Zebra II as A Novel System to Record Electrophysiological Signals in Zebrafish

Zebrafish and their mutant lines have been extensively used in biomedical investigations, cardiovascular studies, and drug screening. In the current ...

Sensoriis Inc.

A chip-based electrochemical biosensor is developed herein for the detection of organophosphate (OP) in food materials. The principle of the sensing platform is based on the inhibition of dimethoate (DMT), a typical OP that specifically inhibits acetylcholinesterase (AChE) activity. Carbon nanotube-modified gold electrodes functionalized with polydiallyldimethylammonium chloride (PDDA) and oxidized nanocellulose (NC) were investigated for the sensing of OP, yielding high sensitivity. Compared with noncovalent adsorption and deposition in bovine serum albumin, bioconjugation with lysine side chain activation allowed the enzyme to be stable over three weeks at room temperature. The total amount of AChE was quantified, whose activity inhibition was highly linear with respect to DMT concentration. Increased incubation times and/or DMT concentration decreased current flow. The composite electrode showed a sensitivity 4.8-times higher than that of the bare gold electrode. The biosensor was challenged with organophosphate-spiked food samples and showed a limit of detection (LOD) of DMT at 4.1 nM, with a limit of quantification (LOQ) at 12.6 nM, in the linear range of 10 nM to 1000 nM. Such performance infers significant potential for the use of this system in the detection of organophosphates in real samples.

A Fluidics-Based Biosensor to Detect and Characterize Inhibition Patterns of Organophosphate to Acetylcholinesterase in Food Materials.

Zebrafish is a powerful and widely-used model system for a host of biological investigations, including cardiovascular studies and genetic screening. Zebrafish are readily assessable during developmental stages; however, the current methods for quantifying and monitoring cardiac functions mainly involve tedious manual work and inconsistent estimations. In this paper, we developed and validated a Zebrafish Automatic Cardiovascular Assessment Framework (ZACAF) based on a U-net deep learning model for automated assessment of cardiovascular indices, such as ejection fraction (EF) and fractional shortening (FS) from microscopic videos of wildtype and cardiomyopathy mutant zebrafish embryos. Our approach yielded favorable performance with accuracy above 90% compared with manual processing. We used only black and white regular microscopic recordings with frame rates of 5-20 frames per second (fps); thus, the framework could be widely applicable with any laboratory resources and infrastructure. Most importantly, the automatic feature holds promise to enable efficient, consistent, and reliable processing and analysis capacity for large amounts of videos, which can be generated by diverse collaborating teams.

Deep learning-based framework for cardiac function assessment in embryonic zebrafish from heart beating videos.

Monitoring of fetal electrocardiogram (fECG) would provide useful information about fetal wellbeing as well as any abnormal development during pregnancy. Recent advances in flexible electronics and wearable technologies have enabled compact devices to acquire personal physiological signals in the home setting, including those of expectant mothers. However, the high noise level in the daily life renders long-entrenched challenges to extract fECG from the combined fetal/maternal ECG signal recorded in the abdominal area of the mother. Thus, an efficient fECG extraction scheme is a dire need. In this work, we intensively explored various extraction algorithms, including template subtraction (TS), independent component analysis (ICA), and extended Kalman filter (EKF) using the data from the PhysioNet 2013 Challenge. Furthermore, the modified data with Gaussian and motion noise added, mimicking a practical scenario, were utilized to examine the performance of algorithms. Finally, we combined different algorithms together, yielding promising results, with the best performance in the F1 score of 92.61% achieved by an algorithm combining ICA and TS. With the data modified by adding different types of noise, the combination of ICA-TS-ICA showed the highest F1 score of 85.4%. It should be noted that these combined approaches required higher computational complexity, including execution time and allocated memory compared with other methods. Owing to comprehensive examination through various evaluation metrics in different extraction algorithms, this study provides insights into the implementation and operation of state-of-the-art fetal and maternal monitoring systems in the era of mobile health.

Investigation of Methods to Extract Fetal Electrocardiogram from the Mother's Abdominal Signal in Practical Scenarios.

Electrocardiogram (ECG) monitoring of the fetus during pregnancy, before and during labor, can provide crucial information for the assessment of fetal well-being and development, as well as labor progress. An out-of-clinics fetal ECG monitoring system may pave the way for instant diagnosis, suggesting immediate intervention, which could help reduce the fetal mortality rate. In this paper, we present an unobtrusive fetal maternal ECG monitoring system which can operate in the home setting. The acquisition of the mother's abdominal ECG is done using the non-contact electrode approach. The extraction of the fetal ECG from the combined fetal/maternal ECG signal is investigated using both Fast Independent Component Analysis (FastICA) and RobustICA algorithms. An accelerometer is integrated for motion artifact detection which would help reduce interferences due to movement. The device also is connected to a cloud server, allowing doctors to access the data in real time.

Home-based mobile fetal/maternal electrocardiogram acquisition and extraction with cloud assistance.

Zebrafish and their mutant lines have been extensively used in cardiovascular studies. In the current study, the novel system, Zebra II, is presented for prolonged electrocardiogram (ECG) acquisition and analysis for multiple zebrafish within controllable working environments. The Zebra II is composed of a perfusion system, apparatuses, sensors, and an in-house electronic system. First, the Zebra II is validated in comparison with a benchmark system, namely iWORX, through various experiments. The validation displayed comparable results in terms of data quality and ECG changes in response to drug treatment. The effects of anesthetic drugs and temperature variation on zebrafish ECG were subsequently investigated in experiments that need real-time data assessment. The Zebra II's capability of continuous anesthetic administration enabled prolonged ECG acquisition up to 1 h compared to that of 5 min in existing systems. The novel, cloud-based, automated analysis with data obtained from four fish further provided a useful solution for combinatorial experiments and helped save significant time and effort. The system showed robust ECG acquisition and analytics for various applications including arrhythmia in sodium induced sinus arrest, temperature-induced heart rate variation, and drug-induced arrhythmia in Tg(SCN5A-D1275N) mutant and wildtype fish. The multiple channel acquisition also enabled the implementation of randomized controlled trials on zebrafish models. The developed ECG system holds promise and solves current drawbacks in order to greatly accelerate drug screening applications and other cardiovascular studies using zebrafish.

A novel wireless ECG system for prolonged monitoring of multiple zebrafish for heart disease and drug screening studies.

Detection of bacterial pathogens is significant in the fields of food safety, medicine, and public health, just to name a few. If bacterial pathogens are not properly identified and treated promptly, they can lead to morbidity and mortality, also possibly contribute to antimicrobial resistance. Current bacterial detection methodologies rely solely on laboratory-based techniques, which are limited by long turnaround detection times, expensive costs, and risks of inadequate accuracy; also, the work requires trained specialists. Here, we describe a cost-effective and portable 3D-printed electrochemical biosensor that facilitates rapid detection of certain  () strains (DH5α, BL21, TOP10, and JM109) within 15 min using 500 μL of sample, and costs only USD 2.50 per test. The sensor displayed an excellent limit of detection (LOD) of 53 cfu, limit of quantification (LOQ) of 270 cfu, and showed cross-reactivity with strains BL21 and JM109 due to shared epitopes. This advantageous diagnostic device is a strong candidate for frequent testing at point of care; it also has application in various fields and industries where pathogen detection is of interest.

A Low-Cost, 3D-Printed Biosensor for Rapid Detection of .

Fetal electrocardiogram (fECG) assessment is essential throughout pregnancy to monitor the wellbeing and development of the fetus, and to possibly diagnose potential congenital heart defects. Due to the high noise incorporated in the abdominal ECG (aECG) signals, the extraction of fECG has been challenging. And it is even a lot more difficult for fECG extraction if only one channel of aECG is provided, i.e., in a compact patch device. In this paper, we propose a novel algorithm based on the Ensemble Kalman filter (EnKF) for non-invasive fECG extraction from a single-channel aECG signal. To assess the performance of the proposed algorithm, we used our own clinical data, obtained from a pilot study with 10 subjects each of 20 min recording, and data from the PhysioNet 2013 Challenge bank with labeled QRS complex annotations. The proposed methodology shows the average positive predictive value (PPV) of 97.59%, sensitivity (SE) of 96.91%, and F1-score of 97.25% from the PhysioNet 2013 Challenge bank. Our results also indicate that the proposed algorithm is reliable and effective, and it outperforms the recently proposed extended Kalman filter (EKF) based algorithm.

Fetal Electrocardiogram Extraction from the Mother's Abdominal Signal Using the Ensemble Kalman Filter.

Simultaneous monitoring of electrocardiogram (ECG) and electroencephalogram (EEG) in studied animal models requires innovative engineering techniques that can capture minute physiological changes. However, this is often administered with a bulky and/or invasive system that may cause discomfort to animals and signal distortions. Here, we develop an integrated bioelectronic sensing system to provide simultaneous recordings of ECG and EEG in real-time for Xenopus laevis. The microelectrode array (MEA) membrane and the distinct anatomy of Xenopus offer noninvasive multi-modal electrophysiological monitoring with favorable spatial resolution. The system was validated under different environmental conditions, including drug exposure and temperature changes. Under the exposure of Pentylenetetrazol (PTZ), an epilepsy-inducing drug, clear ECG and EEG alterations, including frequent ictal and interictal EEG events, 30 dB average EEG amplitude elevations, abnormal ECG morphology, and heart rate changes, were observed. Furthermore, the ECG and EEG were monitored and analyzed under different temperatures. A decrease in relative power of delta band was observed when cold environment was brought about, in contrast to an increase in relative power of other higher frequency bands while the ECG remained stable. Overall, the real-time electrophysiology monitoring system using the Xenopus model holds potential for many applications in drug screening and remote environmental monitoring.

Microelectrode array membranes to simultaneously assess cardiac and neurological signals of xenopus laevis under chemical exposures and environmental changes.

Fetal heart rate (fHR) is an important indicator for monitoring of fetal cardiac health and development. The widely-used method based on ultrasound, however, is not continuous and often requires an expert to perform; thus, it is mostly used in clinics during checkups. The advances in wearable technology have paved the way for home assessment of fHR via the extraction of the mother's abdominal electrocardiogram (ECG) acquired by novel patches. Several methods have been developed for such; however, the computation is either too slow for real-time monitoring or too heavy to be performed in a wearable. In this work, we develop and validate the Lullaby algorithm - a novel method for fetal QRS extraction from aECG. The results showed that Lullaby is almost 7 times faster than existing methods with a better F1-score of 0.815, holding promise to transform perinatal monitoring.

Michael P. H. Lau

Sensoriis Inc.

Zebra II as A Novel System to Record Electrophysiological Signals in Zebrafish