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.

<b><i>Background:</i></b> 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. <b><i>Aim:</i></b> Our study aimed to review all established and novel methods to detect HR in babies giving special consideration to non-invasive techniques. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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. <b><i>Conclusions:</i></b> 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.

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.

Abstract. 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 ͑THG͒ microscopy for morphogenesis/embryogenesis studies in living Caenorhabditis elegans ͑C. elegans͒. 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 nm͒. 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 highresolution four-dimensional imaging of embryogenesis using unstained C. elegans in vivo samples. © 2010 Society of Photo-Optical Instrumentation Engineers.

Abstract:In this paper, we present the generation of high peak-power picosecond optical pulses in the 1.26 μm spectral band from a repetitionrate-tunable quantum-dot external-cavity passively mode-locked laser (QD-ECMLL), amplified by a tapered quantum-dot semiconductor optical amplifier (QD-SOA). The laser emission wavelength was controlled through a chirped volume Bragg grating which was used as an external cavity output coupler. An average power of 208.2 mW, pulse energy of 321 pJ, and peak power of 30.3 W were achieved. Preliminary nonlinear imaging investigations indicate that this system is promising as a high peak-power pulsed light source for nonlinear bio-imaging applications across the 1.0 μm -1.3 μm spectral range.

In this letter, we report the continuous detection of the cardiac electrical activity in embryonic zebrafish using a non-invasive approach. We present a portable and cost-effective platform based on the electric potential sensing technology, to monitor in vivo electrocardiogram activity from the zebrafish heart. This proof of principle demonstration shows how electrocardiogram measurements from the embryonic zebrafish may become accessible by using electric field detection. We present preliminary results using the prototype, which enables the acquisition of electrophysiological signals from in vivo 3 and 5 days-post-fertilization zebrafish embryos. The recorded waveforms show electrocardiogram traces including detailed features such as QRS complex, P and T waves.

Within the first minute of life a newborn must take its first breath to make the transition from life inside the womb to the outside world. If a baby does not start breathing, its heart rate will drop and the circulation of blood carrying oxygen to the organs will be seriously affected. The damage done to a newborn who is deprived of oxygen happens so quickly that rapid response is imperative. During birth, the attending neonatal staff manually listen to the baby´s heart and count the heart rate; however, this has proven inaccurate and inefficient. Nowadays, there is not a reliable method to monitor newborn heart rate promptly throughout birth. In this paper, we report the design and development of a novel smart mattress device to measure the babies' electrocardiogram and respiration non-invasively. The device is based on electrometer-based amplifier sensors combined with novel screen-printing techniques. Proof of concept tests are carried out to demonstrate the suitability of the smart-mattress for new born ECG monitoring. We perform tests with a young infant and demonstrate the potential of this sensing technology to provide a quick and reliable application as ECG readings were displayed within a time < 30 seconds. This will aid the neonatal staff to assess the success of the resuscitation technology aiming to lower the incidence of long-term consequences of poor adaptation to life outside the womb.

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.