Organoids & organ-on-chip

01Overview and value chain

Markers: [EC: Alternative Methods to Animal Testing & REACH Directive | OECD: Guidance on Microphysiological Systems (MPS) | Regulator: FDA (USA), EMA (EU), NMPA (China)]

Organoids and Organ-on-a-Chip (OoC) systems, collectively known as Microphysiological Systems (MPS), represent a cutting-edge interdisciplinary frontier in biomedical engineering. They aim to create in vitro models of human organs and tissues that highly accurately reproduce their three-dimensional structural organization, cellular composition, biochemical microenvironment, mechanical stimulation, and physiological functions. By 2026, MPS have been recognized as the main technological alternative to the use of laboratory animals in toxicology, preclinical drug trials, and personalized medicine, significantly reducing the standard 5 to 7 year preclinical timeline while improving human predictive validity by up to 80%.

The key directions of the industry are:

1. Organoids: Three-dimensional multicellular clusters self-organizing in vitro from induced pluripotent stem cells (hiPSCs) to study disease pathogenesis.
2. Organ-on-a-Chip (OoC): Microfluidic devices containing living cultured human cells in controlled microchannels that recreate dynamic fluid flow and mechanical stress.
3. Multi-Organ Chips: Body-on-a-Chip systems combining multiple “organs” into a single circulatory circuit to analyze systemic drug metabolism and toxicity.
4. Personalized Medicine: Screening patient-derived organoids to select optimal oncological or cystic fibrosis treatments directly tailored to the individual.

Sectoral value chain

[Stem Cells & Biomaterials] ──> [Microfluidic Chip Design] ──> [Cell Seeding & Co-culture]
                                                │
                                    (PDMS, Lithography, ECM)
                                                │
                                                ▼
[Preclinical Drug Testing] <─── [Sensor Integration & Perfusion] <─── [Barrier Maturation]

Value chain levels

Cross-cutting technologies of the sector:

• Precision Photolithography and Micro-molding: Lithography of SU-8 and injection molding of biocompatible thermoplastics enabling micron-scale channel geometries.
• In-channel 3D Bioprinting: Direct printing with living cells inside closed microchannels to instantly form complex blood capillaries.
• TEER Sensor Integration: Real-time, non-invasive measurement of tissue barrier integrity using microelectrodes placed above and below the porous membrane.

02US

The United States pioneered the commercialization of OoC devices, heavily supported by robust academic centers and a progressive regulatory framework.

FDA Modernization Act 2.0, Wyss Institute, Emulate leadership

• FDA Modernization Act 2.0: A revolutionary 2022 law abolishing the mandatory requirement for animal testing of new drugs before human clinical trials, legitimizing MPS data.
• Wyss Institute (Harvard): The birthplace of the world’s first functional “Lung-on-a-Chip,” generating foundational patents for OoC mechanobiology.
• Commercial Leadership: Boston-based Emulate Inc. is the world’s key supplier of standard chips, perfusion installations, and software, holding official validation partnerships with the FDA for toxicology.

03CN

China is rapidly expanding its presence in the OoC industry, focusing on scalable chip production and specialized applications for traditional medicine.

High-throughput screening, TCM screening, Daxiang Biotech

• Traditional Chinese Medicine (TCM) Screening: A unique state priority where “gut-liver-target” chips decipher how complex herbal extracts are absorbed and metabolized to exert systemic effects.
• Commercial Suppliers: Daxiang Biotech develops industrial OoC platforms made of biocompatible plastics replacing PDMS to prevent the absorption of small hydrophobic drug molecules.
• Leading Academic Centers: Institutions like the Dalian Institute of Chemical Physics (DICP) innovate new multi-organ chips and alternative biocompatible materials.

04EU

The European Union prioritizes OoC technologies under strict ethical constraints on animal testing, especially driven by the REACH directive and cosmetic bans.

EUROoCS, multi-organ chips (TissUse), high-throughput platforms (Mimetas)

• Multi-Organ Innovators: German company TissUse developed the proprietary HUMIMIC technology, integrating built-in pneumatic micropumps for long-term (up to 28 days) 4-organ systemic co-culturing.
• High-throughput Systems: Netherlands-based Mimetas created the OrganoPlate, a tubeless microfluidic chip formatted as a standard 384-well plate, enabling automated robotic screening without external pumps.
• European Infrastructure: The ORCHID project and the European Organ-on-Chip Society (EUROoCS) coordinate standardization and regulatory alignment with the EMA.

05Leading companies and research institutes

06Tech stack and innovations

The modern production of microphysiological MPS systems relies on precision engineering and advanced materials.

1. Precision Micro-molding from PDMS:
   • Polydimethylsiloxane (PDMS) provides high optical transparency, elasticity for mechanical stretching, and gas permeability.
   • Injection molding on silicon SU-8 templates ensures channel detailing down to 1 micron.
2. Plasma Covalent Bonding:
   • Low-pressure oxygen plasma treatment of PDMS and glass surfaces generates reactive silanol groups.
   • Instant covalent cross-linking withstands high pumping pressures without channel depressurization.
3. Automated Microsensor Detection:
   • Gold or platinum microelectrodes sputtered onto the glass substrate allow continuous reading of transepithelial resistance (TEER).
   • Enables real-time monitoring of oxygen partial pressure and pH directly in the cell culture zone.

07Value chains and production pipelines

Industrial pipeline of OoC system manufacturing and testing (GLP/GMP)

┌───────────────────────────┐      ┌───────────────────────────┐
│ 1. Chip Fabrication       │ ───> │ 2. Assembly & Bonding     │
└───────────────────────────┘      └───────────────────────────┘
                                                 │
                                                 ▼
┌───────────────────────────┐      ┌───────────────────────────┐
│ 4. Human Cell Seeding     │ <─── │ 3. ECM Functionalization  │
└───────────────────────────┘      └───────────────────────────┘
              │
              ▼
┌───────────────────────────┐      ┌───────────────────────────┐
│ 5. Barrier Maturation     │ ───> │ 6. Drug Screening Assay   │
└───────────────────────────┘      └───────────────────────────┘

Stage 1: Chip Fabrication

In an ISO 5 cleanroom, liquid PDMS polymer is mixed with a curing agent and poured onto a silicon SU-8 master template containing the micro-relief of the channels. The mold is degassed in a vacuum and cured at 65°C for 4 hours.

Stage 2: Assembly & Bonding

The PDMS blank and a glass slide are cleaned and placed in a plasma chamber. Treatment with oxygen plasma activates the surfaces, which are then precisely aligned under a microscope and pressed together for covalent chemical cross-linking.

Stage 3: ECM Functionalization

The assembled chips are sterilized via UV irradiation. A syringe pump injects a solution of extracellular matrix proteins (Type I collagen, fibronectin, or Matrigel) into the channels, incubating at 37°C to create an optimal substrate.

Stage 4: Human Cell Seeding

A suspension of human cells, such as primary lung microvascular endothelial cells, is introduced into the lower channel. After adhesion, alveolar epithelial cells are seeded into the upper channel, and the chip is incubated for 24 hours to form initial monolayers.

Stage 5: Barrier Maturation

The chip is connected to an automated perfusion system simulating blood flow. The upper channel is exposed to air (Air-Liquid Interface), and cyclical vacuum pressure simulates lung breathing movements. Co-cultivation lasts 5–7 days until TEER sensors confirm a dense physiological barrier.

Stage 6: Drug Screening Assay

The investigational drug substance is introduced into the perfusion flow at various concentrations. Sensors continuously record barrier integrity dynamics, while hourly perfusate samples are automatically withdrawn for mass spectrometry analysis of drug metabolites and toxicity markers.