A Microfluidic System for Stable and Continuous EEG Monitoring from Multiple Larval Zebrafish

Along with the increasing popularity of larval zebrafish as an experimental animal in the fields of drug screening, neuroscience, genetics, and developmental biology, the need for tools to deal with multiple larvae has emerged. Microfluidic channels have been employed to handle multiple larvae simultaneously, even for sensing electroencephalogram (EEG). In this study, we developed a microfluidic chip capable of uniform and continuous drug infusion across all microfluidic channels during EEG recording. Owing to the modular design of the microfluidic channels, the number of animals under investigation can be easily increased. Using the optimized design of the microfluidic chip, liquids could be exchanged uniformly across all channels without physically affecting the larvae contained in the channels, which assured a stable environment maintained all the time during EEG recording, by eliminating environmental artifacts and leaving only biological effects to be seen. To demonstrate the usefulness of the developed system in drug screening, we continuously measured EEG from four larvae without and with pentylenetetrazole application, up to 60 min. In addition, we recorded EEG from valproic acid (VPA)-treated zebrafish and demonstrated the suppression of seizure by VPA. The developed microfluidic system could contribute to the mass screening of EEG for drug development to treat neurological disorders such as epilepsy in a short time, owing to its handy size, cheap fabrication cost, and the guaranteed uniform drug infusion across all channels with no environmentally induced artifacts. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.1

Development of EEG recording systems for multiple adult and larval zebrafish

Zebrafish, simultaneous EEG measurement, drug screeningprohibitionAbstract i List of Contents ii List of tables iv List of figures v 1 INTRODUCTION 1 2 RECORDING SYSTEM FOR ADULT ZEBRAFISH 2 Concept of Recording System 2 Experimental Design and Method 2 2.2.1 Animal preparation and maintenance 2 2.2.2 Experimental set-up 3 2.2.3 Statistical methods 5 Result 5 3 RECORDING SYSTEM FOR LARVAL ZEBRAFISH 14 Concept of Recording System 14 Experimental Design and Method 14 3.2.1 Animal preparation and maintenance 14 3.2.2 Design and fabrication of microfluidic chip 15 3.2.3 Test of liquid exchangeability 16 3.2.4 Experimental set-up 17 3.2.5 Statistical methods 17 Result 18 3.3.1 Result of simulation and experiment to test liquid exchangeability 18 3.3.2 Result of EEG recording 18 4 DISCUSSIONS 24 5 CONCLUSION 25 REFERENCES 26MasterdCollectio

A Microfluidic System for Stable and Continuous EEG Monitoring from Multiple Larval Zebrafish

Along with the increasing popularity of larval zebrafish as an experimental animal in the fields of drug screening, neuroscience, genetics, and developmental biology, the need for tools to deal with multiple larvae has emerged. Microfluidic channels have been employed to handle multiple larvae simultaneously, even for sensing electroencephalogram (EEG). In this study, we developed a microfluidic chip capable of uniform and continuous drug infusion across all microfluidic channels during EEG recording. Owing to the modular design of the microfluidic channels, the number of animals under investigation can be easily increased. Using the optimized design of the microfluidic chip, liquids could be exchanged uniformly across all channels without physically affecting the larvae contained in the channels, which assured a stable environment maintained all the time during EEG recording, by eliminating environmental artifacts and leaving only biological effects to be seen. To demonstrate the usefulness of the developed system in drug screening, we continuously measured EEG from four larvae without and with pentylenetetrazole application, up to 60 min. In addition, we recorded EEG from valproic acid (VPA)-treated zebrafish and demonstrated the suppression of seizure by VPA. The developed microfluidic system could contribute to the mass screening of EEG for drug development to treat neurological disorders such as epilepsy in a short time, owing to its handy size, cheap fabrication cost, and the guaranteed uniform drug infusion across all channels with no environmentally induced artifacts

An EEG system to detect brain signals from multiple adult zebrafish

Zebrafish has been widely used as an experimental animal in many biological processes to study brain functions, neurological disorders and drug toxicity. Electroencephalogram (EEG), which directly measures brain activities, has been used to diagnose and study neurological disorders. Previous studies have recorded EEG signals from adult zebrafish, but the recordings have been only possible from a single individual. In this study, we developed a system to record EEG of multiple adult zebrafish simultaneously. To secure multiple zebrafish in a stable condition for a certain time, perfusion and recording systems were mechanically separated, which allowed effective immobilization of the fish. We recorded EEG signals from pentylenetetrazole (PTZ)-induced seizure models and valproic acid (VPA)-treated models to demonstrate the performance of the developed system in validation of the effect of anti-epileptic drugs. The developed system effectively measured individual EEG signals from more than three zebrafish out of four simultaneously on average. Seizure induction by PTZ and seizure suppression by VPA were successfully detected through EEG recording. The scheme of the EEG recording system developed in this study has a potential for expansion and could be further applied to mass drug screening in a short time. © 2020 Elsevier B.V.1

DNN-SAM: Split-and-Merge DNN Execution for Real-Time Object Detection

As real-time object detection systems, such as autonomous cars, need to process input images acquired from multiple cameras, they face significant challenges in delivering accurate and timely inferences often based on machine learning (ML). To meet these challenges, we want to provide different levels of object detection accuracy and timeliness to different portions within each input image with different criticality levels. Specifically, we develop DNN-SAM, a dynamic Split-And-Merge Deep Neural Network (DNN) execution and scheduling framework, that enables seamless split-and-merge DNN execution for unmodified DNN models. Instead of processing an entire input image once in a full DNN model, DNN-SAM first splits a DNN inference task into two smaller sub-tasks-a mandatory sub-task dedicated for a safety-critical (cropped) portion of each image and an optional sub-task for processing a down-scaled image-then executes them independently, and finally merges their results into a complete inference. To achieve DNN-SAM's timely and accurate detection of objects in each image, we also develop two scheduling algorithms that prioritize sub-tasks according to their criticality levels and adaptively adjust the scale of the input image to meet the timing constraints while minimizing the response time of mandatory sub-tasks or maximizing the accuracy of optional sub-tasks. We have implemented and evaluated DNN-SAM on a representative ML framework. Our evaluation shows DNN-SAM to improve detection accuracy in the safety-critical region by 2.0-3.7× and lower average inference latency by 4.8-9.7× over existing approaches without violating any timing constraints. © 2022 IEEE

Self-Expandable Electrode Based on Chemically Polished Nickel–Titanium Alloy Wire for Treating Endoluminal Tumors Using Bipolar Irreversible Electroporation

The application of irreversible electroporation (IRE) to endoluminal organs is being investigated; however, the current preclinical evidence and optimized electrodes are insufficient for clinical translation. Here, a novel self-expandable electrode (SE) made of chemically polished nickel–titanium (Ni–Ti) alloy wire for endoluminal IRE is developed in this study. Chemically polished heat-treated Ni–Ti alloy wires demonstrate increased electrical conductivity, reduced carbon and oxygen levels, and good mechanical and self-expanding properties. Bipolar IRE using chemically polished Ni–Ti wires successfully induces cancer cell death. IRE-treated potato tissue shows irreversibly and reversibly electroporated areas containing dead cells in an electrical strength-dependent manner. In vivo study using an optimized electric field strength demonstrates that endobiliary IRE using the SE evenly induces well-distributed mucosal injuries in the common bile duct (CBD) with the overexpression of the TUNEL, HSP70, and inflammatory cells without ductal perforation or stricture formation. This study demonstrates the basic concept of the endobiliary IRE procedure, which is technically feasible and safe in a porcine CBD as a novel therapeutic strategy for malignant biliary obstruction. The SE is a promising electrical energy delivery platform for effectively treating endoluminal organs