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All-solid-state miniaturized fluorescence sensor array for the determination of critical gases and electrolytes in blood.

We describe a six-channel, all-solid-state, miniaturized fluorescence sensor array for the precise determination of blood analytes for medical diagnostic purposes. The device features superblue LEDs as light sources, GRIN optics, and photodiodes, assembled according to pigtailing procedures (Bruno, A. E.; et al. Trends Anal. Chem. 1994, 13, 190-198). The numerical aperture of the fluorescence optics is 0.46, rendering a collection efficiency of 2.4%. The performance of this instrument has been evaluated in terms of dynamic response, linearity, channel reproducibility, reversibility, long-term drifts, photobleaching of indicator, cross-talk, ionic strength, and selectivity in pH measurements. The responses of the pH sensing membranes were optimized in the physiological range. Responses are linear with typical values of approximately 1.5 V/pH units, with limits of decision of 24 mV, which corresponds to pH resolutions of 0.03 pH unit. Under continuous illumination, using calibration buffers, the sensors display nonstatistical differences within 2 standard deviations over a period of 6 h, and it is shown that, under discontinuous illumination, the membranes can be used in more than 2000 measurements without need of calibration, in contrast to electrochemical sensors which require periodic calibration. After selecting the appropriate combination of LEDs, excitation and emission filters, and sensing membranes, the instrument was used to determine the concentrations of various critical blood analytes in buffer solutions in the various channels. Similar measurements in untreated blood reproduce the reported results.

Biosensing Techniques↗

Differential receptors create patterns diagnostic for ATP and GTP.

Herein we report the combination of a library of resin-bound sensors along with a multicomponent sensor array. This novel combinatorial array sensor system shows selectivity for nucleotide phosphates in solution. The design of the anchored receptor includes a 1,3,5-trisubstituted-2,4,6-triethylbenzene scaffold coupled with peptide libraries. Each chemosensor is placed into a micromachined cavity within a silicon wafer, and the optical changes observed by a charged-coupled device result in near-real-time digital analysis of solutions. A colorimetric displacement assay was performed, and time-dependent imaging studies of the selected sensing ensembles result in a differential responses upon addition of adenosine 5'-triphosphate (ATP), adenosine 5'-monophosphate (AMP), or guanosine 5'-triphosphate (GTP). An advantage to this approach is that it creates an array of sensors that gives a fingerprint response for each analyte. Principal component analysis indicates that the library of chemosensors can differentiate between ATP, GTP, and AMP. On the basis of factor loading values, individual sensors from the library were sequenced to elucidate their chemical composition.

Adenosine Triphosphate↗

An electronic Mach-Zehnder interferometer.

Double-slit electron interferometers fabricated in high mobility two-dimensional electron gases are powerful tools for studying coherent wave-like phenomena in mesoscopic systems. However, they suffer from low visibility of the interference patterns due to the many channels present in each slit, and from poor sensitivity to small currents due to their open geometry. Moreover, these interferometers do not function in high magnetic fields--such as those required to enter the quantum Hall effect regime--as the field destroys the symmetry between left and right slits. Here we report the fabrication and operation of a single-channel, two-path electron interferometer that functions in a high magnetic field. This device is the first electronic analogue of the optical Mach-Zehnder interferometer, and opens the way to measuring interference of quasiparticles with fractional charges. On the basis of measurements of single edge state and closed geometry transport in the quantum Hall effect regime, we find that the interferometer is highly sensitive and exhibits very high visibility (62%). However, the interference pattern decays precipitously with increasing electron temperature or energy. Although the origin of this dephasing is unclear, we show, via shot-noise measurements, that it is not a decoherence process that results from inelastic scattering events.

Journal Article↗

Lithographically patterned nanowire electrodeposition.

Nanowire fabrication methods can be classified either as 'top down', involving photo- or electron-beam lithography, or 'bottom up', involving the synthesis of nanowires from molecular precursors. Lithographically patterned nanowire electrodeposition (LPNE) combines attributes of photolithography with the versatility of bottom-up electrochemical synthesis. Photolithography defines the position of a sacrificial nickel nanoband electrode, which is recessed into a horizontal trench. This trench acts as a 'nanoform' to define the thickness of an incipient nanowire during its electrodeposition. The electrodeposition duration determines the width of the nanowire. Removal of the photoresist and nickel exposes a polycrystalline nanowire--composed of gold, platinum or palladium--characterized by thickness and width that can be independently controlled down to 18 and 40 nm, respectively. Metal nanowires prepared by LPNE may have applications in chemical sensing and optical signal processing, and as interconnects in nanoelectronic devices.

Journal Article↗

A microfluidic device to confine a single cardiac myocyte in a sub-nanoliter volume on planar microelectrodes for extracellular potential recordings.

A hybrid chip is described which combines a microfluidic network fabricated in a silicone elastomer (PDMS) with planar microelectrodes. It was used to measure extracellular potentials from single adult murine cardiac myocytes in a restricted extracellular space. The recorded variations in the extracellular potentials were caused by transmembrane currents associated with spontaneously initiated intracellular calcium waves. Single cells were trapped inside the 100 pl microchamber by pressure gradients and maintained for several hours by continuous perfusion. In addition, the localized delivery of drugs to a portion of the cell was demonstrated. The impedance of the electrodes was reduced by a factor of 10 to 20 after the electrodeposition of platinum black. Biopotentials recorded from single cells with platinum black electrodes showed a three-fold decrease in the noise, resulting in a maximum signal-to-noise ratio of 15:1. Characteristic variations in the frequency and shape of the extracellular potentials were observed among different cells which are most likely due to differences in the sarcoplasmic reticulum Ca(2+) load. Our device architecture permits the integration of electrochemical and optical sensors for multiparameter recordings.

Animals↗

Translocation of structured polynucleotides through nanopores.

We investigate theoretically the translocation of structured RNA/DNA molecules through narrow pores which allow single but not double strands to pass. The unzipping of basepaired regions within the molecules presents significant kinetic barriers for the translocation process. We show that this circumstance may be exploited to determine the full basepairing pattern of polynucleotides, including RNA pseudoknots. The crucial requirement is that the translocation dynamics (i.e. the length of the translocated molecular segment) needs to be recorded as a function of time with a spatial resolution of a few nucleotides. This could be achieved, for instance, by applying a mechanical driving force for translocation and recording force-extension curves (FECs) with a device such as an atomic force microscope or optical tweezers. Our analysis suggests that, with this added spatial resolution, nanopores could be transformed into a powerful experimental tool to study the folding of nucleic acids.

Animals↗

Impact resistance of Transitions Plus spectacle lenses.

Although it has been shown that photochromic glass industrial lenses do not provide adequate occupational impact protection, they are frequently requested by outdoor workers wanting sunglasses. The recent introduction of Transitions Plus (TP), a photochromic plastic lens, may meet the needs of these workers. The impact resistance of 60 TP lenses of dress thickness was studied using a ballistic test. Lenses were edged and mounted in metal industrial frames. The completed spectacles were placed on a headform for ballistic testing using a 6.5 mm (1/4 in) steel ball propelled from an airgun. The lenses were divided into test groups that received: (1) a single impact at the geometrical center by a ball traveling at 18 m/s (59 ft/s) and (2) 50 consecutive impacts at 18 m/s, or (3) a single impact at 46.5 m/s (152 ft/s). All lenses passed the single impact test at 18 m/s. Four lenses broke under repeated impact. All lenses subjected to the high-speed impact test failed, either breaking or being dislodged from the frame. These findings show that dress thickness TP lenses provide impact protection from small blunt missiles traveling at moderate speed, and that they are durable under repeated low energy impact. However, thicker lenses must be used when the wearer has a high risk of ocular exposure to small high-speed missiles in the workplace. It can be concluded that TP lenses may be used in occupational eyewear for many outdoor workers who want photochromic sunglass lenses, provided that other needs for vision and occupational safety are also satisfied.

Equipment Safety↗

Construction of a high-resolution moiré interferometer for investigating microstructural displacement fields in materials.

A high-magnification moiré interferometer has been constructed with a spatial resolution of the order of 1 microm to measure the local in-plane displacement field associated with a material's microstructure. Laser illumination passes through phase-stepping optics and is delivered to the microscope head by polarization-preserving single-mode optical fibres. The head itself is a compact unit consisting of collimating optics, an objective lens and a charge coupled device (CCD) camera. Thin-phase gratings are cast onto the sample surface with a compliant epoxy resin and coated with ca. 5 nm of gold to enhance the fringe contrast and reduce speckle noise. By switching between the laser illumination and white-light illumination, the underlying microstructure is viewed in exact registration with the measured displacement fields. The application of the instrument is illustrated here by visualization of displacement fields in polymer-bonded explosives (PBXs) during deformation to failure. PBXs are highly filled polymers consisting of up to 95% by weight crystalline explosive bound in a variety of polymeric binders. The mechanical properties of PBXs are highly dependent on the microstructure, and moiré interferometry is an ideal tool for investigating the relationship between the 1-100 microm sized crystals and the displacement fields. Methods such as this are required if computer models of inhomogeneous materials are to be accurately validated.

Azocines↗

Surface plasmon polaritons in metal stripes and wires.

Surface plasmon polaritons (SPPs) are collective electron oscillations coupled to a light field which are propagating along the interface of a metal and a dielectric. As a surface wave, SPP modes feature properties essentially different from light-field modes in all dielectric structures. These properties could allow the realization of novel photonic devices that overcome certain limitations of conventional devices. Specifically, the realization of two-dimensional optics and light-field transport in sub-wavelength SPP waveguides seems feasible. In this review we discuss recent experimental advances regarding SPP waveguides, i.e. laterally confined metal thin films that guide SPPs. Electron-beam lithography is applied to tailor these films with widths ranging from a few micrometres (stripes) to nanoscopic values (wires). We investigate SPP properties such as propagation length, mode field profile and reflection or scattering at interfaces. Various techniques for SPP excitation and detection are discussed.

Journal Article↗

Regulated and entangled photons from a single quantum Dot

We propose a new method of generating nonclassical optical field states. The method uses a semiconductor device, which consists of a single quantum dot as active medium embedded in a p- i- n junction and surrounded by a microcavity. Resonant tunneling of electrons and holes into the quantum dot ground states, together with the Pauli exclusion principle, produce regulated single photons or regulated pairs of photons. We propose that this device also has the unique potential to generate pairs of entangled photons at a well-defined repetition rate.

Journal Article↗

Electric polarization rotation in a hexaferrite with long-wavelength magnetic structures.

We report on the control of electric polarization (P) by using magnetic fields (B) in a hexaferrite having magnetic order above room temperature (RT). The material investigated is hexagonal Ba0.5Sr1.5Zn2Fe12O22, which is a nonferroelectric helimagnetic insulator in the zero-field ground state. By applying B, the system undergoes successive metamagnetic transitions, and shows concomitant ferroelectric order in some of the B-induced phases with long-wavelength magnetic structures. The magnetoelectrically induced P can be rotated 360 degrees by external B. This opens up the potential for not only RT magnetoelectric devices but also devices based on the magnetically controlled electro-optical response.

Journal Article↗

Episodic synchronization via dynamic injection.

We report the occurrence of spontaneous synchronizing events between two semiconductor lasers, when the emission of a frequency- and intensity-chaotic driving laser is unidirectionally coupled into a second stable response laser. The driving laser is driven chaotic by delayed optical feedback, the response laser is a device-identical solitary laser. We demonstrate the onset of an episodic synchronization regime when the two lasers are spectrally detuned with respect to each other. By a joint experimental and modeling analysis we can attribute the onset and the duration of the episodes to properties of spectral overlap of both lasers. This effect can even give rise to seemingly anticorrelated intensity behavior. We expect episodic synchronization to be a generic scenario for the loss of synchronization of chaotic oscillators exhibiting frequency cycles.

Journal Article↗

Iris-based cyclotorsional image alignment method for wavefront registration.

In refractive surgery, especially wavefront-guided refractive surgery, correct registration of the treatment to the cornea is of paramount importance. The specificity of the custom ablation formula requires that the ablation be applied to the cornea only when it has been precisely aligned with the mapped area. If, however, the eye has rotated between measurement and ablation, and this cyclotorsion is not compensated for, the rotational misalignment could impair the effectiveness of the refractive surgery. To achieve precise registration, a noninvasive method for torsional rotational alignment of the captured wavefront image to the patient's eyes at surgery has been developed. This method applies a common coordinate system to the wavefront and the eye. Video cameras on the laser and wavefront devices precisely establish the spatial relationship between the optics of the eye and the natural features of the iris, enabling the surgeon to identify and compensate for cyclotorsional eye motion, whatever its cause.

Algorithms↗

Modeling and design optimization of large-deflection piezoelectric folded cantilever microactuators.

This paper presents a novel, large-deflection piezoelectric folded cantilever microactuator (PFCM). A multimorph model for the large-deflection PFCM is derived, in which unified formulas for deflection angle and vertical displacement of N-level PFCM are obtained. Based on the model, multilayer PFCMs using PZT film are designed and optimized. The large-deflection PFCM is extensively applicable to micro-devices or microsystem applications such as micro-optical switches, microelectromechanical systems (MEMS) scanners, and so forth.

Computer Simulation↗

Surface phenomena of coagulation factors in vivo, observed by fluorescence intravital microscopy.

The microcirculatory blood vessels of the exposed rat mesentery have been observed by incident fluorescence microscopy using various optical systems as well as image-intensifier devices and fast-scanning fluorometry techniques. As fluorescence-labeled proteins, albumin, gamma-globulin, fibrinogen, fibronectin, factor VIII-derived polypeptides, and antithrombin III have been injected intravenously. In some experiments two different-labeled proteins were administered consecutively. Whereas albumin and gamma-globulin did not accumulate at the inner surface of the microcirculatory blood vessels , fibrinogen and fibronectin showed a significant affinity to the vessels inner lining, mostly in venular vessels. Both substances accumulated at the same places of the microcirculatory endothelium. Blocking the fibrinolytic system of the animal increased the deposition of both substances. Factor VIII-derived polypeptides accumulated at the vessel inner surface in a different way. Antithrombin III did not show any affinities to the vascular wall. A receptor at the endothelial cell surface for both fibrinogen and fibronectin is postulated.

Animals↗

The role of laser-induced autofluorescence spectroscopy in bladder tumor detection. Dependence on the excitation wavelength.

We assessed the ability of laser-induced autofluorescence spectroscopy to distinguish neoplastic urothelial bladder lesions from normal or nonspecific inflammatory mucosa. Three different pulsed laser excitation wavelengths were used successively: 308 nm (xenium chloride excimer laser), 337 nm (nitrogen laser) and 480 nm (coumarin dye laser). The excitation light was delivered by a specially devised multifiber catheter connected to a 1-mm core diameter silica monofiber introduced through the working channel of a standard cystoscope with saline irrigation. The captured fluorescence light was focused onto an optical multichannel analyzer detection system. Performance of this device was evaluated in 25 patients after obtaining consent and immediately before transurethral resection of a bladder tumor. Spectroscopic results were compared with histological findings. At 337- and 480-nm excitation wavelengths, the overall fluorescence intensity of bladder tumors was clearly decreased compared to normal urothelial mucosa regardless of tumor stage and grade. At the 308-nm excitation wavelength, the shape of the tumor spectra, including carcinoma in situ, was markedly different from that of normal or nonspecific inflammatory mucosa. No absolute intensity determinations were required in this situation, since a definite diagnosis could be established based on the fluorescence intensity ratio at 360 and 440 nm. This spectroscopic study could be particularly useful in designing a simplified autofluorescence imaging device for detection of occult urothelial neoplasms.

Aged↗

Energy dependence of response of new high sensitivity radiochromic films for megavoltage and kilovoltage radiation energies.

The purpose of this paper is to evaluate the energy dependence of the response of two new high sensitivity models of radiochromic films EBT and XR-QA. We determined the dose response curves of these films for four different radiation sources, namely, 6 MV photon beams (6 MVX), Ir-192, I-125, and Pd-103. The first type (EBT) is designed for intensity modulated radiation therapy (IMRT) dosimetry, and the second type (XR-QA) is designed for kilovoltage dosimetry. All films were scanned using red (665 nm) and green (520 nm) light sources in a charge-coupled device-based densitometer. The dose response curves [net optical density (NOD) versus dose] were plotted and compared for different radiation energies and light sources. Contrary to the early GAFCHROMIC film types (such as models XR, HS, MD55-2, and HD810), the net optical densities of both EBT and XR-QA were higher with a green (520 nm) than those with a red (665 nm) light source due to the different absorption spectrum of the new radiochromic emulsion. Both film types yield measurable optical densities for doses below 2 Gy. EBT film response is nearly independent of radiation energy, within the uncertainty of measurement. The NOD values of EBT film at 1 and 2 Gy are 0.13 and 0.25 for green, and 0.1 and 0.17 for red, respectively. In contrast, the XR-QA film sensitivity varies with radiation energy. The doses required to produce NOD of 0.5 are 6.9, 5.4, 0.7, and 0.9 Gy with green light and 19, 13, 1.7, and 1.5 Gy with red light, for 6 MVX, Ir-192, I -125, and Pd-103, respectively. EBT film was found to have minimal photon energy dependence of response for the energies tested and is suitable for dosimetry of radiation with a wide energy spectrum, including primary and scattered radiation. XR-QA film is promising for kilovoltage sources with a narrow energy spectra. The new high sensitivity radiochromic films are promising tools in radiation dosimetry.

Densitometry↗