OoC Devices Research Articles

Recent Progress in PDMS-Based Microfluidics Toward Integrated Organ-on-a-Chip Biosensors and Personalized Medicine

The organ-on-a-chip (OoC) technology holds significant promise for biosensors and personalized medicine by enabling the creation of miniature, patient-specific models of human organs. This review studies the recent advancements in the application of polydimethylsiloxane (PDMS) microfluidics for OoC purposes. It underscores the main fabrication technologies of PDMS microfluidic systems, such as photolithography, injection molding, hot embossing, and 3D printing. The review also highlights the crucial role of integrated biosensors within OoC platforms. These electrochemical, electrical, and optical sensors, integrated within the microfluidic environment, provide valuable insights into cellular behavior and drug response. Furthermore, the review explores the exciting potential of PDMS-based OoC technology for personalized medicine. OoC devices can forecast drug effectiveness and tailor therapeutic strategies for patients by incorporating patient-derived cells and replicating individual physiological variations, helping the healing process and accelerating recovery. This personalized approach can revolutionize healthcare by offering more precise and efficient treatment options. Understanding OoC fabrication and its applications in biosensors and personalized medicine can play a pivotal role in future implementations of multifunctional OoC biosensors.

Functionalization of Polyethylene Terephthalate (PETE) Membranes for the Enhancement of Cellular Adhesion in Organ-on-a-Chip Devices.

Experimental reproducibility in organ-on-chip (OOC) devices is a challenging issue, mainly caused by cell adhesion problems, as OOC devices are made of bioinert materials not suitable for natural cellularization of their surfaces. To improve cell adhesion, several surface functionalization techniques have been proposed, among which the simple use of an intermediate layer of adsorbed proteins has become the preferred one by OOC users. This way, the cells use surface receptors to adhere to the adsorbed proteins, which are in turn attached to the surface. However, as protein adsorption is based on weak electrostatic bonding between the coating proteins and the substrate, this method produces suboptimal results: as the weak electrostatic bonds break, cells detach, leading to poor, heterogeneous cellularization. To solve this problem, we present a surface functionalization method for polyethylene terephthalate (PETE) membranes, commonly used in multilayer organ-on-chip devices to support cellular layers. This protocol involves hydrolyzation of the membrane, followed by (3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) activation, resulting in covalent bonding between the membrane and coating proteins, much stronger than the weak electrostatic bonding provided by simple adsorption. As evaluation, we first measured the effect of the functionalization protocol in the morphological and mechanical integrity of the membranes. Next, we confirmed protein coating efficiency using the ζ potential and surface tension of the functionalized membranes coated with collagen type I, polylysine, gelatin, albumin, fetal bovine serum (FBS), and Matrigel. Finally, we showed that our method significantly improves the attachment of epithelial (A549) and endothelial (EA.hy926) cell lines under static conditions, especially in collagen-coated membranes, which were further tested under dynamic conditions, showing statistically significant improvement in cell attachment compared to uncoated or collagen-adsorbed only membranes.

An ultrathin membrane mediates tissue-specific morphogenesis and barrier function in a human kidney chip.

Organ-on-chip (OOC) systems are revolutionizing tissue engineering by providing dynamic models of tissue structure, organ-level function, and disease phenotypes using human cells. However, nonbiological components of OOC devices often limit the recapitulation of in vivo-like tissue-tissue cross-talk and morphogenesis. Here, we engineered a kidney glomerulus-on-a-chip that recapitulates glomerular morphogenesis and barrier function using a biomimetic ultrathin membrane and human-induced pluripotent stem cells. The resulting chip comprised a proximate epithelial-endothelial tissue interface, which reconstituted the selective molecular filtration function of healthy and diseased kidneys. In addition, fenestrated endothelium was successfully induced from human pluripotent stem cells in an OOC device, through in vivo-like paracrine signaling across the ultrathin membrane. Thus, this device provides a dynamic tissue engineering platform for modeling human kidney-specific morphogenesis and function, enabling mechanistic studies of stem cell differentiation, organ physiology, and pathophysiology.

Tunable In Situ Synthesis of Ultrathin Extracellular Matrix-Derived Membranes in Organ-on-a-Chip Devices.

Thin cell culture membranes in organ-on-a-chip (OOC) devices are used to model a wide range of thin tissues. While early and most current platforms use microporous or fibrous elastomeric or thermoplastic membranes, there is an emerging class of devices using extra-cellular matrix (ECM) protein-based membranes to improve their biological relevance. These ECM-based membranes present physiologically relevant properties, but they are difficult to integrate into OOC devices due to their relative fragility. Additionally, the specialized fabrication methods developed to date make comparison between methods difficult. This work presents the development and characterization of a method to produce ultrathin matrix-derived membranes (UMM) in OOC devices that requires only a preassembled thermoplastic device and a micropipette, decoupling the device and UMM fabrication processes. Control over the thickness and permeability of the UMM is demonstrated, along with integration of the UMM in a device enabling high-resolution on-chip microscopy. The reliability of the UMM fabrication method is leveraged to develop a medium-throughput well-plate format device with 32 independent UMM-integrated samples. Finally, proof-of-concept cell culture experiments are demonstrated. Due to its simplicity and controllability, the presented method has the potential to overcome technical barriers preventing wider adoption of physiologically relevant ECM-based membranes in OOC devices.

Advancing Intelligent Organ-on-a-Chip Systems with Comprehensive In Situ Bioanalysis.

In vitro models are essential to a broad range of biomedical research, such as pathological studies,drug development, and personalized medicine. As a potentially transformative paradigm for 3D in vitro models, organ-on-a-chip (OOC) technology has been extensively developed to recapitulate sophisticated architectures and dynamic microenvironments of human organs by applying the principles of life sciences and leveraging micro- and nanoscale engineering capabilities. A pivotal function of OOC devices is to support multifaceted and timely characterizationof cultured cellsand their microenvironments. However, in-depth analysis of OOC modelstypically requires biomedical assay procedures that are labor-intensive and interruptive. Herein,the latest advances toward intelligent OOC (iOOC) systems, where sensors integrated with OOC devices continuously report cellular and microenvironmental information for comprehensive in situ bioanalysis, are examined. It is proposed that the multimodal data in iOOC systems can support closed-loop control of the in vitromodels and offer holistic biomedical insights for diverse applications. Essential techniques for establishing iOOC systems are surveyed, encompassing in situ sensing, data processing, and dynamic modulation. Eventually, the future development of iOOC systems featuring cross-disciplinary strategies is discussed.

Portable and integrated microfluidic flow control system using off-the-shelf components towards organs-on-chip applications

Organ-on-a-chip (OoC) devices require the precise control of various media. This is mostly done using several fluid control components, which are much larger than the typical OoC device and connected through fluidic tubing, i.e., the fluidic system is not integrated, which inhibits the system’s portability. Here, we explore the limits of fluidic system integration using off-the-shelf fluidic control components. A flow control configuration is proposed that uses a vacuum to generate a fluctuation-free flow and minimizes the number of components used in the system. 3D printing is used to fabricate a custom-designed platform box for mounting the chosen smallest footprint components. It provides flexibility in arranging the various components to create experiment-specific systems. A demonstrator system is realized for lung-on-a-chip experiments. The 3D-printed platform box is 290 mm long, 240 mm wide and 37 mm tall. After integrating all the components, it weighs 4.8 kg. The system comprises of a switch valve, flow and pressure controllers, and a vacuum pump to control the diverse media flows. The system generates liquid flow rates ranging from 1.5 upmuLmin^{-1} to 68 upmuLmin^{-1} in the cell chambers, and a cyclic vacuum of 280 mbar below atmospheric pressure with 0.5 Hz frequency in the side channels to induce mechanical strain on the cells-substrate. The components are modular for easy exchange. The battery operated platform box can be mounted on either upright or inverted microscopes and fits in a standard incubator. Overall, it is shown that a compact integrated and portable fluidic system for OoC experiments can be constructed using off-the-shelf components. For further down-scaling, the fluidic control components, like the pump, switch valves, and flow controllers, require significant miniaturization while having a wide flow rate range with high resolution.

PDMS-based porous membrane for medical applications: design, development, and fabrication

Organ-on-a-chip (OoC) is one of the most popular microfluidic chips and possesses various industrial, biomedical, and pharmaceutical applications. So far, many types of OoCs with different applications have been fabricated, most of which contain porous membranes useful as cell culture substrates. One of the challenging parts of OoC’s chips is porous membrane fabrication, making it a complex and sensitive process, which is an issue in microfluidic design. These membranes are made of various materials, the same as biocompatible polymer polydimethylsiloxane (PDMS). Besides OoC, these PDMS membranes can be applied in diagnosis, cell separating, trapping, and sorting. In the present study, a new approach has been presented to design and fabricate an efficient porous membrane in terms of time and cost. The fabrication method has fewer steps than previous techniques and employs more conventional approaches. The presented method for membrane fabrication is functional and a novel way to continue producing this product with a single mold and peeling off the membrane on each try. Merely one sacrificial layer (polyvinyl alcohol) and an O2 plasma surface treatment have been used for fabrication. Surface modification and sacrificial layer on the mold ease the peeling of the PDMS membrane. Transferring process of the membrane to the OoC device is explained, and a filtration test is presented to show the functionality of the PDMS membranes. Cell viability is investigated by MTT assay to ensure the PDMS porous membranes are suitable for microfluidic devices. Also, cell adhesion, cell count, and confluency are analyzed, showing almost the same results for the PDMS membranes and the control samples.

A User-Centric 3D-Printed Modular Peristaltic Pump for Microfluidic Perfusion Applications.

Microfluidic organ-on-a-chip (OoC) technology has enabled studies on dynamic physiological conditions as well as being deployed in drug testing applications. A microfluidic pump is an essential component to perform perfusion cell culture in OoC devices. However, it is challenging to have a single pump that can fulfil both the customization function needed to mimic a myriad of physiological flow rates and profiles found in vivo and multiplexing requirements (i.e., low cost, small footprint) for drug testing operations. The advent of 3D printing technology and open-source programmable electronic controllers presents an opportunity to democratize the fabrication of mini-peristaltic pumps suitable for microfluidic applications at a fraction of the cost of commercial microfluidic pumps. However, existing 3D-printed peristaltic pumps have mainly focused on demonstrating the feasibility of using 3D printing to fabricate the structural components of the pump and neglected user experience and customization capability. Here, we present a user-centric programmable 3D-printed mini-peristaltic pump with a compact design and low manufacturing cost (~USD 175) suitable for perfusion OoC culture applications. The pump consists of a user-friendly, wired electronic module that controls the operation of a peristaltic pump module. The peristaltic pump module comprises an air-sealed stepper motor connected to a 3D-printed peristaltic assembly, which can withstand the high-humidity environment of a cell culture incubator. We demonstrated that this pump allows users to either program the electronic module or use different-sized tubing to deliver a wide range of flow rates and flow profiles. The pump also has multiplexing capability as it can accommodate multiple tubing. The performance and user-friendliness of this low-cost, compact pump can be easily deployed for various OoC applications.

Biosensors integrated 3D organoid/organ-on-a-chip system: A real-time biomechanical, biophysical, and biochemical monitoring and characterization

As a full-fidelity simulation of human cells, tissues, organs, and even systems at the microscopic scale, Organ-on-a-Chip (OOC) has significant ethical advantages and development potential compared to animal experiments. The need for the design of new drug high-throughput screening platforms and the mechanistic study of human tissues/organs under pathological conditions, the evolving advances in 3D cell biology and engineering, etc., have promoted the updating of technologies in this field, such as the iteration of chip materials and 3D printing, which in turn facilitate the connection of complex multi-organs-on-chips for simulation and the further development of technology-composite new drug high-throughput screening platforms. As the most critical part of organ-on-a-chip design and practical application, verifying the success of organ model modeling, i.e., evaluating various biochemical and physical parameters in OOC devices, is crucial. Therefore, this paper provides a logical and comprehensive review and discussion of the advances in organ-on-a-chip detection and evaluation technologies from a broad perspective, covering the directions of tissue engineering scaffolds, microenvironment, single/multi-organ function, and stimulus-based evaluation, and provides a more comprehensive review of the progress in the significant organ-on-a-chip research areas in the physiological state.

Immunity-on-a-Chip: Integration of Immune Components into the Scheme of Organ-on-a-Chip Systems.

Studying the immune system in vitro aims to understand how, when, and where the immune cells migrate/differentiate and respond to the various triggering events and the decision points along the immune response journey. It becomes evident that organ-on-a-chip (OOC) technology has a superior capability to recapitulate the cell-cell and tissue-tissue interaction in the body, with a great potential to provide tools for tracking the paracrine signaling with high spatial-temporal precision and implementing in situ real-time, non-destructive detection assays, therefore, enabling extraction of mechanistic information rather than phenotypic information. However, despite the rapid development in this technology, integration of the immune system into OOC devices stays among the least navigated tasks, with immune cells still the major missing components in the developed models. This is mainly due to the complexity of the immune system and the reductionist methodology of the OOC modules. Dedicated research in this field is demanded to establish the understanding of mechanism-based disease endotypes rather than phenotypes. Herein,wesystemically present a synthesis of the state-of-the-art of immune-cantered OOC technology.Wecomprehensively outlined what is achieved and identified the technology gaps emphasizing the missing components required to establish immune-competent OOCs and bridge these gaps.

Establishing a Microfluidic Tumor Slice Culture Platform to Study Drug Response.

Accurate models for tumor biology and prediction of drug responses of individual tumors require novel technology to grow tumor tissue ex vivo to maintain tumor growth characteristics in situ. Models containing only tumor cells, without the stromal components of the tumor, are suboptimal for many purposes and are generally problematic because the cells are passed through extensive culture and selection. Therefore, direct culture of (human) tumors is of considerable interest for basic tumor biology and diagnostic purposes. Microfluidic technologies have been proposed to accurately mimic physiological conditions for tissue growth. Most published systems build tissues from individual cell types in so-called Organ-on-Chip (OoC) cultures. We here describe a novel OoC device for growing tumor specimens. Thin tumor slices are grown in a microfluidic 'chip' that allows precisely controlled in vitro culture conditions. The performance of the OoC device was extensively validated for predicting therapeutic responses in human breast cancer patient-derived xenograft (PDX) tumor material. The system is amenable to primary tumor material from surgery or biopsies. In addition to using the model to predict and evaluate therapeutic responses, the model can also be used for mechanistic studies of human cancers, such as clonal evolution or immune responses, or to validate new or repurposed (cancer) drugs. The Bi/ond Cancer-on-Chip (CoC) device is designed to culture tumor slices and investigate aspects of tumor growth and drug responses. Here, we describe the step-by-step process of setting up tumor slice cultures using a Bi/ond CoC device and performing in vitro drug response evaluation. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Establishment of breast cancer tumor slice culture using a microfluidic cancer-on-chip platform for chemotherapy testing ex vivo Basic Protocol 2: Histology and immunohistochemistry-based analysis of tumor tissue architecture, cell proliferation, and cell death.

A Comparison between Different Machine Learning Approaches Combined with Anodic Stripping Voltammetry for Copper Ions and pH Detection in Cell Culture Media

Recently, the scientific community has shown a great interest about the Organ-on-Chip (OoC) devices, a special kind of micro-fabricated platforms capable of recapitulating the human physiology implementing the traditional cell culture methods and the concept of in vivo studies. Copper ions represent a cellular micronutrient that must be monitored for its potential hazardous effects. The application of electrochemical analysis for heavy metal ions detection and quantification in commercial cell culture media presents several issues due to electrolyte complexity and interferents. In fact, to the best of our knowledge, there is a lack of applications and OoC devices that implement the Anodic Stripping Voltammetry as an ion dosing technique due to the reasons reported above. In fact, considering just the peak intensity value from the measurement, it turns out to be challenging to quantify ion concentration since other ions or molecules in the media may interfere with the measurement. With the aim to overcome these issues, the present work aims to develop an automated system based on machine learning algorithms and demonstrate the possibility to build a reliable forecasting model for copper ion concentration on three different commercial cell culture media (MEM, DMEM, F12). Effectively, combining electrochemical measurements with a multivariate machine learning algorithm leads to a higher classification accuracy. Two different pH media conditions, i.e., physiological (pH 7.4) and acidic (pH 4), were considered to establish how the electrolyte influences the measurement. The experimental datasets were obtained using square-wave anodic stripping voltammetry (SWASV) and were used to carry out a machine learning trained model. The proposed method led to a significant improvement in Cu2+ concentration detection accuracy (96.6% for the SVM model and 93.1% for the NB model in MEM) as well as being able to monitor the pH solution.

Vat photopolymerization 3D printed microfluidic devices for organ-on-a-chip applications.

Organs-on-a-chip, or OoCs, are microfluidic tissue culture devices with micro-scaled architectures that repeatedly achieve biomimicry of biological phenomena. They are well positioned to become the primary pre-clinical testing modality as they possess high translational value. Current methods of fabrication have facilitated the development of many custom OoCs that have generated promising results. However, the reliance on microfabrication and soft lithographic fabrication techniques has limited their prototyping turnover rate and scalability. Additive manufacturing, known commonly as 3D printing, shows promise to expedite this prototyping process, while also making fabrication easier and more reproducible. We briefly introduce common 3D printing modalities before identifying two sub-types of vat photopolymerization - stereolithography (SLA) and digital light processing (DLP) - as the most advantageous fabrication methods for the future of OoC development. We then outline the motivations for shifting to 3D printing, the requirements for 3D printed OoCs to be competitive with the current state of the art, and several considerations for achieving successful 3D printed OoC devices touching on design and fabrication techniques, including a survey of commercial and custom 3D printers and resins. In all, we aim to form a guide for the end-user to facilitate the in-house generation of 3D printed OoCs, along with the future translation of these important devices.

Recent Advances of Organ-on-a-Chip in Cancer Modeling Research.

Although many studies have focused on oncology and therapeutics in cancer, cancer remains one of the leading causes of death worldwide. Due to the unclear molecular mechanism and complex in vivo microenvironment of tumors, it is challenging to reveal the nature of cancer and develop effective therapeutics. Therefore, the development of new methods to explore the role of heterogeneous TME in individual patients' cancer drug response is urgently needed and critical for the effective therapeutic management of cancer. The organ-on-chip (OoC) platform, which integrates the technology of 3D cell culture, tissue engineering, and microfluidics, is emerging as a new method to simulate the critical structures of the in vivo tumor microenvironment and functional characteristics. It overcomes the failure of traditional 2D/3D cell culture models and preclinical animal models to completely replicate the complex TME of human tumors. As a brand-new technology, OoC is of great significance for the realization of personalized treatment and the development of new drugs. This review discusses the recent advances of OoC in cancer biology studies. It focuses on the design principles of OoC devices and associated applications in cancer modeling. The challenges for the future development of this field are also summarized in this review. This review displays the broad applications of OoC technique and has reference value for oncology development.

A comparative study of tumour-on-chip models with patient-derived xenografts for predicting chemotherapy efficacy in colorectal cancer patients.

Inter-patient and intra-tumour heterogeneity (ITH) have prompted the need for a more personalised approach to cancer therapy. Although patient-derived xenograft (PDX) models can generate drug response specific to patients, they are not sustainable in terms of cost and time and have limited scalability. Tumour Organ-on-Chip (OoC) models are in vitro alternatives that can recapitulate some aspects of the 3D tumour microenvironment and can be scaled up for drug screening. While many tumour OoC systems have been developed to date, there have been limited validation studies to ascertain whether drug responses obtained from tumour OoCs are comparable to those predicted from patient-derived xenograft (PDX) models. In this study, we established a multiplexed tumour OoC device, that consists of an 8 × 4 array (32-plex) of culture chamber coupled to a concentration gradient generator. The device enabled perfusion culture of primary PDX-derived tumour spheroids to obtain dose-dependent response of 5 distinct standard-of-care (SOC) chemotherapeutic drugs for 3 colorectal cancer (CRC) patients. The in vitro efficacies of the chemotherapeutic drugs were rank-ordered for individual patients and compared to the in vivo efficacy obtained from matched PDX models. We show that quantitative correlation analysis between the drug efficacies predicted via the microfluidic perfusion culture is predictive of response in animal PDX models. This is a first study showing a comparative framework to quantitatively correlate the drug response predictions made by a microfluidic tumour organ-on-chip (OoC) model with that of PDX animal models.

Advances in Organ-on-a-Chip Materials and Devices

The organ-on-a-chip (OoC) paves a way for biomedical applications ranging from preclinical to clinical translational precision. The current trends in the in vitro modeling is to reduce the complexity of human organ anatomy to the fundamental cellular microanatomy as an alternative of recreating the entire cell milieu that allows systematic analysis of medicinal absorption of compounds, metabolism, and mechanistic investigation. The OoC devices accurately represent human physiology in vitro; however, it is vital to choose the correct chip materials. The potential chip materials include inorganic, elastomeric, thermoplastic, natural, and hybrid materials. Despite the fact that polydimethylsiloxane is the most commonly utilized polymer for OoC and microphysiological systems, substitute materials have been continuously developed for its advanced applications. The evaluation of human physiological status can help to demonstrate using noninvasive OoC materials in real-time procedures. Therefore, this Review examines the materials used for fabricating OoC devices, the application-oriented pros and cons, possessions for device fabrication and biocompatibility, as well as their potential for downstream biochemical surface alteration and commercialization. The convergence of emerging approaches, such as advanced materials, artificial intelligence, machine learning, three-dimensional (3D) bioprinting, and genomics, have the potential to perform OoC technology at next generation. Thus, OoC technologies provide easy and precise methodologies in cost-effective clinical monitoring and treatment using standardized protocols, at even personalized levels. Because of the inherent utilization of the integrated materials, employing the OoC with biomedical approaches will be a promising methodology in the healthcare industry.

Concept development of an on-chip PET system

BackgroundOrgans-on-Chips (OOCs), microdevices mimicking in vivo organs, find growing applications in disease modeling and drug discovery. With the increasing number of uses comes a strong demand for imaging capabilities of OOCs as monitoring physiologic processes within OOCs is vital for the continuous improvement of this technology. Positron Emission Tomography (PET) would be ideal for OOC imaging, however, current PET systems are insufficient for this task due to their inadequate spatial resolution. In this work, we propose the concept of an On-Chip PET system capable of imaging OOCs and optimize its design using a Monte Carlo Simulation (MCS).Material and methodsThe proposed system consists of four detectors arranged around the OOC device. Each detector is made of two monolithic LYSO crystals and covered with Silicon photomultipliers (SiPMs) on multiple surfaces. We use a Convolutional Neural Network (CNN) trained with data from a MCS to predict the first gamma-ray interaction position inside the detector from the light patterns that are recorded by the SiPMs on the detector’s surfaces.ResultsThe CNN achieves a mean average prediction error of 0.80 mm in the best configuration. The proposed system achieves a sensitivity of 34.81% for 13 mm thick crystals and does not show a prediction degradation near the boundaries of the detector. We use the trained network to reconstruct an image of a grid of 21 point sources spread across the field-of-view and obtain a mean spatial resolution of 0.55 mm. We show that 25,000 Line of Responses (LORs) are needed to reconstruct a realistic OOC phantom with adequate image quality.ConclusionsWe demonstrate that it is possible to achieve a spatial resolution of almost 0.5 mm in a PET system made of multiple monolithic LYSO crystals by directly predicting the scintillation position from light patterns created with SiPMs. We observe that a thinner crystal performs better than a thicker one, that increasing the SiPM size from 3 mm to 6 mm only slightly decreases the prediction performance, and that certain surfaces encode significantly more information for the scintillation-point prediction than others.

A guide to the organ-on-a-chip

Organs-on-chips (OoCs) are systems containing engineered or natural miniature tissues grown inside microfluidic chips. To better mimic human physiology, the chips are designed to control cell microenvironments and maintain tissue-specific functions. Combining advances in tissue engineering and microfabrication, OoCs have gained interest as a next-generation experimental platform to investigate human pathophysiology and the effect of therapeutics in the body. There are as many examples of OoCs as there are applications, making it difficult for new researchers to understand what makes one OoC more suited to an application than another. This Primer is intended to give an introduction to the aspects of OoC that need to be considered when developing an application-specific OoC. The Primer covers guiding principles and considerations to design, fabricate and operate an OoC, as well as subsequent assaying techniques to extract biological information from OoC devices. Alongside this is a discussion of current and future applications of OoC technology, to inform design and operational decisions during the implementation of OoC systems. Organs-on-chips are microfluidic systems containing miniature tissues with the aim of mimicking human physiology for a range of biomedical and therapeutic applications. Leung, de Haan et al. report practical tips to inform design and operational decisions during the implementation of organ-on-a-chip systems.

Toward a modular, integrated, miniaturized, and portable microfluidic flow control architecture for organs-on-chips applications.

Microfluidic organs-on-chips (OoCs) technology has emerged as the trend for in vitro functional modeling of organs in recent years. Simplifying the complexities of the human organs under controlled perfusion of required fluids paves the way for accurate prediction of human organ functionalities and their response to interventions like exposure to drugs. However, in the state-of-the-art OoC, the existing methods to control fluids use external bulky peripheral components and systems much larger than the chips used in experiments. A new generation of compact microfluidic flow control systems is needed to overcome this challenge. This study first presents a structured classification of OoC devices according to their types and microfluidic complexities. Next, we suggest three fundamental fluid flow control mechanisms and define component configurations for different levels of OoC complexity for each respective mechanism. Finally, we propose an architecture integrating modular microfluidic flow control components and OoC devices on a single platform. We emphasize the need for miniaturization of flow control components to achieve portability, minimize sample usage, minimize dead volume, improve the flowing time of fluids to the OoC cell chamber, and enable long-duration experiments.

Organ-on-a-Chip Platforms for Drug Screening and Delivery in Tumor Cells: A Systematic Review.

Simple SummaryCancer is one of the diseases with a high mortality rate worldwide. Of the current strategies to study new diagnostic and treating tools, organs-on-chip are quite promising regarding the achievement of more personalized medicine. In this work, 75 out of 820 of the most recent published scientific articles were selected and analyzed through a systematic process. The selected articles present the different microfluidic platforms where cell culture was introduced and was used for the evaluation of cancer treatments efficacy and/or toxicity.The development of cancer models that rectify the simplicity of monolayer or static cell cultures physiologic microenvironment and, at the same time, replicate the human system more accurately than animal models has been a challenge in biomedical research. Organ-on-a-chip (OoC) devices are a solution that has been explored over the last decade. The combination of microfluidics and cell culture allows the design of a dynamic microenvironment suitable for the evaluation of treatments’ efficacy and effects, closer to the response observed in patients. This systematic review sums the studies from the last decade, where OoC with cancer cell cultures were used for drug screening assays. The studies were selected from three databases and analyzed following the research guidelines for systematic reviews proposed by PRISMA. In the selected studies, several types of cancer cells were evaluated, and the majority of treatments tested were standard chemotherapeutic drugs. Some studies reported higher drug resistance of the cultures on the OoC devices than on 2D cultures, which indicates the better resemblance to in vivo conditions of the former. Several studies also included the replication of the microvasculature or the combination of different cell cultures. The presence of vasculature can influence positively or negatively the drug efficacy since it contributes to a greater diffusion of the drug and also oxygen and nutrients. Co-cultures with liver cells contributed to the evaluation of the systemic toxicity of some drugs metabolites. Nevertheless, few studies used patient cells for the drug screening assays.