High-Throughput Microfluidic Sorting of C. elegans for Automated Force Pattern Measurement

2011 ◽  
Vol 700 ◽  
pp. 182-187 ◽  
Author(s):  
Shazlina Johari ◽  
Volker Nock ◽  
Maan M. Alkaisi ◽  
Wen Wang
Keyword(s):  
High Throughput ◽  
Force Measurement ◽  
Model Organism ◽  
Pdms Layer ◽  
Fluidic Channel ◽  
Motion Patterns ◽  
C Elegans ◽  
Area Of Interest ◽  
On Chip ◽  
Gas Layer

With a reduced set of 300 neurons and a fully sequenced genome, the multicellular nematodeCaenorhabditis eleganshas recently gained increasing interest as a model organism for neurobiological studies. One particular area of interest is related to worm locomotion and the investigation of the correlation between individual genes, neurons, muscle arms and the motion pattern of the nematodes. To characterize motion patterns of movingC. eleganswe have previously demonstrated an automated force measurement setup using microfabricated polydimethylsiloxane (PDMS) pillars and image processing. In this paper we introduce an integrated microfluidic device for worm sorting and force measurement. The device allows for high-throughput measurements by combining sorting functions on-chip with the existing force pattern measurement system. A horizontal sorting channel and branching vertical pillar array channels are utilized for worm sorting. Using the former, the nematodes can be flow-directed into arrays of 40 µm and 60 µm diameter pillars based on worm size and type. This improves animal survival and increases the relevance of the force measurement by allowing one to match the amplitude of the worm movement to the pillar spacing. The PDMS based device consists of three layers: a fluidic layer with pillars for force measurement at the bottom, a gas layer on top and a thin PDMS layer sandwiched between them. By applying pressure to the gas layer, the membrane in the middle will be deflected thus restricting the worms’ movement in the fluidic channel.

scholarly journals Microfluidic Technologies for High Throughput Screening Through Sorting and On-Chip Culture of C. elegans

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4292 ◽  
Author(s):  
Daniel Midkiff ◽  
Adriana San-Miguel
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Model Organism ◽  
Large Data ◽  
Large Data Sets ◽  
Data Sets ◽  
C Elegans ◽  
Drug Candidates ◽  
On Chip ◽  
And Behavior

The nematode Caenorhabditis elegans is a powerful model organism that has been widely used to study molecular biology, cell development, neurobiology, and aging. Despite their use for the past several decades, the conventional techniques for growth, imaging, and behavioral analysis of C. elegans can be cumbersome, and acquiring large data sets in a high-throughput manner can be challenging. Developments in microfluidic “lab-on-a-chip” technologies have improved studies of C. elegans by increasing experimental control and throughput. Microfluidic features such as on-chip control layers, immobilization channels, and chamber arrays have been incorporated to develop increasingly complex platforms that make experimental techniques more powerful. Genetic and chemical screens are performed on C. elegans to determine gene function and phenotypic outcomes of perturbations, to test the effect that chemicals have on health and behavior, and to find drug candidates. In this review, we will discuss microfluidic technologies that have been used to increase the throughput of genetic and chemical screens in C. elegans. We will discuss screens for neurobiology, aging, development, behavior, and many other biological processes. We will also discuss robotic technologies that assist in microfluidic screens, as well as alternate platforms that perform functions similar to microfluidics.

PDMS filter structures for size-dependent larval sorting and on-chip egg extraction of C. elegans

Lab on a Chip ◽  
2020 ◽  
Vol 20 (1) ◽  
pp. 155-167 ◽  
Author(s):  
Huseyin Baris Atakan ◽  
Furkan Ayhan ◽  
Martin A. M. Gijs
Keyword(s):  
Microfluidic Device ◽  
High Throughput ◽  
High Purity ◽  
C Elegans ◽  
Size Dependent ◽  
On Chip ◽  
Filter Structures

We present a microfluidic device for rapid larvae sorting and on-chip egg extraction of C. elegans at high purity and high throughput.

scholarly journals Automated Platform for Long-Term Culture and High-Content Phenotyping of Single C. elegans Worms

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
H. B. Atakan ◽  
R. Xiang ◽  
M. Cornaglia ◽  
L. Mouchiroud ◽  
E. Katsyuba ◽  
...  
Keyword(s):  
High Throughput ◽  
Agar Plate ◽  
Model Organism ◽  
Suitable Model ◽  
Microfluidic Chips ◽  
Long Term Culture ◽  
C Elegans ◽  
Bleaching Procedure ◽  
Automated Platform

Abstract The nematode Caenorhabditis elegans is a suitable model organism in drug screening. Traditionally worms are grown on agar plates, posing many challenges for long-term culture and phenotyping of animals under identical conditions. Microfluidics allows for ‘personalized’ phenotyping, as microfluidic chips permit collecting individual responses over worms’ full life. Here, we present a multiplexed, high-throughput, high-resolution microfluidic approach to culture C. elegans from embryo to the adult stage at single animal resolution. We allocated single embryos to growth chambers, for observing the main embryonic and post-embryonic development stages and phenotypes, while exposing worms to up to 8 different well-controlled chemical conditions. Our approach allowed eliminating bacteria aggregation and biofilm formation-related clogging issues, which enabled us performing up to 80 hours of automated single worm culture studies. Our microfluidic platform is linked with an automated phenotyping code that registers organism-associated phenotypes at high-throughput. We validated our platform with a dose-response study of the anthelmintic drug tetramisole by studying its influence through the life cycle of the nematodes. In parallel, we could observe development effects and variations in single embryo and worm viability due to the bleaching procedure that is standardly used for harvesting the embryos from a worm culture agar plate.

Investigation of Die Tilting of Packages with Single and Multi-chips

2018 ◽  
Author(s):  
Lo Chea Wee ◽  
Tan Sze Yee ◽  
Gan Sue Yin ◽  
Goh Cin Sheng
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Electron Beam ◽  
Optical Microscopy ◽  
Device Performance ◽  
Electronic Components ◽  
Area Of Interest ◽  
On Chip ◽  
Scanning Electron

Abstract Advanced package technology often includes multi-chips in one package to accommodate the technology demand on size & functionality. Die tilting leads to poor device performance for all kinds of multi-chip packages such as chip by chip (CbC), chip on chip (CoC), and the package with both CbC and CoC. Traditional die tilting measured by optical microscopy and scanning electron microscopy has capability issue due to wave or electron beam blocking at area of interest by electronic components nearby. In this paper, the feasibility of using profilemeter to investigate die tilting in single and multi-chips is demonstrated. Our results validate that the profilemeter is the most profound metrology for die tilting analysis especially on multi-chip packages, and can achieve an accuracy of <2μm comparable to SEM.

scholarly journals Health and longevity studies in C. elegans: the “healthy worm database” reveals strengths, weaknesses and gaps of test compound-based studies

2021 ◽  
Vol 22 (2) ◽  
pp. 215-236
Author(s):  
Nadine Saul ◽  
Steffen Möller ◽  
Francesca Cirulli ◽  
Alessandra Berry ◽  
Walter Luyten ◽  
...  
Keyword(s):  
Healthy Aging ◽  
Model Organism ◽  
Research Field ◽  
Aging Research ◽  
Genetic Manipulations ◽  
C Elegans ◽  
Starting Point ◽  
Health Related ◽  
Phenotype Measurement ◽  
Or Gene

AbstractSeveral biogerontology databases exist that focus on genetic or gene expression data linked to health as well as survival, subsequent to compound treatments or genetic manipulations in animal models. However, none of these has yet collected experimental results of compound-related health changes. Since quality of life is often regarded as more valuable than length of life, we aim to fill this gap with the “Healthy Worm Database” (http://healthy-worm-database.eu). Literature describing health-related compound studies in the aging model Caenorhabditis elegans was screened, and data for 440 compounds collected. The database considers 189 publications describing 89 different phenotypes measured in 2995 different conditions. Besides enabling a targeted search for promising compounds for further investigations, this database also offers insights into the research field of studies on healthy aging based on a frequently used model organism. Some weaknesses of C. elegans-based aging studies, like underrepresented phenotypes, especially concerning cognitive functions, as well as the convenience-based use of young worms as the starting point for compound treatment or phenotype measurement are discussed. In conclusion, the database provides an anchor for the search for compounds affecting health, with a link to public databases, and it further highlights some potential shortcomings in current aging research.

Benefits of Using the Invertebrate Model Organism C. Elegans in an Inquiry-Based Laboratory Activity

2021 ◽  
pp. 009862832110296
Author(s):  
Angy J. Kallarackal
Keyword(s):  
American Psychological Association ◽  
Model Organism ◽  
Learning Goals ◽  
Research Skills ◽  
Final Exam ◽  
Laboratory Activity ◽  
Writing Ability ◽  
C Elegans ◽  
Invertebrate Model ◽  
Laboratory Experiences

Background: The goals of laboratory experiences include developing knowledge base, research skills, and scientific communication abilities. Objective: The aim was to assess an inquiry-based laboratory activity using the model organism Caenorhabditis elegans in relation to learning goals. Method: Students in a Biopsychology laboratory course worked in groups to test the effect of various drugs (e.g., nicotine, ethanol, fluoxetine, and melatonin) on C. elegans behavior. The activity included literature review, experimental design, and a final lab report. A cumulative final exam included a synaptic communication question related to the content of the activity. Results: Students showed better retention of laboratory-related content compared to other topics from the course, as demonstrated through performance on the final exam and were able to replicate previous research demonstrating effects of drug on locomotion. However, students did not improve writing ability compared to performance on a previous American Psychological Association style lab report. Conclusion: This study demonstrates that using a student-designed, multi-week laboratory assignment in an undergraduate Biopsychology course supports the growth of psychology knowledge and the development of research skills. Teaching Implications: Instructors should consider using the described laboratory activity for biopsychology or behavioral neuroscience classes or consider similarly designed laboratory formats for other courses in Psychology.

scholarly journals Wormicloud: a new text summarization tool based on word clouds to explore the C. elegans literature

Database ◽  
2021 ◽  
Vol 2021 ◽  
Author(s):  
Valerio Arnaboldi ◽  
Jaehyoung Cho ◽  
Paul W Sternberg
Keyword(s):  
Search Engines ◽  
Complex Structure ◽  
Model Organism ◽  
Gene Interaction ◽  
Relevant Information ◽  
Biomedical Literature ◽  
C Elegans ◽  
Word Clouds ◽  
Scientific Papers ◽  
Model Organism Databases

Abstract Finding relevant information from newly published scientific papers is becoming increasingly difficult due to the pace at which articles are published every year as well as the increasing amount of information per paper. Biocuration and model organism databases provide a map for researchers to navigate through the complex structure of the biomedical literature by distilling knowledge into curated and standardized information. In addition, scientific search engines such as PubMed and text-mining tools such as Textpresso allow researchers to easily search for specific biological aspects from newly published papers, facilitating knowledge transfer. However, digesting the information returned by these systems—often a large number of documents—still requires considerable effort. In this paper, we present Wormicloud, a new tool that summarizes scientific articles in a graphical way through word clouds. This tool is aimed at facilitating the discovery of new experimental results not yet curated by model organism databases and is designed for both researchers and biocurators. Wormicloud is customized for the Caenorhabditis  elegans literature and provides several advantages over existing solutions, including being able to perform full-text searches through Textpresso, which provides more accurate results than other existing literature search engines. Wormicloud is integrated through direct links from gene interaction pages in WormBase. Additionally, it allows analysis on the gene sets obtained from literature searches with other WormBase tools such as SimpleMine and Gene Set Enrichment. Database URL: https://wormicloud.textpressolab.com

scholarly journals High-throughput behavioral screen in C. elegans reveals Parkinson’s disease drug candidates

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Salman Sohrabi ◽  
Danielle E. Mor ◽  
Rachel Kaletsky ◽  
William Keyes ◽  
Coleen T. Murphy
Keyword(s):  
Neural Network ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
High Throughput ◽  
Potential Candidate ◽  
Automated Scoring ◽  
C Elegans ◽  
Drug Candidates ◽  
Branched Chain ◽  
Approved Drugs

AbstractWe recently linked branched-chain amino acid transferase 1 (BCAT1) dysfunction with the movement disorder Parkinson’s disease (PD), and found that RNAi-mediated knockdown of neuronal bcat-1 in C. elegans causes abnormal spasm-like ‘curling’ behavior with age. Here we report the development of a machine learning-based workflow and its application to the discovery of potentially new therapeutics for PD. In addition to simplifying quantification and maintaining a low data overhead, our simple segment-train-quantify platform enables fully automated scoring of image stills upon training of a convolutional neural network. We have trained a highly reliable neural network for the detection and classification of worm postures in order to carry out high-throughput curling analysis without the need for user intervention or post-inspection. In a proof-of-concept screen of 50 FDA-approved drugs, enasidenib, ethosuximide, metformin, and nitisinone were identified as candidates for potential late-in-life intervention in PD. These findings point to the utility of our high-throughput platform for automated scoring of worm postures and in particular, the discovery of potential candidate treatments for PD.

Behavioral Effects of Volatile Anesthetics in Caenorhabditis elegans

1996 ◽  
Vol 85 (4) ◽  
pp. 901-912 ◽  
Author(s):  
Michael C. Crowder ◽  
Laynie D. Shebester ◽  
Tim Schedl
Keyword(s):  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Time Course ◽  
Model Organism ◽  
Volatile Anesthetic ◽  
Volatile Anesthetics ◽  
Effective Concentration ◽  
Forward Genetics ◽  
C Elegans ◽  
Median Effective Concentration

Background The nematode Caenorhabditis elegans offers many advantages as a model organism for studying volatile anesthetic actions. It has a simple, well-understood nervous system; it allows the researcher to do forward genetics; and its genome will soon be completely sequenced. C. elegans is immobilized by volatile anesthetics only at high concentrations and with an unusually slow time course. Here other behavioral dysfunctions are considered as anesthetic endpoints in C. elegans. Methods The potency of halothane for disrupting eight different behaviors was determined by logistic regression of concentration and response data. Other volatile anesthetics were also tested for some behaviors. Established protocols were used for behavioral endpoints that, except for pharyngeal pumping, were set as complete disruption of the behavior. Time courses were measured for rapid behaviors. Recovery from exposure to 1 or 4 vol% halothane was determined for mating, chemotaxis, and gross movement. All experiments were performed at 20 to 22 degrees C. Results The median effective concentration values for halothane inhibition of mating (0.30 vol%-0.21 mM), chemotaxis (0.34 vol%-0.24 mM), and coordinated movement (0.32 vol% - 0.23 mM) were similar to the human minimum alveolar concentration (MAC; 0.21 mM). In contrast, halothane produced immobility with a median effective concentration of 3.65 vol% (2.6 mM). Other behaviors had intermediate sensitivities. Halothane's effects reached steady-state in 10 min for all behaviors tested except immobility, which required 2 h. Recovery was complete after exposure to 1 vol% halothane but was significantly reduced after exposure to immobilizing concentrations. Conclusions Volatile anesthetics selectively disrupt C. elegans behavior. The potency, time course, and recovery characteristics of halothane's effects on three behaviors are similar to its anesthetic properties in vertebrates. The affected nervous system molecules may express structural motifs similar to those on vertebrate anesthetic targets.

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