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A miniaturization of the multi-degree-of-freedom ultrasonic actuator using a small cylinder fixed on a substrate.

Multi-degree-of-freedom ultrasonic actuator has been studied for robot arms and multidimensional precision table and so on because of its simple structure, silent operation, and holding force. In this study, we aim to miniaturize multi-degree-of-freedom ultrasonic actuator for fabrication on a substrate. This actuator consists of a stainless steel cylinder and a PZT ring. The cylinder is fixed on a substrate and the PZT ring is glued to the substrate near the cylinder. The 1st longitudinal vibration and the 2nd bending vibration are simultaneously excited in the cylinder to make elliptical motion at the top of the cylinder and a ball rotor placed on the cylinder rotates because of the friction force. Length of the cylinder was decided so as to tune the resonance frequency of the 1st longitudinal vibration to the 2nd bending one. Actuator performances are evaluated experimentally using a 14 mm height and 7 mm diameter stainless steel cylinder with a 0.5 mm thickness PZT ring. The rotation about the cylinder axis is tested using the two orthogonal bending vibrations with 90 degrees phase difference. Also, the rotation about horizontal axes were investigated using the combination of the longitudinal vibration and one of two bending vibrations. We measured the rotation speed of a steel ball and obtained 15.8 rps using a 6 mm diameter ball rotor.

Journal Article↗

A miniature ultransonic pump using a bending disk transducer and a gap.

It is known that if a pipe end is faced at a vibrating surface in liquid with a small gap, liquid is suctioned into the pipe. As a miniature configuration, we introduce a bending disk transducer 30 mm in diameter using a ring-shaped PZT element. The disk vibrator is worked at the fundamental resonance frequency of 19 kHz of the bending mode. To optimize the pipe geometry, we experimentally investigated the effect of the outer diameter on the pump performance. As a result, the outer/inner diameter ratio of 3:2 is optimum for the gap smaller than 20 microm. We achieved the maximum pump pressure of 14.8 kPa and the maximum flow rate of 10 ml/min. using the prototype pump.

Journal Article↗

Ultrasonic micro-motor using miniature piezoelectric tube with diameter of 1.0 mm.

At the present moment, the smallest piezoelectric ultrasonic micro-motors utilizing miniature PZT piezoelectric ceramic tubes were developed. The motor consists of a PZT-metal composite tube stator, two steel rotors and a thin shaft that keeps the two rotors pressing on both ends of the stator elastically. The dimensions of the PZT tube are 1.0 mm in outer diameter, 0.6 mm in inner diameter and 5.0 mm in length. The diameter and total length of the assembled micro-motor is 1.0 mm and 8 mm (including an adjusting spring), respectively. The tube-type micro-motor is driven by two pairs of alternative voltages with phase shift 90 degrees between the adjacent electrodes and operated in the first circular-bending vibration mode of the stator with the resonance frequency about 58 kHz. The experimental results show that the tube-type micro-motors have perfect performances: (i) high rotation frequency over 3000 rpm and (ii) large starting torque over 7.8 microN m under the conditions of the input voltage of 110 V(p-p) and the resonance frequency. The micro-motor is well suitable for operating in micro-spaces, such as in intravascular, micro-robots and micro-craft applications.

Journal Article↗

Synergetic driving concepts for bundled miniature ultrasonic linear motors.

Rotary ultrasonic motors have found broad industrial application in camera lens drives and other systems. Linear ultrasonic motors in contrast have only found limited applications. The main reason for the limited range of application of these very attractive devices seems to be their small force and power range. Attempts to build linear ultrasonic motors for high forces and high power applications have not been truly successful yet. To achieve larger force and higher power, multiple miniaturized motors can be combined. This approach, however, is not as simple as it appears at first glance. The electromechanical behaviour of the individual motors differs slightly due to manufacturing and assembly tolerances. The individual motor characteristics are strongly dependent on the driving parameters (frequency, voltage, temperature, pre-stress, etc.) and the driven load and the collective behaviour of the swarm of motors is not just the linear superposition of the individual drive's forces. Thus, the bundle of motors has to be synchronized and controlled appropriately in order to obtain an optimized drive that is not oversized and costly. We have investigated driving and control strategies of a set of linear ultrasonic motors. Our contribution will be divided into three main parts. In part I ultrasonic linear motors will be introduced. In part II driving strategies for a single motor as well as for a bundle of motors will be presented. These concepts will be verified by simulation results and experimental data. In part III a simplified model for the motor's electromechanical behaviour will be given.

Journal Article↗

Canine RPGRIP1 mutation establishes cone-rod dystrophy in miniature longhaired dachshunds as a homologue of human Leber congenital amaurosis.

Cone-rod dystrophy 1 (cord1) is a recessive condition that occurs naturally in miniature longhaired dachshunds (MLHDs). We mapped the cord1 locus to a region of canine chromosome CFA15 that is syntenic with a region of human chromosome 14 (HSA14q11.2) containing the retinitis pigmentosa GTPase regulator-interacting protein 1 (RPGRIP1) gene. Mutations in RPGRIP1 have been shown to cause Leber congenital amaurosis, a group of retinal dystrophies that represent the most common genetic causes of congenital visual impairment in infants and children. Using the newly available canine genome sequence we sequenced RPGRIP1 in affected and carrier MLHDs and identified a 44-nucleotide insertion in exon 2 that alters the reading frame and introduces a premature stop codon. All affected and carrier dogs within an extended inbred pedigree were homozygous and heterozygous, respectively, for the mutation. We conclude the mutation is responsible for cord1 and demonstrate that this canine disease is a valuable model for exploring disease mechanisms and potential therapies for human Leber congenital amaurosis.

Animals↗

A miniaturized monolayer trough with variable surface area in the square-millimeter range.

A new simple concept for a miniaturized monolayer trough is described. The overall monolayer area in the expanded state is approximately 150 mm2 and can be reduced by a factor of 2. The surface area is a function of the shape of the meniscus formed by the subphase and is controlled by the amount of water in the monolayer trough. The controlled compression of monolayers to a desired area per molecule with simultaneous observation of the lateral distribution of fluorescently labeled molecules is shown. A biological reaction between a specific antibody and lipid anchored peptide demonstrates the feasibility of monolayer experiments, which require only very small quantities of substance (in the pmol range). This trough might also be a valuable tool for the 2D crystallization of proteins at lipid layers via specific binding sites such as metal chelators.

1,2-Dipalmitoylphosphatidylcholine↗

Miniature endplate potential frequency and amplitude determined by an extension of Campbell's theorem.

A method based upon an extension of Campbell's theorem is used to measure the amplitude, waveform, and frequency of occurrence of miniature endplate potentials (mepps) at rapidly secreting neuromuscular junctions of frog cutaneous pectoris muscles. Measurements of the variance, skew, and power spectrum of the fluctuations in membrane potential are used to deduce the mepp parameters. These estimates of mepp amplitude and frequency are insensitive to slow drifts in membrane potential that preclude the conventional application of Campbell's theorem, which uses the mean and variance. The new method becomes unreliable at high mepp frequencies because the distribution of the values of membrane potential approaches a Gaussian thereby reducing the accuracy of skew measurements. Frequencies approaching 10(4) s-1 can be measured, however, if the data are high-pass filtered. The method has been tested with computer simulated data and applied to junctions exposed to La3+; the effects of Ca2+ on the La3+-induced secretion have been explored. Some muscles were fixed after treatment with La3+, and changes in nerve terminal ultrastructure were assessed by morphometric analysis of electron micrographs. Horseradish peroxidase was used to obtain information about vesicle recycling.

Animals↗

A mathematical description of miniature postsynaptic current generation at central nervous system synapses.

Variation in the amplitude of miniature postsynaptic currents (mPSCs) generated by individual quanta of neurotransmitter is a major contributor to the variance of evoked synaptic responses. Here we explore the possible origins of this variability by developing a mathematical description of mPSC generation and consider the contribution of "off-center" release to this variability. By "off-center" release we mean variation in the distance between the position where a presynaptic vesicle discharges its content of neurotransmitter into the synaptic cleft and the center of a cluster of postsynaptic receptors (PRCs) that responds to those transmitter molecules by generating an mPSC. We show that when the time course of quantal discharge through a fusion pore (noninstantaneous release) is considered, elementary analytical descriptions of the subsequent diffusion of transmitter within the synaptic cleft (with or without uptake) predict the development of significant gradients of transmitter concentration during the rising phase of mPSCs. This description of diffusion is combined with a description of the pharmacodynamics of receptors in the PRC and of the time dependence of the gradient of transmitter concentration over the area of the PRC to reconstruct the time course and amplitude of an mPSC for a synapse of a given geometry. Within the constraints of known dimensions of presynaptic active zones and postsynaptic receptor clusters at CNS synapses, our analysis suggests that "off-center" release, produced by allowing release to occur anywhere within an anatomically defined presynaptic active zone, can be an important contributor to mPSC variability. Indeed, modulation of the influence of "off-center" release may be a novel way of controlling synaptic efficacy. We also show how noninstantaneous release can serve to focus the action of neurotransmitter within a given synapse and thereby reduce cross-talk between synapses.

Animals↗

Accounting for the shapes and size distributions of miniature endplate currents.

The current model does not account adequately for the characteristics of miniature endplate currents (MEPCs). We do not understand their relatively slow rise, the shape of their rise, their variable and sometimes prolonged decay, and the correlation between amplitude and decay time. If we assume that ACh is released from the vesicle through a pore and that the vesicle enlarges as it takes on additional transmitter, the predictions are more like MEPCs. However, previous measurements showed that after quantal size was increased the vesicles in the terminal were not enlarged. This need not be a problem, because some of the ACh is added to vesicles positioned at the active zones, a process known as second-stage loading. By using the false transmitter precursor monoethylcholine we provide additional evidence for second-stage loading. The distribution of quantal sizes at the junction usually does not follow a normal probability distribution; it is skewed to the right. The skew can be accounted for by a model incorporating second-stage loading in which the vesicles are released randomly, without regard to their ACh content. If the vesicles increase in size when they contain more transmitter, only vesicles at the active zone need swell.

Acetylcholine↗

The temperature sensitivity of miniature endplate currents is mostly governed by channel gating: evidence from optimized recordings and Monte Carlo simulations.

The temperature dependence of miniature endplate current (MEPC) amplitude (A(c)), 20-80% rise time (t(r)), and 90-33% fall-time (t(f)) was determined for lizard (Anolis carolinensis) intercostal muscle using broadband extracellular (EC) and voltage clamp (VC) recordings. Voltage clamp methods were optimized for the fast MEPC rising phase using custom electronics. From 0-43 degrees C, A(c) increased by approximately 4.2-fold, while t(r) and t(f) decreased by approximately 3.6- and approximately 9.5-fold, respectively. Arrhenius plots were smoothly curved, with small apparent Q(10) (A(c)) or (Q(10))(-1) (t(r) and t(f)) values mostly well below 2.0. Nearly identical extracellular and voltage clamp results ruled out measurement artifacts, even for the shortest t(r) values (<60 microseconds). Monte Carlo simulation of MEPCs showed that a single underlying rate cannot determine the observed temperature dependence. To quantitatively reproduce the experimental t(f) results, a minimal model required activation energies of 46.0 (Q(10) approximately 2.0) and 63.6 (Q(10) approximately 2.5) kJ mol(-1) for channel opening and closing, respectively, and accounted for most of the observed changes in A(c) and t(r) as well. Thus, relatively large but offsetting temperature sensitivities of channel gating mostly govern and minimize the temperature dependence of MEPCs, preserving the safety factor for neuromuscular transmission. Additional temperature-sensitive parameters that could fine-tune the minimal model are discussed.

Acetylcholinesterase↗

Evaluation of a miniaturized thermal biosensor for the determination of glucose in whole blood.

A miniaturized thermal biosensor has been evaluated as part of a flow-injection analysis system for the determination of glucose in whole blood. Glucose was determined by measuring the heat evolved when samples containing glucose passed through a small column with immobilized glucose oxidase and catalase. Samples of whole blood (1 microliter) can be measured directly, without any pretreatment. The correlation in the response between the thermal biosensor, the Reflolux S meter (Boehringer Mannheim), the Granutest 100 glucose test kit (Merck Diagnostica) and the Ektachem (Kodak) instrument was evaluated. The influence of the hematocrit value and of possible interferences is reported. The correlation measurements show that the thermal biosensor calibrated with aqueous glucose standards generally gives lower values on blood glucose than the reference methods calibrated for serum or blood measurements. Mean negative biases range from 0.53 to 1.16 mmol/l. Differences in sample treatment clearly complicate comparisons and the proper choice of reference method. There was no influence from substances such as ascorbic acid (0.11 mmol/l), uric acid (0.48 mmol/l), urea (4.3 mmol/l) and acetaminophen (0.17 mmol/l) on the response to 5 mmol/l glucose. The hematocrit value does not influence the glucose determination, for hematocrit values of between 13 and 53%.

Biosensing Techniques↗

The short N-terminus is required for functional expression of the virus-encoded miniature K(+) channel Kcv.

Kcv (K(+) Chlorella virus) is a miniature virus-encoded K(+) channel. Its predicted membrane-pore-membrane structure lacks a cytoplasmic C-terminus and it has a short 12 amino acid (aa) cytoplasmic N-terminus. Kcv forms a functional channel when expressed in human HEK 293 cells. Deletion of the 14 N-terminal aa results in no apparent differences in the subcellular location and expression level of the Kcv protein. However, the truncated protein does not induce a measurable current in transfected HEK 293 cells or Xenopus oocytes. We conclude that the N-terminus controls functional properties of the Kcv channel, but does not influence protein expression.

Base Sequence↗

A miniature extraluminal force transducer for recording in vivo oviductal motility.

A miniature extraluminal force transducer has been developed and used to record acute and chronic motility of the reproductive tract in the rabbit. This device, which contains two matched piezoresistive silicon sensors bonded to a titanium beam strip, is durable, physically stable, and highly sensitive to bending force (gage factor, 140). Acute recordings made in 20 rabbits revealed continuous, rhythmic contractile activity in both the oviduct and uterus. Chronic recordings made in three unanesthetized rabbits revealed periodic bursts of intense activity interspersed with periods of relative quiescence. Chronic implantation of these devices was accomplished with no evidence of infection, adhesions, or other abnormalities, and without disruption of fertility.

Animals↗

Changes in esophageal wall layers during motility: measurements with a new miniature ultrasound suction device.

We have developed a miniaturized ultrasound device that attaches to the gastrointestinal mucosa by suction and produces high-resolution (+/- 0.1 mm) images of the layers of the intestinal wall. The esophageal wall layers in a single sheep were measured during 20 occlusive contractions observed with simultaneous endoscopy, which revealed thickening of the inner circular muscle layer from 1.2 +/- 0.2 mm to 2.2 +/- 0.4 mm (p < 0.01), and during 20 dilations demonstrating thinning of the full thickness of the esophageal wall from 3.6 +/- 0.3 mm to 2.9 +/- 0.3 mm (p < 0.01). Safety experiments performed in two canine stomachs demonstrated no erosions or ulceration at any level of suction. Our investigations indicate that the M-mode suction ultrasound device can safely assess changes occurring in the layers of the esophageal wall during contractions and dilations and should be evaluated for the study of human intestinal motility.

Animals↗

Transendoscopic ultrasound of esophageal and gastric cancer using miniaturized ultrasound catheter probes.

BACKGROUND: The aim of this study was to investigate the value of miniaturized ultrasound catheter probes (miniprobes) for preoperative staging of esophageal and gastric cancer. METHODS: Fifty-one patients with esophageal (n = 21) and gastric cancer (n = 30) underwent endoscopic ultrasound (EUS). All examinations were carried out using mechanical miniprobes (diameter 6F, 12.5 MHz) that were introduced through the instrument channel of the endoscope. RESULTS: EUS with miniprobes was successfully performed in all patients, although stenotic tumors, which could not be traversed with the endoscope, were found in 6 of 21 patients (29%) with esophageal cancer. Miniprobe scanning provided high-resolution images of the gastrointestinal tract. The overall accuracy in the assessment of tumor infiltration depth for esophageal and gastric cancer was 90% and 82%, respectively. However, the value of miniprobe scanning in the assessment of advanced tumors was limited by the imaging depth of the probe (approximately 3 cm). Lymph node involvement was accurately diagnosed in 78% of the patients with esophageal cancer (sensitivity 75%, specificity 80%) and in 80% of the patients with gastric cancer (sensitivity 73%, specificity 89%). CONCLUSIONS: EUS with miniprobes can be performed as single-step procedure during diagnostic endoscopy. The 12.5 MHz transducer provides high-resolution imaging and enables accurate staging of tumors with limited infiltration depth.

Endosonography↗

A miniature radioimmunoassay for melatonin for use with small samples from invertebrates.

Melatonin has been identified in a number of invertebrates, but little is known of its functions or its circadian control. Studies in this area are hindered by the lack of an assay for melatonin that is appropriate for use with the small sample volumes obtainable from most invertebrates and with the large numbers of sequential samples generated by circadian studies. We describe and validate a novel, miniature radioimmunoassay (RIA) protocol for these purposes. Sample volumes of c.50 microl were extracted with methanol and the extracts dried in 6 x 50 mm glass tubes. The entire assay was conducted in these tubes. The incubation volume was 200 microl. Bound ligand was precipitated and washed in these tubes, then 400 microl scintillation fluid was added and the tubes were mounted inside conventional scintillation vials for counting. Losses of material due to transfer between containers were thus eliminated. Previous RIAs for melatonin employed multiple transfers between containers and their use with small sample volumes can result in loss of substantial proportions of the sample. Two hundred samples could be processed together. The assay sensitivity was 2 pg melatonin and recovery of internal standards was c.100%. Two commercially available antisera gave closely similar results. The assay was used to quantify melatonin titers in the haemolymph of the insect Rhodnius prolixus (Hemiptera); scotophase haemolymph contained 270 pg/ml melatonin, compared with minimal values (c.40 pg/ml) during the photophase, revealing a daily rhythm. This assay opens the door for analyses of the functions and circadian regulation of melatonin in invertebrates.

Animals↗

Rapid cooperative two-state folding of a miniature alpha-beta protein and design of a thermostable variant.

There is a great deal of interest in developing small stably folded miniature proteins. A limited number of these molecules have been described, however they typically have not been characterized in depth. In particular, almost no detailed studies of the thermodynamics and folding kinetics of these proteins have been reported. Here we describe detailed studies of the thermodynamics and kinetics of folding of a 39 residue mixed alpha-beta protein (NTL9(1-39)) derived from the N-terminal domain of the ribosomal protein L9. The protein folds cooperatively and rapidly in a two-state fashion to a native state typical of those found for normal globular proteins. At pH 5.4 in 20mM sodium acetate, 100mM NaCl the temperature of maximum stability is 6 degrees C, the t(m) is 65.3 degrees C, deltaH degrees (t(m)) is between 24.6 kcalmol(-1) and 26.3 kcalmol(-1), and deltaC(p) degrees is 0.38 kcalmol(-1)deg(-1). The thermodynamic parameters are in the range expected on the basis of per residue values determined from databases of globular proteins. H/2H exchange measurements reveal a set of amides that exchange via global unfolding, exactly as expected for a normal cooperatively folded globular protein. Kinetic measurements show that folding is two-state folding. The folding rate is 640 s(-1) and the value of deltaG degrees calculated from the folding and unfolding rates is in excellent agreement with the equilibrium value. A designed thermostable variant, generated by mutating K12 to M, was characterized and found to have a t(m) of 82 degrees C. Equilibrium and kinetic measurements demonstrate that its folding is cooperative and two-state.

Circular Dichroism↗

Limitations of implantable, miniature ultrasonic transducers to measure wall movement in the canine jejunum.

BACKGROUND: We used implantable miniature ultrasonic transducers to measure longitudinal distance, circumference, and wall thickness dynamically in vivo in canine jejunum. We hoped to differentiate circular from longitudinal smooth muscle contractions and to correlate physical measurements of change in distance within the jejunal wall with intraluminal manometry. MATERIALS AND METHODS: In acute experiments at the time of celiotomy, longitudinal distances, circumferences, and wall thickness were measured directly and by ultrasonic transducers sewn to serosa and mucosa. Measurements were obtained with the intestine empty and after distention with air, water, or semisolid slurry. In chronic in vivo experiments in conscious dogs with indwelling ultrasonic transducers and intraluminal manometers, sonometric dimensions were correlated with manometric recordings. In acute experiments, sonometric measurements were similar to direct measurements. In chronic experiments in vivo, smallest ultrasonometric measurements of circumferences of the jejunum correlated in a phase-locked temporal manner with both highest intraluminal pressures and greatest wall thickness. RESULTS: Longitudinal distances increased during decreases in circumference. Distances orad to the site maximal intraluminal pressure peaked at 0.58 +/- 0.04 s ( x +/- SEM) before, and those aborad to this point 0.42 +/- 0.04 s after attaining minimum circumferences. CONCLUSIONS: Ultrasonic crystals can monitor geometric changes in the bowel wall with certain limitations, especially when obtained in vivo. Contraction of circular and longitudinal muscles, although phase-locked, do not appear to occur exactly synchronously in canine jejunum.

Animals↗