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Coherent charge transport along ballistic paths can be introduced into graphene by Andreev reflection, for which an electron reflects from a superconducting contact as a hole, while a Cooper pair is transmitted. We use liquid-helium cooled scanning gate microscopy (SGM) to image Andreev reflection in graphene in the magnetic focusing regime, where carriers move along cyclotron orbits between contacts. Images of flow are obtained by deflecting carrier paths and displaying the resulting change in conductance. When electrons enter the superconductor, Andreev-reflected holes leave for the collecting contact. To test the results, we destroy Andreev reflection with a large current and by heating above the critical temperature. In both cases, the reflected carriers change from holes to electrons.
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Portable NMR combining a permanent magnet and a complementary metal-oxide-semiconductor (CMOS) integrated circuit has recently emerged to offer the long desired online, on-demand, or in situ NMR analysis of small molecules for chemistry and biology. Here we take this cutting-edge technology to the next level by introducing parallelism to a state-of-the-art portable NMR platform to accelerate its experimental throughput, where NMR is notorious for inherently low throughput. With multiple (N) samples inside a single magnet, we perform simultaneous NMR analyses using a single silicon electronic chip, going beyond the traditional single-sample-per-magnet paradigm. We execute the parallel analyses via either time-interleaving or magnetic resonance imaging (MRI). In the time-interleaving method, the N samples occupy N separate NMR coils: we connect these N NMR coils to the single silicon chip one after another and repeat these sequential NMR scans. This time-interleaving is an effective parallelization, given a long recovery time of a single NMR scan. To demonstrate this time-interleaved parallelism, we use N = 2 for high-resolution multidimensional spectroscopy such as J-coupling resolved free induction decay spectroscopy and correlation spectroscopy (COSY) with the field homogeneity carefully optimized (<0.16 ppm) and N = 4 for multidimensional relaxometry such as diffusion-edited T2 mapping and T1-T2 correlation mapping, expediting the throughput by 2-4 times. In the MRI technique, the N samples (N = 18 in our demonstration) share 1 NMR coil connected to the single silicon chip and are imaged all at once multiple times, which reveals the relaxation time of all N samples simultaneously. This imaging-based approach accelerates the relaxation time measurement by 4.5 times, and it could be by 18 times if the signal-to-noise were not limited. Overall, this work demonstrates the first portable high-resolution multidimensional NMR with throughput-accelerating parallelism.
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Electrons in graphene can travel for several microns without scattering at low temperatures, and their motion becomes ballistic, following classical trajectories. When a magnetic field B is applied perpendicular to the plane, electrons follow cyclotron orbits. Magnetic focusing occurs when electrons injected from one narrow contact focus onto a second contact located an integer number of cyclotron diameters away. By tuning the magnetic field B and electron density n in the graphene layer, we observe magnetic focusing peaks. We use a cooled scanning gate microscope to image cyclotron trajectories in graphene at 4.2 K. The tip creates a local change in density that casts a shadow by deflecting electrons flowing nearby; an image of flow can be obtained by measuring the transmission between contacts as the tip is raster scanned across the sample. On the first magnetic focusing peak, we image a cyclotron orbit that extends from one contact to the other. In addition, we study the geometry of orbits deflected into the second point contact by the tip.
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A realistic interpretation of the measured contact potential difference (CPD) in Kelvin probe force microscopy (KPFM) is crucial in order to extract meaningful information about the sample. Central to this interpretation is a method to include contributions from the macroscopic cantilever arm, as well as the cone and sharp tip of a KPFM probe. Here, three models of the electrostatic interaction between a KPFM probe and a sample are tested through an electrostatic simulation and compared with experiment. In contrast with previous studies that treat the KPFM cantilever as a rigid object, we allow the cantilever to bend and rotate; accounting for cantilever bending provides the closest agreement between theory and experiment. We demonstrate that cantilever dynamics play a major role in CPD measurements and provide a simulation technique to explore this phenomenon.
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Kelvin probe force microscopy (KPFM) is a widely used technique to measure the local contact potential difference (CPD) between an AFM probe and the sample surface via the electrostatic force. The spatial resolution of KPFM is intrinsically limited by the long range of the electrostatic interaction, which includes contributions from the macroscopic cantilever and the conical tip. Here, we present coaxial AFM probes in which the cantilever and cone are shielded by a conducting shell, confining the tip-sample electrostatic interaction to a small region near the end of the tip. We have developed a technique to measure the true CPD despite the presence of the shell electrode. We find that the behavior of these probes agrees with an electrostatic model of the force, and we observe a factor of five improvement in spatial resolution relative to unshielded probes. Our discussion centers on KPFM, but the field confinement offered by these probes may improve any variant of electrostatic force microscopy.
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We show that a triaxial atomic force microscopy probe creates a noncontact trap for a single particle in a fluid via negative dielectrophoresis. A zero in the electric field profile traps the particle above the probe surface, avoiding adhesion, and the repulsive region surrounding the zero pushes other particles away, preventing clustering. Triaxial probes are promising for three-dimensional assembly and for selective imaging of a particular property of a sample using interchangeable functionalized particles.
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BACKGROUND: Early recurrent hemorrhage after endoscopic intervention for acute upper GI bleeding (UGIB) can approach 20% and leads to increased morbidity and mortality. Little has changed over the past several decades regarding immediate posthemorrhage surveillance, and there has likewise been no significant improvement in outcomes. OBJECTIVE: To develop and test an endoscopically implantable wireless biosensor for real-time detection of fluorescein-labeled blood in ex vivo and in vivo porcine models of UGIB. SETTING: Animal laboratory. DESIGN: Benchtop and acute animal studies. SUBJECTS: Five pigs. INTERVENTIONS: UGIB models were surgically created in living pigs. Biosensors were endoscopically deployed in the stomach using standard endoscopic clips. The ability to detect acute UGIB and estimated blood loss leading to biosensor activation were recorded. Feasibility of wireless data transmission out of the body to an external computer and cell phone was assessed. MAIN OUTCOME MEASUREMENTS: Technical feasibility and immediate complications. RESULTS: A porcine UGIB model was successfully created. Biosensors were able to detect all acute bleeding events and wirelessly transmit out of the body, and successfully sent an emergency text message to the intended cell phone in all cases. Average estimated blood loss leading to biosensor activation was 30 mL (10-75 mL). LIMITATIONS: Animal study; small numbers. CONCLUSIONS: An endoscopically implantable wireless biosensor successfully detected acute hemorrhage in a porcine UGIB model and sent an emergency cell-phone alert in real time.
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Técnicas Biosensibles , Hemorragia Gastrointestinal/diagnóstico , Animales , Teléfono Celular , Modelos Animales de Enfermedad , Endoscopía Gastrointestinal , Fluoresceína , Colorantes Fluorescentes , Hemorragia Gastrointestinal/etiología , Prótesis e Implantes , Recurrencia , Porcinos , Envío de Mensajes de TextoRESUMEN
We study conductance fluctuations (CF) and the sensitivity of the conductance to the motion of a single scatterer in two-dimensional massless Dirac systems. Our extensive numerical study finds limits to the predicted universal value of CF. We find that CF are suppressed for ballistic systems near the Dirac point and approach the universal value at sufficiently strong disorder. The conductance of massless Dirac fermions is sensitive to the motion of a single scatterer. CF of order e(2)/h result from the motion of a single impurity by a distance comparable to the Fermi wavelength. This result applies to graphene systems with a broad range of impurity strength and concentration while the dependence on the Fermi wavelength can be explored via gate voltages. Our prediction can be tested by comparing graphene samples with varying amounts of disorder and can be used to understand interference effects in mesoscopic graphene devices.
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Grafito/química , Modelos Químicos , Nanoestructuras/química , Simulación por Computador , Conductividad EléctricaRESUMEN
We use a scanning gate microscope (SGM) to characterize one-dimensional ultra-thin (diameter ≈ 30 nm) InAs/InP heterostructure nanowires containing a nominally 300 nm long InAs quantum dot defined by two InP tunnel barriers. Measurements of Coulomb blockade conductance versus backgate voltage with no tip present are difficult to decipher. Using the SGM tip as a charged movable gate, we are able to identify three quantum dots along the nanowire: the grown-in quantum dot and an additional quantum dot near each metal lead. The SGM conductance images are used to disentangle information about individual quantum dots and then to characterize each quantum dot using spatially resolved energy-level spectroscopy.
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We present an integrated platform for performing biological and chemical experiments on a chip based on standard CMOS technology. We have developed a hybrid integrated circuit (IC)/microfluidic chip that can simultaneously control thousands of living cells and pL volumes of fluid, enabling a wide variety of chemical and biological tasks. Taking inspiration from cellular biology, phospholipid bilayer vesicles are used as robust picolitre containers for reagents on the chip. The hybrid chip can be programmed to trap, move, and porate individual living cells and vesicles and fuse and deform vesicles using electric fields. The IC spatially patterns electric fields in a microfluidic chamber using 128 × 256 (32,768) 11 × 11 µm(2) metal pixels, each of which can be individually driven with a radio frequency (RF) voltage. The chip's basic functions can be combined in series to perform complex biological and chemical tasks and can be performed in parallel on the chip's many pixels for high-throughput operations. The hybrid chip operates in two distinct modes, defined by the frequency of the RF voltage applied to the pixels: Voltages at MHz frequencies are used to trap, move, and deform objects using dielectrophoresis and voltages at frequencies below 1 kHz are used for electroporation and electrofusion. This work represents an important step towards miniaturizing the complex chemical and biological experiments used for diagnostics and research onto automated and inexpensive chips.
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Biomimética/instrumentación , Microfluídica/instrumentación , Electroforesis , Membrana Dobles de Lípidos , Ondas de RadioRESUMEN
Graphene has opened new avenues of research in quantum transport, with potential applications for coherent electronics. Coherent transport depends sensitively on scattering from microscopic disorder present in graphene samples: electron waves traveling along different paths interfere, changing the total conductance. Weak localization is produced by the coherent backscattering of waves, while universal conductance fluctuations are created by summing over all paths. In this work, we obtain conductance images of weak localization with a liquid-He-cooled scanning probe microscope, by using the tip to create a movable scatterer in a graphene device. This technique allows us to investigate coherent transport with a probe of size comparable to the electron wavelength. Images of magnetoconductance versus tip position map the effects of disorder by moving a single scatterer, revealing how electron interference is modified by the tip perturbation. The weak localization dip in conductivity at B = 0 is obtained by averaging magnetoconductance traces at different positions of the tip-created scatterer. The width Delta B(WL) of the dip yields an estimate of the electron coherence length L(phi) at fixed charge density. This 'scanning scatterer' method provides a new way of investigating coherent transport in graphene by directly perturbing the disorder configuration that creates these interferometric effects.
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We propose a triaxial atomic force microscope contact-free tweezer (TACT) for the controlled assembly of nanoparticles suspended in a liquid. The TACT overcomes four major challenges faced in nanoassembly, as follows. (1) The TACT can hold and position a single nanoparticle with spatial accuracy smaller than the nanoparticle size (approximately 5 nm). (2) The nanoparticle is held away from the surface of the TACT by negative dielectrophoresis to prevent van der Waals forces from making it stick to the TACT. (3) The TACT holds nanoparticles in a trap that is size-matched to the particle and surrounded by a repulsive region so that it will only trap a single particle at a time. (4) The trap can hold a semiconductor nanoparticle in water with a trapping energy greater than the thermal energy. For example, a 5 nm radius silicon nanoparticle is held with 10 k(B)T at room temperature. We propose methods for using the TACT as a nanoscale pick-and-place tool to assemble semiconductor quantum dots, biological molecules, semiconductor nanowires, and carbon nanotubes.
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Microscopía de Fuerza Atómica/métodos , Nanopartículas/química , Nanotecnología/métodos , Puntos Cuánticos , Algoritmos , Fenómenos Electromagnéticos , Diseño de Equipo , Microscopía de Fuerza Atómica/instrumentaciónRESUMEN
We present a technique to locally and rapidly heat water drops in microfluidic devices with microwave dielectric heating. Water absorbs microwave power more efficiently than polymers, glass, and oils due to its permanent molecular dipole moment that has large dielectric loss at GHz frequencies. The relevant heat capacity of the system is a single thermally isolated picolitre-scale drop of water, enabling very fast thermal cycling. We demonstrate microwave dielectric heating in a microfluidic device that integrates a flow-focusing drop maker, drop splitters, and metal electrodes to locally deliver microwave power from an inexpensive, commercially available 3.0 GHz source and amplifier. The temperature change of the drops is measured by observing the temperature dependent fluorescence intensity of cadmium selenide nanocrystals suspended in the water drops. We demonstrate characteristic heating times as short as 15 ms to steady-state temperature changes as large as 30 degrees C above the base temperature of the microfluidic device. Many common biological and chemical applications require rapid and local control of temperature and can benefit from this new technique.
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Calefacción/instrumentación , Técnicas Analíticas Microfluídicas/instrumentación , Microondas , Impedancia Eléctrica , Electrónica , Fluorescencia , Calefacción/economía , Temperatura , Factores de Tiempo , Agua/químicaRESUMEN
A hybrid integrated circuit (IC) / microfluidic chip is presented that independently and simultaneously traps and moves microscopic objects suspended in fluid using both electric and magnetic fields. This hybrid chip controls the location of dielectric objects, such as living cells and drops of fluid, on a 60 × 61 array of pixels that are 30 × 38 µm(2) in size, each of which can be individually addressed with a 50 V peak-to-peak, DC to 10 MHz radio frequency voltage. These high voltage pixels produce electric fields above the chip's surface with a magnitude , resulting in strong dielectrophoresis (DEP) forces . Underneath the array of DEP pixels there is a magnetic matrix that consists of two perpendicular sets of 60 metal wires running across the chip. Each wire can be sourced with 120 mA to trap and move magnetically susceptible objects using magnetophoresis (MP). The DEP pixel array and magnetic matrix can be used simultaneously to apply forces to microscopic objects, such as living cells or lipid vesicles, that are tagged with magnetic nanoparticles. The capabilities of the hybrid IC / microfluidic chip demonstrated in this paper provide important building blocks for a platform for biological and chemical applications.
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We describe the synthesis of magnetic and fluorescent silica microspheres fabricated by incorporating maghemite (gamma-Fe2O3) nanoparticles (MPs) and CdSe/CdZnS core/shell quantum dots (QDs) into a silica shell around preformed silica microspheres. The resultant approximately 500 nm microspheres have a narrow size distribution and show uniform incorporation of QDs and MPs into the shell. We have demonstrated manipulation of these microspheres using an external magnetic field with real-time fluorescence microscopy imaging.
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Cristalización/métodos , Compuestos Férricos/química , Magnetismo/métodos , Nanoestructuras/química , Nanoestructuras/ultraestructura , Puntos Cuánticos , Dióxido de Silicio/química , Sustancias Macromoleculares/química , Ensayo de Materiales , Microesferas , Conformación Molecular , Nanotecnología/métodos , Tamaño de la Partícula , Propiedades de SuperficieRESUMEN
This paper describes a model of the motion of superparamagnetic beads in a microfluidic channel under the influence of a weak magnetic field produced by an electric current passing through a coplanar metal wire. The model based on the conventional expression for the magnetic force experienced by a superparamagnetic bead (suspended in a biologically relevant medium) and the parameters provided by the manufacturer failed to match the experimental data. To fit the data to the model, it was necessary to modify the conventional expression for the force to account for the non-zero initial magnetization of the beads, and to use the initial magnetization and the magnetic susceptibility of the beads as adjustable parameters. The best-fit value of susceptibility deviated significantly from the value provided by the manufacturer, but was in good agreement with the value computed using the magnetization curves measured independently for the beads from the same vial as those used in the experiment. The results of this study will be useful to researchers who need an accurate prediction of the behavior of superparamagnetic beads in aqueous suspensions under the influence of weak magnetic fields. The derivation of the force on a magnetic bead due to a magnetic field also identifies the correct treatment to use for this interaction, and resolves discrepancies present throughout the literature.
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Compuestos Férricos/efectos de la radiación , Microesferas , Modelos Teóricos , Simulación por Computador , Micromanipulación/métodos , Estrés MecánicoRESUMEN
Manipulation of biological cells using a CMOS/microfluidic hybrid system is demonstrated. The hybrid system starts with a custom-designed CMOS (complementary metal-oxide semiconductor) chip fabricated in a semiconductor foundry. A microfluidic channel is post-fabricated on top of the CMOS chip to provide biocompatible environments. The motion of individual biological cells that are tagged with magnetic beads is directly controlled by the CMOS chip that generates microscopic magnetic field patterns using an on-chip array of micro-electromagnets. Furthermore, the CMOS chip allows high-speed and programmable reconfiguration of the magnetic fields, substantially increasing the manipulation capability of the hybrid system. Extending from previous work that verified the concept of the hybrid system, this paper reports a set of manipulation experiments with biological cells, which further confirms the advantage of the hybrid approach. To enhance the biocompatibility of the system, the microfluidic channel is redesigned and the temperature of the device is monitored by on-chip sensors. Combining microelectronics and microfluidics, the CMOS/microfluidic hybrid system presents a new model for a cell manipulation platform in biological and biomedical applications.
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Microfluídica/instrumentación , Integración de Sistemas , Catálisis , MiniaturizaciónRESUMEN
This paper describes a miniaturized, integrated, microfluidic device that can pull molecules and living cells bound to magnetic particles from one laminar flow path to another by applying a local magnetic field gradient, and thus selectively remove them from flowing biological fluids without any wash steps. To accomplish this, a microfabricated high-gradient magnetic field concentrator (HGMC) was integrated at one side of a microfluidic channel with two inlets and outlets. When magnetic micro- or nano-particles were introduced into one flow path, they remained limited to that flow stream. In contrast, when the HGMC was magnetized, the magnetic beads were efficiently pulled from the initial flow path into the collection stream, thereby cleansing the original fluid. Using this microdevice, living E. coli bacteria bound to magnetic nanoparticles were efficiently removed from flowing solutions containing densities of red blood cells similar to that found in blood. Because this microdevice allows large numbers of beads and cells to be sorted simultaneously, has no capacity limit, and does not lose separation efficiency as particles are removed, it may be especially useful for separations from blood or other clinical samples. This on-chip HGMC-microfluidic separator technology may potentially allow cell separations to be carried out in the field outside of hospitals and clinical laboratories.
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Escherichia coli/citología , Microfluídica , Nanopartículas , Separación Celular/instrumentación , Separación Celular/métodos , Magnetismo , Técnicas Analíticas Microfluídicas/instrumentación , Técnicas Analíticas Microfluídicas/métodos , Microfluídica/instrumentación , Microfluídica/métodosRESUMEN
Images of a single-electron quantum dot were obtained in the Coulomb blockade regime at liquid He temperatures using a cooled scanning probe microscope (SPM). The charged SPM tip shifts the lowest energy level in the dot and creates a ring in the image corresponding to a peak in the Coulomb-blockade conductance. Fits to the line shape of the ring determine the tip-induced shift of the energy of the electron state in the dot. SPM manipulation of electrons in quantum dots promises to be useful in understanding, building, and manipulating circuits for quantum information processing.