Eduardo J. Juan

Miniature acoustic guidance system for endotracheal tubes

Ensuring that the distal end of an endotracheal tube (ETT) is properly located within the trachea, and that the tube is not obstructed by mucus deposition, is a major clinical concern in patients that require mechanical ventilation. A novel acoustic system was developed to allow for the continuous monitoring of ETT position and patency. A miniature sound source and two sensing microphones are placed in-line between the ventilator hose and the proximal end of the ETT. Reflections of an acoustic pulse emitted into the ETT lumen and the airways are digitally analyzed to estimate the location and degree of lumen obstruction, as well as the position of the distal end of the tube in the airway. The system was evaluated through in vitro studies and in a rabbit model. The system noninvasively estimated tube position in vivo to within roughly 4.5 mm, and differentiated between proper tracheal, and erroneous bronchial or esophageal intubation in all cases. In addition, the system estimated the area and location of lumen obstructions in vitro to within 14% and 3.5 mm, respectively. These findings indicate that this miniature technology could improve the quality of care provided to the ventilated adult and infant.

Vagus nerve modulation using focused pulsed ultrasound: Potential applications and preliminary observations in a rat

The use of focused ultrasonic waves to modulate neural structures has gained recent interest due to its potential in treating neurological disorders noninvasively. While several articles have focused on the use of ultrasound neuromodulation on peripheral nerves, none of these studies have been performed on the vagus nerve. We present preliminary observations on the effects of focused pulsed ultrasound (FPUS) on the conduction of the left cervical vagus nerve of a Long Evans rat. Ultrasound energy was applied at a frequency of 1.1 MHz, and at spatial‐peak, temporal average intensities that ranged from 13.6 to 93.4 W/cm2. Vagus nerve inhibition was observed in most cases. Results of this preliminary study suggested that there is a proportional relationship between acoustic intensity and the level of nerve inhibition.

Synthesis, stability, cellular uptake, and blood circulation time of carboxymethyl-inulin coated magnetic nanoparticles

Iron oxide nanoparticles were coated with the biocompatible, biodegradable, non-immunogenic polysaccharide inulin by introduction of carboxyl groups into the inulin structure and conjugation with amine groups on the surface of iron oxide nanoparticles grafted with 3-aminopropyltriethoxysilane. The resulting nanoparticles were characterized by FT-IR spectroscopy, transmission electron microscopy, dynamic light scattering, zeta potential, SQUID magnetometry, and with respect to their energy dissipation rate in applied alternating magnetic fields. The nanoparticles had a hydrodynamic diameter in the range of 70 ± 10 nm and were superparamagnetic, with energy dissipation rates in the range of 58-175 W/g for an applied field frequency of 233 kHz and an applied field amplitude in the range of 20-48 kA/m. The nanoparticles were stable in a range of pH, at temperatures between 23°C and 53°C, and in short term storage in water, PBS, and culture media. The particles were non-cytotoxic to the immortalized human cancer cell lines Hey A8 FDR, A2780, MDA 468, MCF-7 and Caco-2. The nanoparticles were readily taken up by Caco-2 cells in a time and concentration dependent fashion, and were found to have a pharmacokinetic time constant of 47 ± 3 min. The small size, non-cytotoxicity, and efficient energy dissipation of the particles could make them useful for biomedical applications such as magnetic fluid hyperthermia.

Development and validation of a 10 kHz–1 MHz magnetic susceptometer with constant excitation field

The design and validation of a mutual inductance AC susceptometer with constant excitation field of up to 4.25 Oe, operating at frequencies from 10 kHz to 1 MHz, is presented. Considerations such as parasitic capacitances between wire turns and sensing bridge electronics were taken into account in order to extend the operating frequency range. An 18AWG wire with considerable insulator thickness was used for coil construction to keep parasitic capacitive reactance negligible relative to coil inductive reactance, and to obtain controlled field operation. A high speed instrumentation amplifier (slew rate over 33 V/μs) was designed and constructed using voltage feedback LM7171 operational amplifiers. The system was calibrated with Dy2O3 to account for mismatches in signal amplitude and phase shifts due to the electronics, coil coupling and imperfections, and external disturbances. AC susceptometer operation in the 10 kHz–1 MHz frequency range was validated by measuring the complex susceptibility of cobalt fer...

HSP70 inhibition synergistically enhances the effects of magnetic fluid hyperthermia in ovarian cancer

Hyperthermia has been investigated as a potential treatment for cancer. However, specificity in hyperthermia application remains a significant challenge. Magnetic fluid hyperthermia (MFH) may be an alternative to surpass such a challenge, but implications of MFH at the cellular level are not well understood. Therefore, the present work focused on the examination of gene expression after MFH treatment and using such information to identify target genes that when inhibited could produce an enhanced therapeutic outcome after MFH. Genomic analyzes were performed using ovarian cancer cells exposed to MFH for 30 minutes at 43°C, which revealed that heat shock protein (HSP) genes, including HSPA6, were upregulated. HSPA6 encodes the Hsp70, and its expression was confirmed by PCR in HeyA8 and A2780cp20 ovarian cancer cells. Two strategies were investigated to inhibit Hsp70-related genes, siRNA and Hsp70 protein function inhibition by 2-phenylethyenesulfonamide (PES). Both strategies resulted in decreased cell viability following exposure to MFH. Combination index was calculated for PES treatment reporting a synergistic effect. In vivo efficacy experiments with HSPA6 siRNA and MFH were performed using the A2780cp20 and HeyA8 ovarian cancer mouse models. A significantly reduction in tumor growth rate was observed with combination therapy. PES and MFH efficacy were also evaluated in the HeyA8 intraperitoneal tumor model, and resulted in robust antitumor effects. This work demonstrated that HSP70 inhibition combination with MFH generate a synergistic effect and could be a promising target to enhance MFH therapeutic outcomes in ovarian cancer. Mol Cancer Ther; 16(5); 966–76. ©2017 AACR.

Closed‐Loop Temperature Control of Cobalt Ferrite Ferrofluids Using Continuous Modes Controllers

Precise temperature control of a cobalt ferrite ferrofluid (2.5% w/w in heptane) was achieved using continuous mode controllers and a custom‐made, variable frequency, magnetic field generator. Proportional‐Integral (PI) and Proportional‐Integral‐Derivative (PID) controllers were implemented using LabVIEW and used to control the amplitude of the magnetic field applied to the ferrofluid. A fluoro‐optic thermometer (Luxtron) was used to record temperature. The applied magnetic field had a maximum value of 7 kA/m (100% controller output), and a frequency of 507 kHz. The temperature (process variable) range was 0–100° C (0–100%). When properly tuned, the proportional‐integral (PI) controller yielded excellent results, achieving 1.1 percent overshoot (%OS), a settling time (Ts) of 50 s, and a steady‐state error of 0.10° C, for a setpoint of 40° C. The implementation of accurate and fast temperature controllers allows for the consideration of transient responses in fields of study in which magnetic nanoparticles...

Computer Simulation Tool for Predicting Sound Propagation in Air-Filled Tubes with Acoustic Impedance Discontinuities

A computer tool, based on an acoustic transmission line model, was developed for modeling and predicting sound propagation and reflections in cascaded tube segments. This subroutine considered the number of interconnected tubes, their dimensions and wall properties, as well as medium properties to create a network of cascaded transmission line model segments, from which the impulse response of the network was estimated. Acoustic propagation was examined in air-filled cascaded tube networks and model predictions were compared to measured acoustic pulse responses. The model was able to accurately predict the location and morphology of reflections. The developed code proved to be a useful design tool for applications such as the guidance of catheters through compliant air-filled biological conduits.

Acoustical characterization of impermeable membranes: hearing aid applications

This investigation explored the feasibility of utilizing impermeable membranes to develop an easy to clean, water resistant hearing aid. A common problem with hearing aids is the accumulation of earwax in the small conduit that communicates the loudspeaker with the exterior of the device. This problem could be overcome by placing an impermeable membrane at the hearing aid surface to prevent earwax (as well as other substances) from entering the device. Placing a membrane between the loudspeaker and the ear canal will probably distort the sound generated by the loudspeaker, since the membrane will attenuate and possibly reflect some of the sound. A microphone and a loudspeaker similar to those utilized for hearing aid applications were used to determine the acoustic transfer characteristics of several types of impermeable membranes. Digital signal processing techniques were employed to compensate for the deleterious effects that the membrane can impart to the sound generated by the loudspeaker.

In-line acoustic system to position and monitor infant-sized endotracheal tubes

Ensuring that the distal end of an endotracheal tube is properly located within the trachea, and that the tube is not obstructed by mucous deposition, is a major clinical concern. This concern is heightened in infant care, where the relatively small geometries predicate higher risks. A novel acoustic system was developed to allow for the continuous monitoring of endotracheal tube position and patency. A miniature sound source and two sensing microphones are placed in-line between the ventilator hose and the proximal end of the endotracheal tube. Reflections of an acoustic pulse from the endotracheal tube lumen and the airways are digitally analyzed to estimate the location and degree of obstruction, as well as the position of the distal end of the tube in the airway. The system was evaluated in a rabbit model. During advancement and retraction of the distal end of the tube within the trachea, changes in position were estimated acoustically to within -0.4/spl plusmn/2.0 mm (mean /spl plusmn/95% CI). Through reflection analysis, the system reliably differentiated tracheal from improper bronchial or esophageal placement in all cases. In addition, the system acoustically estimated the area of intralumenal obstruction to within 5.4/spl plusmn/8.6%.

Estimation of Tube Wall Compliance Using Pulse-Echo Acoustic Reflectometry

This paper focuses on the estimation of tube wall compliance using reflection analysis of acoustic pulses. The wall compliance of a rubber latex tube was found theoretically using an acoustical transmission line model. Wall compliance was also obtained experimentally from acoustical and mechanical measurements. The acoustically estimated, mechanically estimated, and simulated wall compliances were C_wEXP=6.55middot10^-7 cm⁵/dyne C_wMech=6.89middot10^-7 cm⁵/dyne and C _wSim=5.18middot10^-7 cm⁵/dyne respectively. The methods developed and the preliminary results obtained from this research could serve as the groundwork for the development of a device that determines the pathological condition of compliant biological conduits such as the airways