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“Infected Body-on-a-Chip”: Microfluidic Impedance Platform for Antischistosomal Drug Discovery

English title “Infected Body-on-a-Chip”: Microfluidic Impedance Platform for Antischistosomal Drug Discovery
Applicant Hierlemann Andreas
Number 166329
Funding scheme Interdisciplinary projects
Research institution Computational Systems Biology Department of Biosystems, D-BSSE ETH Zürich
Institution of higher education ETH Zurich - ETHZ
Main discipline Other disciplines of Engineering Sciences
Start/End 01.11.2016 - 31.10.2020
Approved amount 862'882.00
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All Disciplines (2)

Discipline
Other disciplines of Engineering Sciences
Tropical Medicine

Keywords (6)

Microfluidics; Impedance measurements; Helminths; Schistosoma; Drug testing; Toxicity

Lay Summary (German)

Lead
Mikrofluidik-basiertes Verfahren zum umfassenden und effektiven Testen von Medikamentenkandidaten gegen die Tropenkrankheit Schistosomiasis
Lay summary

Schistosomiasis ist ein Tropenkrankheit, die durch einen Wurmparasiten hervorgerufen wird und an der Millionen von Menschen erkrankt sind. Wenn die Krankheit nicht behandelt wird, kann sie zu schweren Hirnstörungen und geistigen Behinderungen führen. Die Entwicklung eines wirksamen und billigen Medikaments ist vor allem für arme Leute wichtig, die sich keine teuren Behandlungen leisten können. Leider sind in den letzten Jahren nur wenige Medikamente entwickelt worden, weil der Drug-Screening Prozess in aufwendiger und zeitraubender Handarbeit gemacht wird.  

Mit diesem Projekt wollen wir das Problem des Testings angehen und versuchen ein mikrofluidisches System zur Durchführung umfassender und schneller Tests entwickeln. Das System soll ermöglichen, dass Dose-Response Kurven im Larvenstadium der Parasiten gemessen werden können, so dass der ganze Prozess objektiver und automatisierbar wird. Zudem werden beim Test gleichzeitig metabolische Parameter miteinbezogen und die Toxizität der Medikamentenkandidaten für Herz und Leber abgeschätzt. Dazu werden Spheroide dieser Gewebe direkt im Drug Testing eingesetzt.

Direct link to Lay Summary Last update: 17.10.2016

Responsible applicant and co-applicants

Employees

Publications

Publication
Evaluation of Human Liver Microtissues for Drug Screening on Schistosoma mansoni Schistosomula
Lombardo Flavio C., Ravaynia Paolo S., Modena Mario M., Hierlemann Andreas, Keiser Jennifer (2020), Evaluation of Human Liver Microtissues for Drug Screening on Schistosoma mansoni Schistosomula, in ACS Infectious Diseases, 1.
Parallelized Impedance‐Based Platform for Continuous Dose‐Response Characterization of Antischistosomal Drugs
Ravaynia Paolo S., Lombardo Flavio C., Biendl Stefan, Dupuch Matthias A., Keiser Jennifer, Hierlemann Andreas, Modena Mario M. (2020), Parallelized Impedance‐Based Platform for Continuous Dose‐Response Characterization of Antischistosomal Drugs, in Advanced Biosystems, 4(7), 1900304-1900304.
Parallelized Wireless Sensing System for Continuous Monitoring of Microtissue Spheroids
Dong Lei, Ravaynia Paolo S., Huang Qing-An, Hierlemann Andreas, Modena Mario M. (2020), Parallelized Wireless Sensing System for Continuous Monitoring of Microtissue Spheroids, in ACS Sensors, 5(7), 2036-2043.
Impedance-Based Microfluidic Assay for Automated Antischistosomal Drug Screening
Chawla Ketki, Modena Mario M., Ravaynia Paolo S., Lombardo Flavio C., Leonhardt Martin, Panic Gordana, Bürgel Sebastian C., Keiser Jennifer, Hierlemann Andreas (2018), Impedance-Based Microfluidic Assay for Automated Antischistosomal Drug Screening, in ACS Sensors, 3(12), 2613-2620.
Impedance-based detection of Schistosoma mansoni larvae viability for drug screening
Modena M. M., Chawla K., Lombardo F., Bürgel S. C., Panic G., Keiser J., Hierlemann A. (2017), Impedance-based detection of Schistosoma mansoni larvae viability for drug screening, in 2017 IEEE Biomedical Circuits and Systems Conference (BioCAS), 1-4, IEEE, Piscataway, USA1-4.

Collaboration

Group / person Country
Types of collaboration
InSphero AG Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Industry/business/other use-inspired collaboration

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
MicroTAS 2019 Poster Passive wireless sensing of microtissue properties 27.10.2019 Basel, Switzerland Modena Mario; Hierlemann Andreas;
MPI Research Seminars Individual talk Antischistosomal drug discovery: from visual scoring to impedance-based microfluidic platform 27.02.2019 Basel, Switzerland Ravaynia Paolo; Lombardo Flavio;
MicroTAS 2018 Poster Microfluidic impedance platform for long-term detection of parasite viability 11.11.2018 Kaohsiung, Taiwan Modena Mario; Lombardo Flavio; Hierlemann Andreas; Keiser Jennifer; Ravaynia Paolo;
Swiss Society of Tropical Medicine and Parasitology Poster Microfluidic platform as a drug screening tool to identify novel treatments against schistosomiasis 13.09.2018 Interlaken, Switzerland Lombardo Flavio;
Dechema - 3D cell culture Poster Impedance analysis of viability of Schistosoma mansoni larvae for drug screning applications 07.06.2018 Freiburg, Germany Modena Mario; Hierlemann Andreas; Lombardo Flavio; Keiser Jennifer;
SELECT Bio Lab-on-a-chip and microfluidics Europe conference Talk given at a conference Microfluidic platform for parallelized and automated viability detection of Schistosoma mansoni 05.06.2018 Rotterdam, Netherlands Lombardo Flavio; Hierlemann Andreas; Modena Mario; Ravaynia Paolo; Keiser Jennifer;
International Research and Innovations in Schistosomiasis Talk given at a conference Alternative drugs for schistosomiasis: advances from lab and field 23.05.2018 Washington DC, United States of America Keiser Jennifer;
MALARIA AND NEGLECTED PARASITIC DISEASES: CORE SCIENCE AND PERSPECTIVES Talk given at a conference Tackling schistosomiasis: from bench to field 02.03.2018 Bologna, Italy Keiser Jennifer;
21st International Conference on Miniaturized Systems for Chemistry and Life Sciences (µTAS) Talk given at a conference Microfluidic Impedance Platform for Automated Schistosomal Motility Detection 22.10.2017 Savannah, GA, United States of America Lombardo Flavio; Modena Mario; Hierlemann Andreas;
IEEE Biomedical Circuits and Systems Conference (BioCAS) Poster Impedance-based detection of Schistosoma mansoni larvae viability for drug screening 19.10.2017 Turin, Italy Hierlemann Andreas; Keiser Jennifer; Modena Mario;


Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions 2nd BEL-PEL Conference on Emerging Topics in Science International 2019
Talks/events/exhibitions Open laboratory at D-BSSE of ETHZ Western Switzerland 2019

Associated projects

Number Title Start Funding scheme
173728 Visual processing in foveated retinæ in the presence of self-motion 01.01.2018 Sinergia
188910 Deciphering Neuronal Networks: Advancing Technology and Model Systems 01.10.2020 Project funding (Div. I-III)

Abstract

Schistosomiasis is a disease caused by a neglected tropical worm that parasitizes millions of people annually. Left untreated, it becomes chronically debilitating and is, therefore, known as one of the diseases that perpetuate the “poverty trap”- those who have it are likely to become poorer and those who are poorer are more likely to become infected. Treatment options are limited to a single drug, praziquantel, for which the threat of resistance is real and plausible. The need for new drugs is, therefore, urgent, yet the drug discovery pipeline is woefully dry. A big part of the problem is the in vitro drug screening process: most methods rely on manual microscopic evaluation of drug effects on living parasites, which is slow, arduous, subjective, and offers limited data. Therefore, these evaluation methods urgently need to be updated. Attempts at automation have led to some innovations, but with limited scope. Moreover, once drug leads have been identified in vitro, it can be tremendously difficult to observe corresponding efficacy in vivo. Many new methods in drug discovery originate from the field of microfluidics, which also include innovative methods to monitor the status of cells or tissues by means of electric impedance spectroscopy (EIS). This fact has motivated the Helminth Drug Development Unit (HDDU) at the Swiss Tropical and Public Health Institute and the Bio Engineering Laboratory (BEL) at the ETH Zurich to combine their expertise and innovate on an “infected body-on-a-chip” (iBoC) microfluidic EIS platform for antischistosomal drug discovery. The device will allow, for the first time, to measure continuous, online drug dose-response effects on the larval stage of the worms, rendering the screening process higher throughput, more objective, and richer in quality data. The chip will incorporate spherical myocardial and liver microtissues, which, upon exposure to the drug, will capture two highly relevant toxicity parameters- cardiotoxicity and hepatotoxicity. The liver spheroids, included in the testing procedure with the schistosomes, will also be used to model drug metabolism and enable us to immediately predict, whether a compound will lose its antischistosomal activity in vivo as a result of metabolic processes. By screening compounds directly in the presence of both, newly transformed schistosomula (NTS) and liver spheroids, we may even be able to identify prodrugs. Finally, we will use the chip to analyze, why a set of already tested compounds might have failed in vivo. If we can characterize efficacious in vitro compounds and also the reasons for why they are likely to fail or succeed in vivo, we will not only be able to better predict good candidates for in vivo tests, but also gain a deep understanding of the pivotal aspects in finding effective antischistosomal drugs.
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