TABLE I.
Microfluidic platforms aimed at reproducing mechanical strain in-vitro. The first category summarizes devices aimed at stretching cells cultured on a substrate, while the second category enables emulating in-vivo barriers, based on a thin, elastic, and porous membrane.
| Device type | Type of strain | Cell culture support | Actuation | Applications | Year | References | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| Direction | Level (in %) | Frequency | Membrane | Array | Coating | |||||
| Non barrier | Uni-axial | 10% (linear strain) | Cyclic (1 Hz) | 0.5–1 mm thick PDMS substrate | 2 | Gelatin | A precision linear motor applies cyclic stretch to the PDMS device. | Differentiation of murine embryonic stem cells in cardiomyocytes upon cyclic strain. | 2011 | Wan et al. (46) |
| 4% (linear strain) | Cyclic (0.5 Hz, 10 cycles) | Thin PDMS membrane with 10 μm grooves | 1 | ProNectin F | Two linear actuators operated with a syringe pump. | Ca2+ signaling of tenocytes in response to cyclic strain. | 2013 | Wall et al.62 | ||
| 3–7% (linear strain) | Cyclic (2 Hz) | 100 μm thick PDMS membrane | 1 | Fibronectin | Stretching by actuation of thin walls connected to adjacent channels with cyclic vacuum. | Provide mechanical, electrical, and biochemical stimulation to mesenchymal stem cells. | 2015 | Pavesi et al.86 | ||
| Bi-axial (xy) | 0 up to 60% (surface strain) | Cyclic (1.3 Hz) | 100 μm to 330 μm thick PDMS membrane | 1 | Fibronectin | Combination of hydrodynamic pressure & mechanical pressure with a post. | Hemodynamic stimulation of cardiomyocytes | 2010 | Giridharan et al.55 | |
| Bi-axial (xz) | 2–20% (circumferential strain) | Cyclic (1 Hz) | 35 μm thin PDMS membrane | 5 | Collagen, fibronectin, gelatin | Hydrodynamic actuation (microfluidic channel filled with liquid). | Mimic the circumferential strain to which small blood vessels are exposed | 2012 | Zhou et al.47 | |
| Equi-bi-axial (xy) | 2–15% (circumferential & radial strain) | Cyclic (1 Hz) | 15 μm thin PDMS membrane | 9 × 12 | Collagen | Positive pressure created by flat posts pushed against the culturing membrane. | Activation of the canonical Wnt/b-catenin signaling pathway in cardiac valve mesenchymal progenitor cells | 2010 | Moraes et al.50 | |
| 1, 2, 4, 6% (linear strain) | Cyclic (1 Hz) | 150 μm thick PDMS membrane | 5 × 5 | Fibronectin | The PDMS membrane is stretched with a vacuum around cylindrical, flat micropillars. | Strain of C2C12 skeletal myoblasts. | 2012 | Simmons et al.53 | ||
| Tri-axial | 17–20% (surface strain) | Cyclic (0.2, 1, 5 Hz) | 100 μm thick PDMS membrane | 3 × 8 | Fibronectin | Mechanical movements of small pins that deflect the membrane (Braille display). | Strain of human dermal microvascular endothelial cells | 2008 | Kamotani et al.48 | |
| 15–50% (linear strain) | Cyclic (0.2–0.3 Hz) | 100 μm thick PDMS membrane | 1 | Fibronectin | Fluidic pressure created by a syringe pump (negative pressure). | Combined effects of fluid and solid mechanical stress on alveolar cells (mimic pathophysiology of ventilator induced lung injury). | 2011 | Douville et al.54 | ||
| 3 and 12% (circumferential & radial strain) | Cyclic (1 Hz) | 45 μm and 100 μm thin membranes made of PDMS with PU coating | 12 × 9 | Collagen or fibronectin | Pneumatic positive pressure (microfluidic channel filled with air). | Investigation of mechanobiological response profiles of valvular interstitial cells. | 2013 | Moraes et al.49 | ||
| 6% (linear strain) | Cyclic (1 Hz) | 10 μm thin PDMS membrane | 1 | Collagen | Pneumatic negative pressure created below the thin membrane. | Study of cellular (MSC) responses to cyclical hypoxia and stretch. | 2016 | Campillo et al.56 | ||
| 2.2–3.5% (linear strain) | Cyclic (0.33 Hz) | 130 μm thick PDMS membrane | 5 × 6 | None | Pneumatic negative pressure (vacuum created in microchannels). | Effect of mechanical strain on proliferation and differentiation of mesenchymal stem cells. | 2014 | Gao et al.52 | ||
| 12–20% (circumferential & radial strain) | Cyclic (1 Hz) | 35, 55, 75 μm thin membrane in PDMS | 32 | Fibronectin | Pneumatic positive pressure to deflect the PDMS membrane. | Investigation on effect of cyclic stretch on membrane permeability of both healthy and dystrophic myotube. | 2015 | Michielin et al.51 | ||
| In-vitro barrier | Uniaxial | 5–15% (linear strain) | Cyclic (0.2 Hz) | 10 μm thin, PDMS membrane with 10 μm wide pentagonal pores | 1 | Fibronectin or collagen | Stretching by actuation of thin walls connected to adjacent channels with cyclic vacuum [Fig. 2(a)]. | Lung-on-a-Chip: Mimic the lung alveolar barrier and investigate the effects of the mechanical strain on toxic and inflammatory response. | 2010 | Huh et al.58 |
| Tri-axial | 21% (surface strain) | Cyclic (0.2 Hz) | 3 μm thin, PDMS membrane with 3 or 8 μm pores | 3 | Fibronectin | Stretching by indirect actuation using a bio-inspired microdiaphragm [see Fig. 2(b)]. | Lung-on-a-Chip: Mimic the lung alveolar barrier and investigate the effects of the mechanical strain on primary lung alveolar cells. | 2015 | Stucki et al.59 | |