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Biomedical signal acquisition devices (e.g., Electrocardiography—ECG) are relevant for diagnosing and monitoring persons who have developed a variety of diseases, such as cardiovascular diseases. These devices comply with regulatory requirements before being marketed to prevent misleading measures, and they should also pass through corrective and preventive maintenance to keep them working correctly. We designed and implemented a simulation-based system to support these needs and assist manufacturers and healthcare facilities. This article focuses on demonstrating the effectiveness of our system for validating ECG devices. Our system comprises software in a computing device and a biomedical signals transducer. The system relies on coloured Petri nets modeling language, a frequency-based filtering method, and publicly available databases. We validated the system using the PhysioNet database and comparison tests to verify the expected signal and outputs based on MATLAB filters and the commercial ECG device ENGC901448 from Instramed. The system was proven reliable, low-cost, and portable. Our proposal is relevant to providing evidence for certification and assisting healthcare facilities in conducting testing and corrective and preventive maintenance. [ABSTRACT FROM AUTHOR]

The performance of the 0–3 piezoelectric composite consisting of two piezoelectric materials (PZT5H and PVDF) is analyzed to improve the piezoelectric properties for sensing applications using FEA and validated with the experimental and analytical results. The experimental and predicted results are showing good matches. The average piezoelectric coefficient d33 of the piezoelectric composite and the effective elastic, dielectric and piezoelectric properties of the 0–3 passive matrix piezoelectric composite were determined from the unit cell model. It is observed from the analysis that the performance of 0–3 piezo-composite has excellent piezoelectric properties and also optimized unit cell size and polymer matrix. [ABSTRACT FROM AUTHOR]

The development of sensor technology enables the creation of DNA-based biosensors for biomedical applications. Herein, a quartz tuning fork (QTF) sensing system was employed as a transducer for biomedical applications to address indirect DNA damage associated with gold nanoparticles (GNPs) and enhance the effectiveness of low-dose gamma radiation in radiation therapy. The experiment included two stages, namely during and after irradiation exposure; shift frequencies (Δf) were measured for 20 min in each stage. During the irradiation stage, the QTF response to DNA damage was investigated in a deionized aqueous solution with and without 100 nm GNPs at different concentrations (5, 10, 15, and 20 µg/mL). Upon exposure to gamma radiation for 20 min at a dose rate of 2.4 µGy/min, the ratio of Δf/ΔT indicates increased fork displacement frequencies with or without GNPs. Additionally, DNA damage associated with high and low GNP concentrations was evaluated using the change in the resonance frequency of the QTF. The results indicate that GNPs at 15 and 10 µg/mL were associated with high damage-enhancement ratios, while saturation occurred at 20 µg/mL. At 15 µg/mL, significant radiotherapy enhancement occurred compared to that at 10 µg/mL at 10 min after exposure. In the post-irradiation stage, the frequency considerably differed between 15 and 10 µg/mL. Finally, these results significantly depart from the experimental predictions in the post-radiation stage. They exhibited no appreciable direct effect on DNA repair owing to the absence of an environment that promotes DNA repair following irradiation. However, these findings demonstrate the potential of enhancing damage by combining GNP-mediated radiation sensitization and biosensor technology. Thus, QTF is recommended as a reliable measure of DNA damage to investigate the dose enhancement effect at various GNP concentrations. [ABSTRACT FROM AUTHOR]

Piezoelectric transducers have numerous applications in a wide range of sensing and actuation applications. Such a variety has resulted in continuous research into the design and development of these transducers, including but not limited to their geometry, material and configuration. Among these, cylindrical-shaped piezoelectric PZT transducers with superior features are suitable for various sensor or actuator applications. However, despite their strong potential, they have not been thoroughly investigated and fully established. The aim of this paper is to shed light on various cylindrical piezoelectric PZT transducers, their applications and design configurations. Based on the latest literature, different design configurations such as stepped-thickness cylindrical transducers and their potential application areas will be elaborated on to propose future research trends for introducing new configurations that meet the requirements for biomedical applications, the food industry, as well as other industrial fields. [ABSTRACT FROM AUTHOR]

The force-generating capacity of skeletal muscle is an important metric in the evaluation and diagnosis of musculoskeletal health. Measuring changes in muscle force exertion is essential for tracking the progress of athletes during training, for evaluating patients’ recovery after muscle injury, and also for assisting the diagnosis of conditions such as muscular dystrophy, multiple sclerosis, or Parkinson’s disease. Traditional hardware for strength evaluation requires technical training for operation, generates discrete time points for muscle assessment, and is implemented in controlled settings. The ability to continuously monitor muscle force without restricting the range of motion or adapting the exercise protocol to suit specific hardware would allow for a richer dataset that can help unlock critical features of muscle health and strength evaluation. In this paper, we employ wearable, ultra-sensitive soft strain sensors for tracking changes in muscle deformation during contractions. We demonstrate the sensors’ sensitivity to isometric contractions, as well as the sensors’ capacity to track changes in peak torque over the course of an isokinetic fatiguing protocol for the knee extensors. The wearable soft system was able to efficiently estimate peak joint torque reduction caused by muscle fatigue (mean NRMSE $= 0.15\pm 0.03$ ).

Arterial simulators are a useful tool to simulate the cardiovascular system in many different fields of application and to carry out in vitro tests that would constitute a danger when performed in in vivo conditions. In the literature, a thriving series of in vitro experimental set-up examples can be found. Nevertheless, in the current scientific panorama on this topic, it seems that organic research from a metrological and functional perspective is still lacking. In this regard, the present review study aims to make a contribution by analyzing and classifying the main concerns for the cardiovascular simulators proposed in the literature from a metrological and functional point of view, according to their field of application, as well as for the transducers in the arterial experimental set-ups, measuring the main hemodynamic quantities in order to study their trends in specific testing conditions and to estimate some parameters or indicators of interest for the scientific community. [ABSTRACT FROM AUTHOR]

A patient's respiratory rate is one of the critical vital signs that is a determinant of patient well-being. However, it is all too often neglected or misreported by health care professionals. This study presents the design, build and testing of a low-cost, portable monitor to facilitate accurate reporting of respiratory rate. The monitor comprised a thermistor-based transducer to capture the breath cycle of patients based on the temperature differential created across the thermistor. The signal was conditioned and processed such that the signal could be analysed to identify the peaks and ultimately determine the respiratory rate. For a total cost at the time of development of less than C40, the integrated system demonstrated a modest average error of 5.6% across a range of different ambient temperatures, rate and depth of breathing, and orifice of breathing. This is comparable with other commercial and custom devices. The presented monitor may be of interest for use in an emergency room or clinical setting, especially in severely resource-constrained countries. [ABSTRACT FROM AUTHOR]

The force-generating capacity of skeletal muscle is an important metric in the evaluation and diagnosis of musculoskeletal health. Measuring changes in muscle force exertion is essential for tracking the progress of athletes during training, for evaluating patients’ recovery after muscle injury, and also for assisting the diagnosis of conditions such as muscular dystrophy, multiple sclerosis, or Parkinson’s disease. Traditional hardware for strength evaluation requires technical training for operation, generates discrete time points for muscle assessment, and is implemented in controlled settings. The ability to continuously monitor muscle force without restricting the range of motion or adapting the exercise protocol to suit specific hardware would allow for a richer dataset that can help unlock critical features of muscle health and strength evaluation. In this paper, we employ wearable, ultra-sensitive soft strain sensors for tracking changes in muscle deformation during contractions. We demonstrate the sensors’ sensitivity to isometric contractions, as well as the sensors’ capacity to track changes in peak torque over the course of an isokinetic fatiguing protocol for the knee extensors. The wearable soft system was able to efficiently estimate peak joint torque reduction caused by muscle fatigue (mean NRMSE $= 0.15\pm 0.03$). [ABSTRACT FROM AUTHOR]

• Demonstration of single crystal-based 128 + 128 elements row-column addressing (RCA) transducer. • A new fabrication process of electrode connection for RCA transducers allowing perfect acoustic matching. • Demonstration of 3D imaging with our RCA transducer. In vivo 3D ultrasound imaging with 2D-array transducers is of great importance for both clinical application and biomedical research, but it is complicated in fabrication and also very expensive in hardware due to thousands of electronic channels. In this work, we demonstrate a new fabrication process of 7-MHz 128 + 128 elements row-column-array (RCA) transducer with relaxor ferroelectric PMN-0.28PT single crystal. With piezoelectric single crystal and improved acoustic matching, the optimized performance of −6 dB bandwidth of ∼82 % and insertion loss of −44.6 dB is achieved. The axial and lateral imaging resolutions at different depth of the RCA transducer are quantified by the point spread function (PSF), and the results are respectively 0.20 mm and 0.41 mm at the depth of 7.7 mm, and 0.22 mm and 0.47 mm at the depth of 16.7 mm. The transducer is validated experimentally on a hyperechoic phantom, and 3D view and slices of B-mode images are obtained. The experimental results indicate that our developed RCA transducer can obtain high-quality 3D ultrasound images, demonstrating great potential on ultrafast 3D and functional imaging. [ABSTRACT FROM AUTHOR]

Piezoelectric transducers have numerous applications in a wide range of sensing and actuation applications. Such a variety has resulted in continuous research into the design and development of these transducers, including but not limited to their geometry, material and configuration. Among these, cylindrical-shaped piezoelectric PZT transducers with superior features are suitable for various sensor or actuator applications. However, despite their strong potential, they have not been thoroughly investigated and fully established. The aim of this paper is to shed light on various cylindrical piezoelectric PZT transducers, their applications and design configurations. Based on the latest literature, different design configurations such as stepped-thickness cylindrical transducers and their potential application areas will be elaborated on to propose future research trends for introducing new configurations that meet the requirements for biomedical applications, the food industry, as well as other industrial fields.

Highly sensitive ultrasound probes are needed to expand the capabilities of biomedical ultrasound and industrial nondestructive testing (NDT). Pursuing better imaging quality, while keeping fabrication costs low, is an important trend in the current development of ultrasound imaging systems. In this article, we report the development and characterization of an ultrasonic transducer that (super)focuses ultrasonic waves beyond the so-called diffraction limit, that is, the beamwaist is roughly narrower than one wavelength. The transducer comprises an additive manufactured case with a circular flat piezoelectric actuator fixed at the bottom and a core-shell lens (with a stainless steel core and a polymer shell) placed at the probe’s conical tip. The core-shell lens is responsible to superfocusing effect of ultrasonic waves. Operating at approximately 3 MHz, the transverse and axial resolution for C- and B-scan images are, respectively, ${0.65}\lambda $ and ${3}\lambda /{2}$ , with the wavelength being $\lambda ={{0.5}}\,\,\text {mm}$. The system depth-of-field is ${6.3}\lambda $. To demonstrate the transducer capability to resolve subwavelength structures, we successfully obtain images of a copper wire forming a Y-intersection, whose branches a diameter similar to human hair (${0.15}~\text {mm}\approx {0.3}\lambda $). Our results represent a solid step toward the development of ultrasonic superresolution transducer applied for biomedical imaging and shallow NDT of materials. [ABSTRACT FROM AUTHOR]

Endoscopic photodynamic therapy (PDT) has attracted much attention as a minimally invasive, minimally toxic treatment. PDT can selectively destroy cancer cells by reactive oxygen generated through chemical reaction of photosensitizers that absorb incident light with a certain wavelength. However, the efficacy of PDT is limited due to shallow light penetration mainly caused by Rayleigh scattering in biological tissue. We previously demonstrated that the air bubbles temporarily induced by ultrasound (US) act as a Mie scattering medium, thus increasing light penetration, called US-assisted light penetration increase. For endoscopic applications of the proposed method, the endoscopic probe for US-assisted PDT should be developed; it should be as small as possible while being able to deliver laser for treatment and provide high acoustic energy for air bubble generation in the laser pathway. Satisfying those requirements is very challenging. In this paper, we report a recently developed endoscopic probe for US-assisted PDT that meets the requirements. The probe consists of two 3 MHz US transducers placed side by side and tilted at an angle of 25° and an optical fiber for laser delivery. The probe size was measured at 60.5 mm × 14 mm × 14 mm suitable for endoscopic applications. In the experiment, it was shown that the probe could increase the laser intensity by 28%, compared to the laser only illumination. Even this increase is higher than the previous measurement using a commercial ring-shaped 1.1 MHz HIFU transducer with outer and inner diameters of 64 mm and 22.6 mm.

Objective: This study demonstrates a novel method for pulse arrival time (PAT) segmentation into cardiac isovolumic contraction (IVC) and vascular pulse transit time to approximate central pulse wave velocity (PWV). Methods: 10 subjects (38 ± 10 years, 121 ± 12 mmHg SBP) ranging from normotension to hypertension were repeatedly measured at rest and with induced changes in blood pressure (BP), and thus PWV. ECG was recorded simultaneously with ultrasound-based carotid distension waveforms, a photoplethysmography-based peripheral waveform, noninvasive continuous and intermittent cuff BP. Central PAT was segmented into cardiac and vascular time intervals using a fiducial point in the carotid distension waveform that reflects the IVC onset. Central and peripheral PWVs were computed from (segmented) intervals and estimated arterial path lengths. Correlations with Bramwell-Hill PWV, systolic and diastolic BP (SBP/DBP) were analyzed by linear regression. Results: Central PWV explained more than twice the variability (R2) in Bramwell-Hill PWV compared to peripheral PWV (0.56 vs. 0.27). SBP estimated from central PWV undercuts the IEEE mean absolute deviation threshold of 5 mmHg, significantly lower than peripheral PWV or PAT (4.2 vs. 7.1 vs. 10.1 mmHg). Conclusion: Cardiac IVC onset signaled in carotid distension waveforms enables PAT segmentation to obtain unbiased vascular pulse transit time. Corresponding PWV estimates provide the basis for single-site assessment of central arterial stiffness, confirmed by significant correlations with Bramwell-Hill PWV and SBP. Significance: In a small-scale cohort, we present proof-of-concept for a novel method to estimate central PWV and BP, bearing potential to improve the practicality of cardiovascular risk assessment in clinical routines. [ABSTRACT FROM AUTHOR]

Continuous sacral neuromodulation (SNM) is used to treat overactive bladder, reducing urine leakage and increasing capacity. Conditional SNM applies stimulation in response to changing bladder conditions, and is an opportunity to study neuromodulation effects in various disease states. A key advantage of this approach is saving power consumed by stimulation pulses. This study demonstrated feasibility of automatically applying neuromodulation using a wireless bladder pressure sensor, a real-time control algorithm, and the Medtronic Summit™ RC+S neurostimulation research system. This study tested feasibility of four conditional SNM paradigms over five days in 4 female sheep. Primary outcomes assessed proof of concept of closed-loop system function. While the bladder pressure sensor correlated only weakly to simultaneous catheter-based pressure measurement (correlation 0.26-0.89, median r = 0.52), the sensor and algorithm were accurate enough to automatically trigger SNM appropriately. The neurostimulator executed 98.5% of transmitted stimulation commands with a median latency of 72 ms (n = 1,206), suggesting that rapid decision-making and control is feasible with this platform. On average, bladder capacity increased for continuous SNM and algorithm-controlled paradigms. Some animals responded more strongly to conditional SNM, suggesting that treatment could be individualized. Future research in conditional SNM may elucidate the physiologic underpinnings of differential response and enable clinical translation. [ABSTRACT FROM AUTHOR]

Evaluating the effectiveness of different bone conduction (BC) transducers with controlled coupling force to elicit cervical and ocular vestibular evoked myogenic potentials (cVEMPs, oVEMPs) in healthy subjects by comparing response rates, amplitudes, latencies, thresholds and asymmetry ratios. Prospective experimental study including healthy participants. VEMPs were measured to different stimulation modes; the BC transducer coupling force was controlled to 5.4 (± 0.5) Newton. cVEMPs: to bone conducted vibration (BCV) with the B81 transducer on the mastoid; oVEMPs: to BCV with the B81 on the mastoid, BCV with the B81 on the forehead, and BCV with the Mini-Shaker 4810 on the forehead. Air conducted sound (ACS) with insert earphones was used as reference. Data of 24 normal subjects (mean age 25.3 (± 3.0) years) were analyzed. ACS and BCV with the B81on the mastoid evoked cVEMPs in 100% of ears. The highest oVEMP response rates were obtained with the B81 on the mastoid (83–92%), the lowest with the B81 on the forehead (17–22%). The Mini-Shaker elicited lower response rates (65%) compared to results from the literature without coupling force control and compared to ACS (78–87%). Amplitudes were higher for BCV than ACS. ACS and BCV on the mastoid caused higher asymmetry compared to BCV forehead stimulation. The B81 was feasible to elicit VEMPs with mastoid placement and can be used as an approved medical device to measure BCV VEMPs in a clinical set-up. Normative asymmetry values have to be established due to higher variability for mastoid stimulation. [ABSTRACT FROM AUTHOR]

Transcranial high-intensity focused ultrasound is used in clinics for treating essential tremor (ET) and proposed for many other brain disorders. This promising treatment modality requires high energy resulting eventually in undesired cavitation and potential side effects. The goals of the present work were: 1) to evaluate the potential increase of the cavitation threshold using pseudorandom gated sonications and 2) to assess the heating capabilities with such sonications. The experiments were performed with the transcranial magnetic resonance (MR)-compatible ExAblate Neuro system (InSightec, Haifa, Israel) operating at a frequency of 670 kHz, either in continuous wave (CW) or with pseudorandom gated sonications of 50% duty cycle. Cavitation activity with the two types of sonications was compared using chemical dosimetry of hydroxyl radical production at the focus of the transducer, after propagation in water or through a human skull. Heating trials were performed in a hydrogel tissue-mimicking material embedded in a human skull to mimic a clinical situation. The temperature was measured by MR-thermometry when focusing at the geometrical focus and steering off focus up to 15 mm. Compared with CW sonications, the use of gated sonication did not affect the efficiency (60%) nor the steering abilities of the transducer. After propagation through a human skull, gated sonication required a higher pressure level (10 MPa) to initiate cavitation as compared with CW (5.8 MPa). Moreover, at equivalent acoustic power above the cavitation threshold, the level of cavitation activity initiated with gated sonications was much lower with gated sonication than with continuous sonications, almost half after propagation through water and one-third after propagation through a skull. This lowered cavitation activity may be attributed to a breaking of the dynamic of the bubbles moving from monochromatic to more broadband sonications and to the removal of residual cavitation nuclei between pulses with gated sonications. The heating capability was not affected by the gated sonications, and similar temperature increases were reached at focus with both types of sonications when sonicating at equivalent acoustic power, both in water or after propagation through a human skull (+15 °C at 325 W for 10 s). These data, acquired with a clinical system, suggest that gated sonication could be an alternative to continuous sonications when cavitation onset is an issue. [ABSTRACT FROM AUTHOR]

• PVDF/PCBS NFs possess piezoelectric properties and nonlinear optical conversion. • Embedding PCBS in PVDF NFs increases the piezoelectric response. • Evidence of the coupling between the polarized diploes of PCBS and PVDF. • PVDF/PCBS shows an optical second harmonic generation at optimum concentrations. • PVDF/PCBS NFs can be multi-functionalized sensors/transducer membranes. This paper presents a nonlinear optical piezoelectric electrospun nanocomposite of polyvinylidene fluoride (PVDF) nanofibers with embedded nanomaterial of poly {1-[p-(3'-carboxy-4'- hydroxyphenylazo) benzenesulfonamido]-1, 2-ethandiyl} (PCBS). PCBS of different weight ratios are added in-situ to the synthesized PVDF nanofibers. The generated nanofibers mats have been proved to possess both properties of piezoelectric response and nonlinear optical conversion due to the presence of both PVDF and PCBS, respectively. Innovatively, embedding PCBS within the PVDF nanofibers increases the piezoelectric response of the nanocomposite, compared to the case of neat PVDF nanofibers, at certain optimum weight concentrations of PCBS. This has been proved by different piezoelectric measurements at different applied forces and vibration frequencies, along with d 33 coefficient measurements and supported by FTIR analysis of beta-sheets. Our results support the evidence of the coupling between the polarized diploes of PCBS and PVDF, which can enhance the overall piezoelectric response. Furthermore, the synthesized nanocomposite shows an optical second harmonic generation (SHG) at optimum concentration of added PCBS within the PVDF nanofibers of around 1 wt.%. The synthesized nonlinear optical nanocomposite of PVDF/PCBS can be multi-functionalized sensors/transducer membranes for biomedical and sensing applications. [Display omitted] [ABSTRACT FROM AUTHOR]

Piezoelectric composites with 1–3 connectivity have attracted great attentions recently in ultrasonic transducers such as biomedical imaging and industrial flaw detection. However, data related to piezoelectric temperature stability of the composites can be rarely found in the literature. Thus, it is vital to study the piezoelectric temperature stability for practical applications. We chose a commercially available excellent PZT-51 ceramic to prepare a 1–3 PZT/epoxy piezoelectric composite with an improved dice-fill method and examined both its room-temperature piezoelectric performances and electromechanical temperature stability in this study. This composite shows the well-balanced overall performance with high thickness-mode electromechanical coupling coefficient kt of 0.73, large piezoelectric voltage coefficient g33 of 65 × 10−3 Vm/N, and moderate acoustic impedance Z of 13.8 Mrayl. Most importantly, kt is very stable with nearly no temperature dependence in the common usage temperature range from − 30 to 100 °C. This work indicates that selecting a proper PZT ceramic is an essential precondition for obtaining the excellent piezoelectric composites. [ABSTRACT FROM AUTHOR]

Deeply implanted biomedical devices (DIBDs) are a challenging application of wireless power transfer because of the requirement for miniaturization while minimizing patient exposure to tissue heating. This article proposes a capacitively coupled conductive power transfer method for DIBDs, which allows for the safe transfer of power into the body while using minimum implant volume. The method uses parallel insulated capacitive electrodes to couple uniform current flow into the tissue and implants. Analytical analyses are presented, which result in a two-port network that describes circuit operation. The two-port network is further simplified for typical DIBD applications where coupling to the external electrodes is low. This results in a simple circuit model of power transfer for which the parameters are easily obtained by experimental measurements. The proposed circuit model has been validated using circuit coupled finite-element analysis (COMSOL) and benchtop experiments using a tissue phantom. In addition, the safety aspect of the method has been evaluated via COMSOL simulation of the specific absorption rate for various implanted receiver dimensions and implantation depths. Finally, a completed power supply, unaffected by the implantation depth, running at 6.78 MHz, delivering 10 mW deep into the body while meeting the IEEE C95.1 basic restriction is presented. [ABSTRACT FROM AUTHOR]

The prevalence and impact of imaging findings detected during screening procedures in patients undergoing transcranial MR-guided Focused Ultrasound (tcMRgFUS) thalamotomy for functional neurological disorders has not been assessed yet. This study included 90 patients who fully completed clinical and neuroradiological screenings for tcMRgFUS in a single-center. The presence and location of preoperative imaging findings that could impact the treatment were recorded and classified in three different groups according to their relevance for the eligibility and treatment planning. Furthermore, tcMRgFUS treatments were reviewed to evaluate the number of transducer elements turned off after marking as no pass regions the depicted imaging finding. A total of 146 preoperative imaging findings in 79 (87.8%) patients were detected in the screening population, with a significant correlation with patients' age (rho = 483, p < 0.001). With regard of the group classification, 119 (81.5%), 26 (17.8%) were classified as group 1 or 2, respectively. One patient had group 3 finding and was considered ineligible. No complications related to the preoperative imaging findings occurred in treated patients. Preoperative neuroradiological findings are frequent in candidates to tcMRgFUS and their identification may require the placement of additional no-pass regions to prevent harmful non-targeted heating. [ABSTRACT FROM AUTHOR]

This work presents an integrated electrochemical and electrophysiological biomonitoring system, enabling the study of molecular signaling along the gut-brain-axis (GBA). In vitro gut cell cultures provide a controllable, accessible platform to study gut physiology. Similarly, the ex vivo crayfish abdominal nerve cord provides a model for the electrophysiological study of nerve signaling. For the first time, our system integrates these platforms to enable the study of signaling from gut to nervous system, which in vivo would influence the brain. The platform consists of two interconnected modules: (I) the electrochemistry module (ECM), mimicking a Transwell platform for cell growth and enabling neurotransmitter (serotonin (5-HT)) detection, and (II) the electrophysiology module (EPM), hosting a dissected crayfish nerve cord and allowing electrode accessibility for the assessment of nerve responses to 5-HT. Whole system integration is aided by the inclusion of a flexible heater to maintain cells near body temperature (38° C), transwell membrane modification to improve molecular diffusion (450-fold) while maintaining good cell compatibility, and precise flow-controlled 5-HT transport from ECM to EPM. This work achieves module-specific environmental control, which will ultimately enable the study of molecular signaling between gut and nerve cells to facilitate real-time monitoring of both tissues within the GBA. [2020-0151] [ABSTRACT FROM AUTHOR]

This study reports on the development of vertical, partially encapsulated nanoelectrodes for electrically contacting the interior of electrogenic cells with microelectronics. Intracellular electrical stimulation and recording with single cell resolution enables new insights into the electrophysiology of cells embedded in a complex multicellular network, providing detailed understanding of fundamental processes affecting cell to cell communication and thereby paving the way for novel applications including pharmacological studies and other neuromodulation techniques like focused ultrasound and electroceuticals. In order to minimize the influence of the measurement system, an approach based on nano-sized hollow electrodes, achieving an adhesion based intracellular access, is used. The focus of the presented work is on the novel fabrication technology and the characterization of the resulting nanoelectrodes. In CMOS compatible processes, the hollow geometry is achieved using a sacrificial layer technique combining deep reactive ion etching and atomic layer deposition of Ru. For decoupling the extracellular milieu, a partial passivation of the nanoelectrodes by Ta2O5 is realized. The monolithic integration allows an application specific fine-tuning of geometry and placement of the nanoelectrodes. A discrete microelectrode array was designed to electrically and electrochemically characterize the nanoelectrodes. Resistance measurements, cyclic voltammetry and electrochemical impedance spectroscopy show the feasibility of the developed electrodes as an electronic interface to electrochemical fluids. Specifically, an electrode resistance of 2.92 $\text{k}\Omega $ and charge delivery capacitance of $748.13~\frac {\mu \text {C}}{\text {cm}^{2}}$ were observed. Confocal microscopy analyses of neural cells interfaced with the nanoelectrodes indicate an adhesion based intracellular access as well as biostability and biocompatibility. [2020-0224] [ABSTRACT FROM AUTHOR]

Fe3O4 with different shapes are reported herein to modify the glassy carbon electrode and then they are used to detect dopamine (DA), a member of the catecholamine and phenethylamine families. Cyclic voltammetry, electrochemical impedance spectroscopy, differential pulse voltammetry and linear sweep voltammetry are all chosen to characterise the sensor's performance to DA. Under the optimal conditions, the modified sensor (N‐rGO/Fe3O4 NRs/GCE) had some good performance, followed as short response time (∼3 s), wide linear range (0.2–176 μM), low detection limit (0.05 μM, S/N = 2), good stability and reproducibility. The fabricated DA biosensor was further investigated for DA determination in human blood serum, suggesting its great potential in biological samples. [ABSTRACT FROM AUTHOR]

In this article, a flexible piezo-composite transducer composed of the active piezoelectric material (PZT-5H) and passive polymer matrix [polydimethylsiloxane (PDMS)] is developed to achieve excellent flexibility, sensitivity, and bandwidth for biomedical and industrial applications. The flexible electrodes [silver nanowires (AgNWs) mixed with PDMS] are deposited on the transducers using a spray coating method, providing a sufficient conductivity of an electrode through repeated bending tests. The flexible 1–3 composite transducer exhibits robust mechanical flexibility (curved radius <5 mm) without failure due to the stretchable mechanical properties of PDMS and AgNWs network, which indicates that the AgNW/PDMS electrode is a promising alternative to conventional metal-type electrodes, such as Au film. The acoustic characterization suggests that the −6 dB fractional bandwidth (∼49%) and transmitting sensitivity (∼107 mV/V) of the prototyped transducer are promising for nondestructive testing, biomedical imaging, and therapy. [ABSTRACT FROM AUTHOR]

Sensing implants that can be deployed by catheterization or by injection are preferable over implants requiring invasive surgery. However, present powering methods for active implants and present interrogation methods for passive implants require bulky parts within the implants that hinder the development of such minimally invasive devices. In this article, we propose a novel approach that potentially enables the development of passive sensing systems overcoming the limitations of previous implantable sensing systems in terms of miniaturization. In this approach implants are shaped as thread-like devices suitable for implantation by injection. Their basic structure consists of a thin elongated body with two electrodes at opposite ends and a simple and small circuit made up of a diode, a capacitor and a resistor. The interrogation method to obtain measurements from the implants consists in applying innocuous bursts of high frequency (≥1 MHz) alternating current that reach the implants by volume conduction and in capturing and processing the voltage signals that the implants produce after the bursts. As proof-of-concept, and for illustrating how to put in practice this novel approach, here we describe the development and characterization of a system for measuring the conductivity of tissues surrounding the implant. We also describe the implementation and the in vitro validation of a 0.95 mm-thick, flexible injectable implant made of off-the-shelf components. For conductivities ranging from about 0.2 to 0.8 S/m, when compared to a commercial conductivity meter, the accuracy of the implemented system was about ±10%. [ABSTRACT FROM AUTHOR]

The article present a study related to the recruitment-to-inflation ratio in acute respiratory distress syndrome. Topics discussed include identifying airway opening pressure (AOP) on the ventilator using the pressure-time curve; calibration of airway pressure and esophageal pressure transducers by using a water manometer; and also mentions about the AOP during dynamic ventilation (tidal breaths) and heterogeneity of AOP.

Introduction: This study is concerned with the control of hand prostheses based on electromyograms. As the prosthesis is moved in space, the socket and electrodes can shift on the residual limb, causing changes in the observed electromyograms. These changes can be misinterpreted by the electronic controller and cause the hand to move unintentionally or fail to execute solicited movements. The goal of this study was to explore the mechanisms related to these myoelectric control failures. Materials and Methods: To study these phenomena, conventional prosthetic EMG electrodes were augmented with force sensors to record the forces through the devices. These multimodal sensors were then used to control prosthetic hands by 15 users with losses below the elbow. The subjects performed four tasks resembling activities of daily living while the electromyogram signals, force signals, and the performance of the hands (including video images) were recorded. Eight subjects reported a total of 38 control errors, each of which was assigned to one of four failure classes and analyzed. Results: The article shows examples of the electromyogram and force signals recorded during the control failures and discusses possible causes of the failures. Involuntary opening of the hand was identified as the most common failure, and these failures seemed to be associated with changes in the electrode-skin contact forces. It was not possible to attribute clear causes for 26.2% of the failures. Conclusions: Knowledge of common failure mechanisms can guide improved design of sockets and electrodes and signal processing to reduce the errors experienced by prosthesis users. [ABSTRACT FROM AUTHOR]

This work proposes a miniaturized respiratory transducer array that utilizes the sharp temperature dependence of the resistivity characteristic of acrylate-based composites with a positive temperature coefficient. The proposed device employs an array configuration consisting of three sensing elements with the composites of different glass transition temperatures to achieve a wide operational temperature range. The temperature transient responses caused by different breathing conditions were clearly resolved by the device, and the corresponding respiration rates were easily extracted. The transducer array was characterized in a room temperature range from 23 °C to 29 °C. In addition, the device effectively detected the respiration rate up to a distance of 30 cm. It was also demonstrated that the device is capable of quantifying the breathing rate over a practical range of frequencies (from 0.1 Hz to 2 Hz). The respiration rates measured by the proposed device were also in good agreement with the results measured simultaneously by using a commercially available nasal pressure transducer. Comparison of the results demonstrated an excellent linear correlation (r = 0.953 and P < 0.001). The measured results suggest the feasibility of using this miniaturized device to monitor patients' respiration rates in clinical institutes and in other point-of-care applications. [ABSTRACT FROM AUTHOR]

Objectives. Transducer-like enhancer of split 1 (TLE1) immunohistochemistry is widely used as a biomarker of synovial sarcoma. Spindle cell or desmoplastic melanoma can morphologically mimic synovial sarcoma. The aim of this study was to investigate the expression of TLE1 in melanomas with a spindle cell morphology. Methods. A search of the surgical pathology files resulted in 57 cases of melanomas diagnosed with a spindle cell or desmoplastic component. After review, 8 cases had no definitive dermal spindle cell component and 7 cases had insufficient tissue remaining and were excluded from the study. A total of 42 melanomas were examined for TLE1 immunohistochemistry using a mouse monoclonal antibody (Cell Marque, clone 1F5). Strength and percentage of nuclear TLE1 positivity was graded on a scale from 0 to 3+. Staining for TLE1 was considered positive for 2 to 3+ and negative for 0 to 1+. Results. Nuclear TLE1 expression was identified in 24 (57%) of the 42 melanoma cases with spindle cell morphology (2+, n = 14; 3+, n = 10). TLE1 was considered negative in 18 cases (43%), of which most contained weak staining (1+, n = 14 [33%]) and only a small subset did not show any staining (0, n = 4 [10%]). Conclusion. TLE1 frequently highlights melanomas with spindle cell morphology and is a potential diagnostic pitfall. Therefore, when evaluating spindle cell tumors in which the differential may include both a melanoma and synovial sarcoma, TLE1 expression should be interpreted with caution and in conjunction with an immunohistochemical panel. [ABSTRACT FROM AUTHOR]

Background: A forward-viewing linear (FVL) echoendoscope has been developed with the aim of overcoming some of the limitations of standard curved linear-array (CLA) echoendoscopes. There are no existing studies comparing the performance of the two echoendoscopes for endoscopic ultrasound-guided tissue acquisition (EUS-TA) of solid lesions other than subepithelial lesions.Methods: This was a prospective, multicenter, randomized trial with a noninferiority design comparing FVL vs. CLA echoendoscopes in patients with solid lesions of the gastrointestinal tract or adjacent organs. Primary outcomes were successful identification of the lesion and success of EUS-TA. Secondary outcomes were safety, sensitivity, specificity, and diagnostic accuracy of the two different scopes for EUS-TA.Results: 126 patients with solid lesions were randomly assigned to the CLA group (63 patients) or the FVL group (63 patients). The two groups were homogeneous with no differences in terms of needle type used, mean number of passes, and site of EUS-TA. No differences were observed between the FVL vs. CLA scopes in identification of the lesion (96.8 % vs. 98.4 %; P > 0.99) and technical success of EUS-TA (92.1 % vs. 96.8 %; P = 0.44). No adverse events occurred. Overall, diagnostic accuracy (77.8 % vs. 84.1 %), sensitivity (76.6 % vs. 84.1 %), and specificity (81.3 % vs. 84.2 %) did not differ between the two groups.Conclusions: Our results strongly suggest that the FVL echoendoscope is noninferior to the CLA scope for the detection and performance of EUS-TA in patients with solid lesions of the gastrointestinal tract and adjacent organs. In addition, the FVL scope has the same diagnostic yield, accuracy, and safety as the CLA scope. [ABSTRACT FROM AUTHOR]

Ultrasound-mediated transdermal delivery is a promising parenteral administration method for large-molecule or unstable medications. This study evaluated skin health and systemic delivery when administering enfuvirtide, an injectable anti-retroviral medication, over a 1-mo period in a porcine model using a low-frequency cymbal transducer. Three groups received twice-daily treatments: (i) enfuvirtide injection control (n = 12); (ii) saline ultrasound control (n = 6); and (iii) enfuvirtide ultrasound treatment (n = 13). Ultrasound parameters were as follows: 30-min exposure, 90 mW/cm², 24-26 kHz and 15% duty cycle. No statistical difference in trans-epidermal water loss, a measure of skin health and function, was seen between ultrasound-treated and control skin sites for either saline (p = 0.50) or enfuvirtide (p = 0.29) groups. Average trough plasma concentrations of enfuvirtide were 0.6 ± 0.2 and 2.8 ± 0.8 μg/mL for ultrasound and injection, respectively. Tolerability and efficacy results indicate that chronic, low-frequency ultrasound exposure can be a practical means for transdermal delivery of medications such as enfuvirtide. [ABSTRACT FROM AUTHOR]

The introduction of ultrasound into medical student education is well underway in many locations around the world, but is still in its infancy or has yet to begin in others. Proper incorporation of ultrasound education into medical training requires planning and resources, both capital and human. In this article, we discuss the state of the art of ultrasound in medical education throughout the world, as well as various methodologies utilized to improve student education and to incorporate ultrasound into every facet of training. Experiences from various educational systems and available evidence regarding the impact of ultrasound education are summarized. Representing multiple societies and specialties throughout the world, we discuss established modern as well as novel education structures and different successful approaches. [ABSTRACT FROM AUTHOR]

G protein coupled receptors (GPCRs) are central players in recognizing a variety of stimuli to mediate diverse cellular responses. This myriad of functions is accomplished by their modular interactions with downstream intracellular transducers, such as heterotrimeric G proteins and arrestins. Assembling a specific GPCR–G protein pair as a purified complex for their structural and functional investigations remains a challenging task, however, because of the low affinity of the interaction. Here, we optimized fusion constructs of the Gα subunit of the heterotrimeric G protein and engineered versions of rat Neurotensin receptor 1 (NTR1), coexpressed and assembled in vivo with Gβ and Gγ. This was achieved by using the baculovirus-based MultiBac system. We thus generated a functional receptor–G protein fusion complex, which can be efficiently purified using ligand-based affinity chromatography on large scales. Additionally, we utilized a purification method based on a designed ankyrin repeat protein tightly binding to Green Fluorescent Protein (GFP-DARPin) that may be used as a generic approach for a large-scale purification of GPCR–G protein fusion complexes for which no ligands column can be generated. The purification methods described herein will support future studies that aim to understand the structural and functional framework of GPCR activation and signaling. [ABSTRACT FROM AUTHOR]

The article presents author's views on the development of microfabricated medical sensors and actuators and their impact on the health care industry. Topics discussed include development of MicroElectroMechanical Systems (MEMS) transducers, measurement and monitoring of physiological parameters of a patient like blood pressure and development of microfluidic diagnostics.

Abstract Scanning laser Doppler vibrometry (LDV) has been used extensively to investigate the movement of the middle and inner ear, but has never been used to measure vibrations from a bone transducer travelling over the skin, subcutaneous tissue and cranium in a live subject. Using three scanning laser Doppler vibrometers we measured the displacement of the cranium in 3D in a live subject when stimulated by a B71 bone transducer placed 55 mm posterior to the external auditory canal. Four pure tones (250 Hz, 500 Hz, 1000 Hz, 2000 Hz) were presented separately via the bone transducer. The displacement of the scalp was imaged in four different areas (Ipsilateral to the bone transducer in the temporoparietal region, contralateral temporoparietal region, occipital region and vertex) and linked to the phase of stimulation. Measured scalp motion was consistent with expected displacement of the underlying cranium. Rigid-body motion was the dominant mode of vibration at 250 Hz. At 1000 Hz a mass-spring effect was seen. At 500 Hz there was a transition frequency between vibration as a rigid-body and as a mass-spring. Higher frequencies (2000 Hz) showed that wave transmission was the primary vibrational mode of sound transmission over the cranium. These results broadly support previous research studies but open up potential areas of interest in the investigation of differing skull resonance frequencies. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the efficiency of STAT-1 and STAT-3 proteins that exist in hepatic tissue of broilers as a basis for making synthetic STAT protein that would promote broiler growth and is safe for humans. This study used 25 male Lohman broilers. The broilers were placed in battery cages with capacity of one broiler per cage and fed twice daily (10% less than the standard feed) at 6:00 AM and 6:00 PM. At the age of 21 days, the broilers were sacrificed by cutting the esophagus, trachea, carotid artery and jugular vein, and a sample of 5 g hepatic tissue was obtained to examine the amino acid sequence of proteins STAT-1 and STAT-3 by MALDI-TOP method. Results showed that molecular weights of STAT-1 and STAT-3 were 59.3 kDa and 59.4 kDa, respectively. Identifying the amino acid structure of the STAT protein can allow for the creation of STAT synthetic protein, which is expected to prolong the action or effect of growth hormone, thus, promoting growth of broilers. [ABSTRACT FROM AUTHOR]

Abstract Vibrio related illnesses are increasing worldwide in humans and marine animals. The detection of these bacteria is still mainly performed using traditional microbiological methods based on culture grown on differential agar media which are labor intensive, time consuming and unsuitable for in-field and high-throughput analysis. To overcome these limitations, biosensing platforms have emerged as promising alternative tools for rapid, sensitive, and real-time detection of Vibrio species in clinical, food and environmental samples. In this review, we will focus on strip test devices, and on optical and electrochemical biosensors developed for Vibrio analysis. Particular attention is given to sample preparation techniques. Graphical abstract fx1 Highlights • Vibrio prevalence is currently increasing in the world. • Biosensing platforms constitute interesting alternative techniques for Vibrio detection. • This paper reviews strip test, optical and electrochemical biosensor devices developed for Vibrio spp. detection. • Sample preparation techniques have been described. [ABSTRACT FROM AUTHOR]

Abstract Wireless chemical sensors are increasingly finding use as analytical devices in healthcare diagnostics, wearable sensing (sweat analysis) and in the rapidly emerging area of the Sensor Internet of Things (SIoT). In such wireless scenarios, the application of fluorescence-based sensors is lagging behind other types of transduction mechanisms. In this work a new low-cost and highly portable wireless fluorimeter for optical chemical fluorescence intensity measurements is presented (bill-of-materials approximately €20). The fluorimeter is programmed and communicates wirelessly with mobile devices or personal computers by radio-frequency identification (RFID) or near-field communication (NFC). This novel mobile analytical system is highly adaptable for use with different fluorescent sensor chemistries and analytes. The fluorimeter has been evaluated in the laboratory in two sets of proof-of-concept experiments: firstly fluorimetry in solution, where the fluorescence intensities of fluorescein were recorded, and secondly chloride sensing via a paper-immobilised quinine sulphate fluorescent indicator. The latter represents the first demonstration of wireless (radio-frequency) fluorescence-based chloride sensing. Satisfactory analytical performance was achieved in the entire range of sweat chloride concentrations. The wireless fluorimeter system presented here could make a significant contribution to several emerging areas of mobile chemical sensor research, including wearable sensors for healthcare and sport, mobile point-of-sample diagnostics as well as more generally for the Sensor Internet of Things. [ABSTRACT FROM AUTHOR]

Introduction: Magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) treatments of mobile organs require locking the HIFU beam on the targeted tissue to maximise heating efficiency. We propose to use a standalone 3 D ultrasound (US)-based motion correction technique using the HIFU transducer in pulse-echo mode. Validation of the method was performed in vitro and in vivo in the liver of pig under MR-thermometry. Methods: 3 D-motion estimation was implemented using ultrasonic speckle-tracking between consecutive acquisitions. Displacement was estimated along four sub-apertures of the HIFU transducer by computing the normalised cross-correlation of backscattered signals followed by a triangulation algorithm. The HIFU beam was steered accordingly and energy was delivered under real-time MR-thermometry (using the proton resonance frequency shift method with online motion compensation and correction of associated susceptibility artefacts). An MR-navigator echo was used to assess the quality of the US-based motion correction. Results: Displacement estimations from US measurements were in good agreement with 1 D MR-navigator echo readings. In vitro, the maximum temperature increase was improved by 37% as compared to experiments performed without motion correction and temperature distribution remained much more focussed. Similar results were reported in vivo, with an increase of 35% on the maximum temperature using this US-based HIFU target locking. Conclusion: This standalone 3D US-based motion correction technique is robust and allows maintaining the HIFU focal spot in the presence of motion without adding any burden or complexity to MR thermal imaging. In vitro and in vivo results showed about 35% improvement in heating efficiency when focus position was locked on the target using the proposed technique. [ABSTRACT FROM AUTHOR]

Human neuroblastoma cells, SH-SY5Y, are often used as a neuronal model to study Parkinson's disease and dopamine release in the substantia nigra, a midbrain region that plays an important role in motor control. Using amperometric single-cell recordings of single vesicle release events, we can study molecular manipulations of dopamine release and gain a better understanding of the mechanisms of neurological diseases. However, single-cell analysis of neurotransmitter release using traditional techniques yields results with very low throughput. In this paper, we will discuss a monolithically-integrated CMOS sensor array that has the low-noise performance, fine temporal resolution, and 1024 parallel channels to observe dopamine release from many single cells with single-vesicle resolution. The measured noise levels of our transimpedance amplifier are 415, 622, and 1083 ${\text{fA}}_{{\text{RMS}}}$ , at sampling rates of 10, 20, and 30 kS/s, respectively, without additional filtering. Post-CMOS processing is used to monolithically integrate 1024 on-chip gold electrodes, with an individual electrode size of 15 μm × 15 μm, directly on 1024 transimpedance amplifiers in the CMOS device. SU-8 traps are fabricated on individual electrodes to allow single cells to be interrogated and to reject multicellular clumps. Dopamine secretions from 76 cells are simultaneously recorded by loading the CMOS device with SH-SY5Y cells. In the 42-s measurement, a total of 7147 single vesicle release events are monitored. The study shows the CMOS device's capability of recording vesicle secretion at a single-cell level, with 1024 parallel channels, to provide detailed information on the dynamics of dopamine release at a single-vesicle resolution. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this review is to illustrate and discuss the seldom used technique of three-dimensional (3D) saline infusion sonohysterography (SIS) based on instillation of sterile saline through a catheter into the uterus under real-time vaginal transducer observation for assessment of the endometrial cavity. Material and methods: The cases for this pictorial review were selected from the imaging material collected at the Ultrasound Unit, Clinical Imaging Department, Women's Hospital of Hamad Medical Corporation during a sevenyear period from 2011 to 2017. This was a retrospective collection of 216 consecutive cases that underwent twodimensional (2D) and 3D SIS for evaluation of the uterine cavity, followed by verification of results with histopathology. An open-sided speculum is inserted into the vagina. An intrauterine catheter is then threaded into the endometrial cavity. After that, the speculum is removed carefully, and a vaginal transducer is inserted. Using a 60-ml syringe attached to the catheter, saline solution is instilled under direct real-time observation (2D SIS). Subsequently, reconstruction of the three-dimensional anatomy of the intrauterine cavity is performed. Pictorial review: The review presents the most common indication for SIS, like abnormal bleeding in pre- and postmenopausal patients. SIS allows us to distinguish between focal lesions and global endometrial thickening. SIS should be supported as a second-line diagnostic procedure for abnormal uterine bleeding, when findings from transvaginal ultrasound are inconclusive. Conclusions: The addition of 3D techniques to SIS procedure helps in the distinction between endometrial and myometrial lesions, also it facilitates delineation of uterine anatomy, resulting in more precise and accurate diagnosis. [ABSTRACT FROM AUTHOR]

Rapid and highly sensitive detection of biomolecules is greatly needed for pathogen diagnosis in clinical samples, but the method needs to be significantly improved in terms of sensitivity and specificity for actual use in clinical settings. Here, we report the development of an improved molecular diagnostics tool that utilizes CRISPR/dCas9-mediated biosensor that couples a nuclease inactivated Cas9 (dCas9) and single microring resonator biosensor, enables label-free and real-time detection of pathogenic DNA and RNA. We addressed the clinical utility of this CRISPR/dCas9-mediated biosensor in tick-borne illnesses including scrub typhus (ST) and severe fever with thrombocytopenia syndrome (SFTS), whose clinical presentations are too similar to be easily differentiated. By using CRISPR/dCas9-mediated biosensor, we achieved single molecule sensitivity for the detection of ST (0.54 aM) and SFTS (0.63 aM); this detection sensitivity is 100 times more sensitive than that of RT-PCR assay. Finally, CRISPR/dCas9-mediated biosensor was able to clearly distinguish between ST and SFTS in serum samples within 20 min. We believe that CRISPR/dCas9-mediated biosensor will be useful for rapid and accurate molecular diagnostic tool that is suitable for immediate clinical applications. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Novel screening system for VDR ligands was constructed by using split luciferase. • The novel split luciferase dramatically increased the light intensity with VDR ligands. • This system is useful to evaluate CYP27B1 mutants from patients with rickets. Abstract Recently, we successfully generated a novel detection system for vitamin D receptor (VDR) ligands in vivo and in vitro, using a split-luciferase technique called the LucN-LBD-LucC biosensor that is a chimeric fusion protein of firefly luciferase with the ligand binding domain (LBD) of VDR. In this system, the luciferase light intensity of the LucN-LBD-LucC biosensor was decreased by binding of VDR ligands. Although this system is quite useful for evaluation of VDR ligands in a short time, the sensitivity of the LucN-LBD-LucC biosensor is not high enough. In this study, LXXLL motif peptides involved in the interaction between LBD and coactivators, such as the steroid receptor coactivator-1 (SRC-1), transcriptional intermediary factor 2 (TIF2), and the vitamin D receptor interacting protein 205 (DRIP205) were each inserted between LucN and LBD of the LucN-LBD-LucC biosensor. Surprisingly, the resulting LucN-LXXLL-LBD-LucC biosensor increased the light intensity in response to natural VDR ligands. This high-sensitivity biosensor system may be a powerful tool for discovery of high-affinity ligands for the mutant VDR. In addition, we have successfully estimated the activity of the wild-type and mutant CYP27B1 using the LucN-LXXLL-LBD-LucC biosensor in living cells within 90 min. [ABSTRACT FROM AUTHOR]