Table 2.
Benchmarking Parameters for Heart-on-a-Chip, Liver-on-a-Chip, Kidney-on-a-Chip, and Adipose-on-a-Chip Organ Models
| Model | Benchmarking parameters |
|---|---|
| Heart-on-a-chip | Elongated, rod-like cardiomyocytes149 |
| Expression of adult ventricular genes (MYH7, MYL2, and TNNI3)149 | |
| Contractile stress 30–60 mN/mm3,150,151 | |
| Positive force-frequency ratio, characteristic notch at the top of upstroke152 | |
| RMP −90 mV, action potential amplitude 100–110 mV, action potential duration 230–300 ms152 | |
| Depolarization velocity 250–300 V/s, conduction velocity 30–100 cm/s152 | |
| Well-developed sarcoplasmic reticulum structure and function, gene expression of calcium-handling machinery149 | |
| Cytosolic calcium concentration 1 μm during systole, 100 nmol/L during diastole153 | |
| Reliance on fatty acid oxidation (>70%)154 | |
| Liver-on-a-chip | Albumin production >37 μg per day/1 million hepatocytes155 |
| Urea synthesis >56 μg per day/1 million hepatocytes155 | |
| Expression of phase I and II CYP450 enzymes, hepatocyte uptake, and efflux transports155 | |
| Polygonal, nonrounded, polarized hepatocytes155 | |
| Presence of bile canaliculi (BSEP, MRP2, and AQP1) and bile acid synthesis155 | |
| Presence of Kupffer cells (CD68) and stellate cells (desmin)155 | |
| Kidney-on-a-chip | Albumin reabsorption efficiency of at least 80%156 |
| Glucose reabsorption efficiency of at least 95%157 | |
| Transepithelial electrical resistance 6–10 Ω·cm2 (proximal tubule),158 100–500 Ω·cm2 (renal cell lines)159 | |
| Expression of podocyte markers (NPSH1, NPSH2, and WT1)160 | |
| Expression of mesangial cell markers (GATA3, PDGFRA, and ITGA8)160 | |
| Expression of glomerular endothelial cell markers (EHD3, EMCN, KDR, and CD31)160 | |
| Brush border enzyme activity: Na+/K+-ATPase, alkaline phosphatase, γ-glutamyltransferase160 | |
| Adipose-on-a-chip | Adipocytes >55 μm in diameter161 |
| Unilocular lipid contents, expression of maturation markers (PPARG, FABP4, and adiponectin)162 | |
| Evidence of insulin-stimulated glucose uptake162 | |
| Evidence of lipid metabolism (free fatty acid uptake, glycerol release)162 | |
| Incorporation of resident immune cells (CD68) and stromovascular cells (CD31, ACTA2)162 |
Parameters are reflective of values normally observed for mature cardiomyocytes, hepatocytes, proximal tubule epithelial cells/glomerular cells, and adipocytes. ACTA2 indicates alpha-smooth muscle actin; AQP1 indicates aquaporin 1; BSEP, bile salt export pump; CD, cluster of differentiation; CYP450, cytochrome P450; DES, desmin; EHD3, EH domain containing 3; EMCN, endomucin; FABP4, fatty acid-binding protein 4; GATA3, GATA-binding protein 3; ITGA8, integrin alpha 8; KDR, Kinase Insert Domain Receptor; MRP2, multidrug resistance-associated protein 2; MYH7, myosin heavy chain 7; MYL2, myosin light chain 2; NPSH1, nephrin; NPSH2, podocin; PDGFRA, platelet-derived growth factor receptor alpha; PPARG, peroxisome proliferator-activated receptor gamma; RMP, resting membrane potential; TNNI3, troponin I type 3; WT1, Wilms tumor-1; and WT, wild-type.