Organ Chip Technology

Life science companies seeking FDA approval must not only establish a new medicine’s efficacy but also comply with rigorous safety protocols and procedures. The process is time-consuming and costly: the financial burden associated with developing and securing market approval for a new compound is estimated at $2.5 billion and can take over a decade, with failure possible at any stage in the process. Seeking to reduce the staggering cost and accelerate the approval time frame, many researchers are exploring an exciting, new methodology as an alternative to traditional pre-clinical studies: "organ-on-a-chip"

Organ-on-a-chip (OOAC) involves growing real tissue from a human organ on a small structure that mimics what that organ tissue would experience inside a body. These structures are not computer chips but “microfluidic” devices. Such devices typically consist of hollow channels embedded in silicone-based polymers about the size of a computer thumb drive. The channels are lined with living cells and tissues from organs such as the brain, liver, lung, and kidney. Fluids flow through the devices, bringing nutrients to mimic what the blood does in the body when flowing past cells. In recent years, more sophisticated microfluidic devices have been created to expand and contract tissue to simulate, for example, conditions within the lungs.

Developments in OOAC Research

In January 2023, the FDA opened the door for further development of OOAC technology by approving the FDA Modernization Act 2.0. This law allows for drug approval using new alternative methodologies designed to accurately represent human biology, including OOAC technology.

To encourage research in chip technology, the FDA also entered into a multi-year research and development agreement with the private sector to evaluate the technology’s effectiveness. There are three main components to this research:

1. Design: The chip aims to replicate the physiological environment of specific organs in the human body. Living human cells derived from human tissues or stem cells are cultured with microfluidic channels to recreate the structure and function of a specific organ.
2. Instrumentation: These chips are placed in a research system designed to mimic the human body's environment, including blood flow and breathing. Scientists can study biological processes, disease mechanisms, and drug responses more accurately.
3. Software Apps: Data from various analyses are processed, quantified, and analyzed using computational tools and mathematical models, often through software apps. These analyses assist researchers in interpreting experimental results, identifying trends, and developing hypotheses.

Research into chip technology has yielded promising results. One compelling example is the lung-on-a-chip model, a microfluidic device that replicates the alveolar-capillary interface of the human lung. This model serves as a platform for studying lung diseases such as asthma, chronic obstructive pulmonary disease (COPD), and pulmonary edema, offering valuable insights into disease progression and potential therapeutic interventions.

Similarly, liver-on-a-chip models mimic the hepatic microenvironment, allowing researchers to study drug metabolism, toxicity, and liver diseases. This allows researchers to evaluate the effects of pharmaceutical compounds and identify drug candidates with enhanced safety profiles. By running a series of in vitro trials using 870 advanced liver-chips, scientists established that OOAC technology can correctly identify 27 known toxic or non-toxic drugs, with a sensitivity of 87% and a specificity of 100%. This significant achievement demonstrated the ability of the field to select better drug candidates for clinical trials, with the potential to save an estimated $3 billion in annual drug development costs.

Scientists have taken OOAC experimentation even further. Researchers have been working to create interconnected systems known as “body-on-a-chip” platforms. These cutting-edge and sophisticated setups attempt to replicate interactions among multiple organs at once to provide a more comprehensive, accurate, and informative model of the human body. Such platforms are exceptionally promising tools for disease simulations, pharmaceutical testing, and the development of individualized medical treatments.

Benefits of OOAC Technology

OOAC offers an alternative to the traditional drug discovery process, which is often time-consuming, expensive, and prone to failure. Organ chip technology enables clinical trial sponsors to screen clinical trial participants more efficiently and at a lower cost, accelerating drug discovery and development.

Another benefit of organ chip technology is its ability to personalize medicine. While in its infancy, OOAC technology may allow researchers to test the efficacy and safety of drugs on patient-specific organ models. By utilizing patient-derived cells in the chip platform, the medical field can tailor treatment strategies to an individual patient's needs.

Lastly, as explained above, scientists are working to take chip technology a step further by developing interconnected OOAC systems, i.e., body-on-a-chip platforms, to study organ-to-organ interactions. Using this technology to study the interaction between different organs offers an avenue to overcome hurdles associated with studying complex disease mechanisms through chip technology.

Challenges of OOAC

At a minimum, the commercialization of organ chip technology requires scientists to overcome regulatory concerns and convince stakeholders of the value of chip technology compared to existing research methods. One way to achieve this is to establish standardized protocols and validation criteria so that results are reproducible and reliable across different research laboratories and applications.

Despite advances, organ chip technology remains a significant challenge from a technological standpoint. The ability to replicate the entire physiological environment of a human organ within an OOAC requires cutting-edge advancements in tissue engineering, biomaterials, and microfabrication techniques. Moreover, researching and analyzing interactions between multiple organs pose technical challenges for OOAC scientists. Although it can provide actionable information and valuable insights, OOAC models are not yet perfect and may not completely and reliably capture all the many intricacies and variables of organ capabilities, functions, and interactions. Ensuring consistency and accuracy remains a challenging objective, particularly for more complex organ systems.

Another limitation of OOAC technology is its scalability. As noted by Stefaan Verbruggen, PhD in Technology Networks, “current devices are primarily designed for small-scale experiments, limiting their applicability in high-throughput screening and large-scale drug testing. Researchers are actively working on optimizing fabrication techniques and experimental protocols to address this limitation. Scalable OOAC platforms would significantly enhance their utility in drug discovery and development, allowing researchers to test a broader range of compounds efficiently.”

From both a technological and practical standpoint, continued advancements in OOAC-based platforms are necessary to enable scientists to accurately assess chronic disease and drug response.

The Future is Promising

Organ chip technology offers unprecedented opportunities to revolutionize biomedical research and drug discovery. Advances in microfluidics and tissue engineering will enable the development of more sophisticated multi-organ systems, allowing researchers to study complex physiological processes and diseases involving multiple organs. As this technology matures, it will be crucial in disease modeling, biomarker discovery, and developing targeted therapies for precision medicine applications. The advancement of organ chip technology will require continued innovation, collaboration, and investment across the scientific community.

Authored by Lisa Krist, VP, Chief Customer Focus Officer