Overview of Organs-on-Chips
Product Manager：Harrison Michael
1. Introduction
Organs-on-Chips (OoCs) technology is an important innovation in the biomedical field in recent years. It aims to construct miniaturized, three-dimensional biological models that can simulate human organ functions through microfluidic technology. These chips can culture human cells in a controlled microenvironment, allowing them to exhibit physiological functions, making them crucial research tools for drug screening, disease modeling, and personalized medicine. Through OoC technology, researchers can obtain more realistic experimental data while reducing the need for animal testing, thus improving research efficiency.
2. Basic Construction and Operation Process of Organs-on-Chips
The construction of organs-on-chips typically includes the following steps:
2.1 Material Selection and Chip Design
The base materials for organs-on-chips are often polydimethylsiloxane (PDMS), polymethyl methacrylate (PMMA), or glass. These materials have good biocompatibility and transparency, making them suitable for microfluidic applications. The chip design must consider the spatial arrangement for cell culture, fluid flow paths, and sensor locations.
2.2 Cell Culture
In organs-on-chips, cells are typically cultured from patient-derived primary cells or stem cells. The biochemical reagents needed for cell culture include:
• Culture Medium: Use culture media that match the cell type, such as DMEM or RPMI 1640.
• Developmental Factors: For example, fibroblast developmental factor (FGF) and epidermal developmental factor (EGF) to promote cell proliferation and differentiation.
2.3 Establishment of Microfluidic Systems
Cells are injected into the chip using microfluidic technology, controlling fluid flow with micro-pumps to maintain an appropriate environment for cell developmental. Microfluidic systems can simulate the in vivo environment under physiological conditions, such as variations in oxygen, nutrient, and metabolic product concentrations.
2.4 Functional Assessment
To evaluate the function of organs-on-chips, several techniques are commonly used:
• Imaging Techniques: Such as fluorescence microscopy and confocal microscopy to observe cell morphology and functional changes.
• Biochemical Analysis: Using enzyme-linked immunosorbent assays (ELISA) and flow cytometry to detect cytokines and metabolic products secreted by the cells.
3. Applications of Organs-on-Chips in Experiments
3.1 Drug Screening
The application of organs-on-chips in drug screening has achieved significant results. For instance, researchers used intestinal organs-on-chips for antibiotic screening, discovering a novel antibiotic with significant efficacy against specific bacterial infections. This high-throughput screening method allows for rapid evaluation of drug efficacy and safety, greatly enhancing drug development efficiency.
3.2 Cancer Research
In cancer research, organs-on-chips are widely used to simulate the tumor microenvironment to study tumor developmental and metastasis. A recent study utilized breast cancer organoids to assess the effects of different chemotherapy drugs, finding that certain drugs exhibited stronger anti-tumor activity in the organoid model, providing a theoretical basis for personalized treatment. For example, liver cancer organoids were used to study the mechanisms of drug resistance to chemotherapy, revealing how tumor cells evade drug effects through alterations in the extracellular matrix within the microenvironment.
3.3 Disease Modeling
Organs-on-chips can simulate various disease states, providing more realistic disease models. For example, researchers established heart organoids to investigate the pathogenesis and drug responses of heart disease. This research revealed new therapeutic targets for heart disease and provided a theoretical foundation for subsequent clinical trials. Analysis of the impact of a novel drug on cardiac fibrosis using heart organoids showed that the drug effectively reduced fibrosis, laying the groundwork for clinical application.
3.4 Metabolic Studies
Liver organoids show important applications in metabolic research. Researchers study the metabolism of drugs using liver organoids, revealing differences in the metabolism of various drugs in the liver. By investigating the metabolism of anti-cancer drugs in liver organoids, it was found that the metabolites of these drugs have high biological activity, providing important clues for subsequent drug improvement.
3.5 Immune Response Studies
The application of organs-on-chips in immune response studies has also garnered attention. For example, researchers used lung organoids to study the infection mechanisms of the COVID-19 virus and the immune responses to vaccines. By analyzing immune cell responses in lung organoids, scientists can better understand the protective effects of vaccines against the COVID-19 virus.
4. Related Biochemical Reagents
In organs-on-chips experiments, the selection and application of biochemical reagents are crucial. Here are some commonly used biochemical reagents and their roles in organoid experiments:
4.1 Culture Media
• DMEM (Dulbecco's Modified Eagle Medium): Widely used for culturing various cell lines, containing high concentrations of amino acids and vitamins, suitable for rapidly proliferating cells.
• RPMI 1640: Used for culturing immune and tumor cells, containing various nutrients that support cell developmental and proliferation.
4.2 Developmental Factors
• Fibroblast Developmental Factor (FGF): Promotes cell proliferation and differentiation, commonly used in organoid construction.
• Epidermal Developmental Factor (EGF): Stimulates cell proliferation and developmental, especially important for culturing epithelial cell organoids.
4.3 Extracellular Matrix
• Matrigel: Provides a matrix for three-dimensional culture, supporting cell adhesion and developmental.
• Gelatin: A biocompatible material that supports cell adhesion and developmental.
4.4 Drugs
• Chemotherapeutic Agents (e.g., Cisplatin, Paclitaxel): Used to assess the response of organoids to drugs.
• Small Molecular Inhibitors: Used to study the effects of specific signaling pathways on cell behavior.
5. 5. Practical Cases and Research Achievements
5.1 COVID-19 Research
During the COVID-19 pandemic, organs-on-chips were widely applied to study virus infection mechanisms and drug screening. Researchers used lung organoids to simulate the virus infection process, screening various effective antiviral drugs, such as Remdesivir. This research not only helped scientists understand the infection mechanisms of the virus but also provided important evidence for the development of new drugs.
5.2 Regenerative Medicine
The potential applications of organs-on-chips in regenerative medicine have also attracted widespread attention. Scientists constructed organoids with various cell types using 3D printing technology, which can be used for tissue engineering and regenerative therapies. Organs-on-chips have successfully transplanted heart tissue into animal models, demonstrating good biocompatibility and functionality.
5.3 Education and Training
Organs-on-chips are also applied in medical education and training. Many medical education institutions have begun using organoid models for experimental training, enabling students to better understand human physiological and pathological processes and enhance their experimental skills.
6. Conclusion
The rapid development of organs-on-chips technology has brought new opportunities for biomedical research. Through practical applications, organs-on-chips demonstrate significant value in drug screening, disease modeling, and regenerative medicine, advancing biomedical research. As the technology continues to mature, organs-on-chips will play a key role in biomedical research, providing new insights for clinical treatments.
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