EXECUTIVE SUMMARY
Organ-on-chip (OoC) devices—also called microphysiological systems (MPS)—are microfluidic platforms that recreate human organ function using living cells in controlled microenvironments. In September 2024, Emulate's Liver-Chip S1 became the first OoC to receive FDA ISTAND acceptance, demonstrating 87% sensitivity and 100% specificity for detecting drug-induced liver injury. The technology is now deployed across 17+ of the top 25 pharmaceutical companies.
IN THIS GUIDE
How Organ-on-Chip Works
An organ-on-chip is a microfluidic cell culture device—typically the size of a USB drive or AA battery—that contains hollow channels lined with living human cells. These devices recreate the key functional units of human organs by providing:
- Microfluidic Flow: Continuous perfusion of media mimics blood flow, delivering nutrients and removing waste
- Tissue-Tissue Interfaces: Porous membranes enable cells from different tissues to interact (e.g., epithelial-endothelial)
- Mechanical Forces: Cyclic stretching replicates breathing motions, heartbeats, or peristalsis
- Physiological Gradients: Oxygen, nutrient, and chemical gradients mirror in vivo conditions
The first organ-on-chip was the lung-on-chip, developed by Don Ingber and colleagues at the Wyss Institute for Biologically Inspired Engineering at Harvard in 2010. This breakthrough device demonstrated that human lung alveolar cells could be cultured at an air-liquid interface while experiencing cyclic mechanical strain mimicking breathing—something impossible in traditional cell culture.
Types of Organ Chips
Organ-on-chip technology has expanded to cover virtually every major organ system. Each type is engineered to replicate the specific physiological features critical for drug testing:
Recreates hepatic metabolism with CYP450 enzyme activity (CYP3A4, CYP2C9) comparable to primary hepatocytes. Used for ADME/Tox profiling and DILI prediction. First FDA ISTAND acceptance (Emulate, Sept 2024).
Two-channel alveolar/capillary interface with cyclic breathing motion and air-liquid interface. Used for respiratory disease modeling, inhaled drug testing, and COVID-19 research (Wyss Institute 2010).
Beating cardiomyocytes (often iPSC-derived) with electrical pacing and force measurements. Critical for detecting QT prolongation and cardiotoxicity—the leading cause of drug withdrawals.
Proximal tubule epithelial cells with active renal transporters (OAT1, OAT3, OCT2). Detects nephrotoxicity from cisplatin, tenofovir, aristolochic acid. Potential 20% reduction in late-stage failures.
Villus structures with enterocytes, goblet cells, and enteroendocrine cells. Supports microbiome co-culture for host-microbe interaction studies. Critical for oral drug absorption prediction.
Blood-brain barrier models with tight junctions, efflux transporters (P-gp), and astrocyte/pericyte support. Essential for CNS drug development where 98% of small molecules fail to cross the BBB.
Leading Organ-on-Chip Companies
Emulate, Inc.
Boston-based company founded by Don Ingber (Wyss Institute). First and only FDA ISTAND acceptance for organ-on-chip (Liver-Chip S1, September 2024). Launched AVA Emulation System (June 2025). 17+ of top 25 pharma customers.
PhysioMimix platform. First IND approval supported by organ-on-chip efficacy data (Inipharm metabolic liver disease). $21M Series B (April 2024).
OrganoPlate platform with 384-well format for high-throughput screening. Partners: Roche, BASF, GSK, Pfizer, AbbVie, Janssen, Biogen, Astellas. Leading €134.78M CPBT initiative.
Pumpless Human-on-a-Chip technology. First digital twin generated from organ-on-chip data (July 2025, Advanced Science). Multi-organ systems up to 5 organs.
Bio-AI platform combining organ-on-chip with machine learning. Acquired Nortis (Oct 2024). Merck KGaA platform adoption (Jan 2025). $50M+ raised (SoftBank $37M seed).
Drug Development Applications
Organ-on-chip technology addresses multiple stages of the drug development pipeline:
PRIMARY APPLICATIONS (58-62% of Use Cases)
ADME/Tox Profiling
Absorption, distribution, metabolism, excretion, and toxicity testing. Liver-chips for hepatotoxicity, kidney-chips for nephrotoxicity.
Safety Pharmacology
Heart-chips for cardiotoxicity/QT prolongation, lung-chips for respiratory effects, brain-chips for neurotoxicity.
Disease Modeling
Patient-derived cells enable modeling of NASH, COPD, IBD, cancer, and rare diseases in human-relevant systems.
Efficacy Testing
Target engagement and therapeutic response in human tissue context. First IND approval via OoC efficacy data (CN Bio/Inipharm, 2024).
Key Advantage: Drug-induced liver injury (DILI) causes approximately 20% of acute liver failure cases and is responsible for numerous drug withdrawals. Emulate's Liver-Chip demonstrated 87% sensitivity and 100% specificity in detecting hepatotoxicity—significantly outperforming traditional animal models.
Regulatory Acceptance
🏆 FIRST FDA ISTAND ACCEPTANCE
In September 2024, Emulate's Liver-Chip S1 became the first organ-on-chip to receive FDA Innovative Science and Technology Approaches for New Drugs (ISTAND) acceptance. This landmark decision validates organ-on-chip as a qualified tool for detecting drug-induced liver injury in IND-enabling studies.
The regulatory pathway for organ-on-chip acceptance includes:
- FDA ISTAND Pilot: Established under 21st Century Cures Act for qualifying novel drug development tools
- FDA Modernization Act 2.0: Explicitly authorizes organ chips as valid alternatives to animal testing (December 2022)
- IQ Consortium MPS Affiliate: 22 major pharma companies collaborating on qualification standards
Multi-Organ & Body-on-Chip Systems
The next frontier in organ-on-chip technology is connecting multiple organ chips to create "body-on-chip" or "human-on-chip" systems that model systemic drug effects:
Published Multi-Organ Configurations
- 4-Organ System: Intestine → Liver → Skin → Kidney (28-day culture demonstrated)
- 6-Organ System: Liver, cardiac, lung, endothelium, brain, testes (interconnected)
- 10-Organ Interrogator: DARPA-funded Wyss Institute platform with robotic liquid handling
OFF-TARGET TOXICITY DETECTION
Multi-organ systems can detect toxicity that emerges only through organ-organ interactions. Example: Capecitabine (cancer drug) is metabolized by the liver into 5-FU, which then causes cardiotoxicity—a systemic effect impossible to predict with single-organ models.