Table 1.

Human disease states and clinical responses replicated in single organ chips

Human organ chip	Platform	Cell types	Disorder or disease model	Clinical mimicry	Ref.
Brain or BBB	2-Channel PDMS Microporous	Neuron, microglial, astrocyte, pericyte, endo (all iPS)	Parkinson disease	α-Synuclein pathology	84
	2-Channel PDMS Nanoporous	Endo, pericyte, astrocyte	Inflammation	Neuroinflammation	87
	2-Channel PDMS Microporous	Endo, astrocyte, neuron (all iPS)	Huntington disease, MCT8 deficiency	Blood toxicity	86
	2-Channel PDMS Microporous	Endo (iPS), pericyte, astrocyte	BBB transport	Drug and antibody transport	85
	2-Channel PDMS Microporous	Endo (iPS), pericyte, astrocyte	BBB transport	Tumour extracellular vesicle transport	90
	3-Channel PDMS ECM gel	Endo, pericyte, astrocyte	BBB transport	Nanocarrier transport	89
	2-Channel PDMS Microporous	Endo (iPS), pericyte, astrocyte	BBB transport	Drug transport	88
	3-Channel PDMS ECM gel	Endo, pericyte, neuro stem, fungal	Fungal meningitis	Fungal invasion of BBB	91
Blood vessel	1-Channel in ECM gel Plastic	Endo	Tumour endothelium transport	Nanomaterial delivery	126
	1-Channel PDMS	Aortic smooth muscle (iPS)	Progeria, inflammation, mechanosensitivity	Drug efficacy	96
	2-Channel PDMS Microporous	Endo	Thrombosis	mAb toxicity	3
	1-Channel in ECM gel Plastic	Endo, kidney cancer (patient)	Tumour angiogenesis	mAb efficacy	18
	3-Channel PDMS ECM gel	Epi, endo, cancer	Inflammation	Nanocarrier delivery	58
	3-Channel PDMS ECM gel	Lymphatic endo, breast cancer	Breast cancer	Breast cancer lymphangiogenesis	19
	1-Channel PDMS	Aortic smooth muscle	Aortic valve insufficiency, mechanosensitivity	Aortic valve injury, drug efficacy	97
	3-Channel PDMS ECM gel	Endo, fibroblast, colorectal cancer	Colorectal cancer	Drug efficacy	98
	Multichannel PDMS	Aortic smooth muscle, endo, immune	Atherosclerosis, vascular stenosis	Vascular inflammation	127
	1-Channel Plastic	Stromal cell, bone marrow mononuclear	Implant-associated metal accumulation in bone	Implant toxicity	46
	2-Channel PDMS ECM gel	Haematopoietic, endo, stromal	Radiation injury, Shwachman–Diamond syndrome	Mimic drug toxicity with clinical exposure profiles	45
Cartilage	2-Channel PDMS 3 ECM gel channels	Synovial fibroblast, chondrocyte, immune, synovial fluid	Osteoarthritis	Monocyte extravasation, drug efficacy	38
Eye	2-Channel PDMS 2 ECM gel channels	Retinal pigmented epithelial, endo	Choroidal angiogenesis	Drug efficacy	92
	2-Channel PDMS Nanoporous	Retinal pigmented epithelial, 7 retinal (iPS org)	Retinopathy	Drug toxicity	93
	2-Channel PDMS Nanoporous	Retinal pigmented epithelial, 7 retinal (iPS org)	Gene therapy delivery	AAV vector delivery	128
Fat	2-Channel PDMS Nanoporous	Adipocyte	Obesity	Drug efficacy	129
	3-Channel PDMS ECM gel	Epi, endo, adipocyte (stem)	Obesity	Leptin production	58
Heart	1-Channel Plastic	Cardiomyocyte (iPS)	Cardiotoxicity	Drug toxicity	51
	3D printed PDMS + plastic	Cardiomyocyte (iPS), endo (3D printed)	Heart contractility, cardiotoxicity	Drug toxicity	24
Immune system	2-Channel PDMS with ECM gel	Immune, cancer (patient)	Immuno-oncology	CAR T cell efficacy	100
	2-Channel PDMS with ECM gel	Immune, cancer (patient)	Immune checkpoint blockade	Drug efficacy	99
	1-Channel Plastic	Surgically explanted tumour biopsy tissues (patient)	Immune checkpoint blockade	Drug efficacy	101
	2-Channel PDMS Microporous	Lung epi, intestine epi (org), immune	Tumour-targeted T cell bispecific Ab toxicity	mAb toxicity	37
	2-Channel PDMS with ECM gel	Immune	Immunization, vaccination	Vaccine and adjuvant efficacy	44
Small intestine	2-Channel Plastic Nanoporous	Epi (line), bacteria	Host–microbiome interactions, hypoxia gradient	Effects of microbiome metabolites on host	72
	2-Channel PDMS Microporous	Epi (line)	Enteric virus infection	Infection-associated injury	130
	2-Channel PDMS Microporous	Epi (line), endo, lymphatic endo, immune, bacteria	Bacterial infection, inflammation	Inflammatory bowel disease, probiotic drug delivery, ileus	43
	2-Channel PDMS Microporous	Epi (line), endo	Radiation injury	Radiation toxicity, drug efficacy	75
	3-Channel ECM gel	Epi (org), immune	Inflammatory bowel disease	Inflammation-associated gene expression	131
	2-Channel PDMS Microporous	Epi (org), endo	Intestinal differentiation	Transcriptome profile	36
	2-Channel PDMS Microporous	Epi (line and org), endo	Host–microbiome interactions, hypoxia gradient	Complex microbiome–host interactions	47
	2-Channel PDMS Microporous	Epi (line), endo, virus	SARS-CoV-2 virus infection	Infection-associated injury, inflammation	71
	2-Channel PDMS Microporous	Epi (org), endo, immune, virus	Enteric virus infection	Drug efficacy, inflammation	70
	2-Channel PDMS Microporous	Epi (org)	Environmental enteric dysfunction	Clinical phenotype and nutritional dependency	76
Colon	2-Channel PDMS Microporous	Epi (org)	Bacterial infection, microbiome	Species-specific sensitivity to Escherichia coli infection	73
	2-Channel PDMS Microporous	Epi (org), bacteria	Bacterial infection, mechanosensitivity	Shigella infection	74
	2-Channel PDMS Microporous	Epi (org)	Inflammation, mechanosensitivity	Mucus layer formation	69
	2-Channel PDMS Microporous	Epi (org), endo	Inflammation, bacterial growth	Human milk oligosaccharide effects on gut barrier	132
	2-Channel PDMS Microporous	Epi (org)	Inflammatory bowel disease	Inflammation-associated injury	133
Kidney tubule	2-Channel PDMS Microporous	Epi	Renal transport, nephrotoxicity	Renal reabsorption, drug toxicity	77
	3D printed in ECM gel	Epi	Renal transport, nephrotoxicity	Renal reabsorption, drug toxicity	22
	2-Channel PDMS Nanoporous	Epi	Viral infection	Replication of clinical phenotype	78
	3D printed in ECM gel	Epi, endo	Renal transport, hyperglycaemia	Renal reabsorption, drug efficacy	23
	2-Channel Plastic ECM gel	Epi	Lowe syndrome, Dent II disease	Replication of clinical phenotype	79
Kidney glomerulus	3-Channel Plastic ECM gel	Epi (line)	Nephrotoxicity	Drug toxicity and transport	134
	2-Channel PDMS Nanoporous	Endo (line), podocyte (line)	Hypertensive nephropathy, mechanosensitivity	Replication of clinical phenotype	80
	2-Channel PDMS Microporous	Endo, podocyte (iPS)	Filtration barrier	Urinary clearance, drug toxicity	81
	3-Channel Plastic ECM gel	Endo, podocyte	Filtration barrier, autoimmune toxicity	Drug toxicity	83
	2-Channel PDMS Microporous	Endo (iPS), podocyte (iPS)	Personalized drug testing	Drug toxicity	82
Liver	2-Channel PDMS Microporous	Hep	Metabolism-dependent toxicity	Drug toxicity	65
	2-Chamber Plastic Microporous	Hep	Inflammation effects on drug metabolism	Drug metabolism, clearance	62
	2-Chamber Plastic Microporous	Hep, Küpffer	CYP450 metabolism, drug–drug interactions	Drug metabolism, mAb–drug interactions	63
	2-Chamber Plastic Microporous	Hep	Drug metabolism	Drug metabolism, patient variability	64
	1-Channel Plastic	Hep, endo	Steatosis	Drug toxicity	135
	1-Channel Plastic	Hep	Drug- and toxin-induced liver injury	Drug metabolism and toxicity	136
	1-Channel Plastic	Hep, Küpffer	Virus (Hepatitis B) infection, inflammation	Viral infection-associated injury	67
	2-Channel PDMS Microporous	Hep, endo, hepatic stellate, Küpffer	Drug-induced liver injury	Human and cross species drug toxicities	66
	3-Channel Plastic ECM gel	Hep, endo, hepatic stellate, Küpffer	Nonalcoholic steatohepatitis	Drug efficacy	137
	2-Channel Plastic ECM gel	Hep (iPS), endo, immune	Hepatotoxicity	Drug toxicity screen, high throughput	120
	2-Channel PDMS Microporous	Hep, endo, hepatic stellate, Küpffer	Drug-induced liver injury	Replicate human drug toxicities	118
Lung alveolus	2-Channel PDMS Microporous	Epi (line), endo, immune	Inflammation, mechanosensitivity	Breathing-dependent nanoparticulate toxicity	11
	2-Channel PDMS Microporous	Epi (line), endo	Pulmonary oedema	Drug toxicity	52
	2-Channel PDMS Microporous	Epi, endo	Thrombosis	Drug efficacy	54
	2-Channel PDMS Microporous	Epi, endo, cancer	Non-small cell lung cancer	Site-specific and mechanosensitive tumour growth, drug efficacy	57
	2-Channel PDMS Microporous	Epi, endo	Pulmonary oedema, gene therapy delivery	AAV vector delivery, drug efficacy	138
	3-Channel PDMS ECM gel	Epi, endo, cancer	Lung cancer	Drug efficacy	58
	2-Channel PDMS Microporous	Epi (line), endo, immune	Virus infection (SARS-CoV-2), inflammation	Drug efficacy	41
	2-Channel PDMS Microporous	Epi, endo	Virus infection (influenza, SARS-CoV-2, MERS-CoV), inflammation	RNA therapy efficacy	60
	2-Channel PDMS Microporous	Epi, endo	Virus infection (influenza), inflammation, mechanosensitivity	Drug efficacy against viral inflammation	59
	1-Channel PDMS	Epi (line)	Nanoparticle delivery and toxicity	Nanoparticle toxicity	53
Lung airway	1-Channel PDMS	Epi	Mechanical injury to airway cells	Reproduction of respiratory crackle sound	12
	2-Channel PDMS Nanoporous	Epi, endo, immune	Asthma, COPD	Inflammation, COPD exacerbations, drug efficacy	39
	2-Channel PDMS Nanoporous	Epi	COPD exacerbation by smoke inhalation	Replication of clinical phenotype	55
	2-Chamber Plastic Nanoporous	Epi	Glucocorticoid metabolism, mucus production	Drug metabolism & clearance	139
	2-Channel PDMS Microporous	Epi, endo, immune, bacteria	Cystic fibrosis, inflammation, bacterial infection	Hyperinflammation in cystic fibrosis	40
	2-Channel PDMS Microporous	Epi, endo, cancer	Non-small cell lung cancer	Site-dependent cancer growth	57
	2-Channel PDMS Microporous	Epi, immune	Asthma exacerbation by virus infection	Drug efficacy	56
	2-Channel PDMS Microporous	Epi, endo, immune	Virus infection (influenza, pseudotyped SARS-CoV-2), inflammation	Drug repurposing, drug efficacy	42
	2-Channel PDMS Microporous	Epi, endo	Virus infection (influenza, SARS-CoV-2, MERS-CoV), inflammation	RNA therapy efficacy	60
	2-Channel PDMS Microporous	Epi, endo	Virus evolution (influenza)	Resistance to drug therapy	61
	2-Channel Plastic Nanoporous	Epi	Virus infection (SARS-CoV-2, HCoV-NL63, influenza), inflammation	Viral infectivity, inflammation, high thoughput	21
Mammary gland	2-Channel in an ECM gel	Epi, endo	Breast cancer	Mutation-induced cancer progression, angiogenesis	94
Nerve	2-Channel PDMS Microporous	Spinal neuron, endo (iPS)	Vascular–neuronal interactions	Neuronal maturation	140
	3-Channel Plastic ECM gel	Neuron	Motor neuron injury	Drug toxicity and efficacy	141
Pancreas	1-Channel Plastic	Whole isolated pancreatic islets	Diabetes mellitus	Glucose-sensitive insulin secretion	142
Placenta	2-Channel PDMS Microporous	Trophoblast (line), endo	Placental barrier	Drug transport	95
Skin	2-Chamber Plastic Nanoporous	Keratinocyte	Skin irritation	Drug and chemical toxicity	143
Teeth	3-Channel PDMS Dentin fragment	Dental stem, dentin	Dental material toxicities	Biomaterials toxicity	144
	3-Channel PDMS Dentin fragment	Dental stem, dentin, bacteria	Biofilm formation	Biomaterials efficacy	145
Uterus	2-Channel PDMS Microporous	Epi, stromal	Endometrial remodelling	Uterine contraception, drug efficacy	146
	5-Channel PDMS 2 ECM gels	Epi, endo, stromal	Endometrial remodelling	Menstrual cycle-dependent endometrial differentiation	147

Platform indicates the device design, including channel or chamber configuration (including number), material composition (polydimethylsiloxane (PDMS) or plastic), porosity of intervening membrane (microporous or nanoporous), whether a channel is filled with an intervening extracellular matrix (ECM) gel, or whether the microfluidic channel is formed within an ECM gel. All cells are primary cells unless indicated as follows: established cell line (line); chips lined with organotypic cells derived from human induced pluripotent stem cells (iPS); patient-derived primary cells (patient); patient organoid-derived cells (org); cells isolated from organoids derived from iPS cells (iPS org); stem cells (stem); or cells deposited with 3D printing (3D printed). All cells are human except for the microbial cells mentioned. AAV, adeno-associated virus; BBB, blood–brain barrier; COPD, chronic obstructive pulmonary disease; CoV, coronavirus; endo, vascular endothelial cell; epi, epithelial cell; hep, hepatocyte; mAb, monoclonal antibody; MCT8, monocarboxylate transporter 8; neuron, brain neuronal cell.