An Experimental Method for Bio-Signal Denoising Using Unconventional Sensors.

In bio-signal denoising, current methods reported in the literature consider purely simulated environments, requiring high computational powers and signal processing algorithms that may introduce signal distortion. To achieve an efficient noise reduction, such methods require previous knowledge of the noise signals or to have certain periodicity and stability, making the noise estimation difficult to predict. In this paper, we solve these challenges through the development of an experimental method applied to bio-signal denoising using a combined approach. This is based on the implementation of unconventional electric field sensors used for creating a noise replica required to obtain the ideal Wiener filter transfer function and achieve further noise reduction. This work aims to investigate the suitability of the proposed approach for real-time noise reduction affecting bio-signal recordings. The experimental evaluation presented here considers two scenarios: (a) human bio-signals trials including electrocardiogram, electromyogram and electrooculogram; and (b) bio-signal recordings from the MIT-MIH arrhythmia database. The performance of the proposed method is evaluated using qualitative criteria (i.e., power spectral density) and quantitative criteria (i.e., signal-to-noise ratio and mean square error) followed by a comparison between the proposed methodology and state of the art denoising methods. The results indicate that the combined approach proposed in this paper can be used for noise reduction in electrocardiogram, electromyogram and electrooculogram signals, achieving noise attenuation levels of 26.4 dB, 21.2 dB and 40.8 dB, respectively.

Characterisation of Textile Embedded Electrodes for Use in a Neonatal Smart Mattress Electrocardiography System.

Heart rate monitoring is the predominant quantitative health indicator of a newborn in the delivery room. A rapid and accurate heart rate measurement is vital during the first minutes after birth. Clinical recommendations suggest that electrocardiogram (ECG) monitoring should be widely adopted in the neonatal intensive care unit to reduce infant mortality and improve long term health outcomes in births that require intervention. Novel non-contact electrocardiogram sensors can reduce the time from birth to heart rate reading as well as providing unobtrusive and continuous monitoring during intervention. In this work we report the design and development of a solution to provide high resolution, real time electrocardiogram data to the clinicians within the delivery room using non-contact electric potential sensors embedded in a neonatal intensive care unit mattress. A real-time high-resolution electrocardiogram acquisition solution based on a low power embedded system was developed and textile embedded electrodes were fabricated and characterised. Proof of concept tests were carried out on simulated and human cardiac signals, producing electrocardiograms suitable for the calculation of heart rate having an accuracy within ±1 beat per minute using a test ECG signal, ECG recordings from a human volunteer with a correlation coefficient of ~ 87% proved accurate beat to beat morphology reproduction of the waveform without morphological alterations and a time from application to heart rate display below 6 s. This provides evidence that flexible non-contact textile-based electrodes can be embedded in wearable devices for assisting births through heart rate monitoring and serves as a proof of concept for a complete neonate electrocardiogram monitoring system.

Two-photon fluorescence imaging with 30 fs laser system tunable around 1 micron.

We developed a low-cost, low-noise, tunable, high-peak-power, ultrafast laser system based on a SESAM-modelocked, solid-state Yb tungstate laser plus spectral broadening via a microstructured fiber followed by pulse compression. The spectral selection, tuning, and pulse compression are performed with a simple prism compressor. The output pulses are tunable from 800 to 1250 nm, with the pulse duration down to 25 fs, and average output power up to 150 mW, at 80 MHz pulse repetition rate. We introduce the figure of merit (FOM) for the two-photon and multi-photon imaging (or other nonlinear processes), which is a useful guideline in discussions and for designing the lasers for an improved microscopy signal. Using a 40 MHz pulse repetition rate laser system, with twice lower FOM, we obtained high signal-to-noise ratio two-photon fluorescence images with or without averaging, of mouse intestine section and zebra fish embryo. The obtained images demonstrate that the developed system is capable of nonlinear (TPE, SHG) imaging in a multimodal operation. The system could be potentially used in a variety of other techniques including, THG, CARS and applications such as nanosurgery.

Non-invasive sensor methods used in monitoring newborn babies after birth, a clinical perspective.

BACKGROUND: Reducing the global new-born mortality is a paramount challenge for humanity. There are approximately 786,323 live births in the UK each year according to the office for National Statistics; around 10% of these newborn infants require assistance during this transition after birth. Each year around, globally around 2.5 million newborns die within their first month. The main causes are complications due to prematurity and during delivery. To act in a timely manner and prevent further damage, health professionals should rely on accurate monitoring of the main vital signs heart rate and respiratory rate. AIMS: To present a clinical perspective on innovative, non-invasive methods to monitor heart rate and respiratory rate in babies highlighting their advantages and limitations in comparison with well-established methods. METHODS: Using the data collected in our recently published systematic review we highlight the barriers and facilitators for the novel sensor devices in obtaining reliable heart rate measurements. Details about difficulties related to the application of sensors and interfaces, time to display, and user feedback are explored. We also provide a unique overview of using a non-invasive respiratory rate monitoring method by extracting RR from the pulse oximetry trace of newborn babies. RESULTS: Novel sensors to monitor heart rate offer the advantages of minimally obtrusive technologies but have limitations due to movement artefact, bad sensor coupling, intermittent measurement, and poor-quality recordings compared to gold standard well established methods. Respiratory rate can be derived accurately from pleth recordings in infants. CONCLUSION: Some limitations have been identified in current methods to monitor heart rate and respiratory rate in newborn babies. Novel minimally invasive sensors have advantages that may help clinical practice. Further research studies are needed to assess whether they are sufficiently accurate, practical, and reliable to be suitable for clinical use.

Magnetic Field Triggerable Macroporous PDMS Sponge Loaded with an Anticancer Drug, 5-Fluorouracil.

This study aims to prepare, optimize, and characterize magnetic-field-sensitive sugar-templated polydimethylsiloxane (PDMS) sponges for localized delivery of an anticancer drug, 5-fluorouracil (FLU). For this purpose, different concentrations of carbonyl iron (CI) and magnetite Fe3O4 nanopowders were embedded as magnetosensitive materials in PDMS resins for the fabrication of macroporous sponges via a sugar-template process. The process is environmentally friendly and simple. The fabricated interconnected macroporous magnetic particles loaded PDMS sponges possess flexible skeletons and good recyclability because of their recoverability after compression (deformation) without any breakdown. The prepared magnetic PDMS sponges were evaluated for their morphology (SEM and EDS), porosity (absorbency), elastic modulus, deformation under a magnetic field, thermostability, and in vitro cell studies. All physicochemical and magnetomechanical analysis confirmed that the optimized magnetic-field-sensitive PDMS sponge can provide an efficient method for delivering an on-demand dose of anticancer drug solutions at a specific location and timing with the aid of controlled magnetic fields.

Novel 3D printed device with integrated macroscale magnetic field triggerable anti-cancer drug delivery system.

With the growing demand for personalized medicine and medical devices, the impact of on-demand triggerable (e.g., via magnetic fields) drug delivery systems increased significantly in recent years. The three-dimensional (3D) printing technology has already been applied in the development of personalized dosage forms because of its high-precision and accurate manufacturing ability. In this study, a novel magnetically triggerable drug delivery device composed of a magnetic polydimethylsiloxane (PDMS) sponge cylinder and a 3D printed reservoir was designed, fabricated and characterized. This system can realize a switch between "on" and "off" state easily through the application of different magnetic fields and from different directions. Active and repeatable control of the localized drug release could be achieved by the utilization of magnetic fields to this device due to the shrinking extent of the macro-porous magnetic sponge inside. The switching "on" state of drug-releasing could be realized by the magnetic bar contacted with the side part of the device because the times at which 50%, 80% and 90% (w/w) of the drug were dissolved are observed to be 20, 55 and 140 min, respectively. In contrast, the switching "off" state of drug-releasing could be realized by the magnetic bar placed at the bottom of the device as only 10% (w/w) of the drug could be released within 12 h. An anti-cancer substance, 5-fluorouracil (FLU), was used as the model drug to illustrate the drug release behaviour of the device under different strengths of magnetic fields applied. In vitro cell culture studies also demonstrated that the stronger the magnetic field applied, the higher the drug release from the deformed PDMS sponge cylinder and thus more obvious inhibition effects on Trex cell growth. All results confirmed that the device can provide a safe, long-term, triggerable and reutilizable way for localized disease treatment such as cancer.

Heart Rate Monitoring in Newborn Babies: A Systematic Review.

BACKGROUND: Around 10% of newborn infants require assistance during transition after birth. Heart rate (HR) is the most important clinical indicator to evaluate the clinical status of a newborn. AIM: Our study aimed to review all established and novel methods to detect HR in babies giving special consideration to non-invasive techniques. METHODS: We performed a systematic literature search on the following databases: MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and CINAHL. The inclusion criteria were studies on methods to detect HR in both term and preterm infants in comparison to one of the current gold standards: pulse oximetry (PO) or electrocardiography (ECG) published in the last 15 years. Two independent reviewers screened titles and abstracts for eligibility. Data extracted in an Excel table were analysed to produce a narrative review structured around the type of monitoring, identified obstacles in use, as well as methods to overcome these limitations. RESULTS: The search revealed 649 studies after duplicates were removed. Full article analysis was performed on 26 studies of which 25 met the inclusion criteria. Well established methods such as auscultation and palpation, although rapid and easily available, have been shown to be inaccurate. ECG and PO were both more precise but the delay in obtaining a reliable HR signal from birth often exceeded 1-2 min. Novel sensors offered the advantages of minimally obtrusive technologies but have limitations mainly due to movement artefact, bad sensor coupling, intermittent measurement, and poor-quality recordings. CONCLUSIONS: The limitations of existing methods have a potential impact on short- and long-term morbidity and mortality outcomes. The development of a technological solution to determine HR accurately and quickly in babies at birth has immense implications for further research and can guide interventions, such as placental transfusion and resuscitation.

Measurement and correction of in vivo sample aberrations employing a nonlinear guide-star in two-photon excited fluorescence microscopy.

We demonstrate that sample induced aberrations can be measured in a nonlinear microscope. This uses the fact that two-photon excited fluorescence naturally produces a localized point source inside the sample: the nonlinear guide-star (NL-GS). The wavefront emitted from the NL-GS can then be recorded using a Shack-Hartmann sensor. Compensation of the recorded sample aberrations is performed by the deformable mirror in a single-step. This technique is applied to fixed and in vivo biological samples, showing, in some cases, more than one order of magnitude improvement in the total collected signal intensity.

Compact ultrafast semiconductor disk laser: targeting GFP based nonlinear applications in living organisms.

We present a portable ultrafast Semiconductor Disk Laser (SDL) (or vertical extended cavity surface emitting laser-VECSELs), to be used for nonlinear microscopy. The SDL is modelocked using a quantum-dot semiconductor saturable absorber mirror (SESAM), delivering an average output power of 287 mW, with 1.5 ps pulses at 500 MHz and a central wavelength of 965 nm. Specifically, despite the fact of having long pulses and high repetition rates, we demonstrate the potential of this laser for Two-Photon Excited Fluorescence (TPEF) imaging of in vivo Caenorhabditis elegans (C. elegans) expressing Green Fluorescent Protein (GFP) in a set of neuronal processes and cell bodies. Efficient TPEF imaging is achieved due to the fact that this wavelength matches the peak of the two-photon action cross section of this widely used fluorescent marker. The SDL extended versatility is shown by presenting Second Harmonic Generation images of pharynx, uterus, body wall muscles and its potential to be used to excite other different commercial dyes. Importantly this non-expensive, turn-key, compact laser system could be used as a platform to develop portable nonlinear bio-imaging devices.

Third-harmonic generation for the study of Caenorhabditis elegans embryogenesis.

Live microscopy techniques (i.e., differential interference contrast, confocal microscopy, etc.) have enabled the understanding of the mechanisms involved in cells and tissue formation. In long-term studies, special care must be taken in order to avoid sample damage, restricting the applicability of the different microscopy techniques. We demonstrate the potential of using third-harmonic generation (THG) microscopy for morphogenesis/embryogenesis studies in living Caenorhabditis elegans (C. elegans). Moreover, we show that the THG signal is obtained in all the embryo development stages, showing different tissue/structure information. For this research, we employ a 1550-nm femtosecond fiber laser and demonstrate that the expected water absorption at this wavelength does not severely compromise sample viability. Additionally, this has the important advantage that the THG signal is emitted at visible wavelengths (516 nm). Therefore, standard collection optics and detectors operating near maximum efficiency enable an optimal signal reconstruction. All this, to the best of our knowledge, demonstrates for the first time the noninvasiveness and strong potential of this particular wavelength to be used for high-resolution four-dimensional imaging of embryogenesis using unstained C. elegans in vivo samples.