Microfluidics Gradient Generators |
Arbitrary shape of gradients [17, 25]
Combinatorial gradients of multiple species [30]
Gradients of soluble [25], insoluble [75], gaseous [22], and mechanical [43, 58] factors
Temporal control of the shape of gradients [34]
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Pneumatic valve controls can quickly become unmanageable with increasing complexity |
Keep number of conditions limited |
++ |
Automate pneumatic valve control [34] |
++++ |
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Absorption of biochemicals due to high surface area to volume ratio |
Check for absorption profile of biochemical factor in pdms [71] |
++++ |
Long term differentiation assays with perfusion |
Combinatorial combinations of various factors [13]
High throughput perturbations and observations
Screening over large dose responses [19, 32]
Precise temporal control of dosage and combinations [34]
Combination of mechanical, physical and biochemical factors [30]
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Shear stress |
Use H-chip designs to avoid direct flow of fluid over cells |
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Dampen flow by specialized perfusion[24, 26] |
+++ |
Culture cells in protected etched channels or microwells[25, 63] |
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Loss of autocrine paracrine signaling[62] |
Maintain pulsatile flow with long periods (5–6 hours) with no flow [24] |
++++ |
Use no flow conditions, and culture cells in high throughput microwells with media replenishment every 6–12 hours [46, 76] |
+++ |
Co-culture |
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Sophisticated requirements for temporal control[49] |
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+++++ |
Control of shear and rigidity |
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Difficult to ascertain effect on cell viability by shear alone [60] |
Ex-chip control always suggested with comparable cell density and media |
++ |
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Temporal control of rigidity difficult and require sophisticated set ups[59] |
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+++++ |
Control of topography |
Highly precise mimicking of substrate topography
Biodegradable and biocompatible polymers
Spatial gradients of topography
Ease of culture and experimentations
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Expensive to fabricate [77–79] |
CFL [80] and electrospinning[60] are cheaper but difficult to fabricate |
+++++ |
Small surface area prohibiting biochemical experiments [70] |
Use CFL substrata from commercial or expert laboratories to minimize optimizations |
+ |
3D control not available in all topographical features |
Electrospinning allows 3D control. CFL allows 2.5D control |
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