Abstract
Organ-on-a-chip (OoC) technology and its counterpart, 3D organoids, both promise to revolutionize drug discovery and disease modeling by offering more accurate human-specific data than traditional animal models. However, realizing this potential often requires collaboration and material sharing across different laboratories and institutions. While some labs are experts at engineering these miniature systems, others have biological discovery or analysis capability and possibly clinical pharmacology expertise.
A major, yet often overlooked, challenge in these collaborations is the logistics of sharing these bio-physical systems, particularly transporting live, functional chips and delicate organoids between labs while preventing contamination and ensuring the viability of the engineered tissues.
The Contamination Minefield
Contamination is an ever-present and potentially devastating risk in any cell culture environment, and it is exponentially more challenging with both OoC systems and 3D organoids.
- Organ-on-a-Chip Systems: The very nature of OoC devices (also called MicroPhysiological Systems MPS)—involving pumps, intricate microfluidic channels, tubing, and media reservoirs—creates numerous potential entry points for bacteria, fungi, or other microbes. The manual handling required for packaging, transit, and unpacking dramatically increases the risk compared to static, in-lab cultures.
- 3D Organoids: While typically maintained in static culture plates, organoids are highly sensitive to their environment and the handling involved in preparing them for transit. Maintaining a sterile, sealed environment during transit is difficult, and any break in aseptic technique compromises the entire batch.
A single contamination event can result in the complete failure of an experiment, wasting significant time, resources, and the valuable human cells used to create the model.
The Logistical Nightmare
Beyond sterility, the sheer logistics of moving functioning biological systems pose significant hurdles for both technologies:
Problem | Description |
Portability Issues | Most OoC systems and 3D organoid cultures are tricky to transport. They often rely on speciality plates and plate carriers to seal the media to prevent evaporation. Often, the microfluidic ports or miniature chambers, need to be properly managed prior to transportation. |
Incompatibility with Cryo-freezing | Almost all OoC systems and most 3D organoid cultures cannot be cryo-frozen for transportation. The complexity of the 3D design or the inability to rapidly freeze internal structures of the bio-physical system, eliminates this as a solution. Moreover, cell viability is significantly impacted by freeze-thaw cycles, and for these delicately designed systems, it could completely destroy function. |
Extra-high dependence on maintaining physiological conditions | Live cells require a constant supply of nutrients, proper oxygenation, pH control, humidity and precise temperature control. A loss of environmental gas conditions, a delay in shipping, or improper temperature management can quickly lead to cell death. Temperature fluctuations are particularly detrimental to delicate tissues like retinal organoids, affecting their biological activity and structural integrity. |
Complexity of Operation | Operating these systems often requires specialized skills. A receiving lab might not have the specific expertise or equipment needed to seamlessly take over the operation of a chip or a specific organoid protocol developed in another facility. Coordinating the timing of transport requires constant communication with numerous human-error fail points. |
Movement sensitivity and susceptibility | Many OoC systems and 3D organoids are sensitive to movement. This may be particular important for brain (neural) organoids, that continually sense the environment and change firing patterns. Transport in regular styrofoam boxes that are not specially designed to minimize external vibrations can cause unintended biological functional impacts, or worse, complete system disintegration. |
Towards a Solution
Addressing these challenges is critical for the wider adoption and validation of both OoC and 3D organoid technology in multi-center studies and pharmaceutical pipelines. The field is moving towards:
- Standardized Protocols: The development and adoption of standardized protocols for both the creation and handling of these models would help ensure consistency between labs and ease the transition process.
- User-Friendly Designs: Designing more robust and user-friendly platforms can reduce operational complexity and minimize handling errors, thereby cutting down contamination risks.
- Inclusion of Digital Technologies: Remote real-time monitoring of physiological conditions (including temperature, humidity, gas concentrations CO2, physical orientation) can allow both source and destination labs to track the movement of material and better coordinate transfers. Notifications and alarms can warn all parties to take action if environmental thresholds are breached.
- Commercial Solutions: An ecosystem of new biotechnology companies is emerging to provide solutions, including optimized shipping methods (e.g., specific shipping media or climate-controlled containers) and commercialized platforms that are easier to integrate into various workflows. 37degrees, Inc. is a pioneer in this field bring to users a first-of-kind fully native-environment controlled portable incubator called CultureON 100, with seamless digital connectivity.
Overcoming these logistical and contamination challenges, will expand the promise of widespread, collaborative OoC and 3D organoid research. Technical collaborators will focus on designing new and exciting bio-physical systems, while their biological and pharma collaborators will be able to access these materials in living format. Systems such as the CultureON 100 will efficiently provide a robust and trustable transport pod to enable these collaborations in nearby or distant geo-locations.