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Record W4402340874 · doi:10.1101/2024.09.03.611092

A Digital Microfluidic Platform for the Microscale Production of Functional Immune Cell Therapies

2024· preprint· en· W4402340874 on OpenAlexaff
Samuel R. Little, Niloufar Rahbari, Mehri Hajiaghayi, Fatemeh Gholizadeh, Fanny-Meï Cloarec-Ung, Joel Phillips, Hugo Sinha, Alison Hirukawa, David J.H.F. Knapp, Peter J. Darlington, Steve C. C. Shih

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2024
Typepreprint
Languageen
FieldMedicine
TopicCAR-T cell therapy research
Canadian institutionsInstitute for Research in Immunology and CancerUniversité de MontréalConcordia University
Fundersnot available
KeywordsMicroscale chemistryMicrofluidicsProduction (economics)Immune systemNanotechnologyComputer scienceBiologyMaterials scienceImmunologyEconomicsMathematics

Abstract

fetched live from OpenAlex

Abstract Genetically engineering human immune cells has been shown to be an effective approach for developing novel cellular therapies to treat a wide range of diseases. To expand the scope of these cellular therapies while solving persistent challenges, extensive research and development is still required. Electroporation has recently emerged as one of the most popular techniques for inserting biological payloads into human immune cells to perform genetic engineering. However, several recent studies have reported that electroporation can negatively impact cell functionality. Additionally, the requirement to use large amounts of cells and expensive payloads to achieve efficient delivery can drive up the costs of development efforts. Here we use a digital microfluidic enabled electroporation system (referred to as triDrop) and compare them against two state-of-the-art commercially available systems for the engineering of human T cells. We describe the ability to use triDrop for highly viable, highly efficient transfection while using substantially fewer cells and payload. Subsequently, we perform transcriptomic analysis on cells engineered with each of the three systems and show that electroporation with triDrop lead to less dysregulation of several functionally relevant pathways. Finally, in a direct comparison of immunotherapeutic functionality, we show that T cells engineered with triDrop have an improved ability to mount an immune response when presented with tumor cells. These results show that the triDrop platform is uniquely suited to produce functionally engineered immune cells while also reducing the costs of cell engineering compared to other commercially available systems.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.001
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.023
GPT teacher head0.248
Teacher spread0.225 · 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 source (direct Gemma or distilled Codex), 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

Citations1
Published2024
Admission routes1
Has abstractyes

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Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicCAR-T cell therapy researchFrench-language works237,207