Mechanoporation

A physical method for putting molecules inside cells. Cells flow through a microfluidic constriction that briefly opens pores in the membrane, cargo diffuses in, and the membrane reseals within seconds — no electrical pulse, no viral vector, no lipid carrier.

Why mechanoporation, vs. other delivery methods?

Method

How it works

Cargos it handles

Effect on the cell

Practical limit

Electroporation

Brief electric pulse permeabilizes the membrane.

Most cargo classes.

Wide transcriptional disruption (330+ misregulated genes at q<0.05). Reduced viability and proliferation.

Often requires cell pre-activation to survive the pulse.

Lipofection / LNPs

Lipid carrier shuttles cargo across the membrane via endocytosis.

Mostly RNA and DNA.

Variable cell-type response; lipid- and endocytosis-dependent toxicity.

Not a route for proteins, RNPs, or small molecules.

Viral vectors (AAV, lentivirus)

Capsid binds the cell and delivers a packaged genome.

Genes, within a size limit.

Immunogenic; risk of integration or unwanted persistence.

Slow and expensive to produce; cargo size capped.

Mechanoporation

Cells flow through a constriction; transient pores form by mechanical deformation.

Any cargo class — proteins, RNPs, mRNA, small molecules, DELs, etc.

Effectively no transcriptional disruption (0 misregulated genes at q<0.05).

Cartridge selected per cell type.

Performance, in the data

90%+ GFP expression

Unstimulated human T cells. No pre-activation required.

0 misregulated genes

At q<0.05, 6h post-treatment vs 330+ for electroporation. DiTommaso 2018, PNAS.

>1B cells / minute

Clinical-scale throughput with MilliBooster.

Validated cell types and cargos

Mechanoporation is one platform that handles cells and payloads other methods can't. If yours isn't listed, we run feasibility studies.

Cell types

  • T cells — activated and unstimulated
  • NK cells
  • iPSCs
  • CD34+ HSCs
  • B cells
  • PBMCs — mixed populations, no isolation step
  • Monocytes & TILs
  • RBCs — including whole blood
  • Neurons
  • HeLa and other cell lines

Cargos

  • mRNA — including unmodified mRNA
  • Circular RNA (circRNA)
  • CRISPR ribonucleoproteins (Cas9, Cas12, base editors)
  • Proteins — including transcription factors, antibodies
  • Peptides & macrocycles
  • Small molecules — including membrane-impermeable compounds
  • siRNA, ASOs, and other oligos
  • DNA-encoded libraries (DELs)
  • Polymers and nanoparticles

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
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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
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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
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Talk to a scientist

Schedule a consultation with a Portal applications scientist to discuss your cell type, cargo, and scale requirements. Most feasibility studies reach initial results within 2–4 weeks.

Frequently asked questions

Q: How is mechanoporation different from electroporation?
A: Both create transient pores in the cell membrane to let cargo in. Electroporation uses an electric field; mechanoporation uses physical compression at a microfluidic constriction. The downstream consequences are very different: in DiTommaso et al., 2018 (PNAS), mechanoporation showed 0 misregulated genes at q<0.05 vs 330+ for electroporation, 16x better T cell proliferation, and 3x better HSC engraftment in vivo at comparable editing efficiency.
Q: What can mechanoporation deliver?
A: mRNA (including unmodified mRNA), CRISPR RNPs, proteins, peptides, small molecules, DNA, circRNA, siRNA, polymers, nanoparticles, antibodies, and DNA-encoded libraries (DELs). The mechanism does not depend on cargo properties, so it generalizes across most molecule classes.
Q: What cell types have been validated?
A: T cells (activated and unstimulated), NK cells, iPSCs, CD34+ HSCs, B cells, PBMCs (mixed, no pre-isolation), monocytes, HeLa, RBCs, TILs, neurons, and whole blood. If your cell type isn't listed, we offer feasibility studies.
Q: Does it work on resting / unstimulated cells?
A: Yes. One of mechanoporation's main practical advantages is that it does not require cell activation. Portal has demonstrated 90%+ delivery into unstimulated human T cells, eliminating the stimulation step that most electroporation workflows depend on.
Q: Can it scale to clinical manufacturing?
A: Yes. The MilliBooster cartridge processes >1 billion cells per minute and integrates in-line with GMP equipment from Fresenius Kabi (Lovo), Thermo Scientific (Rotea), Limula, and MultiplyLabs. No standalone instrument is required.
Q: What does a feasibility study look like?
A: We ship a Gateway instrument and cell type-specific MicroBooster cartridges to your lab. Our applications scientists work with you to optimize delivery conditions for your cargo and cell type. Most studies reach initial results within 2–4 weeks.
Q: How does pricing work?
A: Portal uses an instrument + consumables model. Gateway instruments are available for purchase or evaluation. MicroBooster and MilliBooster cartridges are single-use consumables. Academic pricing is available. Contact us for a quote.