Multi organ serial co culture chip microphysiological system

（1） Functional application

There are many limitations to in vivo models: high experimental costs, limited throughput, ethical issues, and differences in genetic backgrounds. More importantly, compared to humans, they exhibit significant physiological differences in drug efficacy and/or disease phenotype, which explains why clinical trials often fail.

Quasi Vivo from Kirkstall Ltd ® The organ chip microphysiological system, also known as the microfluidic "organ on chip" system, has interconnected cell culture units that provide a more physiologically relevant in vivo microenvironment for organoid growth. By providing a near physiological in vitro model that simulates the cellular microenvironment, it has a more complete structure and function, solves the species differences between animals and humans, and can simulate various organ specific disease states in vitro, reflecting the dynamic changes of drugs in the body and the true response of human organs to drug stimuli, capturing complex physiological responses, and meeting high-throughput requirements. It is a multi chamber flow system that provides a compact and easy-to-use solution for organoid culture, including 2D, 3D, barrier, or multi organ. It is widely used in disease modeling, drug screening and toxicity testing, regenerative medicine and tissue engineering, developmental biology research, infection and immune research, personalized medicine, cancer research and other fields.

（2） Performance characteristics

Quasi Vivo ® As an excellent organ chip system, specifically designed to solve the main problems encountered by academic and industrial researchers in conducting in vitro and in vivo research, it has the following performance advantages:
1. Strong functional extensibility
Diversified cultivation methods with selectable gas-liquid interfaces, liquid-liquid interfaces, scaffolds, and flow schemes
Allow independent and controllable laminar flow of air, gas, or liquid towards the top and outer side of the substrate
Meet the experimental requirements of multi organ/multi cell co culture and intercellular signal transmission. Accelerate the differentiation and maturation of organoid cells, enhance cell vitality, suitable for long-term cultivation
2.成像友好
Equipped with optical windows on the top or bottom surface for ideal real-time high-resolution imaging
3. Easy to obtain samples
Directly collect samples and obtain tissue or liquid samples
4. Simulate biomechanics and concentration gradients
Strictly controlling multiple variables can simulate physiological characteristics such as blood circulation, interstitial fluid flow dynamics, etc., providing biomechanical signals for cells; Can achieve complex model construction such as co culture of immune cells and vascularization; Used for studying various physiological processes, such as cell migration, differentiation, immune response, and cancer metastasis
5. Portable and easy to operate
Compact modular chamber structure with higher physiological relevance to the human body
Small footprint, space saving, compatible with standard laboratory incubators

（3） Product application cases and published literature

1) Berger E, Magliaro C, Paczia N, Monzel AS, Antony P, Linster CL, Bolognin S, Ahluwalia A, Schamborn JC. Millifluidic culture improves human midbrain organoid vitality and differentiation.

Multi organ co culture chip microphysiological systemIn this study, the author established a study on Kirkstall Quasi Vivo ® Stable brain organoid cultures under microfluidic conditions using organ chips were compared with continuous orbital oscillation methods using computational fluid dynamics (CFD) and conventional experimental methods. CFD analysis is conducted to determine whether the difference in oxygen levels calculated in two experimental setups can be used to explain any observed differences in organoids cultured under the two conditions. This comparison demonstrates an improvement in culture quality, including a reduced "dead core" and has been confirmed by the model, as well as an increase in dopaminergic differentiation.

2) Ramachandran S, Schirmer K, Münst B, Heinz S, Ghafoory S, Wölfl S, Simon-Keller K, Marx A, Øie C, Ebert M, Walles H, Braspenning J and Breitkopf-Heinlein K (2015). In Vitro Generation of Functional Liver Organoid-Like Structures Using Adult Human Cells.

Multi organ co culture chip microphysiological systemIn this study, the author used upcyte ® Human liver cells generate liver like organs in vitro, as demonstrated by Kirkstall Quasi Vivo ® After further cultivation in the organ chip for 10 days, these liver like organs exhibited typical liver parenchymal functional characteristics, including the activity of cytochrome P450, CYP3A4, CYP2B6, and CYP2C9, as well as mRNA expression of some marker genes and other enzymes.

3) Cancer cells grown in 3D under fluid flow exhibit an aggressive phenotype and reduced responsiveness to the anti-cancer treatment doxorubicin, Tayebeh Azimi, Marilena Loizidou & Miriam V. Dwek

The importance of tumor microenvironment (TME) as a regulator of cancer cell behavior has been recognized, leading to the development of 3D in vitro cancer models. The 3D laboratory in vitro model of cancer aims to summarize the biochemical and biophysical characteristics of the tumor microenvironment, and to enable the study of cancer and new treatment approaches in a physiologically relevant manner. In this paper, the authors studied breast cancer cells under 2D, 3D and 3D microfluidic conditions, and compared the cell viability and expression levels of apoptosis, proliferation and hypoxia related genes of breast cancer cells under different culture conditions.

During the experiment, cancer cells were prepared into a dense 3D mass, creating an image in Kirkstall Quasi Vivo ® Under the fluid flow conditions of organ chips, tumor like organs are exposed to physiological conditions of fluid and pressure, which can lead to changes in their growth, morphology, and sensitivity to challenges. This model system provides key evidence for the role of tissue density and fluid flow, and serves as a reference for researchers using 3D models as cancer drug testing platforms.

4）Geddes, L., Themistou, E., Burrows, J. F., Buchanan, F. J., & Carson, L. (2021). Evaluation of the In Vitro Cytotoxicity and Modulation of the Inflammatory Response by the Bioresorbable Polymers Poly(D,L-lactide-coglycolide) and Poly(L-lactide-co-glycolide).
Medical devices must undergo a series of tests to ensure their safety in clinical use, which are specified by the International Organization for Standardization (ISO). Every medical device requires cytotoxicity analysis, which is typically the first step in in vitro biocompatibility testing. These tests provide an efficient method to determine the cytotoxicity of a substance or substance to living cells, however, their use is limited as they cannot be used to determine the cause of cell death. Testing in vitro immune responses in the early stages of biomaterial development has not yet been included in standard procedures. A deeper understanding of the response of in vitro cells to biomaterials will aid in early detection and prediction of potential adverse reactions.

In order to replicate the internal environment and increase physiological relevance, the author of this article used Kirkstall Quasi Vivo ® The "Organ on Chip" flow culture system is used to test polymer samples.

5）Susanne Reinhold, Christian Herr, Yiwen Yao , Mehdi Pourrostami, Felix Ritzmann. Modeling of lung-liver interaction during infection in a human microfluidic organ-on-a-chip

Respiratory infections such as pneumonia cause high mortality and incidence rate worldwide. Organ chip technology has developed in the past few years to establish human based disease models, study basic disease mechanisms, and provide tools for accelerating drug development. The purpose of this study is to establish a lung liver microfluidic system to investigate the interaction between two organ modules during the infection process.

The author utilized primary human bronchial (HBECs) or alveolar epithelial cells and human liver cancer Huh-7 cells through Kirkstall Quasi Vivo assay ® The organ chip established a dual organ (lung/liver) microfluidic system and conducted co culture/stimulation experiments. Apply non subtyping Haemophilus influenzae (NTHi) and Pseudomonas aeruginosa (PAO1) to lung modules. Screen and quantify secreted mediators through dot blot analysis. Analyze the impact of pulmonary epithelial bacterial stimulation on the transcriptome of liver cells through mRNA sequencing.

（4） Product User Profile

*Using Kirkstall Quasi Vivo ® There are over 100 academic and research institutions specializing in organ chip microphysiological systems, located in countries such as the United States, United Kingdom, France, Sweden, Austria, Italy, Netherlands, Switzerland, and Japan. At present, the organ chip microphysiological system has been successfully used for the construction of the following organ models:

（5） Brand Manufacturer Introduction

Kirkstall Ltd. was founded in 2006 and is a subsidiary of Braveheart Investment Group plc, headquartered in York, UK. Kirkstall has developed an innovative organ chip model called Quasi Vivo for microphysiological systems ®。 As a leading player in organ chip technology, Kirkstall has established a large user base in renowned university laboratories such as the Institute of Biomedical Engineering at Oxford University, and its products enjoy a high reputation within the industry.

Beijing Kilby Biotechnology Co., Ltd. is the authorized general agent of Kirkstall Ltd. for Weiyi and Dujia in China, responsible for the sales, marketing, and technical support of all Kirkstall products in China.