Table 1 Membranes in OOC studies, characteristics, and applications

PDMS

Gut: Recapitulation of intestine

Coculture with L. rhamnosus⁴¹

30 mL/h

0.02 dyne/cm²

Cyclic strain (10%; 0.15 Hz)

Soft lithography (casting on a microfabricated silicon wafer from MEMS and Nanotechnology Exchange)

Oxygen plasma

30 μm

10 µm; 25 µm

Matrigel® and collagen Type I (Caco-2)

PDMS

Small intestine: Biopsy-derived epithelium cultured on-chip for transcriptomic comparison; duodenum-like¹¹⁸

60 μl/h

Strain (10%; 0.2 Hz)

Both fabricated (Kim 2012 soft lithography) & purchased from Emulate, Inc.

Oxygen plasma

50 μm

7 μm; 40 μm

Matrigel® and collagen Type I (HIMECs)

PDMS

Gut: Transepithelial barrier structure and tissue structure (impedance spectroscopy)¹¹⁷

30 μl/hr.

4.1 × 10⁻⁴ dyne/cm² (41 μPa)

Electrical stimulation AC current of 10 μA at 50 frequencies in the range of 100–10 Hz

Kim 2012–soft lithography (casting on a microfabricated silicon wafer)

Oxygen plasma

50 μm

7 μm; 40 μm

Matrigel® and collagen Type I (Caco-2)

PDMS

Intestine: Host-microbiome interactions³³

60 μl/hr.

N/A

Huh 2013 - silicon wafer using photolithography, removing silicon by DRIE. Obtained from MEMS and Nanotechnology Exchange

Organ Chip (Emulate Inc.)

Oxygen plasma

10 μm

10 µm; 25 µm

Matrigel® and collagen Type I (Caco-2, HIMECs)

PDMS

Kidney: coculture of primary glomerular endothelial and hiPS-derived podocyte

Recapitulation of glomerulus, selective permeability⁴³

60 μL/h

Top channel: 0.0007 dyne/cm² Bottom channel: 0.017 dyne/cm²

Cyclic strain (10%; 1 Hz, −85 kPa)

Huh, 2010. Stereolithography molds (ProtoLabs) and spincoating

Oxygen plasma

50 μm

7 μm; 40 μm

Laminin (hiPS-derived podocytes)

PDMS

Alveolus: Thrombosis model

Primary human lung alveolar epithelial cells culture, human whole blood used.

Evaluation of therapeutic alternative: protease activated receptor-1 (PAR-1) antagonist.²⁴

Wall shear rate ~10 dyne/cm² (250 s⁻¹)

N/A

Casting against DRIE silicon wafer

Oxygen plasma

50 μm

7 μm; 40 μm

Collagen I, fibronectin (Primary alveolar cells, HUVECs)

PDMS

Gut: Independent control of fluid flow and mechanical deformations to explore the influence of each in morphogenesis³⁴

30 mL/h

Cyclic strain (10%; 0.15 Hz)

Kim 2012–soft lithography (casting on a microfabricated silicon wafer)

Oxygen plasma

20 μm

10 µm; 25 µm

Matrigel® and collagen Type I (Caco-2)

PDMS

Alveolus: Replication of breathing motion, air‒blood barrier and air-liquid interface

Coculture: primary human lung alveolar cells (hAEpCs) and primary lung endothelial cells⁴⁸

N/A

Cyclic strain (0.2 Hz)

Microstructuring-lamination

Oxygen plasma

3.5 μm

3 µm; 800,000 pores/cm²

Collagen IV (epithelial cell line, 16HBE14o), collagen I (primary cell line, hAEpC)

PDMS

Lung: Replication of idiopathic pulmonary fibrosis (IPF), pathological study on wound healing

Treatment with recombinant human hepatic growth factor (rhHGF)⁴

N/A

Cyclic strain (10%; 0.2 Hz)

Microstructuring-lamination

Clamping (sandwich)

3.5 μm

3 µm; 800,000 pores/cm²

Fibronectin (A549 epithelial cells)

PDMS

Vessel: Coculture of aortic endothelial cells (ECs) and human aortic vascular smooth muscle cells (VSMCs)

Mimicking of arterial wall⁴⁴

20 μl/min

shear stress of 1–1.5 Pa and strain of 5–8%

Pressure flow: 1 mbar/h increments until 15 mbar ( ≈ 1–1.5 Pa endothelial shear stress)

Vacuum pressure −10 mbar/hr. steps until −200 mbar

Laser excimer (UV)

Oxygen plasma (asher)

10 μm

10 µm; 28 µm

Fibronectin (ECs- HaVECs, VSMCs- hAoSMCs)

PDMS

Microfluidic device: Combine temperature, pressure, and moisture to generate micron-scale pores on a PDMS membrane. Relate those parameters with pore size and adhesion to DNA, and collagen.⁷⁹

20 μl/min

N/A

High-pressure saturated steam

Thermal treatment

40 μm

5 µm

Parylene-C, collagen (platelets)

PDMS

Organ-on-a-chip: Viability of cell culturing: Human umbilical endothelial cells (HUVEC) and MDA-MB-231 (MDA) cells¹⁴

N/A

N/A

Photolithography, dry and wet etching

PDMS/toluene mortar; Oxygen plasma

1–4 μm

2–10 μm; 8–65%

Fibronectin (HUVEC-primary, MDA-cancer)

SiO₂

Chip: Ultrathin membrane for support of physiologically relevant cellular interactions

Optically transparent

Human umbilical vein endothelial cells (HUVECs) spread and proliferate on these membranes.⁶⁹

N/A

N/A

Photolithography and reactive ion etching

Ozone

300 nm (comparable in thickness to the vascular basement membrane of 100–300 nm)

0.5 and 3 μm; 27.5%

Geltrex (Life Technologies, California) HUVECs

PLGA

Lung tumor: Gefitinib drug testing

Permeability, coculture¹

N/A

N/A

Electrospinning

PLGA direct sealing

3 μm

NA, nanofiber

(A549 epithelial cells)

Collagen-elastin

Lung: Air‒blood barrier replication, exposed to mechanical forces

Gold mesh to mimic alveolar size and structure³

N/A

Strain 10%; 4.0 kPa

Gelation

Double tape

10 μm

hAEpCs (primary cells)

Collagen

Kidney: Endothelial-epithelial exchange interface, reabsorption mechanism¹³⁷

10 µl/min

Wall shear stress ~1–10 dyne/cm²

N/A

Compression molding

Screwing

25 μm

NA

hRVTU, HUVECs

Collagen

Colon: Suitability of membrane for OOC, comparison w/Transwell ®

Microstructure, transport and cell viability¹³⁶

N/A, media changed daily

N/A

Lyophilization

Sandwiching

~15 μm

~10.2 μm

Caco-2

Collagen

Microfluidic device: Cell attachment, growth

physiologically relevant in vitro cell culture models¹⁹

70–100 µl/hr.

N/A

Vitrification

PDMS mortar

20 μm

250 nm

HUVECs

PDMS*

Colon: Mucus layer physiology¹¹⁹

60 µl/hour

N/A

CHIP-S1 Stretchable Chip, RE00001024 Basic Research

1680

Kit; Emulate, Inc

50 μm

7 μm; 40 μm

Matrigel® and collagen Type I (primary colonic intestinal epithelial cells)

PDMS*

Spinal cord: Vascular-neural interaction

Specific gene activation enhanced neuronal function and in vivo-like signatures.¹⁰²

N/A

N/A

Emulate, Inc.

50 μm

7 μm; 40 μm

Matrigel® (neural, spMNs)

Collagen IV and fibronectin (vascular, BMECs)

Polyester*

Intestine: Long-term culture up to 30 days

Rhohdamine 123 basal to apical flow¹⁰³

N/A

Magnetic stir bar to pump media

Corning (Transwell ®)

Oxygen plasma

10 μm

0.4 μm

Type I collagen (Caco-2)

Polyester*

Kidney: Primary rat inner medullary collecting duct (IMCD) cells¹¹⁵

Primary kidney epithelial cells

Enhanced epithelial cell polarization and primary cilia formation.

Cisplatin toxicity and Pgp efflux transporter activity measured on-chip.¹¹⁰

0.2 dyne/cm² (physiological conditions renal system: 0.2–20 dyne/cm², ~10% of the endothelial cell)

1 dyne/cm² for 5 h

N/A

Corning (Transwell ®)

Oxygen plasma

10 μm

0.4 μm

Fibronectin, Collagen Type IV (PTEpiC, primary)

PET*

Gut: Immune response, microbial pathogenicity mechanisms, and quantification of cellular dysfunction

Probiotic L. rhamnosus

Pathogen Candida albicans¹⁶¹

Flow rate: 50 μl/min

Endothelial: 0.07 Pa

Luminal: 0.01 Pa

N/A

TRAKETCH Sabeu, Radeberg, Germany

Polystyrol (PS) foil (microfluidic ChipShop, Germany)

12 μm

8 μm; 1 × 10⁵ pores/cm²

HUVECs, Caco-2

PET*

Gut: Transport study of amoxicillin, antipyrine, ketoprofen and digoxin²⁷

100 μL/h

N/A

N/A

Clamping

12 μm

0.4 μm; 1.6 × 10⁶ pore density

Caco-2

PET*

Small intestine-Liver: Caco-2, HepG2, and A549 cell cultures were used as organ models of the small intestine, liver, and lung, respectively.

Pharmacokinetics: —epirubicine (EPI), irinotecan (CPT-11), and cyclophosphamide (CPA)¹⁰⁴

Rotation frequency of 1600 rpm to generate a flow rate of 0.16 µL/s

N/A

N/A

Oxygen plasma

--

--

Collagen (Caco-2, HepG2)

PET*

Heart: Centrifugally assisted cell loading⁵⁰

Flow rate: 50 µL/h

Centrifugation (3 min at 138 · g)

SABEU 030444

Oxygen plasma

3 μm

--

Fibronectin (hiPSC-derived CMs)

Teflon*

Gut: Electrodes for transepithelial electrical resistance (TEER) measurements for real-time monitoring of barrier integrity

Permeability studies to evaluate differentiation.

Mucus production¹¹⁶

Day 1 flow rate of 0.5 μl/min, upper layer

Day 2 onward 3 μl/min, both chambers, shear stress ~ 0.008 dyne/cm² at

(Physiological conditions epithelial cells: 1 to 5 dyne/cm²)

N/A

Millipore, Denmark

UV radiation

40 μm

0.4 μm; ~ 75%

Matrigel® and collagen Type I (Caco-2)

PC*

Lung: 3D culture-specific-morphology, maintained excellent barrier integrity, secreted mucus, and expressed cell surface functional P-glycoprotein

Effects of cigarette smoke extract (CSE) on Interleukin-6 (IL-6) and Interleukin-8 (IL-8) release⁹⁰

30 μl/h

N/A

Merck, Germany

Oxygen plasma

10 μm

0.4 μm; 15%

Matrigel® and collagen Type I (Calu-3, epithelial)

PC*

Blood Brain-Barrier: TEER measurements for any organ-on-chip device with two channels separated by a membrane.¹⁶²

N/A

N/A

Corning (Transwell ®)

PDMS/toluene mortar

10 μm

0.4 μm; 15%

Fibronectin (hCMEC/D3)

PC*

Intestine: Coculture of human and microbial cells under representative conditions

Lactobacillus rhamnosus GG, Bacteroides caccae¹⁰⁸

25 ml/min

N/A

GE Healthcare

Gasketing

NS

1 μm;

Collagen, fibronectin (Caco-2; BeWo trophoblast)

PC*

Placenta: Screen drug compounds for their ability to cross the placenta

Heparin, glyburide⁴⁰

Flow rate 100 µl/h.

N/A

GE Healthcare

PDMS mortar

NS

1 μm;

Fibronectin (HPVEC)