Portal Enables Novel Insights in Drug Discovery

Portal Unlocks Novel Drug Discovery Opportunities

Hit Identification

Direct intracellular access for poorly permeable molecules . Use the drug screening cell cartoon

Appnote

Assay Reagent Delivery

Impermeable tagged probes, proteins, and antibodies

Appnote

Primary Cell Assays

Gene edit or modulate primary cells for assays

Appnote

Direct to Biology Assays

intracellular delivery of DEL libraries

Appnote

HT Primary Cell CRISPR Screens

Conduct large library crispr screening

Appnote

Portal is Developing a Universal Cell Engineering Solution

Portal’s proprietary membrane technology uses mechanical disruption and enables massive parallelization

Portal Lets You Bring Your Favorite Assay Into the Cell

Today

Biochemical screening does not capture the complexity of the intracellular space

With Portal

Cytosolic delivery of candidate molecules enables novel insights regardless of permeability

DELs in Cells: Portal has demonstrated robust delivery of DNA encoded libraries

Portal Makes it Easy to Probe the Intracellular Space

Today

Most molecular probes, such as antibodies, are cell impermeable - restricting their utility

With Portal

Portal enables delivery of diverse probe molecules into cells for intracellular insights

Probes with Portal: Protein detection probes can be used to measure protein levels and their degradation in live cells

Intracellular Antibody-based Detection of Proteins

Portal technology has been integrated with your favorite tool providers

Products

Gateway

Research Scale

Benchtop instrument for discovery research

0.5-10M cells per run

50-200 µl volume range

compact benchtop unit that fits in any hood

Available now

Galaxy-i

High-Throughput Screening

High throughput scale instrument for screening applications with multi well plates.

96/384-well plate compatibility

Integrate with existing automation

Ideal for DEL, PROTAC, crispr screening

Available now

Millibooster

Clinical Manufacturing

GMP-ready clinical production system

1 billion+ cells/minute throughput

Attach to existing equipment via tube-weld or luer lock connection

2-100mL volume range

Available Now

Portal vs Traditional Approaches

Application	Traditional Approach	Key Issues	Avg Delay and Cost	Portal's Approach	Key Advantages
DEL Screening	Cell-free biochemical or lysate screens	DNA tags cause impermeability; miss cellular context	6–12 months; $500K–$1M MedChem before cell testing	Delivers DEL compounds into cytosol, enabling live-cell screening despite DNA barcode impermeability	Early biological de-risking; bypass MedChem for non-viable hits; immediate cellular testing
Target Engagement	Cell lysates or permeabilized cells (CETSA, BRET, FRET)	Destroys native environment; impermeable tracers require lysis	2–4 weeks per compound; limited to permeable probes	Delivers NanoBRET/CETSA reagents into intact cells, enabling real-time drug-target measurement	Real-time kinetics in intact cells; preserves target conformation and post-translational modifications
PROTAC Discovery	Lysate-based assays; engineered lines; endpoint measurements	Miss temporal dynamics; cannot use primary cells; destroys degradation machinery	4–8 weeks validation; $200K–$500K per candidate	Delivers LgBiT for intracellular HiBiT complementation, enabling real-time degradation monitoring	Live-cell kinetic profiling; test in primary cells; real-time pharmacology
Macrocyclic or Linear Peptides	Limited to permeable peptides; low-efficiency endocytosis	80% of chemical space inaccessible; modifications compromise activity	12–18 months permeability optimization; frequent failures	Achieves ~80% delivery in HEK293 with linear dose-response, decoupling permeability from binding optimization	Access full peptide chemical space; optimize binding without permeability constraints
Hit-to-Lead	Biochemical screen → MedChem → cell testing	MedChem investment before validation	~1 year; $1M+ before cell validation	Enables direct-to-biology screening—test hits immediately in live cells before MedChem investment	Verify activity before MedChem; save time and money on non-viable scaffolds
Phenotypic Screening	Engineered lines; electroporation causes dysfunction	Primary cells difficult to transfect; electroporation alters phenotypes	3–6 months; limited to model lines	Delivers compounds into primary cells at HTS scale, preserving function in iPSCs, T cells, disease-relevant types	Disease-relevant primary cell screens; preserved phenotypes; efficient multiplex delivery; HTS compatible