This article and associated images are based on a poster originally authored by Wambeke E, Boribong BP, Sinha H, Patel M, Vo PQN, Chin AB, Ellouzi A, Barlan K and Hirukawa A and presented at ELRIG Drug Discovery 2025 in affiliation with Abbvie and DropGenie.
This poster is being hosted on this website in its raw form, without modifications. It has not undergone peer review but has been reviewed to meet AZoNetwork's editorial quality standards. The information contained is for informational purposes only and should not be considered validated by independent peer assessment.
Introduction
Arrayed gene editing screens enable high dimentional data generation
Image Credit: Image courtesy of Wambeke E et al., in partnership with ELRIG (UK) Ltd.
Editing biologically relevant models like primary cells at scale is challenging
Image Credit: Image courtesy of Wambeke E et al., in partnership with ELRIG (UK) Ltd.
Sample scarcity
- Limited proliferative runway
- Bottlenecks to donor access
Cost
- Expensive to culture and procure cells
- Reagent costs rise quickly with scale
Digital microfluidics enables 100x miniaturized cell engineering
Digital microfluidics enables highly miniaturized electroporation for cell engineering. DropGenie digital microfluidic (DMF) cartridges (left) use patterned electrodes and a modular top plate to manipulate nanoliter-scale droplets. Editing cargo (Cas9 nuclease and sgRNA) and human cells are combined in discrete droplets (top right) and electroporated within microchambers (center). Cross-sectional schematic (bottom) illustrates the DMF architecture, with cells and reagents confined between the coated top plate and PCB substrate. This platform enables 100× miniaturization compared to conventional systems, reducing input requirements to as few as 10,000 cells per edit. Image Credit: Image courtesy of Wambeke E et al., in partnership with ELRIG (UK) Ltd.
With seamless integration into automation workflows for scale
DropGenie Workflow. Guides are deposited onto the DropGenie Chip using an ECHO acoustic dispenser (BCLS), and cells with payload are loaded into the cartridge with a Liquid Handler (Integra Assist+). The system runs with user-defined parameters, after which cells are plated for culture and recovery. Transfection efficiency is then assessed via flow cytometry, sequencing, or fluorescence microscopy. Image Credit: Image courtesy of Wambeke E et al., in partnership with ELRIG (UK) Ltd.
For robust, miniaturized editing of primary immune cells
Miniaturized DMF electroporation enables efficient TRAC knockout in primary human T cells. Representative flow cytometry gating strategy (top left) shows singlet, live, and CD4⁺/CD8⁺ T cell populations used to quantify TCRα/β knockout efficiency. Example plots demonstrate loss of TCR expression following TRAC sgRNA editing compared to non-targeting control (NTC). Editing efficiency (top right) was robust in both CD4⁺ and CD8⁺ subsets, reaching ~88–90 % KO across 40 replicates, while controls exhibited only background signal. Cell viability (bottom left) remained >90 % across all conditions. Summary statistics (bottom right) confirm high knockout efficiency with low variability (CD4⁺ mean 88.4 % ± 4.9 %; CD8⁺ mean 89.8 % ± 4.2 %) and strong reproducibility across donors. A total of 10,000 cells per edit were used, representing a 100× reduction in input compared to conventional electroporation systems. Image Credit: Image courtesy of Wambeke E et al., in partnership with ELRIG (UK) Ltd.
Study objectives and methods
- Reduce gene editing cell input requirements to enable use of patient-derived material at scale
- Quantify the cost saving of efficient editing through reagent and workflow miniaturization
- Optimize a miniaturized, automation-compatible CRISPR editing protocol for primary cell models relevant to Rheumatoid Arthritis (RA)
- Primary Fibroblast Like Synoviocytes (FLS) cells from RA donor, used at 70 % confluence
- Validate platform with mRNA transfection
- GFPmRNA (Tri-Link). Evaluate %GFP Imaging: Operetta CLS (Revvity), 24 hours post transfection
- Achieve robust and reproducible gene knockout
- Multi-guide CD81 gene knockout
- synthetic guide RNA (IDT), Cas9 nuclease (IDT), Electroporation enhancer (IDT)
- 3 sequences targeting CD81 (IDT)
- At 7 d, cells fixed and stained with Hoechst (nuclei) and anti-CD81 + fluorescent secondary. Imaging: Operetta CLS (Revvity), 5× magnification, 2 fields/sample. %CD81⁻ quantified as (#CD81⁺/# nuclei).
Miniaturized CRISPR editing in primary synoviocytes
High-efficiency delivery of GFP mRNA into primary fibroblast-like synoviocytes
Image Credit: Image courtesy of Wambeke E et al., in partnership with ELRIG (UK) Ltd.
High-efficiency CRISPR knockout of CD81 in primary fibroblast-like synoviocytes
Image Credit: Image courtesy of Wambeke E et al., in partnership with ELRIG (UK) Ltd.
Quantification of cost savings per RNP mediated CRISPR KO edit
Conventional Electroporation
Cell input/ reaction
Source: ELRIG (UK) Ltd.
| . |
. |
. |
| Primary FLS cells |
25,000 |
3,000 |
Reagent cost/ reaction
Source: ELRIG (UK) Ltd.
| . |
. |
. |
| Cas9 nuclease |
30 pmol |
3 pmol |
| sgRNA |
60 pmol |
5 pmol |
| Electroporation Enhancer |
30 pmol |
3 pmol |
| Total cost per reaction |
$17.87 |
$1.69 |
Conclusions
- Miniaturized DMF electroporation enables high efficiency CRISPR KO in primary FLS
- >8× reduction in cells per reaction (3,000 FLS cells / edit)
- GFP mRNA delivery: >90 % transfection
- CD81 KO up to 85 % across Rheumatoid Arthritis donors
- Automation-integrated workflow ensures precision, reproducibility and scale
- Consumable compatibility wih ECHO 655T
- Seamless integration with Integra Assist+ Liquid handler minimizes handling loss
- >10× cost savings while preserving scarce patient cells
- Cost reduction from $17.87 → $1.69 per edit
- Unlocks scalable functional genomics in Rheumatoid Arthirtis-relevant primary cells, enabling discovery of new therapeutic targets
Disclosures
AbbVie authors may hold stock and shares in AbbVie. DropGenie authors may hold shares in DropGenie. Platform used for Research Use Only (RUO).
About DropGenie
DropGenie has optimized the miniaturization and parallelization of cell engineering reactions using patented chip technology. This is achieved by precisely delivering a wide range of editing reagents into diverse cell types at low volumes, enabled through intelligent tuning of electrical parameters and a proprietary electrode configuration.
About ELRIG (UK) Ltd.
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Last Updated: Jan 6, 2026