Tip End Research Articles

Switchable-magnetization planar probe MFM sensor for imaging magnetic textures of complex metal oxide perovskite

We introduce an alternative method for switching-magnetization magnetic force microscopy that utilizes planar tip-on-chip probes. Unlike conventional needle-like tips, the planar probe technique incorporates a microdevice near the tip apex on a 1×1mm2 chip, which allows for thin-film engineering and micro/nano-customization aimed at application-specific tip functionalization. In this study, we establish a microscale current pathway near the tip end to manage the tip magnetization state. This planar probe was used to investigate the intricate disordered magnetic domain structure of an epitaxial thin film of the transition metal oxide perovskite LaMnO3, a material previously demonstrated to exhibit complex domains related to superparamagnetism, antiferromagnetism, and ferromagnetism. We successfully visualized an inhomogeneous distribution of magnetic islands near the Curie temperature, with a resolution exceeding 10nm.

Development Of An Endoscopic, Absorption Corrected And Calibrated OH Laser Induced Fluorescence Probe System for High Pressure Combustion Diagnostics

We present the design and preliminary results of an endoscopic OH laser-induced fluorescence (LIF) system that is capable of acquiring 1D-line measurements in high pressure combustion processes within large-scale test facilities. The system can be exploited to acquire line-of-sight OH-chemiluminescence images and absorption corrected absolute OH-species concentration from which additionally temperature distribution can be extracted in case of lean mixtures in chemical equilibrium. Different critical components, such as light guides for high power UV laser pulses and flexible UV image guides, were first tested and characterized in a laboratory setup. Optimization regarding pulse energy and beam quality led to the selection of an 1m long hollow core fiber for laser light delivery as a central element for the experimental setup despite high losses caused by bending the fiber. The image transfer is accomplished by a 7m long flexible UV image bundle, which is preferred to the use of a rigid borescope in harsh environments. We designed the endoscopic UV optics using readily available parts and achieved an approximated image resolution of 21.6 line pairs/mm. Additionally, post-processing methods, such as flat-field correction, can improve the image quality substantially and remove the pixilation effect of the fiber bundle structure nearly completely. To validate the complete system, probe-based qualitative OH-LIF measurements were performed in a well-known laminar flame of a matrix burner, which serves as a mock-up for anticipated applications in an industrial test environment with a technology readiness level (TRL) greater than 4. The final step consists of the integration of the miniaturized optics into a cooled probe system which protects the sensitive optics against the harsh environment of an aero-engine sector combustor. For this purpose, two probe systems were designed to include, on the one hand, the endoscope optics together with the fiber image bundle end tip and, on the other hand, the laser emitting and receiving system for performing an absorption measurement needed to quantify the recorded LIF signal.

Control of edgewise vibration of a pre-twisted rotating beam with shunted piezoelectric tuned mass damper

The edgewise vibration control of a pre-twisted beam, rotating in the vertical plane, is considered in this study. A piezoelectric tuned mass damper (PTMD) comprising a spring–mass–damper system and a piezoelectric transducer with its associated shunt circuit is considered the control device. A finite element formulation of the pre-twisted rotating beam with the attached PTMD is developed while considering the effect of centrifugal stiffening due to rotation and the effect of gravity force. The natural frequencies of the beam (without PTMD) obtained using the present formulation are corroborated by comparing them with the results derived from Ansys. A single PTMD attached at the tip end of the beam can effectively suppress the response of the beam subjected to a distributed load in the edgewise direction. The best values of resistance and inductance of the shunt circuit are obtained through a parametric study on the peak and root mean square value of the beam tip response. A qualitative difference in the uncontrolled as well as in the controlled responses can be noticed while considering the effect of the gravity load component in the edgewise direction. Further, it has been observed that the conventional Tuned Mass Damper (TMD) provides better control than the PTMD system for ideally tuned conditions, however, the control performance of TMD degrades rapidly as compared to the PTMD in the presence of detuning. This demonstrates the effectiveness of PTMD in a practical implementation where achieving the perfectly tuned condition is seldom realized. The control performance of PTMD marginally degrades when the beam is subjected to multi-directional excitation. Hence, the proposed control system has the potential for application in rotating beam-type structures, such as wind turbine blades.

Strain-rate effect on mechanical properties of rock-like specimens with narrow crack under uniaxial compression

Uniaxial compression tests were carried out on rock-like specimens containing prefabricated narrow crack under various strain rates. Experimental observations and numerical results show that narrow crack will close or partially close or expand under low compressive stress. Due to the unidirectional loading of loading device, the deformation degree of crack tip near the loading end was different with that of crack tip near the bearing end. With the increase of strain rate, the cracking modes can be divided into 3 categories, near vertical splitting failure affected by horizontal crack (α = 0°), anti-N-wing crack (15°≤α ≤ 60°) and wing crack (60°<α ≤ 90°). Both of the initiation angle θ1 of crack tip near the loading end and θ2 of crack tip near the bearing end decreased with the increase of α and strain rate. Specially, when α = 90°, both θ1 and θ2 rose with the increase of strain rate. Moreover, the value of θ2 was greater than that of θ1 under the same α value because of the different deformation characteristics at two tips. Besides, the mechanical properties of fissured rock including peak compressive stress, residual compressive stress, strain at peak stress, elastic modulus and post-peak softening modulus were significantly influenced by the strain rate and inclination angles.

Helicopter rotor in a propeller slipstream: Aerodynamic and rotor blade flapping responses

During helicopter air-to-air refueling the helicopter's rotor can engage the tanker aircraft's wing and flap end tip vortices and the slipstream of its propellers. The tip vortices represent a swirl around an axis that is essentially parallel to the rotor longitudinal axis. The slipstream of the propellers includes a strong air jet downstream that can cover a significant amount of the helicopter's main rotor. This phenomenon was recently treated analytically for a rigid rotor by means of blade-element momentum theory and the rotor control angles required to reject the disturbance were computed. In this article, the rotor blade flapping is introduced as degree of freedom. It is shown that the rotor coning is affected by the slipstream position with respect to the rotor hub. Without retrim, the largest amount of coning and cyclic flapping occurs for slipstream positions on the retreating side of the rotor.

Measurement of distances and locations of thoracic and lumbar vertebral bodies from CT scans in cases of spinal deformation

BackgroundSpinal deformations, except for acute injuries, are among the most frequent reasons for visiting an orthopaedic specialist and musculoskeletal treatment in adults and adolescents. Data on the morphology and anatomical structures of the spine are therefore of interest to orthopaedics, physicians, and medical scientists alike, in the broad field from diagnosis to therapy and in research.MethodsAlong the course of developing supplementary methods that do not require the use of ionizing radiation in the assessment of scoliosis, twenty CT scans from females and males with various severity of spinal deformations and body shape have been analysed with respect to the transverse distances between the vertebral body and the spinous process end tip and the skin, respectively, at thoracic and lumbar vertebral levels. Further, the locations of the vertebral bodies have been analysed in relation to the patient’s individual body shape and shown together with those from other patients by normalization to the area encompassed by the transverse body contour.ResultsWhile the transverse distance from the vertebral body to the skin varies between patients, the distances from the vertebral body to the spinous processes end tips tend to be rather similar across different patients of the same gender. Tables list the arithmetic mean distances for all thoracic and lumbar vertebral levels and for different regions upon grouping into mild, medium, and strong spinal deformation and according to the range of spinal deformation.ConclusionsThe distances, the clustering of the locations of the vertebral bodies as a function of the vertebral level, and the trends therein could in the future be used in context with biomechanical modeling of a patient’s individual spinal deformation in scoliosis assessment using 3D body scanner images during follow-up examinations.

A self-powered magnetoelectric 3D tactile sensor with adjustable sensitivity for robot arms

With the rapid development of robot arms in various industries, the interactions between the tip ends of robot arms and the target surfaces or objects play an important role. Tactile sensors, particularly for force measurement, are widely used at the tip ends of robot arms for information exchange. Currently, most of the tactile sensors used at the tip ends of robot arms are with one planar or arc sensing surface (2D sensing area), which can only measure the contact force when the surfaces or objects are facing the sensing surface (around 180° working space range). However, contact forces may come from any direction (360° working space range), which needs tactile sensors with 3D sensing area to measure multi-direction contact forces. To tackle this problem, a self-powered magnetoelectric 3D tactile sensor (SM3D-TS) is proposed in this paper. Firstly, the design and fabrication of the SM3D-TS are described in detail. Secondly, the mechanical properties of the SM3D-TS are tested. Thirdly, the voltage-force relationship of the SM3D-TS is calibrated in single direction. Then, the force measuring and random points positioning performances are validated. Without power input, the SM3D-TS can measure contact forces from multiple directions with speed-dependent sensitivity. The experimental results show that the SM3D-TS can not only accurately measure the contact forces at given speed by independently using the induced voltages in the three axes, but also can position random points at given contact speed with high accuracy.

A rare case of conjunctival granuloma in Aurolab aqueous drainage implant (AADI) with supramid

Conjunctival granuloma (CG) can be caused by a foreign body, surgically related inflammation, an allergen, an infectious organism, or as part of a systemic disease. We are reporting the first case of CG related to 5-0 prolene as supramid, which is used as an intraluminal stent in AADI to prevent hypotony. A 70-year-old female diagnosed with POAG in both eyes with posterior PCIOL on MMT with advanced disc damage and uncontrolled IOP in the right eye underwent AADI with supramid. The patient developed mild irritation and redness in RE in the fourth month of follow-up. On slit-lamp examination, there was localized CG at the end of the supramid tip. CG resolved with the removal of the supramid suture and medical treatment. Supramid-related CG is rare and generally causes non-fatal material-related hypersensitivity reactions that can be treated well with medications and removal of inciting factors.

Multileaf collimator characterization and modeling for a 1.5 T MR-linac using static synchronous and asynchronous sweeping gaps

Objective. The Elekta unity MR-linac delivers step-and-shoot intensity modulated radiotherapy plans using a multileaf collimator (MLC) based on the Agility MLC used on conventional Elekta linacs. Currently, details of the physical Unity MLC and the computational model within its treatment planning system (TPS) Monaco are lacking in published literature. Recently, a novel approach to characterize the physical properties of MLCs was introduced using dynamic synchronous and asynchronous sweeping gap (aSG) tests. Our objective was to develop a step-and-shoot version of the dynamic aSG test to characterize the Unity MLC and the computational MLC models in the Monaco and RayStation TPSs. Approach. Dynamic aSG were discretized into a step-and-shoot aSG by investigating the number of segments/sweep and the minimal number of monitor units (MU) per segment. The step-and-shoot aSG tests were compared to the dynamic aSG tests on a conventional linac at a source-to-detector distance of 143.5 cm, mimicking the Unity configuration. the step-and-shoot aSG tests were used to characterize the Unity MLC through measurements and dose calculations in both TPSs. Main results. The step-and-shoot aSGs tests with 100 segments and 5 MU/segment gave results very similar to the dynamic aSG experiments. The effective tongue-and-groove width of the Unity gradually increased up to 1.4 cm from the leaf tip end. The MLC models in RayStation and Monaco agreed with experimental data within 2.0% and 10%, respectively. The largest discrepancies in Monaco were found for aSG tests with >10 mm leaf interdigitation, which are non-typical for clinical plans. Significance. The step-and-shoot aSG tests accurately characterize the MLC in step-and-shoot delivery mode. The MLC model in RayStation 2023B accurately describes the tongue-and-groove and leaf tip effects whereas Monaco overestimates the tongue-and-groove shadowing further away from the leaf tip end.

Study of Topography of Stylomastoid Foramen With Respect to Nearby Landmarks to Carry Out Facial Nerve Block With Minimum Complications.

Nadbath facial nerve block is the most common procedure to anesthetize the facial nerve at stylomastoid foramen in intraocular surgeries, but it is associated with complications. Also, this foramen exhibits ethnic and racial variations with regard to its location. There is scanty literature describing the topographical location of this foramen. So, the study is carried out. The purpose of the study is to describe the topography of stylomastoid foramen from the surrounding landmarks so that Nadbath facial nerve block can be performed with minimum complications. The study was conducted using 80 adult dry skulls of unknown age and sex, and the distance of this foramen was measured from the tip, upper end, and lower end of the anterior border of the mastoid process and jugular foramen. The statistical analysis consisting of mean, SD, median, range mode, and t test was calculated. Mean distances of stylomastoid foramen from the upper end, the lower end of anterior border and tip of mastoid process and jugular foramen on right side were 1.5±0.16, 1.02±0.09, 0.84±0.09, and 0.49±0.06cm and those on left side were 1.5±0.16, 1.02±0.09, 0.84±0.09, and 0.5±0.06cm, respectively. The mode of these distances was 1.5, 1, 0.8, and 0.5, both on the right and left sides. The topographic information about stylomastoid foramen given in this study is useful to anesthetists to carry out Nadbath facial nerve block successfully with minimum complications.

Simultaneous Multipass Resistive-Pulse Sensing and Fluorescence Imaging of Liposomes.

Simultaneous multipass resistive-pulse sensing and fluorescence imaging have been used to correlate the size and fluorescence intensity of individual E. coli lipid liposomes composed of E. coli polar lipid extracts labeled with membrane-bound 3,3-dioctadecyloxacarbocyanine (DiO) fluorescent molecules. Here, a nanopipet serves as a waveguide to direct excitation light to the resistive-pulse sensing zone at the end of the nanopipet tip. Individual DiO-labeled liposomes (>50 nm radius) were multipassed back and forth through the orifices of glass nanopipets' 110-150 nm radius via potential switching to obtain subnanometer sizing precision, while recording the fluorescence intensity of the membrane-bound DiO molecules. Fluorescence was measured as a function of liposome radius and found to be approximately proportional to the total membrane surface area. The observed relationship between liposome size and fluorescence intensity suggests that multivesicle liposomes emit greater fluorescence compared to unilamellar liposomes, consistent with all lipid membranes of the multivesicle liposomes containing DiO. Fluorescent and nonfluorescent liposomes are readily distinguished from each other in the same solution using simultaneous multipass resistive-pulse sensing and fluorescence imaging. A fluorescence "dead zone" of ∼1 μm thickness just outside of the nanopipet orifice was observed during resistive-pulse sensing, resulting in "on/off" fluorescent behavior during liposome multipassing.

Multiparameter Remote Contact Force Sensor With Embedded Bend Sensing for Tendon-Driven Hand Robots

Integrating multiple sensors without increasing the structural complexity and their original form factor is a major concern in robotic applications, particularly in tendon-driven systems. This study proposes a multiparameter contact force sensor with bend sensing by utilizing an improved Bowden cable design. The proposed sensor consists of an end tip with an elastomer membrane, a Bowden cable consisting of a sheath and dual inner wires, and a remotely separated sensing component. The electrical wirings are decoupled from the mechanical Bowden cable system. The displacement difference between the force-sensing and bend-sensing wires is transmitted through the sheath, indicating the contact force on the end tip. The modeling and experiments verify that the contact force applied on the end tip is linearly related to the sensor output signal and is reliable after repeated measurements. The proposed sensor, utilizing the flexible Bowden cable as its sensing modality, can be integrated into a diverse range of tendon-driven robotic applications. These applications include a robotic hand with tactile and angle sensing capabilities, as well as a soft wearable robot for the hand (Exo-glove Poly II). The compact form factor of the proposed sensor enables geometric sensing without increasing structural complexity for multiparameter sensing in robotic applications.

Mechanical and wear behavior of al-steel solid state cladding produced by friction stir surfacing

Friction surfacing (FS) is a solid-state cladding method that produces a coating with minimum dilution and good metallurgical bonding. Deposition of aluminium over mild steel with using fusion based joining process is not feasible sue to the formation of iron aluminide and Fe and Al are metallurgically immiscible to each other. Hence, deposition of aluminium on steel with solid-state condition is feasible and most viable option. During the process, a rotating consumable rod is rubbed against the substrate plate under an applied axial load. The friction between rod and substrate generates a visco-plastic layer at the end of rod tip. The high temperature and pressure at interfaces aids in the cladding of the rod material on the substrate. Aluminium alloy 6351 T6 rod of 22 mm diameter was used as consumable material for surfacing on a 6mm thick SA516 Gr70 steel substrate plate. Optimized process parameters were used for the final experimental trials. Multilayer samples generated at constant Friction Surfacing variables were subjected to Pin-on-disc wear test at 40N load. Mechanical interlocking was also observed at the interface of the layers. The process was also observed to produce extremely fine grain microstructures of the deposited material due to the hot forging action involved resulting in superior wear properties.

High-frequency wearable ultrasound array belt for small animal echocardiography.

Wearable ultrasound has been widely developed for long-term, continuous imaging without the need for bulky system manipulation and repeated manual locating. To potentially lead to more accurate and reliable imaging monitoring, this work presents the design, fabrication, and evaluation of a novel high-frequency wearable ultrasound array belt (WUAB) for small animal echocardiography. The fabrication process involved precise dicing technology for a λ-pitch design. The 20 MHz WUAB consists of two matching layers, piezoelectric composite with 128 channels, customized flexible circuit substrate, acoustic backing layer, and customized belt structure with designed end tip and insertion point for wearability. The resulting WUAB demonstrates sensitivity of -5.69 ± 2.5 dB and fractional bandwidth of 57 ± 5 %. In vivo experiments on rat model showed expected echocardiography and B-mode images of rat heart. These results represent significant promise for future longitudinal studies in small animals and real-time physiological monitoring.

Pentaerythritol tetraacrylate microcavity sensor for high performance relative humidity detection

A pentaerythritol tetraacrylate (PETA) microcavity sensor for high performance relative humidity (RH) detection is presented. The fiber tip all-polymer microcavity, with a maximum size of 99.27 µm, consists of a circular truncated cone on the fiber tip end surface and is manufactured by photopolymerization of PETA using two-photon polymerization technology, which is characterized by miniaturization and rapid manufacturing. Experimental results show that its RH sensitivity reaches 108.05 pm/%RH in the range of 14.7–84.3%RH. In particular, respiration monitoring experiments show that its response time and recovery time are 0.55 s and 2.5 s, respectively. The sensor shows the inherent advantages of compact structure, fast response, good repeatability, low hysteresis error, good stability, and high sensitivity. Therefore, it is a promising candidate for potential applications in chemical, medical and biological fields related to RH detection.

Electrical Conductivity Measurements of the Binary NaCl-CaCl2, the Ternary NaCl-CaCl2-BaCl2 and the Quaternary NaCl-CaCl2-BaCl2-ZnCl2 Molten Salts

An emerging set of batteries, called the molten salts or all liquid battery, are designed for cheap energy storage and electrical grid buffering purposes (1). Some molten salt batteries are commercial or close to commercial like the ZEBRA, NaS and Ambri batteries, however, most of these battery technologies are still on an experimental, lower TRL level but can become increasingly important in the future as the shift towards more intermittent energy sources emerge and as the development of these batteries become more mature. One suggested battery technology is the Na-Zn battery (2). This battery technology is currently further investigated in the EU funded SOLSTICE project (Grant Agreement No 963599). The Na-Zn battery will have Na and Zn electrodes and the electrolyte – the molten salt – will be a NaCl-CaCl2 based electrolyte, with additions of BaCl2 or perhaps even BaCl2 and SrCl2. The NaCl content of the electrolyte gives the charge of the battery, CaCl2 lowers the operating temperature and BaCl2 and SrCl2 increases the density of the electrolyte. The operating temperature of the battery is approximately 600 °C and joule heat generated inside battery during charging and discharging due to resistance of the electrolyte allows to maintain this operating temperature. The composition of electrolyte changes with the battery state of charge hence the internal resistance of battery is not constant during normal operation. Therefore, precise data of electrical conductivity of the electrolyte is required for modelling its performance thermal balance.A method for measuring electrical conductivity has been built in the SINTEF laboratory. The setup used for the measurements is presented in Figure 1a. It consists of two tungsten electrodes immersed in molten electrolyte – one electrode is stationary and the other is moving inside a capillary. Position of the moving electrode inside the capillary is precisely controlled by a height gauge. Shielded thermocouple is used for measuring temperature. To avoid polarization of electrodes during measurement, electrical impedance spectroscopy (EIS) at open circuit potential is used. The principle of the method is that resistance between the electrodes is measured at different positions of the moving electrode inside the capillary. Measured resistance can be expressed by the following formula: R=R0+ρ·(l/A) Where R0 is the offset resistance of electrolyte outside capillary including resistance of electrodes and leads,ρ is the resistivity of electrolyte, l is the length between end of capillary and tip of the moving electrode, A is the area of the capillary. The measurement of resistance is repeated at different positions of the moving electrode relative to the chosen reference position. Since R0 and A are constant, resistivity can be calculated knowing only the tangent of function R = f(l) (Figure 1b) divided by A. The presented approach is characterized by high precision and robustness due to no requirement of cell constant values, which is problematic to estimate at high temperature. It is only based on relative movement of one electrode which is easy to control. In addition, a higher number of positions of the moving electrode at which the measurement is performed effectively helps to eliminate errors. Conductivity is the inverse resistivity. Electrical conductivity measurements were done at a range of temperatures, from 600 °C to 800 °C with 50 °C steps and the results are presented in the form of linear formulas intended for use in User Defined Functions in modelling.Conductivity of various chloride salt compositions containing NaCl, CaCl2, BaCl2 and ZnCl2 have been investigated using the presented technique. It is generally found that the electrical conductivity is almost linear with temperature increase in the range of liquidus temperature up to approximately 800 °C for the investigated electrolyte compositions. Above that region the relationship is not linear anymore. This region is not presented in this presentation. It is also found that the conductivity increases with increasing NaCl content and that larger cations like Ca and Ba reduce the conductivity of the molten salt. The method has proven very powerful to measure electrical conductivity on molten salts and the results are comparable to experimental results found in literature (3).

Multi-objective optimization of a U-shaped water jacket with a guide vane for improving the thermal performance of 20 kW in-wheel motor

In-wheel motors (IWMs) are considered to replace centralized motors in electric vehicles due to a high efficiency. However, heat dissipation is a significant challenge in IWMs because of their limited space. In this study, a U-shaped water jacket with a guide vane design is newly proposed to improve the heat dissipation performance of IWMs. An IWM simulation model is developed and validated based on experimental data. Using six independent design variables, the multi-objective optimization is performed to maximize Q·V−1 while minimizing the pressure drop. The optimal design obtained from Pareto solutions indicates that the maximum coil temperature is reduced by 8.2 °C, while its lifespan increased by 83.9 % compared to the baseline. For the guide vane, the pressure drop is reduced by 26.7 %, while Q·V−1 is increased by 2.5 % compared to the initial design. The thickness of the guide vane and its distance from the end tip of the water jacket curved section, the two key design variables of the guide vane, have the most influential effect on Q·V−1 and pressure drop respectively. Finally, as the continuous rated power increases, the proposed design has a significant impact on the improved heat dissipation performance of the IWM.

Deformation Mechanisms and surface/interface Characteristics of Titanium-based Thermoplastic FMLs under Ultrasonic Impact Loading

Some typical defects like delamination, fiber fracture, non-uniform resin distribution and springback are inevitable as titanium-based thermoplastic FMLs are formed by general stamping process at elevated temperature due to the significant differences of various constituent materials in mechanical and thermal properties as well as deformation mechanism. Thus, a novel ultrasonic impact sizing/shaping process method was proposed in the present work, in which a stepped horn and impact tools with a cylindrical tip end was designed by means of vibration modal and harmonic response analysis, and the corresponding experiment setup was established to verify the process mentioned above. Moreover, ultrasonic impact tests were carried out for titanium-based FMLs stacked by titanium sheet, thermoplastic resin film and carbon fiber reinforced fabric to reveal their sizing/shaping mechanism and the effect of key process parameters such as ultrasonic amplitude, scanning speed of impact tool and its tip end diameter on the surface and interface characteristics of titanium-based FMLs. The research results show that the ultrasonic impact scheme with the ultrasonic amplitude of 12 μm, the scanning speed of impact tool within 2 mm/s ∼ 3 mm/s, the tip end diameter of impact tool within Ø4mm∼Ø6mm are proper for the ultrasonic impact sizing/shaping process of titanium-based FMLs.

Rapid Droplet Sampling Interface for Low-Volume, High-Throughput Mass Spectrometry Analysis.

Here, we present a rapid droplet sampling interface (RDSI) electrospray ionization mass spectrometry (ESI-MS) system as a high-throughput, low-volume, noncontact, and minimal-carryover approach for characterization of liquids. Liquid characterization was achieved by combining droplet ejection with an open-face microflow capillary with a 2.5 μL/min continuous flow of carrier solvent. Through this implementation, single 0.3 nL droplets containing the analyte effectively mix with 4-8 nL of carrier solvent and create a combined electrospray plume. The carrier solvent continuously cleaned the system, eliminating carryover. A sampling rate of 5 Hz was achieved for droplets containing 1 μM propranolol or 5 μM leu-enkephalin with each droplet fully baseline-resolved (138 ± 32 ms baseline-to-baseline). Using a SCIEX API4000 mass spectrometer, a lower limit of quantification (LLOQ) of propranolol was 15 nM, corresponding to 1.16 fg of propranolol in the droplet, and was linear across 3 orders of magnitude. Quantitation could be achieved by adding an isotopically labeled internal standard, as done in conventional ESI. Signal transients were faster than the acquisition speed of the mass spectrometer, resulting in artificially high reproducibility of 15-30% RSD droplet-to-droplet. Analyte-solvent mixing ratios could be controlled by adjusting droplet positioning along the open-face capillary with an optimal position about 0.4 mm from the tip end. The range of analyte coverage was exemplified by measures of peptides and drugs in methanol, water, and buffer solutions. In a comparison to the Open Port Sampling Interface (OPSI) implemented on the same system, the RDSI had 78× greater sensitivity, 6× greater throughput and used significantly less carrier solvent.

An injectable and biodegradable zwitterionic gel for extending the longevity and performance of insulin infusion catheters.

Continuous subcutaneous insulin infusion (CSII) is an essential insulin replacement therapy in the management of diabetes. However, the longevity of clinical CSII is limited by skin complications, by impaired insulin absorption and by occlusions associated with the subcutaneous insertion of CSII catheters, which require replacement and rotation of the insertion site every few days. Here we show that a biodegradable zwitterionic gel covering the tip end of commercial off-the-shelf CSII catheters fully resolves early skin irritations, extends the longevity of catheters and improves the rate of insulin absorption (also with respect to conventional syringe-based subcutaneous injection) for longer than 6 months in diabetic mice, and by 11 days in diabetic minipigs (from 2 to 13 days, under standard CSII-wearing conditions of insulin pump therapy and in a continuous basal-plus-bolus-infusion setting). The implanted gel displayed anti-inflammatory and anti-foreign-body-reaction properties and promoted the local formation of new blood vessels. The gel is subcutaneously injected before the tip of catheter is inserted into it, and should be generally applicable to CSII catheters and other implantable devices.