BenchMasteryMolecular biology techniques & virtual lab

Organ-on-chip

Epithelial cells (gut, airway, kidney, brain endothelium) grow on a porous membrane between two flow channels, often with endothelial cells underneath. Barrier formation is followed with on-chip TEER and confirmed with a fluorescent tracer whose appearance in the other channel gives Papp.

TEER · functionSimulator readyCore simulatorEngine: Materials, mechanics & devices
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Barrier models

Epithelial cells (gut, airway, kidney, brain endothelium) grow on a porous membrane between two flow channels, often with endothelial cells underneath. Barrier formation is followed with on-chip TEER and confirmed with a fluorescent tracer whose appearance in the other channel gives Papp.

How it differs from the standard method

  • Coat the membrane with extracellular matrix before seeding.
  • Use gentle apical flow (tens of µL per hour) and degassed medium.
  • Subtract a cell-free chip from TEER, and check TEER against tracer permeability.
In this lesson · about 2 min read
  1. Tissue interfaces, under flow, at small scale
  2. Shear stress is the main design number
  3. Measuring a barrier on a chip
  4. How chips fail
  5. Key terms
  6. When to use it
  7. Sub-techniques

1Tissue interfaces, under flow, at small scale

An organ-on-chip is a microfluidic device in which living cells are arranged to reproduce one functional unit of an organ: an epithelium facing a lumen, an endothelium lining a vessel, or the two facing each other across a thin porous membrane. What a chip adds over a dish or a Transwell is control of the physical environment.

Barrier

Epithelium over endothelium

Gut, lung, kidney or blood–brain barrier cells on a porous membrane between two channels; read out by TEER and tracer permeability.

Vessel

Perfused endothelial channel

Endothelial cells lining all walls of a channel or a hydrogel lumen, aligned by shear, used for permeability, inflammation and drug transport.

Readout

Function, not just morphology

Resistance, permeability, secreted factors, transport and imaging, sampled from the effluent or measured in place.

2Shear stress is the main design number

In a wide, shallow channel the wall shear stress is τ = 6μQ/(wh²): it rises linearly with flow but with the inverse square of the channel height. A gut epithelium is typically perfused at tens of µL per hour, giving a few hundredths of a dyn/cm², while endothelial cells need roughly 1–20 dyn/cm² to behave like vessel lining, which takes flows of tens to hundreds of µL per minute.

3Measuring a barrier on a chip

Transepithelial electrical resistance is measured between electrodes on either side of the cell layer. In a chip the narrow channels and the membrane carry a resistance of their own, often larger than that of the cells, so the reading from a cell-free chip must be subtracted before the result is multiplied by the culture area to give Ω·cm².

4How chips fail

  • Bubbles: medium warming up releases gas, and a bubble sweeping through tears the monolayer.
  • Wrong shear: pump units confused, or a design change in channel height that was not recalculated.
  • Poor coverage: membranes or channels not coated, roofs never seeded, flow started before cells attached.
  • Absorption into PDMS: small hydrophobic drugs and hormones partition into the material and their concentration falls.
  • TEER reported without a cell-free blank, which flatters a weak barrier.

Key terms

Practise these as flashcards →
Wall shear stress

Frictional force per area that flowing medium exerts on cells; 6μQ/(wh²) in a shallow channel, quoted in Pa or dyn/cm².

TEER

Transepithelial (or endothelial) electrical resistance across a cell layer, blanked and normalised to area, in Ω·cm².

Apparent permeability (Papp)

Rate a tracer crosses a barrier per area per donor concentration, in cm/s.

Porous membrane

A thin PDMS, PET or polycarbonate sheet with micropores separating the two compartments of a barrier chip.

Mechanotransduction

Conversion of mechanical cues such as shear or stretch into cell signalling and gene expression.

Orientation index

Mean cos 2θ of the cells' long axes to the flow: 0 for random orientation, 1 for perfect alignment.

Bubble trap

An in-line chamber that catches gas before it reaches the cells.

When to use it

  • When flow, shear or two-compartment transport is part of the biology you want to study, such as absorption, barrier disruption or immune cell recruitment.
  • To test drug transport or toxicity across a human barrier with separately sampled compartments.
  • When a Transwell gives a barrier that is too leaky or too undifferentiated compared with tissue.

Compared with alternatives

Co-culture →

A static Transwell co-culture is simpler, cheaper and higher throughput when flow is not essential.

3D culture & organoids →

Organoids self-organise more complex tissue but lack perfusion and an accessible lumen.

Microfluidic fabrication →

How the PDMS device itself is made and sealed.

Bioreactor culture →

Perfused culture at larger scale, for tissue or cell production rather than a modelled interface.

Sub-techniques

Choosing one here switches the whole page, including the protocol and the lab, to it.

Epithelial cells (gut, airway, kidney, brain endothelium) grow on a porous membrane between two flow channels, often with endothelial cells underneath. Barrier formation is followed with on-chip TEER and confirmed with a fluorescent tracer whose appearance in the other channel gives Papp.

  • Coat the membrane with extracellular matrix before seeding.
  • Use gentle apical flow (tens of µL per hour) and degassed medium.
  • Subtract a cell-free chip from TEER, and check TEER against tracer permeability.