WORKFLOW KIT · COMPOUND SCREENING

Intracellular DEL
Screening Kit

Deliver DNA-encoded libraries into live cells for unbiased intracellular target screening and on-DNA hit validation.

Every kit includes: Your DEL library + Portal reagents · Optimized protocols · MicroBooster™ cartridges · Delivery tracer · Suggested selection & sequencing readouts

Upgrade Your Workflow

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

What's in the Kit

The cargo and protocols below make this kit specific. The core consumables, settings, and support ship with every Portal kit.

Your Library

  • Your DNA-encoded library (DEL)
  • A single pool or several pools
  • Small or large libraries

Don't see your cargo? Ask us about custom configurations

Reagents & Consumables

  • Delivery tracer
  • MicroBooster™
  • Portal reagents

Protocol & Settings

  • Protocol for intracellular DEL delivery
  • Recommended cell concentrations
  • Suggested selection & sequencing readouts

Support

  • Screen and cell-type design with a Portal scientist
  • Optional: hands-on implementation visit

Your Library

  • Your DNA-encoded library (DEL)
  • A single pool or several pools
  • Small or large libraries

Don't see your cargo? Ask us about custom configurations

Reagents & Consumables

  • Delivery tracer
  • MicroBooster™
  • Portal reagents

Protocol & Settings

  • Protocol for intracellular DEL delivery
  • Recommended cell concentrations
  • Suggested selection & sequencing readouts

Support

  • Screen and cell-type design with a Portal scientist
  • Optional: hands-on implementation visit

Proof Points

A Single Boost Delivers the Library into iPSCs and HeLa

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.

The Library Is Delivered Proportionally, Without Bias

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.

Broad Compatibility

Portal’s platform supports delivery to a diverse range of cell types and cargoes

Delivery materials
Validated cell types
mRNA, siRNA, saRNA
Proteins & Peptides
CRISPR RNPs
Small Molecules
Polymers
Nanoparticles
Antibodies
Virus
PBMCs
T cells
B cells
NK cells
iPSCs
Monocytes
RBCs
HSCs
Delivery materials
mRNA, siRNA, saRNA
Proteins & Peptides
CRISPR RNPs
Small Molecules
Polymers
Nanoparticles
Antibodies
Virus
Validated cell types
PBMCs
T cells
B cells
NK cells
iPSCs
Monocytes
RBCs
HSCs

Check out our other kits

Validated live-cell workflows for target engagement, compound profiling, and beyond.

Every kit includes: Cargoes · Optimized protocols · MicroBooster™ cartridges · Suggested readouts · Reagents

Impermeable Candidate Validation in Live Cells

  • Solves: Permeability engineering as a prerequisite for testing cellular activity
  • Cargo: Your impermeable drug candidate
  • Validate and test your candidates in live cells, regardless of permeability
  • e.g. small molecules, macrocycles, peptides
Download Info

Live-Cell Protein Detection

  • Solves: Live-cell context lost to lysis, and target labeling that requires cell engineering.
  • Cargo: Intracellular antibodies (primary & secondary)
  • Measure endogenous intracellular proteins in live cells
  • e.g. p-BTK, p-ERK, p-AKT, p-STAT3, p-MET Compatible with LgBiT/HgBiT reagents
Download Info

Live-Cell Target Engagement

  • Solves: Live-cell context lost to lysis and detergents, and the need to create cell-permeable tracers
  • Cargoes: Your tracers (e.g. NanoBRET) and compounds
  • Enables live-cell target engagement without lysis; supports impermeable tracers
  • e.g. kinase inhibitor profiling, degrader engagement
Download Info

Controllable Surface Antigen Expression

  • Solves: Fixed, hard-to-modulate surface antigen expression in cell lines
  • Cargo: Custom antigen/receptor RNA — single or combinations
  • Express any antigen on any cell in hours
  • e.g. CD19+CD3, BCMA+CD3, HER2+CD3
Download Info

Direct-to-Assay

  • Solves: The stable-line bottleneck: infeasible in primary cells, slow and laborious elsewhere
  • Cargo: Custom RNA encoding tagged POI
  • Run NanoBRET or LgBiT/HgBiT without stable lines
  • e.g. VHL-NanoLuc, HgBiT-tagged POI, HA-tagged POI
Download Info

Questions before your first run

Ready to run the Intracellular DEL Screening Kit?

Request the kit and a Portal scientist will spec it for your cells, cargo, and readout.