What is OoC
An organ-on-a-chip (OoC) is a microengineered system that integrates living cells within a microfluidic device to reproduce the key structural and functional features of human tissues and organs. It combines advances in tissue engineering and microfabrication to create an in vitro model that more closely mimics human physiology than traditional cell culture systems.OoC features parallel microchannels lined with living human organ-specific cells. These channels are separated by a thin, porous membrane coated with an extracellular matrix, which promotes cell attachment and communication. The design enables precise control of cell arrangement, nutrient exchange, and fluid flow, allowing for the recreation of essential physiological interfaces, such as those found in the lung, intestine, or vasculature.
Compared to spheroids and organoids, OoC systems involve the active control of the physical and chemical environment through continuous flow and mechanical stimulation. This dynamic design allows the reproduction of organ-level functions that static three-dimensional cultures cannot achieve. OoC systems (and extended Body-on-Chip platforms) further enable the integration of multiple organ models to study inter-organ communication, systemic drug metabolism, and whole-body physiological responses in vitro.
Why should we use OoC
Drug discovery and development remain slow, expensive, and failure prone. It often takes more than a decade and billions of dollars to bring a single drug to market, yet nearly 90% of candidates that enter Phase I clinical trials eventually fail. A major reason is the limited predictive value of conventional preclinical models. Two-dimensional cell cultures lack native tissue architecture and mechanical cues, while animal models, though widely used, are labor intensive, ethically constrained, and poor predictors of human safety and efficacy. As a result, many drugs that perform well in animals show unexpected toxicity or poor effectiveness in humans. This gap between preclinical testing and clinical outcomes highlights the urgent need for human-relevant in vitro models that can better replicate physiological and disease processes.
Why Now: FDA/NIH Momentum
How to build OoC
Building an organ on a chip involves integrating biological tissues with engineered microenvironments to recreate organ-level structure and function. A typical OoC device includes several key components: geometrically defined cell compartments, continuous fluid flow, environmental control, and built-in sensing modules for real-time readouts. These systems are designed to reproduce tissue-specific barriers, parenchymal tissue organization, and inter-organ interactions within a microfluidic platform.
Reproducing Tissue Barrier Function
Barrier models are one of the most common and essential OoC designs. They aim to replicate physiological interfaces such as the alveolar-capillary membrane in the lung, the intestinal epithelium, or the blood–brain barrier. These barriers are typically constructed using microfluidic membranes, scaffolds, or hydrogels that separate two cell populations while allowing selective transport of molecules and signals.
Reproducing Parenchymal Tissue
To model the metabolic or contractile function of specific organs, OoCs incorporate parenchymal tissues that reflect the organ’s core physiological activity. Two main categories are used: elongated tissues such as cardiac, skeletal, or smooth muscle; and spherical tissues such as liver, pancreatic, or tumor models.
Inter-Organ Interactions
A major advancement in OoC technology is the ability to connect multiple tissue modules to study systemic responses and organ–organ communication. Interconnected devices, often referred to as Body-on-a-Chip systems, integrate multiple organ units through perfusable microfluidic circuits that simulate blood flow and nutrient exchange.
These multi-organ platforms use patterned spheroids, perfusable channels, and integrated pumps or valves to maintain circulation between modules. Built-in biosensors continuously monitor parameters such as oxygen, pH, electrical resistance, and metabolite levels, enabling real-time assessment of tissue function. High-throughput formats, such as 96-well interconnected tissue chips, further allow scalable pharmacokinetic and pharmacodynamic (PK–PD) studies. Such integrated systems provide a physiologically relevant framework for modeling drug absorption, metabolism, and toxicity across multiple organ types.
Organ on a plate vs. Organ on a chip
Challenges and opportunities
Manufacturability as the Key Challenge
Manufacturability remains one of the most critical bottlenecks in translating Organ on a Chip (OoC) technologies from academic prototypes to industrial and regulatory applications. Most current OoC devices are fabricated using polydimethylsiloxane (PDMS) through soft lithography, a process ideal for rapid prototyping but poorly suited for large-scale production. PDMS devices require manual steps such as casting, bonding, and surface treatment, which introduce variability and limit throughput. The elastomeric nature of PDMS also leads to challenges in maintaining dimensional accuracy, long-term stability, and material reproducibility across fabrication batches.
In addition, PDMS absorbs small hydrophobic molecules, which complicates quantitative drug testing and reduces assay reliability. Its gas permeability, though beneficial for cell culture, can lead to water evaporation and concentration changes during long-term perfusion. These factors collectively hinder PDMS-based OoCs from meeting the consistency, reproducibility, and scalability demanded by pharmaceutical and regulatory standards.
Opportunities for Improvement
PDMS remains the gold standard for Organ on a Chip (OoC) development due to its excellent optical transparency, biocompatibility, elasticity, and gas permeability. It enables rapid prototyping and supports complex microstructures such as membranes, valves, and multilayer configurations. The next step in advancing OoC technology lies in improving the reliability, reproducibility, and scalability of PDMS-based fabrication. Traditional soft lithography, while flexible, is labor-intensive and difficult to scale for industrial or regulatory applications. PDMS also presents challenges such as small-molecule absorption and surface aging, which can affect assay consistency and long-term stability.
HiComp provides a practical solution to these challenges through its integrated PDMS fabrication and microfluidic engineering services. With advanced molding, precision alignment, and automated bonding capabilities, HiComp achieves high uniformity and batch-to-batch consistency while maintaining design flexibility. The platform supports both single-layer and multilayer PDMS devices with tunable membrane thickness, embedded valves, and optical-grade transparency. HiComp’s expertise extends beyond fabrication to include custom coating, device assembly, and hybrid PDMS–thermoplastic integration, enabling users to move seamlessly from concept to pilot-scale production. By combining research-level precision with scalable manufacturing workflows, HiComp helps transform PDMS-based OoC systems into reliable, reproducible, and industry-ready platforms for diagnostics, drug discovery, and biological research.