RESUMEN

Nanofluidic devices exhibit unique, tunable transport properties that may lead to breakthroughs in molecular separations and sensing. However, the throughput of these devices is orders of magnitude too small for the processing of macroscopic samples. Here we overcome this problem by combining two technological innovations. First, nanofluidic channels are made as vertical slits connecting the two sides of a silicon nitride membrane. Arbitrary arrays of such nanoslits down to 15 nm wide with <6 Å uniformity were made by merging the idea of templating with chemical mechanical polishing to create a scalable, nanolithography-free wafer level process. Second, we provide for efficient solute transport to and from the openings of the nanoslits by incorporating the nanofluidic membrane into a microfluidic tangential-flow system, which is also fabricated at wafer level. As an exemplary application, we demonstrate charge-based continuous flow separation of small molecules with a selectivity of 100 and constant flux over more than 100 hours of operation. This proves the exciting possibility of exploiting transport phenomena governed by precision-engineered nanofluidic devices at a macroscopic scale.

RESUMEN

Microelectrode arrays (MEAs) are state-of-the-art devices for extracellular recording and stimulation on biological tissue. Furthermore, they are a relevant tool for the development of biomedical applications like retina, cochlear and motor prostheses, cardiac pacemakers and drug screening. Hence, research on functional cell-sensor interfaces, as well as the development of new surface structures and modifications for improved electrode characteristics, is a vivid and well established field. However, combining single-cell resolution with sufficient signal coupling remains challenging due to poor cell-electrode sealing. Furthermore, electrodes with diameters below 20 µm often suffer from a high electrical impedance affecting the noise during voltage recordings. In this study, we report on a nanocavity sensor array for voltage-controlled stimulation and extracellular action potential recordings on cellular networks. Nanocavity devices combine the advantages of low-impedance electrodes with small cell-chip interfaces, preserving a high spatial resolution for recording and stimulation. A reservoir between opening aperture and electrode is provided, allowing the cell to access the structure for a tight cell-sensor sealing. We present the well-controlled fabrication process and the effect of cavity formation and electrode patterning on the sensor's impedance. Further, we demonstrate reliable voltage-controlled stimulation using nanostructured cavity devices by capturing the pacemaker of an HL-1 cell network.

Asunto(s)

RESUMEN

In the area of biomimetics, engineers use inspiration from natural systems to develop technical devices, such as sensors. One example is the lateral line system of fish. It is a mechanoreceptive system consisting of up to several thousand individual sensors called neuromasts, which enable fish to sense prey, predators, or conspecifics. So far, the small size and high sensitivity of the lateral line is unmatched by man-made sensor devices. Here, we describe an artificial lateral line system based on an optical detection principle. We developed artificial canal neuromasts using MEMS technology including thick film techniques. In this work, we describe the MEMS fabrication and characterize a sensor prototype. Our sensor consists of a silicon chip, a housing, and an electronic circuit. We demonstrate the functionality of our µ-biomimetic flow sensor by analyzing its response to constant water flow and flow fluctuations. Furthermore, we discuss the sensor robustness and sensitivity of our sensor and its suitability for industrial and medical applications. In sum, our sensor can be used for many tasks, e.g. for monitoring fluid flow in medical applications, for detecting leakages in tap water systems or for air and gas flow measurements. Finally, our flow sensor can even be used to improve current knowledge about the functional significance of the fish lateral line.

Asunto(s)

RESUMEN

The beetle Melanophila acuminata uses a specialized organ to detect infrared radiation. The organ consists of about 100 individual sensilla. The main component of the sensillum is a pressure chamber. Upon absorption of radiation, the pressure increases, and the tip of a dendrite is deformed. A unique feature of the organ is a compensation mechanism that prevents large pressures. The beetle uses this organ to detect forest fires and to navigate inside burning woods. However, the sensitivity is part of a long-lasting discussion, providing thresholds between [Formula: see text] and [Formula: see text]. To end the decade-long discussion and to provide a novel type of infrared sensor, we are developing an uncooled µ-biomimetic infrared (IR) sensor inspired by Melanophila acuminata using MEMS technology. Here, we present the development of a µ-capacitor that is used to detect pressure changes and the characterization of the compensation mechanism. We describe the microtechnological fabrication process for air-filled capacitors with a ratio of diameter-to-electrode distance of 1000 and a technique to fill the sensor bubble-free with water. Finally, we estimate the sensitivity of the beetle using a theoretical model of the sensillum.

Asunto(s)

RESUMEN

Charging of physical phase plates is a problem that has prevented their routine use in transmission electron microscopy of weak-phase objects. In theory, electrostatic phase plates are superior to thin-film phase plates since they do not attenuate the scattered electron beam and allow freely adjustable phase shifts. Electrostatic phase plates consist of multiple layers of conductive and insulating materials, and are thus more prone to charging than thin-film phase plates, which typically consist of only one single layer of amorphous material. We have addressed the origins of charging of Boersch phase plates and show how it can be reduced. In particular, we have performed simulations and experiments to analyze the influence of the insulating Si3N4 layers and surface charges on electrostatic charging. To optimize the performance of electrostatic phase plates, it would be desirable to fabricate electrostatic phase plates, which (i) impart a homogeneous phase shift to the unscattered electrons, (ii) have a low cut-on frequency, (iii) expose as little material to the intense unscattered beam as possible, and (iv) can be additionally polished by a focused ion-beam instrument to eliminate carbon contamination accumulated during exposure to the unscattered electron beam (Walter et al., 2012, Ultramicroscopy, 116, 62-72). We propose a new type of electrostatic phase plate that meets the above requirements and would be superior to a Boersch phase plate. It consists of three free-standing coaxial rods converging in the center of an aperture (3-fold coaxial phase plate). Simulations and preliminary experiments with modified Boersch phase plates indicate that the fabrication of a 3-fold coaxial phase plate is feasible.

RESUMEN

Beetles of the genus Melanophila acuminata detect forest fires from distances as far as 130 km with infrared-sensing organs. Inspired by this extremely sensitive biological device, we are developing an IR sensor that operates at ambient temperature using MEMS technology. The sensor consists of two liquid-filled chambers that are connected by a micro-fluidic system. Absorption of IR radiation by one of these chambers leads to heating and expansion of a liquid. The increasing pressure deflects a membrane covered by one electrode of a plate capacitor. The micro-fluidic system and the second chamber represent a fluidic low-pass filter, preventing slow, but large pressure changes. However, the strong frequency dependence of the filter demands a precise characterization of its properties. Here, we present a theoretical model that describes the frequency-dependent response of the sensor based on material properties and geometrical dimensions. Our model is divided into four distinct parts that address different aspects of the sensor. The model describes the frequency-dependent behaviour of the fluidic filter and a thermal low-pass filter as well as saturation effects at low frequencies. This model allows the calculation of optimal design parameters, and thereby provides the foundation for the development of such a sensor.

Asunto(s)

RESUMEN

Implementation of physical phase plates into transmission electron microscopes to achieve in-focus contrast for ice-embedded biological specimens poses several technological challenges. During the last decade several phase plates designs have been introduced and tested for electron cryo-microscopy (cryoEM), including thin film (Zernike) phase plates and electrostatic devices. Boersch phase plates (BPPs) are electrostatic einzel lenses shifting the phase of the unscattered beam by an arbitrary angle. Adjusting the phase shift to 90° achieves the maximum contrast transfer for phase objects such as biomolecules. Recently, we reported the implementation of a BPP into a dedicated phase contrast aberration-corrected electron microscope (PACEM) and demonstrated its use to generate in-focus contrast of frozen-hydrated specimens. However, a number of obstacles need to be overcome before BPPs can be used routinely, mostly related to the phase plate devices themselves. CryoEM with a physical phase plate is affected by electrostatic charging, obliteration of low spatial frequencies, and mechanical drift. Furthermore, BPPs introduce single sideband contrast (SSB), due to the obstruction of Friedel mates in the diffraction pattern. In this study we address the technical obstacles in detail and show how they may be overcome. We use X-ray photoelectron spectroscopy (XPS) and Auger electron spectroscopy (AES) to identify contaminants responsible for electrostatic charging, which occurs with most phase plates. We demonstrate that obstruction of low-resolution features is significantly reduced by lowering the acceleration voltage of the microscope. Finally, we present computational approaches to correct BPP images for SSB contrast and to compensate for mechanical drift of the BPP.

Asunto(s)