principle and complete characterization of a single-chip unit formed by microelectromechanical system magnetometers to sense the 3-D magnetic field vector and a Tang resonator. The three sensors, nominally with the same resonance frequency, are operated 200-Hz off-resonance through an ac current whose reference frequency is provided by the resonator embedded in an oscillating circuit. The sensors gain is increased by adopting a current recirculation strategy using metal strips directly deposited on the structural polysilicon. At a driving value of 100 \mu \textA\mathrm{ rms} flowing in series through the three devices, the magnetometers show a sub-185 nT/ $\vphantom {{\sqrt {\mathrm{ Hz}}}^{a}}\sqrt {\mathrm{ Hz}}$ resolution with a selectable bandwidth up to 50 Hz. Over a ±5-mT full-scale range, the sensitivity curves show linearity errors lower than 0.2%, with high cross-axis rejection and immunity to external accelerations. Under temperature changes, the stability of the 200-Hz difference between the magnetometers and the resonator frequency is within 55 ppm/K. Offset is trimmed down to the microtesla range, with an overall measured Allan stability of about 100 nT at 20-s observation time. [2016-0030] [ABSTRACT FROM PUBLISHER] more...

The main scientific issue hindering the development of tissue engineering technologies is the lack of proper vascularization. Among the various approaches developed for boosting vascularization, scaffold design has attracted increasing interest over the last few years. The aim of this article is to illustrate a scaffold design strategy for enhancing vascularization based on sacrificial microfabrication of embedded microchannels. This approach was combined with an innovative poly(ether urethane urea) (PEUtU) porous scaffold to provide an alternative graft substitute material for the treatment of tissue defects. Fluorescent and chemiluminescent imaging combined with computed tomography were used to study the behavior of the scaffold composition within living subjects by analyzing angiogenesis and inflammation processes and observing the variation in x-ray absorption, respectively. For this purpose, an Integri-Sense 680 probe was used in vivo for the localization and quantification of integrin αvβ3, due to its critical involvement in angiogenesis, and a XenoLight RediJect Inflammation Probe for the study of the decline in inflammation progression during healing. Overall, the collected data suggest the advantages of embedding a synthetic vascular network into a PEUtU porous matrix to enhance in vivo tissue integration, maturation, and regeneration. Moreover, our imaging approach proved to be an efficient and versatile tool for scaffold in vivo testing. [ABSTRACT FROM AUTHOR] more...

Microelectromechanical system (MEMS) sensors based on nanoscale piezoresistive sensing elements (nanogauges) can have mechanical modes either related only to micrometric springs or related also to nanogauge constraints. Due to the different impact that fabrication process imperfections have on these two kinds of modes, their correlation can be poorer from part to part than in sensors based on capacitive readout. In this context, this paper compares the correlation between two modes in MEMS with and without nanogauges. Experiments show a ±30% relative variation in the modes difference over 26 samples of the former type, which is more than 3.5 times more than what observed on similar structures with no nanogauges. A theoretical model identifies the sources of this fluctuation (local etching and height nonuniformities), and predicts the behavior and improvements using different springs design. [ABSTRACT FROM AUTHOR] more...

This paper demonstrates bandwidth extension for Lorentz force microelectromechanical systems magnetometers operated at a frequency slightly lower than the mechanical resonance. This off-resonance mode of operation also minimizes the critical tradeoff between maximum sensing bandwidth and minimum measurable field, enabling low-pressure operation and the associated resolution improvement. The experimental verification is obtained using two identical devices packaged at two different pressures and tested with a suitable low-noise board-level electronics. The first device, packaged at 1 mbar, has a (mechanical) sensing bandwidth of $\sim$50 Hz, and a resolution per unit bandwidth and driving current of 290 \nT\cdot\mA/\surd\Hz. With the second device, packaged at 0.25 mbar and operated off-resonance, roughly twice better resolution (160 \nT\cdot\mA/\surd\Hz) and four times larger bandwidth ( $>$200 Hz) are obtained. [ABSTRACT FROM PUBLISHER] more...

The paper discusses the operation of Lorentz-force-based microelectromechanical magnetometers at a driving-current frequency slightly lower than the device resonance frequency. Among the advantages with respect to operation at resonance, there are a higher achievable signal to noise ratio (thanks to the lower permitted pressure and damping coefficient, which have now no influence on the maximum sensing bandwidth) and the possibility of driving more magnetometers in series through a single current source, enabling the fabrication of low-power 3-axis magnetic field sensors. A partial drawback is represented by a loss in gain-factor. Experimental results obtained on a sample device confirm the trade-off between gain-factor decrease and bandwidth increase. Guidelines for an optimized design of Lorentz force magnetometers are given together with a comparison with other state-of-the-art technologies through the introduction of a figure of merit. In particular, it is shown how Lorentz force devices can reach better performance in terms of minimum detectable magnetic flux density per unit current consumption and bandwidth. [ABSTRACT FROM PUBLISHER] more...

This paper discusses the constraints in the design of circuits for microelectromechanical systems (MEMS) resonant sensors in consumer applications, presents a novel integrated circuit implementation, and shows that this approach can be competitive with respect to the mostly used capacitive readout. From a circuit design perspective, it is shown how the large equivalent resistance typical of MEMS resonators, their operation close to mechanical nonlinearity, and the effect of feedthrough capacitances on the oscillating loop constrain the power requirements of the driving/readout electronics. As a case study, a resonant accelerometer built in an industrial process is coupled to a suitably designed transimpedance amplifier with a low-power “hard limiter.” The performance shown in terms of linearity across the measurement range (\pm8 g), minimum measurable acceleration (1 mg with a readout bandwidth of 100 Hz), and power consumption ( \approx\!\! 100\ \mu\W per axis) is comparable to those of state-of-the-art capacitive inertial sensors. [ABSTRACT FROM PUBLISHER] more...

This paper presents a biaxial silicon resonant microaccelerometer characterized by a high sensitivity and a low cross-axis sensitivity. The device has a detection structure with a single inertial mass and two pairs of resonating beams allowing for the simultaneous differential measurement of acceleration acting along two different axes. The design of the accelerometer and in particular the geometrical configuration of the resonating elements is analytically optimized and finalized through finite element simulations. Experimental results on a fabricated device demonstrate a mean differential sensitivity of 250 Hz g−1 at a polarization voltage of 4 V, around a resonance frequency of 84 kHz. [ABSTRACT FROM AUTHOR] more...

The combination of multiaxis and multiparameter microelectromechanical systems (MEMS) in the same technology would result in very cheap and smart inertial measurement units (IMUs). In this paper, a Z-axis Lorentz-force-based magnetometer whose design and optimization are reviewed taking into account the constraints of an industrial MEMS technology (process and packaging) already used for accelerometers and gyroscopes is presented. How this impacts the design guidelines is shown; in particular, a very compact device that can fit in the same package of the gyroscope to realize an all-MEMS seven-degree-of-freedom IMU is proposed and experimentally tested. The device shows a mechanical sensitivity of around 0.8 \aF/(\mu\T \cdot \mA) with a resolution of 520 (\nT \cdot \mA)/\sqrt\Hz over a signal bandwidth of 50 Hz at room temperature. Coupled to a transimpedance amplifier, the system shows an overall sensitivity of 150 \mu\V/\mu\T at 250 \mu\A of peak driving current. [ABSTRACT FROM PUBLISHER] more...

We report a novel reliable and repeatable technologic manufacturing protocol for the realization of micro-patterned freestanding hydrogel layers based on thermo-responsive poly-(N-isopropyl)acrylamide (PNIPAAm), which have potential to be employed as temperature-triggered smart surfaces for cells-on-chip applications. PNIPAAm-based films with controlled mechanical properties and different thicknesses (100-300 &mgr;m thickness) were prepared by injection compression moulding at room temperature. A 9 × 9 array of 20 &mgr;m diameter through-holes is machined by means of the KrF excimer laser on dry PNIPAAm films which are physically attached to flat polyvinyl chloride (PVC) substrates. Machining parameters, such as fluence and number of shots, are optimized in order to achieve highly resolved features. Micro-structured freestanding films are then easily obtained after hydrogels are detached from PVC by gradually promoting the film swelling in ethanol. In the PNIPAAm water-swollen state, the machined holes' diameter approaches a slight larger value (30 &mgr;m) according to the measured hydrogel swelling ratio. Thermo-responsive behaviour and through-hole tapering characterization are carried out by metrology measurements using an optical inverted and confocal microscope setup, respectively. After the temperature of freestanding films is raised above 32 °C, we observe that the shrinkage of the whole through-hole array occurs, thus reducing the holes' diameter to less than a half its original size (about 15 &mgr;m) as a consequence of the film dehydration. Different holes' diameters (10 and 30 &mgr;m) are also obtained on dry hydrogel employing suitable projection masks, showing similar shrinking behaviour when hydrated and undergone thermo-response tests. Thermo-responsive PNIPAAm-based freestanding layers could then be integrated with other suitable micro-fabricated thermoplastic components in order to preliminary test their feasibility in operating as temperature-activated components in the frame of the development of microfluidic devices in multilayer hybrid materials. [ABSTRACT FROM AUTHOR] more...

A new differential microelectromechanical systems accelerometer based on fringe-field sensing is presented. The basic working principle relies on the generation of fringe electric fields in the volume in between and over two biased coplanar interconnections; a grounded suspended micromachined mass, moving in this fringe volume, differently intercepts the electric field lines for different positions, giving rise to capacitance changes between the interconnections, used as electrodes. The capacitance variation can be then transformed into a voltage signal using standard capacitive readout techniques. The design exploits a new geometry, a technological scaling, and for the first time, a differential configuration to reach a measured sensitivity of 2.7 fF/g in the tested range of \pm2 g of external acceleration. With respect to parallel-plate configurations, the device is immune from in-plane pull-in instability as the suspended mass does not face fixed parts biased at different voltages. [ABSTRACT FROM AUTHOR] more...

Born from the marriage of nanotechnology and medicine, nanomedicine is set to bring advantages in the fight against unmet diseases. The field is recognized as a global challenge, and countless worldwide research and business initiatives are in place to obtain a significant market position. However, nanomedicine belongs to those emerging sectors in which business development methods have not been established yet. Open issues include which type of business model best fits these companies and which strategies would lead them to sustained growth. This paper describes the financial and strategic decisions by nanomedicine start-ups to reach the market successfully, obtain a satisfactory market share, and build and maintain a competitive defendable advantage. Walking nanomedicine-product from the hands of the inventor to those of the doctor, we explored the technological transfer process, which connects laboratories or research institutions to the marketplace. The process involves detailed analysis to evaluate the potentials of end-products, and researches to identify market segment, size, structure, and competitors, to ponder a possible market entry and the market share that managers can realistically achieve at different time horizons. Attracting funds is crucial but challenging. However, investors are starting to visualize the potentials of this field, magnetized by the business of "nano." [ABSTRACT FROM AUTHOR] more...

In this paper, a MEMS motion sensor is described which uses fringe field capacitances as sensing elements. Each capacitance basic cell is formed using thin strips of standard electrical paths, running side by side, and close one another in a plane parallel to the substrate: in this way, the capacitance between the paths is mainly formed by the fringe field streamlines. A grounded seismic mass, suspended in the air volume where the electric fringe field streamlines are concentrated, determines changes in the capacitance value when subject to an external force that makes it move. With respect to parallel plates capacitive sensors, this implementation has the advantage to be more immune from the pull-in instability. A test device is built using an industrial surface micromachining process. The experimental results show a sensitivity close to 1 fF of capacitance variation per unit of earth acceleration for a device taking up an area of (430\ \mum)^2. A detailed analysis performed through FEM simulations predicts possible consistent sensitivity improvements. [ABSTRACT FROM PUBLISHER] more...

A new micromachined uniaxial silicon resonant accelerometer characterized by a high sensitivity and very small dimensions is presented. The device's working principle is based on the frequency variations of two resonating beams coupled to a proof mass. Under an external acceleration, the movement of the proof mass causes an axial load on the beams, generating opposite stiffness variations, which, in turn, result in a differential separation of their resonance frequencies. A high level of sensitivity is obtained, owing to an innovative and optimized geometrical design of the device that guarantees a great amplification of the axial loads. The acceleration measure is obtained, owing to a properly designed oscillating circuit. In agreement with the theoretical prediction, the experimental results show a sensitivity of 455 Hz/\mmbg ( g being the gravity acceleration) with a resonant frequency of about 58 kHz and a good linearity in the range of interest.\hfill[2010-0035] [ABSTRACT FROM PUBLISHER] more...

Cancer cells have been increasingly grown in pharmaceutical research to understand tumorigenesis and develop new therapeutic drugs. Currently, cells are typically grown using two-dimensional (2-D) cell culture approaches, where the native tumor microenvironment is difficult to recapitulate. Thus, one of the main obstacles in oncology is the lack of proper infection models that recount main features present in tumors. In recent years, microtechnology-based platforms have been employed to generate three-dimensional (3-D) models that better mimic the native microenvironment in cell culture. Here, we present an innovative approach to culture Kaposi’s sarcoma-associated herpesvirus (KSHV) infected human B cells in 3-D using a microwell array system. The results demonstrate that the KSHV-infected B cells can be grown up to 15 days in a 3-D culture. Compared with 2-D, cells grown in 3-D had increased numbers of KSHV latency-associated nuclear antigen (LANA) dots, as detected by immunofluorescence microscopy, indicating a higher viral genome copy number. Cells in 3-D also demonstrated a higher rate of lytic reactivation. The 3-D microwell array system has the potential to improve 3-D cell oncology models and allow for better-controlled studies for drug discovery., Version of Record more...

The ability to cryopreserve natural killer (NK) cells has a significant potential in modern cancer immunotherapy. Current cryopreservation protocols cause deterioration in NK cell viability and functionality. This work reports the preservation of human cytokine‐activated NK cell viability and function following cryopreservation using a cocktail of biocompatible bioinspired cryoprotectants (i.e., dextran and carboxylated ε‐poly‐L‐lysine). Results demonstrate that the recovered NK cells after cryopreservation and rewarming maintain their viability immediately after thawing at a comparable level to control (dimethyl sulfoxide‐based cryopreservation). Although, their viability drops in the first day in culture compared to controls, the cells grow back to a comparable level to controls after 1 week in culture. In addition, the anti‐tumor functional activity of recovered NK cells demonstrates higher cytotoxic potency against leukemia cells compared to control. This approach presents a new direction for NK cell preservation, focusing on function and potentially enabling storage and distribution for cancer immunotherapy. Cryopreservation of natural killer (NK) cells has a potential to create great impact on modern cancer immunotherapy. Current cryopreservation methods utilize toxic cryoprotectants (e.g., dimethyl sulfoxide) causing deterioration in NK cell viability and functionality. An innovative approach to preserve human NK cell viability and functionality following cooling and rewarming is developed using a cocktail of biocompatible bioinspired cryoprotectants. [ABSTRACT FROM AUTHOR] more...

The first Organ Banking Summit was convened from Feb. 27 - March 1, 2015 in Palo Alto, CA, with events at Stanford University, NASA Research Park, and Lawrence Berkeley National Labs. Experts at the summit outlined the potential public health impact of organ banking, discussed the major remaining scientific challenges that need to be overcome in order to bank organs, and identified key opportunities to accelerate progress toward this goal. Many areas of public health could be revolutionized by the banking of organs and other complex tissues, including transplantation, oncofertility, tissue engineering, trauma medicine and emergency preparedness, basic biomedical research and drug discovery – and even space travel. Key remaining scientific sub-challenges were discussed including ice nucleation and growth, cryoprotectant and osmotic toxicities, chilling injury, thermo-mechanical stress, the need for rapid and uniform rewarming, and ischemia/reperfusion injury. A variety of opportunities to overcome these challenge areas were discussed, i.e. preconditioning for enhanced stress tolerance, nanoparticle rewarming, cyroprotectant screening strategies, and the use of cryoprotectant cocktails including ice binding agents. [ABSTRACT FROM AUTHOR] more...