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Record W4405916781 · doi:10.1002/smll.202409571

Heart‐on‐a‐Miniscope: A Miniaturized Solution for Electrophysiological Drug Screening in Cardiac Organoids

2024· article· en· W4405916781 on OpenAlexafffund
Pouria Tirgar, Abigail Vikstrom, José Miguel Romero Sepúlveda, Luv Kishore Srivastava, Ali Amini, Tomoka Tabata, Shuichiro Higo, Gil Bub, Allen J. Ehrlicher

Bibliographic record

VenueSmall · 2024
Typearticle
Languageen
FieldNeuroscience
TopicNeuroscience and Neural Engineering
Canadian institutionsMcGill University
FundersFonds de recherche du Québec – Nature et technologiesFonds de Recherche du Québec - SantéCanadian Institutes of Health ResearchNatural Sciences and Engineering Research Council of CanadaGovernment of CanadaMcGill University
KeywordsOrganoidInduced pluripotent stem cellCardiotoxicityCardiac electrophysiologyDrugPharmacologyElectrophysiologyQuinidineMedicineBiologyNeuroscienceInternal medicineToxicity

Abstract

fetched live from OpenAlex

Cardiovascular toxicity remains a primary concern in drug development, accounting for a significant portion of post-market drug withdrawals due to adverse reactions such as arrhythmias. Traditional preclinical models, predominantly based on animal cells, often fail to replicate human cardiac physiology accurately, complicating the prediction of drug-induced effects. Although human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) provide a more genetically relevant system, their use in 2D, static cultures does not sufficiently mimic the dynamic, 3D environment of the human heart. 3D cardiac organoids made from human iPSC-CMs can potentially bridge this gap. However, most traditional electrophysiology assays, developed for single cells or 2D monolayers, are not readily adaptable to 3D organoids. This study uses optical calcium analysis of human organoids combined with miniaturized fluorescence microscopy (miniscope) and heart-on-a-chip technology. This simple, inexpensive, and efficient platform provides robust on-chip calcium imaging of human cardiac organoids. The versatility of the system is demonstrated through cardiotoxicity assay of drugs known to impact cardiac electrophysiology, including dofetilide, quinidine, and thapsigargin. The platform promises to advance drug testing by providing a more reliable and physiologically relevant assessment of cardiovascular toxicity, potentially reducing drug-related adverse effects in clinical settings.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.033
Threshold uncertainty score0.501

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.044
GPT teacher head0.279
Teacher spread0.235 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations11
Published2024
Admission routes2
Has abstractyes

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