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Purpose To assess the feasibility, image quality, diagnostic accuracy, therapeutic impact and tolerance of diagnostic and hemodynamic assessment using a novel miniaturized multiplane transesophageal echocardiography (TEE) probe in ventilated ICU patients with cardiopulmonary compromise. Study design Prospective, descriptive, single-center study. Methods Fifty-seven ventilated patients with acute circulatory or respiratory failure were assessed, using a miniaturized multiplane TEE probe and a standard TEE probe used as reference, randomly by two independent experienced operators. Measurements of hemodynamic parameters were independently performed off-line by a third expert. Diagnostic groups of acute circulatory failure ( n  = 5) and of acute respiratory failure ( n  = 3) were distinguished. Hemodynamic monitoring was performed in 9 patients using the miniaturized TEE probe. TEE tolerance and therapeutic impact were reported. Results The miniaturized TEE probe was easier to insert than the standard TEE probe. Despite lower imaging quality of the miniaturized TEE probe, the two probes had excellent diagnostic agreement in patients with acute circulatory failure (Kappa: 0.95; 95 % CI: 0.85–1) and with acute respiratory failure (Kappa: 1; 95 % CI: 1.0–1.0). Accordingly, therapeutic strategies derived from both TEE examinations were concordant (Kappa: 0.82; 95 % CI: 0.66–0.97). The concordance between quantitative hemodynamic parameters obtained with both TEE probes was also excellent. No relevant complication secondary to TEE probes insertion occurred. Conclusions Hemodynamic assessment of ventilated ICU patients with cardiopulmonary compromise using a miniaturized multiplane TEE probe appears feasible, well-tolerated, and relevant in terms of diagnostic information and potential therapeutic impact. Further larger-scale studies are needed to confirm these preliminary results.

Small, lightweight LED implants and a radio-frequency transducer as a power source enable wireless optogenetic stimulation in the brain, spinal cord and peripheral nervous system of behaving mice. To enable sophisticated optogenetic manipulation of neural circuits throughout the nervous system with limited disruption of animal behavior, light-delivery systems beyond fiber optic tethering and large, head-mounted wireless receivers are desirable. We report the development of an easy-to-construct, implantable wireless optogenetic device. Our smallest version (20 mg, 10 mm 3 ) is two orders of magnitude smaller than previously reported wireless optogenetic systems, allowing the entire device to be implanted subcutaneously. With a radio-frequency (RF) power source and controller, this implant produces sufficient light power for optogenetic stimulation with minimal tissue heating (<1 °C). We show how three adaptations of the implant allow for untethered optogenetic control throughout the nervous system (brain, spinal cord and peripheral nerve endings) of behaving mice. This technology opens the door for optogenetic experiments in which animals are able to behave naturally with optogenetic manipulation of both central and peripheral targets.

Gordon Moore famously observed that the number of transistors in state-of-the-art integrated circuits (units per chip) increases exponentially, doubling every 12–24 months. Analysts have debated whether simple exponential growth describes the dynamics of computer processor evolution. We note that the increase encompasses two related phenomena, integration of larger numbers of transistors and transistor miniaturization. Growth in the number of transistors per unit area, or chip density, allows examination of the evolution with a single measure. Density of Intel processors between 1959 and 2013 are consistent with a biphasic sigmoidal curve with characteristic times of 9.5 years. During each stage, transistor density increased at least tenfold within approximately six years, followed by at least three years with negligible growth rates. The six waves of transistor density increase account for and give insight into the underlying processes driving advances in processor manufacturing and point to future limits that might be overcome.

We have developed a miniature two-photon microscope equipped with an axial scanning mechanism and a long-working-distance miniature objective to enable multi-plane imaging over a volume of 420 × 420 × 180 μm3 at a lateral resolution of ~1 μm. Together with the detachable design that permits long-term recurring imaging, our miniature two-photon microscope can help decipher neuronal mechanisms in freely behaving animals.A two-photon miniature microscope with enlarged field of view and axial scanning capabilities has been developed and applied in freely moving mice.

The ability to implant electronic systems in the human body has led to many medical advances. Progress in semiconductor technology paved the way for devices at the scale of a millimeter or less (“microimplants”), but the miniaturization of the power source remains challenging. Although wireless powering has been demonstrated, energy transfer beyond superficial depths in tissue has so far been limited by large coils (at least a centimeter in diameter) unsuitable for a microimplant. Here, we show that this limitation can be overcome by a method, termed midfield powering, to create a high-energy density region deep in tissue inside of which the power-harvesting structure can be made extremely small. Unlike conventional near-field (inductively coupled) coils, for which coupling is limited by exponential field decay, a patterned metal plate is used to induce spatially confined and adaptive energy transport through propagating modes in tissue. We use this method to power a microimplant (2 mm, 70 mg) capable of closed-chest wireless control of the heart that is orders of magnitude smaller than conventional pacemakers. With exposure levels below human safety thresholds, milliwatt levels of power can be transferred to a deep-tissue (>5 cm) microimplant for both complex electronic function and physiological stimulation. The approach developed here should enable new generations of implantable systems that can be integrated into the body at minimal cost and risk.

FHIRM-TPM is a miniature two-photon microscope capable of imaging fluorescently labeled neurons in the brains of freely behaving mice. It allows for imaging of spines or recording of neural activity with a frame rate up to 40 Hz. Developments in miniaturized microscopes have enabled visualization of brain activities and structural dynamics in animals engaging in self-determined behaviors. However, it remains a challenge to resolve activity at single dendritic spines in freely behaving animals. Here, we report the design and application of a fast high-resolution, miniaturized two-photon microscope (FHIRM-TPM) that accomplishes this goal. With a headpiece weighing 2.15 g and a hollow-core photonic crystal fiber delivering 920-nm femtosecond laser pulses, the FHIRM-TPM is capable of imaging commonly used biosensors (GFP and GCaMP6) at high spatiotemporal resolution (0.64 μm laterally and 3.35 μm axially, 40 Hz at 256 × 256 pixels for raster scanning and 10,000 Hz for free-line scanning). We demonstrate the microscope's robustness with hour-long recordings of neuronal activities at the level of spines in mice experiencing vigorous body movements.

A miniature epifluorescence microscope that can be carried by a freely-moving adult mouse allows cellular-level imaging of neuronal spiking or measurement of microcirculation during normal behavioral activities. A central goal in biomedicine is to explain organismic behavior in terms of causal cellular processes. However, concurrent observation of mammalian behavior and underlying cellular dynamics has been a longstanding challenge. We describe a miniaturized (1.1 g mass) epifluorescence microscope for cellular-level brain imaging in freely moving mice, and its application to imaging microcirculation and neuronal Ca 2+ dynamics.

Electrochemical biosensors hold the exciting potential to integrate molecular detection with signal processing and wireless communication in a miniaturized, low‐cost system. However, as electrochemical biosensors are miniaturized to the micrometer scale, their signal‐to‐noise ratio degrades and reduces their utility for molecular diagnostics. Studies have reported that nanostructured electrodes can improve electrochemical biosensor signals, but since the underlying mechanism remains poorly understood, it remains difficult to fully exploit this phenomenon to improve biosensor performance. In this work, electrochemical aptamer biosensors on nanoporous electrode are optimized to achieve improved sensitivity by tuning pore size, probe density, and electrochemical measurement parameters. Further, a novel mechanism in which electron transfer is physically accelerated within nanostructured electrodes due to reduced charge screening, resulting in enhanced sensitivity is proposed and experimentally validated. In concert with the increased surface areas achieved with this platform, this newly identified effect can yield an up to 24‐fold increase in signal level and nearly fourfold lower limit of detection relative to planar electrodes with the same footprint. Importantly, this strategy can be generalized to virtually any electrochemical aptamer sensor, enabling sensitive detection in applications where miniaturization is a necessity, and should likewise prove broadly applicable for improving electrochemical biosensor performance in general. In this work, nanostructured electrodes with tunable porosity for electrochemical biosensing that offer increased signal level and lower limit of detection than conventional planar electrodes are reported. Importantly, a novel mechanism in which electron transfer is physically accelerated within nanostructured electrodes due to reduced charge screening, resulting in enhanced sensitivity is proposed and experimentally validated.

In order to overcome the challenges associated with a limited number of airway epithelial cells that can be obtained from clinical sampling and their restrained capacity to divide ex vivo, miniaturization of respiratory drug discovery assays is of pivotal importance. Thus, a 96-well microplate system was developed where primary human small airway epithelial (hSAE) cells were cultured at an air–liquid interface (ALI). After four weeks of ALI culture, a pseudostratified epithelium containing basal, club, goblet and ciliated cells was produced. The 96-well ALI cultures displayed a cellular composition, ciliary beating frequency, and intercellular tight junctions similar to 24-well conditions. A novel custom-made device for 96-parallelized transepithelial electric resistance (TEER) measurements, together with dextran permeability measurements, confirmed that the 96-well culture developed a tight barrier function during ALI differentiation. 96-well hSAE cultures were responsive to transforming growth factor β1 (TGF-β1) and tumor necrosis factor α (TNF-α) in a concentration dependent manner. Thus, the miniaturized cellular model system enables the recapitulation of a physiologically responsive, differentiated small airway epithelium, and a robotic integration provides a medium throughput approach towards pharmaceutical drug discovery, for instance, in respect of fibrotic distal airway/lung diseases.