DEL Screening
Deliver DNA-encoded libraries into live cells for unbiased intracellular target screening and on-DNA hit validation.
Boost your DNA-encoded library into live cells, and run the selection against a target inside the cell instead of on purified protein or lysate. The library enters in proportion to its abundance, not its permeability, so enrichment after selection reflects on-DNA binding at the target. The cells stay alive through the boost, so the screen reaches intracellular targets that DNA-tagged compounds cannot enter on their own.
The Current Workflow is Broken
DEL screens can't normally be done in live cells. The DNA tags that encode each compound also keep the library from crossing the membrane, so conventional selections are limited to purified protein and extracellular targets. Intracellular targets, and proteins that only fold or partner correctly inside a cell, stay out of reach.
01
Screen DEL library
02
Hits limited to extracellular targets
03
Intracellular targets remain inaccessible
Dead End
Portal has the Solution
01
Prepare
Cells of choice (iPSC, HeLa, PBMCs…)
02
Mix
Cells + DEL library
03
Boost
Gateway™ mechanoporation
04
Incubate
Allow intracellular interaction
05
Readout
Selection / sequencing
Unbiased, validated intracellular hits
Any cell type
iPSCs · HeLa · PBMCs
No library bias
Proportional delivery R²=0.93
Intracellular access
Screen targets previously out of reach
The cargo and protocols below make this kit specific. The core consumables, settings, and support ship with every Portal kit.
Your Library
Reagents & Consumables
Protocol & Settings
Support
Your Library
Reagents & Consumables
Protocol & Settings
Support
We boosted a DNA-encoded library into iPSCs and HeLa cells and read delivery with a co-delivered probe by flow cytometry. About 80% of live cells were DEL-probe positive in both cell types, against effectively none in the unboosted control. The boost is gentle enough that the cells stay alive to go into selection.
We compared the delivered library against the diluted input across every member. The two track closely (R² = 0.93), and two replicate boosts agree even more tightly (R² = 0.98), so members enter in proportion to how abundant they are rather than by how permeable each one is. After selection against the target the correlation with the input drops to R² = 0.77 as true binders enrich.
DNA-encoded chemical libraries are screened against purified protein outside of cells. Portal changes that — delivering full DEL constructs directly into the cytoplasm of live cells, so selections can run against targets in their native environment.
mRNA, siRNA, saRNA
Proteins & Peptides
CRISPR RNPs
Small Molecules
Polymers
Nanoparticles
Antibodies
Virus
PBMCs
T cells
B cells
NK cells
iPSCs
Monocytes
RBCs
HSCsmRNA, siRNA, saRNAProteins & PeptidesCRISPR RNPsSmall MoleculesPolymersNanoparticlesAntibodiesVirusPBMCsT cellsB cellsNK cellsiPSCsMonocytesRBCsHSCsValidated live-cell workflows for target engagement, compound profiling, and beyond.
Every kit includes: Cargoes · Optimized protocols · MicroBooster™ cartridges · Suggested readouts · Reagents
