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1
Gyimah, Nafisat, Ott Scheler, Toomas Rang, and Tamas Pardy. "Can 3D Printing Bring Droplet Microfluidics to Every Lab?—A Systematic Review." Micromachines 12, no. 3 (2021): 339. http://dx.doi.org/10.3390/mi12030339.
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In recent years, additive manufacturing has steadily gained attention in both research and industry. Applications range from prototyping to small-scale production, with 3D printing offering reduced logistics overheads, better design flexibility and ease of use compared with traditional fabrication methods. In addition, printer and material costs have also decreased rapidly. These advantages make 3D printing attractive for application in microfluidic chip fabrication. However, 3D printing microfluidics is still a new area. Is the technology mature enough to print complex microchannel geometries, such as droplet microfluidics? Can 3D-printed droplet microfluidic chips be used in biological or chemical applications? Is 3D printing mature enough to be used in every research lab? These are the questions we will seek answers to in our systematic review. We will analyze (1) the key performance metrics of 3D-printed droplet microfluidics and (2) existing biological or chemical application areas. In addition, we evaluate (3) the potential of large-scale application of 3D printing microfluidics. Finally, (4) we discuss how 3D printing and digital design automation could trivialize microfluidic chip fabrication in the long term. Based on our analysis, we can conclude that today, 3D printers could already be used in every research lab. Printing droplet microfluidics is also a possibility, albeit with some challenges discussed in this review.
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Li, Xiangke, Meng Wang, Thomas P. Davis, Liwen Zhang, and Ruirui Qiao. "Advancing Tissue Culture with Light-Driven 3D-Printed Microfluidic Devices." Biosensors 14, no. 6 (2024): 301. http://dx.doi.org/10.3390/bios14060301.
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Three-dimensional (3D) printing presents a compelling alternative for fabricating microfluidic devices, circumventing certain limitations associated with traditional soft lithography methods. Microfluidics play a crucial role in the biomedical sciences, particularly in the creation of tissue spheroids and pharmaceutical research. Among the various 3D printing techniques, light-driven methods such as stereolithography (SLA), digital light processing (DLP), and photopolymer inkjet printing have gained prominence in microfluidics due to their rapid prototyping capabilities, high-resolution printing, and low processing temperatures. This review offers a comprehensive overview of light-driven 3D printing techniques used in the fabrication of advanced microfluidic devices. It explores biomedical applications for 3D-printed microfluidics and provides insights into their potential impact and functionality within the biomedical field. We further summarize three light-driven 3D printing strategies for producing biomedical microfluidic systems: direct construction of microfluidic devices for cell culture, PDMS-based microfluidic devices for tissue engineering, and a modular SLA-printed microfluidic chip to co-culture and monitor cells.
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Lepowsky, Eric, Reza Amin, and Savas Tasoglu. "Assessing the Reusability of 3D-Printed Photopolymer Microfluidic Chips for Urine Processing." Micromachines 9, no. 10 (2018): 520. http://dx.doi.org/10.3390/mi9100520.
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Three-dimensional (3D) printing is emerging as a method for microfluidic device fabrication boasting facile and low-cost fabrication, as compared to conventional fabrication approaches, such as photolithography, for poly(dimethylsiloxane) (PDMS) counterparts. Additionally, there is an increasing trend in the development and implementation of miniaturized and automatized devices for health monitoring. While nonspecific protein adsorption by PDMS has been studied as a limitation for reusability, the protein adsorption characteristics of 3D-printed materials have not been well-studied or characterized. With these rationales in mind, we study the reusability of 3D-printed microfluidics chips. Herein, a 3D-printed cleaning chip, consisting of inlets for the sample, cleaning solution, and air, and a universal outlet, is presented to assess the reusability of a 3D-printed microfluidic device. Bovine serum albumin (BSA) was used a representative urinary protein and phosphate-buffered solution (PBS) was chosen as the cleaning agent. Using the 3-(4-carboxybenzoyl)quinoline-2-carboxaldehyde (CBQCA) fluorescence detection method, the protein cross-contamination between samples and the protein uptake of the cleaning chip were assessed, demonstrating a feasible 3D-printed chip design and cleaning procedure to enable reusable microfluidic devices. The performance of the 3D-printed cleaning chip for real urine sample handling was then validated using a commercial dipstick assay.
4
Lin, Jiaqi, Lijuan Cui, Xiaokun Shi, and Shuping Wu. "Emerging Trends in Microfluidic Biomaterials: From Functional Design to Applications." Journal of Functional Biomaterials 16, no. 5 (2025): 166. https://doi.org/10.3390/jfb16050166.
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The rapid development of microfluidics has driven innovations in material engineering, particularly through its ability to precisely manipulate fluids and cells at microscopic scales. Microfluidic biomaterials, a cutting-edge interdisciplinary field integrating microfluidic technology with biomaterials science, are revolutionizing biomedical research. This review focuses on the functional design and fabrication of organ-on-a-chip (OoAC) platforms via 3D bioprinting, explores the applications of biomaterials in drug delivery, cell culture, and tissue engineering, and evaluates the potential of microfluidic systems in advancing personalized healthcare. We systematically analyze the evolution of microfluidic materials—from silicon and glass to polymers and paper—and highlight the advantages of 3D bioprinting over traditional fabrication methods. Currently, despite significant advances in microfluidics in medicine, challenges in scalability, stability, and clinical translation remain. The future of microfluidic biomaterials will depend on combining 3D bioprinting with dynamic functional design, developing hybrid strategies that combine traditional molds with bio-printed structures, and using artificial intelligence to monitor drug delivery or tissue response in real time. We believe that interdisciplinary collaborations between materials science, micromachining, and clinical medicine will accelerate the translation of organ-on-a-chip platforms into personalized therapies and high-throughput drug screening tools.
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Amoyav, Benzion, Yoel Goldstein, Eliana Steinberg, and Ofra Benny. "3D Printed Microfluidic Devices for Drug Release Assays." Pharmaceutics 13, no. 1 (2020): 13. http://dx.doi.org/10.3390/pharmaceutics13010013.
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Microfluidics research for various applications, including drug delivery, cell-based assays and biomedical research has grown exponentially. Despite this technology’s enormous potential, drawbacks include the need for multistep fabrication, typically with lithography. We present a one-step fabrication process of a microfluidic chip for drug dissolution assays based on a 3D printing technology. Doxorubicin porous and non-porous microspheres, with a mean diameter of 250µm, were fabricated using a conventional “batch” or microfluidic method, based on an optimized solid-in-oil-in-water protocol. Microspheres fabricated with microfluidics system exhibited higher encapsulation efficiency and drug content as compared with batch formulations. We determined drug release profiles of microspheres in varying pH conditions using two distinct dissolution devices that differed in their mechanical barrier structures. The release profile of the “V” shape barrier was similar to that of the dialysis sac test and differed from the “basket” barrier design. Importantly, a cytotoxicity test confirmed biocompatibility of the printed resin. Finally, the chip exhibited high durability and stability, enabling multiple recycling sessions. We show how the combination of microfluidics and 3D printing can reduce costs and time, providing an efficient platform for particle production while offering a feasible cost-effective alternative to clean-room facility polydimethylsiloxane-based chip microfabrication.
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Niioka, Takuma, and Yasutaka Hanada. "Surface Microfabrication of Conventional Glass Using Femtosecond Laser for Microfluidic Applications." International Journal of Automation Technology 11, no. 6 (2017): 878–82. http://dx.doi.org/10.20965/ijat.2017.p0878.
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Recently, a lot of attention has been paid to a single-cell analysis using microfluidic chips, since each cell is known to have several different characteristics. The microfluidic chip manipulates cells and performs high-speed and high-resolution analysis. In the meanwhile, femtosecond (fs) laser has become a versatile tool for the fabrication of microfluidic chips because the laser can modify internal volume solely at the focal area, resulting in three-dimensional (3D) microfabrication of glass materials. However, little research on surface microfabrication of materials using an fs laser has been conducted. Therefore, in this study, we demonstrate the surface microfabrication of a conventional glass slide using fs laser direct-writing for microfluidic applications. The fs laser modification, with successive wet etching using a diluted hydrofluoric (HF) acid solution, followed by annealing, results in rapid prototyping of microfluidics on a conventional glass slide for fluorescent microscopic cell analysis. Fundamental characteristics of the laser-irradiated regions in each experimental procedure were investigated. In addition, we developed a novel technique combining the fs laser direct-writing and the HF etching for high-speed and high-resolution microfabrication of the glass. After establishing the fs laser surface microfabrication technique, a 3D microfluidic chip was made by bonding the fabricated glass microfluidic chip with a polydimethylsiloxane (PDMS) polymer substrate for clear fluorescent microscopic observation in the microfluidics.
7
Adamopoulos, Christos, Asmaysinh Gharia, Ali Niknejad, Vladimir Stojanović, and Mekhail Anwar. "Microfluidic Packaging Integration with Electronic-Photonic Biosensors Using 3D Printed Transfer Molding." Biosensors 10, no. 11 (2020): 177. http://dx.doi.org/10.3390/bios10110177.
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Multiplexed sensing in integrated silicon electronic-photonic platforms requires microfluidics with both high density micro-scale channels and meso-scale features to accommodate for optical, electrical, and fluidic coupling in small, millimeter-scale areas. Three-dimensional (3D) printed transfer molding offers a facile and rapid method to create both micro and meso-scale features in complex multilayer microfluidics in order to integrate with monolithic electronic-photonic system-on-chips with multiplexed rows of 5 μm radius micro-ring resonators (MRRs), allowing for simultaneous optical, electrical, and microfluidic coupling on chip. Here, we demonstrate this microfluidic packaging strategy on an integrated silicon photonic biosensor, setting the basis for highly multiplexed molecular sensing on-chip.
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Wang, Shaoxi, Yue Yin, and Xiaoya Fan. "The Chip Cooling Model and Route Optimization with Digital Microfluidics." Xibei Gongye Daxue Xuebao/Journal of Northwestern Polytechnical University 37, no. 1 (2019): 107–13. http://dx.doi.org/10.1051/jnwpu/20193710107.
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Using microfluidic technology to achieve integrated chip cooling is becoming a promising method to extend Moore law effective period. The thermal management is always critical for 3D integrated circuit design. Hot spots due to spatially non-uniform heat flux in integrated circuits can cause physical stress that further reduces reliability. The critical point for chip cooling is to use microfluidic cooling accurately on the hot spots. First, based on electro-wetting on dielectric, the paper presents an adaptive chip cooling technique using the digital microfluidics. Then, a two-plans 3D chip cooling model has been given with its working principle and characteristics. And single plan chip cooling model is presented, including its capacitance performance and models. Moreover, the dentate electrode is designed to achieve droplet continuing movement. Next, the ant colony optimization is adopted to get optimal route during electrode moving. Last, the experiments demonstrate the adaptive chip cooling technique proposed in this paper is effective and efficiency.
9
Kim, Jeong Hwa, Ju Young Park, Songwan Jin, Sik Yoon, Jong-Young Kwak, and Young Hun Jeong. "A Microfluidic Chip Embracing a Nanofiber Scaffold for 3D Cell Culture and Real-Time Monitoring." Nanomaterials 9, no. 4 (2019): 588. http://dx.doi.org/10.3390/nano9040588.
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Recently, three-dimensional (3D) cell culture and tissue-on-a-chip application have attracted attention because of increasing demand from the industries and their potential to replace conventional two-dimensional culture and animal tests. As a result, numerous studies on 3D in-vitro cell culture and microfluidic chip have been conducted. In this study, a microfluidic chip embracing a nanofiber scaffold is presented. A electrospun nanofiber scaffold can provide 3D cell culture conditions to a microfluidic chip environment, and its perfusion method in the chip can allow real-time monitoring of cell status based on the conditioned culture medium. To justify the applicability of the developed chip to 3D cell culture and real-time monitoring, HepG2 cells were cultured in the chip for 14 days. Results demonstrated that the cells were successfully cultured with 3D culture-specific-morphology in the chip, and their albumin and alpha-fetoprotein production was monitored in real-time for 14 days.
10
Sekhwama, Masindi, Kelvin Mpofu, and Patience Mthunzi-Kufa. "Using 3D printing to fabricate microfluidic chips for biosensing applications." MATEC Web of Conferences 388 (2023): 05001. http://dx.doi.org/10.1051/matecconf/202338805001.
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This paper gives details on the use of 3D smart printing technology to fabricate microfluidic chips for integration into biosensors for the detection and diagnosis of diseases. Additive manufacturing, also known as 3D printing, is a process used to create complex, three-dimensional objects by adding layer upon layer of material until the desired shape is formed. Microfluidic chips are used to manipulate fluids through separation and mixing. Conventional microfluidic chip fabrication methods are expensive, require much experience to operate, and are time consuming, while 3D printing offers a solution to these challenges. The 3D printing technique prints models designed using a computer-aided design software such as Autodesk Fusion 360. In this work the authors show example microfluidic chips which were printed using a 3D printer, these include an X-channel chip, Y-channel chip and a lateral flow chip which can all be integrated with biosensing setups.
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Duan, Kai, Mohamad Orabi, Alexus Warchock, et al. "Monolithically 3D-Printed Microfluidics with Embedded µTesla Pump." Micromachines 14, no. 2 (2023): 237. http://dx.doi.org/10.3390/mi14020237.
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Microfluidics has earned a reputation for providing numerous transformative but disconnected devices and techniques. Active research seeks to address this challenge by integrating microfluidic components, including embedded miniature pumps. However, a significant portion of existing microfluidic integration relies on the time-consuming manual fabrication that introduces device variations. We put forward a framework for solving this disconnect by combining new pumping mechanics and 3D printing to demonstrate several novel, integrated and wirelessly driven microfluidics. First, we characterized the simplicity and performance of printed microfluidics with a minimum feature size of 100 µm. Next, we integrated a microtesla (µTesla) pump to provide non-pulsatile flow with reduced shear stress on beta cells cultured on-chip. Lastly, the integration of radio frequency (RF) device and a hobby-grade brushless motor completed a self-enclosed platform that can be remotely controlled without wires. Our study shows how new physics and 3D printing approaches not only provide better integration but also enable novel cell-based studies to advance microfluidic research.
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Moussus, Michel, and Matthias Meier. "A 3D-printed Arabidopsis thaliana root imaging platform." Lab on a Chip 21, no. 13 (2021): 2557–64. http://dx.doi.org/10.1039/d1lc00149c.
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Here, we developed and characterized 3D printed microfluidic chip designs and materials for plant culturing. One general open microfluidic chip has been established for high-resolution live imaging of plant roots under changing microenvironments.
13
Ahmed, Isteaque, Katherine Sullivan, and Aashish Priye. "Multi-Resin Masked Stereolithography (MSLA) 3D Printing for Rapid and Inexpensive Prototyping of Microfluidic Chips with Integrated Functional Components." Biosensors 12, no. 8 (2022): 652. http://dx.doi.org/10.3390/bios12080652.
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Stereolithography based 3D printing of microfluidics for prototyping has gained a lot of attention due to several advantages such as fast production, cost-effectiveness, and versatility over traditional photolithography-based microfabrication techniques. However, existing consumer focused SLA 3D printers struggle to fabricate functional microfluidic devices due to several challenges associated with micron-scale 3D printing. Here, we explore the origins and mechanism of the associated failure modes followed by presenting guidelines to overcome these challenges. The prescribed method works completely with existing consumer class inexpensive SLA printers without any modifications to reliably print PDMS cast microfluidic channels with channel sizes as low as ~75 μm and embedded channels with channel sizes as low ~200 μm. We developed a custom multi-resin formulation by incorporating Polyethylene glycol diacrylate (PEGDA) and Ethylene glycol polyether acrylate (EGPEA) as the monomer units to achieve micron sized printed features with tunable mechanical and optical properties. By incorporating multiple resins with different mechanical properties, we were able to achieve spatial control over the stiffness of the cured resin enabling us to incorporate both flexible and rigid components within a single 3D printed microfluidic chip. We demonstrate the utility of this technique by 3D printing an integrated pressure-actuated pneumatic valve (with flexible cured resin) in an otherwise rigid and clear microfluidic device that can be fabricated in a one-step process from a single CAD file. We also demonstrate the utility of this technique by integrating a fully functional finger-actuated microfluidic pump. The versatility and accessibility of the demonstrated fabrication method have the potential to reduce our reliance on expensive and time-consuming photolithographic techniques for microfluidic chip fabrication and thus drastically lowering our barrier to entry in microfluidics research.
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Li, Lei, Kurtulus Gokduman, Aslihan Gokaltun, Martin L. Yarmush, and Osman Berk Usta. "A microfluidic 3D hepatocyte chip for hepatotoxicity testing of nanoparticles." Nanomedicine 14, no. 16 (2019): 2209–26. http://dx.doi.org/10.2217/nnm-2019-0086.
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Aim: To develop a practical microfluidic 3D hepatocyte chip for hepatotoxicity testing of nanoparticles using proof of concept studies providing first results of the potential hepatotoxicity of superparamagnetic iron oxide nanoparticles (SPION) under microfluidic conditions. Methods: A microfluidic 3D hepatocyte chip with three material layers, which contains primary rat hepatocytes, has been fabricated and tested using different concentrations (50, 100 and 200 μg/ml) of SPION in 3-day (short-term) and 1-week (long-term) cultures. Results: Compared with standard well plates, the hepatocyte chip with flow provided comparable viability and significantly higher liver-specific functions, up to 1 week. In addition, the chip recapitulates the key physiological responses in the hepatotoxicity of SPION. Conclusion: Thus, the developed 3D hepatocyte chip is a robust and highly sensitive platform for investigating hepatotoxicity profiles of nanoparticles.
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Zhao, Qianbin, Tim Cole, Yuxin Zhang, and Shi-Yang Tang. "Mechanical Strain-Enabled Reconstitution of Dynamic Environment in Organ-on-a-Chip Platforms: A Review." Micromachines 12, no. 7 (2021): 765. http://dx.doi.org/10.3390/mi12070765.
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Organ-on-a-chip (OOC) uses the microfluidic 3D cell culture principle to reproduce organ- or tissue-level functionality at a small scale instead of replicating the entire human organ. This provides an alternative to animal models for drug development and environmental toxicology screening. In addition to the biomimetic 3D microarchitecture and cell–cell interactions, it has been demonstrated that mechanical stimuli such as shear stress and mechanical strain significantly influence cell behavior and their response to pharmaceuticals. Microfluidics is capable of precisely manipulating the fluid of a microenvironment within a 3D cell culture platform. As a result, many OOC prototypes leverage microfluidic technology to reproduce the mechanically dynamic microenvironment on-chip and achieve enhanced in vitro functional organ models. Unlike shear stress that can be readily generated and precisely controlled using commercial pumping systems, dynamic systems for generating proper levels of mechanical strains are more complicated, and often require miniaturization and specialized designs. As such, this review proposes to summarize innovative microfluidic OOC platforms utilizing mechanical actuators that induce deflection of cultured cells/tissues for replicating the dynamic microenvironment of human organs.
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Trujillo-de Santiago, Grissel, Brenda Giselle Flores-Garza, Jorge Alfonso Tavares-Negrete, et al. "The Tumor-on-Chip: Recent Advances in the Development of Microfluidic Systems to Recapitulate the Physiology of Solid Tumors." Materials 12, no. 18 (2019): 2945. http://dx.doi.org/10.3390/ma12182945.
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The ideal in vitro recreation of the micro-tumor niche—although much needed for a better understanding of cancer etiology and development of better anticancer therapies—is highly challenging. Tumors are complex three-dimensional (3D) tissues that establish a dynamic cross-talk with the surrounding tissues through complex chemical signaling. An extensive body of experimental evidence has established that 3D culture systems more closely recapitulate the architecture and the physiology of human solid tumors when compared with traditional 2D systems. Moreover, conventional 3D culture systems fail to recreate the dynamics of the tumor niche. Tumor-on-chip systems, which are microfluidic devices that aim to recreate relevant features of the tumor physiology, have recently emerged as powerful tools in cancer research. In tumor-on-chip systems, the use of microfluidics adds another dimension of physiological mimicry by allowing a continuous feed of nutrients (and pharmaceutical compounds). Here, we discuss recently published literature related to the culture of solid tumor-like tissues in microfluidic systems (tumor-on-chip devices). Our aim is to provide the readers with an overview of the state of the art on this particular theme and to illustrate the toolbox available today for engineering tumor-like structures (and their environments) in microfluidic devices. The suitability of tumor-on-chip devices is increasing in many areas of cancer research, including the study of the physiology of solid tumors, the screening of novel anticancer pharmaceutical compounds before resourcing to animal models, and the development of personalized treatments. In the years to come, additive manufacturing (3D bioprinting and 3D printing), computational fluid dynamics, and medium- to high-throughput omics will become powerful enablers of a new wave of more sophisticated and effective tumor-on-chip devices.
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Su, Ruitao, Jiaxuan Wen, Qun Su, et al. "3D printed self-supporting elastomeric structures for multifunctional microfluidics." Science Advances 6, no. 41 (2020): eabc9846. http://dx.doi.org/10.1126/sciadv.abc9846.
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Microfluidic devices fabricated via soft lithography have demonstrated compelling applications such as lab-on-a-chip diagnostics, DNA microarrays, and cell-based assays. These technologies could be further developed by directly integrating microfluidics with electronic sensors and curvilinear substrates as well as improved automation for higher throughput. Current additive manufacturing methods, such as stereolithography and multi-jet printing, tend to contaminate substrates with uncured resins or supporting materials during printing. Here, we present a printing methodology based on precisely extruding viscoelastic inks into self-supporting microchannels and chambers without requiring sacrificial materials. We demonstrate that, in the submillimeter regime, the yield strength of the as-extruded silicone ink is sufficient to prevent creep within a certain angular range. Printing toolpaths are specifically designed to realize leakage-free connections between channels and chambers, T-shaped intersections, and overlapping channels. The self-supporting microfluidic structures enable the automatable fabrication of multifunctional devices, including multimaterial mixers, microfluidic-integrated sensors, automation components, and 3D microfluidics.
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Qiu, Jingjiang, Junfu Li, Zhongwei Guo, et al. "3D Printing of Individualized Microfluidic Chips with DLP-Based Printer." Materials 16, no. 21 (2023): 6984. http://dx.doi.org/10.3390/ma16216984.
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Microfluidic chips have shown their potential for applications in fields such as chemistry and biology, and 3D printing is increasingly utilized as the fabrication method for microfluidic chips. To address key issues such as the long printing time for conventional 3D printing of a single chip and the demand for rapid response in individualized microfluidic chip customization, we have optimized the use of DLP (digital light processing) technology, which offers faster printing speeds due to its surface exposure method. In this study, we specifically focused on developing a fast-manufacturing process for directly printing microfluidic chips, addressing the high cost of traditional microfabrication processes and the lengthy production times associated with other 3D printing methods for microfluidic chips. Based on the designed three-dimensional chip model, we utilized a DLP-based printer to directly print two-dimensional and three-dimensional microfluidic chips with photosensitive resin. To overcome the challenge of clogging in printing microchannels, we proposed a printing method that combined an open-channel design with transparent adhesive tape sealing. This method enables the rapid printing of microfluidic chips with complex and intricate microstructures. This research provides a crucial foundation for the development of microfluidic chips in biomedical research.
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Wu, Chuang, Jiju Sun, and Binfeng Yin. "Research on Integrated 3D Printing of Microfluidic Chips." Micromachines 14, no. 7 (2023): 1302. http://dx.doi.org/10.3390/mi14071302.
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Microfluidic chips have the advantages of miniaturization, integration, and portability, and are widely used in the early diagnosis of major diseases, personalized medical treatment, environmental detection, health quarantine, and other fields. The existing microfluidic chip manufacturing process is difficult to operate because of complex three-dimensional channels, complicated manufacturing steps, limited printing materials, the difficulty of operating the bonding process, and the need to purchase expensive new equipment. In this paper, an integrated molding method for microfluidic chips that integrates 3D printing and polymer dissolution technology is proposed. First, the channel mold of poly(vinyl alcohol) (PVA) or high impact polystyrene (HIPS) is dissolved to complete the manufacturing of the microfluidic chip channel. The integrated 3D-forming method of microfluidic chips proposed in this paper can manufacture microchannels inside the microfluidic chip, avoid the bonding process, and eliminate the need for rapid alignment of microchannels, material modification, and other operations, thus improving the stability of the process. Finally, by comparing the microchannels made by PVA and HIPS, it is concluded that the quality of the microchannels made by HIPS is obviously better than that made by PVA. This paper provides a new idea for the fabrication of microfluidic chips and the application of HIPS.
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Bissardon, Caroline, Xavier Mermet, Sophie Morales, et al. "Light sheet fluorescence microscope for microfluidic chip." EPJ Web of Conferences 238 (2020): 04005. http://dx.doi.org/10.1051/epjconf/202023804005.
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We present a light sheet fluorescence microscope dedicated to image “Organ-on-chip”-like biostructures in microfluidic chip. Based on a simple design, the setup is built around the chip and its environment to allow 3D imaging inside the chip in a microfluidic laboratory. The experimental setup, its optical characterization and first volumetric images are reported.
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Nam, Sung-Wook, Dong-Gyu Jeon, Young-Ran Yoon, Gang Ho Lee, Yongmin Chang, and Dong Il Won. "Hemagglutination Assay via Optical Density Characterization in 3D Microtrap Chips." Biosensors 13, no. 7 (2023): 733. http://dx.doi.org/10.3390/bios13070733.
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Hemagglutination assay has been used for blood typing and detecting viruses, thus applicable for the diagnosis of infectious diseases, including COVID-19. Therefore, the development of microfluidic devices for fast detection of hemagglutination is on-demand for point-of-care diagnosis. Here, we present a way to detect hemagglutination in 3D microfluidic devices via optical absorbance (optical density, OD) characterization. 3D printing is a powerful way to build microfluidic structures for diagnostic devices. However, mixing liquid in microfluidic chips is difficult due to laminar flow, which hampers practical applications such as antigen-antibody mixing. To overcome the issue, we fabricated 3D microfluidic chips with embedded microchannel and microwell structures to induce hemagglutination between red blood cells (RBCs) and antibodies. We named it a 3D microtrap chip. We also established an automated measurement system which is an integral part of diagnostic devices. To do this, we developed a novel way to identify RBC agglutination and non-agglutination via the OD difference. By adapting a 3D-printed aperture to the microtrap chip, we obtained a pure absorbance signal from the microchannels by eliminating the background brightness of the microtrap chip. By investigating the underlying optical physics, we provide a 3D device platform for detecting hemagglutination.
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Ballacchino, Giulia, Edward Weaver, Essyrose Mathew, et al. "Manufacturing of 3D-Printed Microfluidic Devices for the Synthesis of Drug-Loaded Liposomal Formulations." International Journal of Molecular Sciences 22, no. 15 (2021): 8064. http://dx.doi.org/10.3390/ijms22158064.
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Microfluidic technique has emerged as a promising tool for the production of stable and monodispersed nanoparticles (NPs). In particular, this work focuses on liposome production by microfluidics and on factors involved in determining liposome characteristics. Traditional fabrication techniques for microfluidic devices suffer from several disadvantages, such as multistep processing and expensive facilities. Three-dimensional printing (3DP) has been revolutionary for microfluidic device production, boasting facile and low-cost fabrication. In this study, microfluidic devices with innovative micromixing patterns were developed using fused deposition modelling (FDM) and liquid crystal display (LCD) printers. To date, this work is the first to study liposome production using LCD-printed microfluidic devices. The current study deals with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes with cholesterol (2:1) prepared using commercial and 3D-printed microfluidic devices. We evaluated the effect of microfluidic parameters, chip manufacturing, material, and channel design on liposomal formulation by analysing the size, PDI, and ζ-potential. Curcumin exhibits potent anticancer activity and it has been reported that curcumin-loaded liposomes formulated by microfluidics show enhanced encapsulation efficiency when compared with other reported systems. In this work, curcumal liposomes were produced using the developed microfluidic devices and particle sizing, ζ-potential, encapsulation efficiency, and in vitro release studies were performed at 37 °C.
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SUN, HAO, ZHANDONG LI, and JIANGUO TAO. "INTEGRATED 3D MULTI-PHYSICAL SIMULATION OF A MICROFLUIDIC SYSTEM USING FINITE ELEMENT ANALYSIS." Journal of Mechanics in Medicine and Biology 15, no. 06 (2015): 1540043. http://dx.doi.org/10.1142/s0219519415400436.
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Microfluidics technology has emerged as an attractive approach in physics, chemistry and biomedical science by providing increased analytical accuracy, sensitivity and efficiency in minimized systems. Numerical simulation can improve theoretical understanding, reduce prototyping consumption, and speed up development. In this paper, we setup a 3D model of an integrated microfluidic system and study the multi-physical dynamics of the system via the finite element method (FEM). The fluid–structure interaction (FSI) of fluid and an immobilized single cell within the cell trapping component, and the on-chip thermodynamics have been analyzed. The velocity magnitude and streamline of flow field, the distribution of von Mises stress and Tresca stress on the FSI interface have been studied. In addition, the on-chip heat transfer performance and temperature distribution in the heating zone have been evaluated and analyzed respectively. The presented approach is capable of optimizing microfluidic design, and revealing the complicated mechanism of multi-physical fields. Therefore, it holds the potential for improving microfluidics application in fundamental research and clinical settings.
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Baczyński, Szymon, Piotr Sobotka, Kasper Marchlewicz, Artur Dybko, and Katarzyna Rutkowska. "Low-cost, widespread and reproducible mold fabrication technique for PDMS-based microfluidic photonic systems." Photonics Letters of Poland 12, no. 1 (2020): 22. http://dx.doi.org/10.4302/plp.v12i1.981.
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In this letter the possibility of low-cost fabrication of molds for PDMS-based photonic microstructures is considered. For this purpose, three different commercially available techniques, namely UV-curing of the capillary film, 3D SLA printing and micromilling, have been analyzed. Obtained results have been compared in terms of prototyping time, quality, repeatability, and re-use of the mold for PDMS-based microstructures fabrication. Prospective use for photonic systems, especially optofluidic ones infiltrated with liquid crystalline materials, have been commented. Full Text: PDF References:K. Sangamesh, C.T. Laurencin, M. Deng, Natural and Synthetic Biomedical Polymers (Elsevier, Amsterdam 2004). [DirectLink]A. Mata et. al, "Characterization of Polydimethylsiloxane (PDMS) Properties for Biomedical Micro/Nanosystems", Biomed. Microdev. 7(4), 281 (2005). [CrossRef]I. Rodríguez-Ruiz et al., "Photonic Lab-on-a-Chip: Integration of Optical Spectroscopy in Microfluidic Systems", Anal. Chem. 88(13), 6630 (2016). [CrossRef]SYLGARD™ 184 Silicone Elastomer, Technical Data Sheet [DirectLink]N.E. Stankova et al., "Optical properties of polydimethylsiloxane (PDMS) during nanosecond laser processing", Appl. Surface Science 374, 96 (2016) [CrossRef]J.C. McDonald et al., "Fabrication of microfluidic systems in poly(dimethylsiloxane)", Electrophoresis 21(1), 27 (2000). [CrossRef]T. Fujii, "PDMS-based microfluidic devices for biomedical applications", Microelectronic Eng. 61, 907 (2002). [CrossRef]F. Schneider et al., "Process and material properties of polydimethylsiloxane (PDMS) for Optical MEMS", Sensors Actuat. A: Physical 151(2), 95 (2009). [CrossRef]T.K. Shih et al., "Fabrication of PDMS (polydimethylsiloxane) microlens and diffuser using replica molding", Microelectronic Eng. 83(11-12), 2499 (2006). [CrossRef]K. Rutkowska et al. "Electrical tuning of the LC:PDMS channels", PLP, 9, 48-50 (2017). [CrossRef]D. Kalinowska et al., "Studies on effectiveness of PTT on 3D tumor model under microfluidic conditions using aptamer-modified nanoshells", Biosensors Bioelectr. 126, 214 (2019).[CrossRef]N. Bhattacharjee et al., "The upcoming 3D-printing revolution in microfluidics", Lab on a Chip 16(10), 1720 (2016). [CrossRef]I.R.G. Ogilvie et al., "Reduction of surface roughness for optical quality microfluidic devices in PMMA and COC", J. Micromech. Microeng. 20(6), 065016 (2010). [CrossRef]D. Gomez et al., "Femtosecond laser ablation for microfluidics", Opt. Eng. 44(5), 051105 (2005). [CrossRef]Y. Hwang, R.N. Candler, "Non-planar PDMS microfluidic channels and actuators: a review", Lab on a Chip 17(23), 3948 (2017). [CrossRef]
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Casali, Veronica, Ingrid Clerc Guithon, Boudewijn van der Sanden, et al. "Is a real-time quantifiable liquid biopsy achievable using a microfluidic lab-on-chip ?" EuroBiotech Journal 7, no. 4 (2023): 189–95. http://dx.doi.org/10.2478/ebtj-2023-0014.
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Abstract An increasingly relevant functional measurement is a liquid biopsy to assist in the diagnosis of cancers. The existing approach for liquid biopsy is to utilize microfluidic chips for the isolation of circulating tumor cells (CTCs) or exosomes or extracellular vesicles (EV) from patient samples, and then for the analysis of the cargo contained inside the CTCs, exosomes or EVs. However, such an analysis does not provide a real-time liquid biopsy, since there is a long delay between the time of sample collection and the results from the analysis. Microfluidic chip-formats also provide the capability to mimic tissue functions from the analysis of small numbers of cells cultured in the chip. Analysis of the secreted molecules from such cells could provide a measurement of the secretome, which could be analogous to a liquid biopsy. A 3D structural organization of cells in microfluidic chips is usually in the form of organoids or spheroids. The analysis of organoids or spheroids is well-adapted for immunohistochemistry or ELISA-type identification of surface markers, but not for real-time analysis of secreted molecules since the fluid and molecules in the interior volume of the organoid or spheroid is not accessible in real-time. We have recently proposed an alternative novel design for a microfluidic chip format comprising 3D micro-niches that provide a real-time analysis of secretions produced directly from small numbers of cells. The microfluidic chip with 3D micro-niches then analyses the secretions from these monolayers in real-time (“secretome”). The microfluidic chip includes electronic biosensors that provide real-time measurement of secreted molecules. This short review concludes with a proposition for the means to utilize this novel microfluidic chip to function as a real-time and quantifiable diagnostic screening device to differentiate cancerous cells from healthy cells.
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Jung, Woojun, Seonghyeon Lee, and Yongha Hwang. "Truly 3D microfluidic heating system with iterative structure of coil heaters and fluidic channels." Smart Materials and Structures 31, no. 3 (2022): 035016. http://dx.doi.org/10.1088/1361-665x/ac4e50.
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Abstract A microfluidic chip, in which both the coil heater and the fluidic channel are designed in a 3D iterative structure, is developed and experimentally demonstrated. Using the empty surrounding 3D space, the microfluidic chip increases the heat transfer area, thereby increasing the fluid temperature by 51.3%, with the same power consumption, compared to heaters and channels typically designed on a 2D plane. After casting polydimethylsiloxane (PDMS) into a sacrificial mold printed using a 3D printer and dissolving the mold, the 3D coil Joule heater is fabricated by filling the interior part of the coil with liquid gallium by vacuuming. By adding an insulation wall filled with air having low thermal conductivity, an additional heating of 8.7% is achieved; this demonstrates the advantage of the 3D-printed soluble-mold technique, which can allow faster prototyping than the typical microfabrication based on soft lithography. Thus, this technique enables convenient design modifications with high priority for performance improvement. As all the components are manufactured simultaneously within a biocompatible, single PDMS body (because of the absence of bonding process between the devices), the risk of leakage in the device is inherently avoided, and the device can be bent without causing any fracture. Therefore, the reported fabrication process and devices are expected to contribute to miniaturization and performance enhancement of microfluidics; this will lead to the development of wearable 3D lab-on-a-chip devices in future.
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Salmon, Idris, Sergei Grebenyuk, Abdel Rahman Abdel Fattah, et al. "Engineering neurovascular organoids with 3D printed microfluidic chips." Lab on a Chip 22, no. 8 (2022): 1615–29. http://dx.doi.org/10.1039/d1lc00535a.
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Organoid vascularization using an open-well microfluidic chip allows for interaction of organoids with vasculature in a temporally and spatially controllable manner. Chip are printed using a consumer-grade 3D printer, making the approach inexpensive and widely accessible.
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Zhang, Siyuan, and Lin Fu. "Research Progress of 3D Printing Microfluidic Chip." Journal of Physics: Conference Series 1549 (June 2020): 052055. http://dx.doi.org/10.1088/1742-6596/1549/5/052055.
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Gong, Hua, Adam T. Woolley, and Gregory P. Nordin. "3D printed high density, reversible, chip-to-chip microfluidic interconnects." Lab on a Chip 18, no. 4 (2018): 639–47. http://dx.doi.org/10.1039/c7lc01113j.
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Xu, Jingjing, Michael Harasek, and Margit Gföhler. "From Soft Lithography to 3D Printing: Current Status and Future of Microfluidic Device Fabrication." Polymers 17, no. 4 (2025): 455. https://doi.org/10.3390/polym17040455.
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The advent of 3D printing has revolutionized the fabrication of microfluidic devices, offering a compelling alternative to traditional soft lithography techniques. This review explores the potential of 3D printing, particularly photopolymerization techniques, fused deposition modeling, and material jetting, in advancing microfluidics. We analyze the advantages of 3D printing in terms of cost efficiency, geometric complexity, and material versatility while addressing key challenges such as material transparency and biocompatibility, which have represented the limiting factors for its widespread adoption. Recent developments in printing technologies and materials are highlighted, underscoring the progress in overcoming these barriers. Finally, we discuss future trends and opportunities, including advancements in printing resolution and speed, the development of new printable materials, process standardization, and the emergence of bioprinting for organ-on-a-chip applications. Sustainability and regulatory frameworks are also considered critical aspects shaping the future of 3D-printed microfluidics. By bridging the gap between traditional and emerging fabrication techniques, this review aims to illuminate the transformative potential of 3D printing in microfluidic device manufacturing.
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Zhang, Aodong, Jian Xu, Yucen Li, et al. "Three-Dimensional Large-Scale Fused Silica Microfluidic Chips Enabled by Hybrid Laser Microfabrication for Continuous-Flow UV Photochemical Synthesis." Micromachines 13, no. 4 (2022): 543. http://dx.doi.org/10.3390/mi13040543.
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We demonstrate a hybrid laser microfabrication approach, which combines the technical merits of ultrafast laser-assisted chemical etching and carbon dioxide laser-induced in situ melting for centimeter-scale and bonding-free fabrication of 3D complex hollow microstructures in fused silica glass. With the developed approach, large-scale fused silica microfluidic chips with integrated 3D cascaded micromixing units can be reliably manufactured. High-performance on-chip mixing and continuous-flow photochemical synthesis under UV irradiation at ~280 nm were demonstrated using the manufactured chip, indicating a powerful capability for versatile fabrication of highly transparent all-glass microfluidic reactors for on-chip photochemical synthesis.
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Guo, Mingyi, Yan Deng, Junqiu Huang, Yanping Huang, Jing Deng, and Huachang Wu. "Fabrication and Validation of a 3D Portable PEGDA Microfluidic Chip for Visual Colorimetric Detection of Captured Breast Cancer Cells." Polymers 15, no. 15 (2023): 3183. http://dx.doi.org/10.3390/polym15153183.
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To guide therapeutic strategies and to monitor the state changes in the disease, a low-cost, portable, and easily fabricated microfluidic-chip-integrated three-dimensional (3D) microchamber was designed for capturing and analyzing breast cancer cells. Optimally, a colorimetric sensor array was integrated into a microfluidic chip to discriminate the metabolites of the cells. The ultraviolet polymerization characteristic of poly(ethylene glycol) diacrylate (PEGDA) hydrogel was utilized to rapidly fabricate a three-layer hydrogel microfluidic chip with the designed structure under noninvasive 365 nm laser irradiation. 2-Hydroxyethyl methacrylate (HEMA) was added to the prepolymer in order to increase the adhesive capacity of the microchip’s surface for capturing cells. 1-Vinyl-2-pyrrolidone (NVP) was designed to improve the toughness and reduce the swelling capacity of the hydrogel composite. A non-toxic 3D hydrogel microarray chip (60 mm × 20 mm × 3 mm) with low immunogenicity and high hydrophilicity was created to simulate the real physiological microenvironment of breast tissue. The crisscross channels were designed to ensure homogeneous seeding density. This hydrogel material displayed excellent biocompatibility and tunable physical properties compared with traditional microfluidic chip materials and can be directly processed to obtain the most desirable microstructure. The feasibility of using a PEGDA hydrogel microfluidic chip for the real-time online detection of breast cancer cells’ metabolism was confirmed using a specifically designed colorimetric sensor array with 16 kinds of porphyrin, porphyrin derivatives, and indicator dyes. The results of the principal component analysis (PCA), the hierarchical cluster analysis (HCA), and the linear discriminant analysis (LDA) suggest that the metabolic liquids of different breast cells can be easily distinguished with the developed PEGDA hydrogel microfluidic chip. The PEGDA hydrogel microfluidic chip has potential practicable applicability in distinguishing normal and cancerous breast cells.
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Khorsandi, Danial, Mehrab Nodehi, Tayyab Waqar, et al. "Manufacturing of Microfluidic Sensors Utilizing 3D Printing Technologies: A Production System." Journal of Nanomaterials 2021 (August 11, 2021): 1–16. http://dx.doi.org/10.1155/2021/5537074.
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3D integrated microfluid devices are a group of engineered microelectromechanical systems (MEMS) whereby the feature size and operating range of the components are on a microscale. These devices or systems have the ability to detect, control, activate, and create macroscale effects. On this basis, microfluidic chips are systems that enable microliters and smaller volumes of fluids to be controlled and moved within microscale-sized (one-millionth of a meter) channels. While this small scale can be compared to microfluid chips of larger applications, such as pipes or plumbing practices, their small size is commonly useful in controlling and monitoring the flow of fluid. Through such applications, microfluidic chip technology has become a popular tool for analysis in biochemistry and bioengineering with their most recent uses for artificial organ production. For this purpose, microfluidic chips can be instantly controlled by the human body, such as pulse, blood flow, blood pressure, and transmitting data such as location and the programmed agents. Despite its vast uses, the production of microfluidic chips has been mostly dependent upon conventional practices that are costly and often time consuming. More recently, however, 3D printing technology has been incorporated in rapidly prototyping microfluid chips at microscale for major uses. This state-of-the-art review highlights the recent advancements in the field of 3D printing technology for the rapid fabrication, and therefore mass production, of the microfluid chips.
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Lee, Bo-Eun, Do-Kyung Kim, Hyunil Lee, et al. "Recapitulation of First Pass Metabolism Using 3D Printed Microfluidic Chip and Organoid." Cells 10, no. 12 (2021): 3301. http://dx.doi.org/10.3390/cells10123301.
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The low bioavailability of oral drugs due to first pass metabolism is a major obstacle in drug development. With significant developments in the field of in vitro organ modeling and microfluidic chip three-dimensional (3D) printing, the challenge is to apply these for the production and evaluation of new drug candidates. This study aimed to produce a microfluidic chip to recapitulate and assess the feasibility of the first pass metabolism. The infill condition of the polycarbonate transparent filament and layer height was optimized to visualize and maintain the organoid or spheroid on the chip. Next, the chip was fabricated using a 3D printer after a computer-aided design (CAD). The chip consisted of three wells of different heights. The small intestinal (SI) organoid and colorectal adenocarcinoma spheroids were placed on the second and third wells, respectively. No additional equipment was assembled, and the tilted tunnel was connected to each well to transport the material by gradient force. The chip was fabricated using 50% and 0.1 um thickness. Among the three different prototypes of chip (chips 1, 2, and 3), the highest distribution of plasmids in the Matrigel of the second well was observed in Chip 2 at 48 h. The effect of first pass metabolism was analyzed using docetaxel. In the chip without an SI organoid, there was a marked decrease in the viability of colorectal adenocarcinoma spheroids due to drug efficacy. However, in the chip with the SI organoid, no significant change in viability was observed because of first pass metabolism. In conclusion, we presented a simple, fast, and low-cost microfluidic chip to analyze the efficacy change of candidate drug by the first pass metabolism.
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Sekhwama, Masindi, Kelvin Mpofu, Phumulani Mcoyi, Sudesh Sivarasu, and Patience Mthunzi-Kufa. "3D printed microfluidic chip design for diagnostic studies." MATEC Web of Conferences 406 (2024): 08004. https://doi.org/10.1051/matecconf/202440608004.
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In this study, additive manufacturing (3D printing) is utilised to fabricate lateral flow microfluidic chips (LFMC). Our chips were designed using Autodesk design software and printed using a Formlabs 3D printer. They are printed using Formlabs V4 resin polymer. In this work, the design process is highlighted in detail and shows an LFMC design that is made for potential applications in diagnostics studies. Our study also tested the performance of one of the chip designs in actual diagnostics experiment on an optical transmittance setup with a peristaltic pump. The LFMC was integrated onto a custom-built transmittance optical biosensor to measure the transmission intensity. A real-time kinetic study was conducted using an HIV-1 oligonucleotide probe. The study involved performing real-time transmittance analysis by pumping the HIV-1 oligonucleotide probe at different flow rates, ranging from 9. 5 μm/min to 13 μm/min with intervals of 0.5 μm/min. During the experiment, transmission intensity or transmitted light was measured in real time as the oligonucleotide HIV probe bound to neutravidin immobilised on the Au metal surface. These measurements were recorded using a USB400 spectrometer, with a broad- band UV light source that emits wavelengths ranging from 400 to 800 nm. The study underscored the significance of microfluidic chips as devices capable of enhancing the performance of biosensors as well as the use of 3D printing in the design and manufacture of these microfluidic chips.
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Jiao, Zhiqiang, Lei Zhao, Chu Tang, Hongyan Shi, Fu Wang, and Bo Hu. "Droplet-based PCR in a 3D-printed microfluidic chip for miRNA-21 detection." Analytical Methods 11, no. 26 (2019): 3286–93. http://dx.doi.org/10.1039/c9ay01108k.
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Duzagac, Fahriye, Gloria Saorin, Lorenzo Memeo, Vincenzo Canzonieri, and Flavio Rizzolio. "Microfluidic Organoids-on-a-Chip: Quantum Leap in Cancer Research." Cancers 13, no. 4 (2021): 737. http://dx.doi.org/10.3390/cancers13040737.
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Organ-like cell clusters, so-called organoids, which exhibit self-organized and similar organ functionality as the tissue of origin, have provided a whole new level of bioinspiration for ex vivo systems. Microfluidic organoid or organs-on-a-chip platforms are a new group of micro-engineered promising models that recapitulate 3D tissue structure and physiology and combines several advantages of current in vivo and in vitro models. Microfluidics technology is used in numerous applications since it allows us to control and manipulate fluid flows with a high degree of accuracy. This system is an emerging tool for understanding disease development and progression, especially for personalized therapeutic strategies for cancer treatment, which provide well-grounded, cost-effective, powerful, fast, and reproducible results. In this review, we highlight how the organoid-on-a-chip models have improved the potential of efficiency and reproducibility of organoid cultures. More widely, we discuss current challenges and development on organoid culture systems together with microfluidic approaches and their limitations. Finally, we describe the recent progress and potential utilization in the organs-on-a-chip practice.
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Wei, Chunyang, Chengzhuang Yu, Shanshan Li, Tiejun Li, Jiyu Meng, and Junwei Li. "Easy-to-Operate Co-Flow Step Emulsification Device for High-Throughput Three-Dimensional Cell Culture." Biosensors 12, no. 5 (2022): 350. http://dx.doi.org/10.3390/bios12050350.
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Cell culture plays an essential role in tissue engineering and high-throughput drug screening. Compared with two-dimensional (2D) in vitro culture, three-dimensional (3D) in vitro culture can mimic cells in vivo more accurately, including complex cellular organizations, heterogeneity, and cell–extracellular matrix (ECM) interactions. This article presents a droplet-based microfluidic chip that integrates cell distribution, 3D in vitro cell culture, and in situ cell monitoring in a single device. Using the microfluidic “co-flow step emulsification” approach, we have successfully prepared close-packed droplet arrays with an ultra-high-volume fraction (72%) which can prevent cells from adhering to the chip surface so as to achieve a 3D cell culture and make scalable and high-throughput cell culture possible. The proposed device could produce droplets from 55.29 ± 1.52 to 95.64 ± 3.35 μm, enabling the diverse encapsulation of cells of different sizes and quantities. Furthermore, the cost for each microfluidic CFSE chip is approximately USD 3, making it a low-cost approach for 3D cell culture. The proposed device is successfully applied in the 3D culture of saccharomyces cerevisiae cells with an occurrence rate for proliferation of 80.34 ± 3.77%. With low-cost, easy-to-operate, high-throughput, and miniaturization characteristics, the proposed device meets the requirements for 3D in vitro cell culture and is expected to be applied in biological fields such as drug toxicology and pharmacokinetics.
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Glinkowska Mares, Adrianna, Natalia Feiner-Gracia, Yolanda Muela, et al. "Towards Cellular Ultrastructural Characterization in Organ-on-a-Chip by Transmission Electron Microscopy." Applied Nano 2, no. 4 (2021): 289–302. http://dx.doi.org/10.3390/applnano2040021.
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Organ-on-a-chip technology is a 3D cell culture breakthrough of the last decade. This rapidly developing field of bioengineering intertwined with microfluidics provides new insights into disease development and preclinical drug screening. So far, optical and fluorescence microscopy are the most widely used methods to monitor and extract information from these models. Meanwhile transmission electron microscopy (TEM), despite its wide use for the characterization of nanomaterials and biological samples, remains unexplored in this area. In our work we propose a TEM sample preparation method, that allows to process a microfluidic chip without its prior deconstruction, into TEM-compatible specimens. We demonstrated preparation of tumor blood vessel-on-a-chip model and consecutive steps to preserve the endothelial cells lining microfluidic channel, for the chip’s further transformation into ultrathin sections. This approach allowed us to obtain cross-sections of the microchannel with cells cultured inside, and to observe cell adaptation to the channel geometry, as well as the characteristic for endothelial cells tight junctions. The proposed sample preparation method facilitates the electron microscopy ultrastructural characterization of biological samples cultured in organ-on-a-chip device.
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Mi, Shengli, Zhichang Du, Yuanyuan Xu, and Wei Sun. "The crossing and integration between microfluidic technology and 3D printing for organ-on-chips." Journal of Materials Chemistry B 6, no. 39 (2018): 6191–206. http://dx.doi.org/10.1039/c8tb01661e.
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Wan Yahya, Wan Nurlina, Fatimah Ibrahim, Aung Thiha, Nurul Fauzani Jamaluddin, and Marc Madou. "Fabrication of a 3D carbon electrode for potential dielectrophoresis-based hepatic cell patterning application using carbon micro-electrical-mechanical system (CMEMS)." Journal of Micromechanics and Microengineering 32, no. 5 (2022): 055005. http://dx.doi.org/10.1088/1361-6439/ac60a8.
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Abstract Cell patterning of hepatocyte cells is one of the techniques to construct liver tissue engineering. This work presents the development of a 3D carbon dielectrophoresis (carbonDEP) microfluidic chip for cell patterning using carbon micro-electrical-mechanical system microfabrication approach. The new design of electrode named interdigitated radiating-strips electrode (IRSE) was fabricated to generate positive DEP (pDEP) force for cell patterning mimicking the biological hepatic lobule. The electrical characterization of the fabricated carbon electrode shows that the average electrode resistivity is 4.61 ± 1.19 × 10−4 Ω m which is low enough to generate effective DEP force using 10 of volts. Results also show the shrinkage of the SU-8 structures during pyrolysis which gives impact to the final dimension of the carbon electrode. The functioning of the DEP microfluidic chip was demonstrated through DEP polystyrene microbeads patterning as a model of hepatocyte cells. 3D carbon IRSE presents a 67% increase in trapping efficiency of pDEP microbeads as compared to the planar carbon IRSE and the microbeads were pattern along the electrical field induced to form a hepatic lobule mimicking pattern. These results suggest that the 3D carbonDEP microfluidic chip has a great potential to be used for 3D hepatic cells patterning for liver tissue engineering applications.
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Hu, Wei, Bingxing Wu, Soumya K. Srivastava, and Suat Utku Ay. "Comparative Study and Simulation of Capacitive Sensors in Microfluidic Channels for Sensitive Red Blood Cell Detection." Micromachines 13, no. 10 (2022): 1654. http://dx.doi.org/10.3390/mi13101654.
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Microfluidics provides an indispensable platform for combining analytical operations such as sample preparation, mixing, separation/enrichment, and detection onto a single compact platform, defined as a lab-on-a-chip (LOC) device with applicability in biomedical and life science applications. Due to its ease of integration, 1D interdigital capacitive (IDC) sensors have been used in microfluidic platforms to detect particles of interest. This paper presents a comparative study on the use of capacitive sensors for microfluidic devices to detect bioparticles, more specifically red blood cells (RBCs). The detection sensitivities of 1D, 2D, and 3D capacitive sensors were determined by simulation using COMSOL Multiphysics® v5.5. A water-filled 25 μm × 25 μm PDMS microfluidic channel was used with different sizes (5–10 μm) of red blood cells passing across the capacitive sensor regions. The conformal mapping was used for translating the 1D IDC sensor dimensions into equivalent 2D/3D parallel plate capacitance (PPC) sensor dimensions, creating similar absolute sensor capacitance. The detection sensitivity of each capacitive sensor is determined, and a new 3D PPC sensor structure was proposed to improve the sensitivity for high-resolution RBC detection in microfluidic channels. Proposed 2D and 3D sensors provide a 3× to 20× improvement in sensitivity compared to the standard 1D IDC structures, achieving a 100 aF capacitance difference when a healthy RBC passes in the structure.
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Palacio-Castañeda, Valentina, Rik Oude Egberink, Arbaaz Sait, et al. "Mimicking the Biology of Engineered Protein and mRNA Nanoparticle Delivery Using a Versatile Microfluidic Platform." Pharmaceutics 13, no. 11 (2021): 1944. http://dx.doi.org/10.3390/pharmaceutics13111944.
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To investigate the delivery of next-generation macromolecular drugs, such as engineered proteins and mRNA-containing nanoparticles, there is an increasing push towards the use of physiologically relevant disease models that incorporate human cells and do not face ethical dilemmas associated with animal use. Here, we illustrate the versatility and ease of use of a microfluidic platform for studying drug delivery using high-resolution microscopy in 3D. Using this microfluidic platform, we successfully demonstrate the specific targeting of carbonic anhydrase IX (CAIX) on cells overexpressing the protein in a tumor-mimicking chip system using affibodies, with CAIX-negative cells and non-binding affibodies as controls. Furthermore, we demonstrate this system’s feasibility for testing mRNA-containing biomaterials designed to regenerate bone defects. To this end, peptide- and lipid-based mRNA formulations were successfully mixed with colloidal gelatin in microfluidic devices, while translational activity was studied by the expression of a green fluorescent protein. This microfluidic platform enables the testing of mRNA delivery from colloidal biomaterials of relatively high densities, which represents a first important step towards a bone-on-a-chip platform. Collectively, by illustrating the ease of adaptation of our microfluidic platform towards use in distinct applications, we show that our microfluidic chip represents a powerful and flexible way to investigate drug delivery in 3D disease-mimicking culture systems that recapitulate key parameters associated with in vivo drug application.
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Tang, Jiukai, Guangyu Qiu, Xiaobao Cao, et al. "Self-aligned 3D microlenses in a chip fabricated with two-photon stereolithography for highly sensitive absorbance measurement." Lab on a Chip 20, no. 13 (2020): 2334–42. http://dx.doi.org/10.1039/d0lc00235f.
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Alexandre-Franco, María F., Rahmani Kouider, Raúl Kassir Al-Karany, Eduardo M. Cuerda-Correa, and Awf Al-Kassir. "Recent Advances in Polymer Science and Fabrication Processes for Enhanced Microfluidic Applications: An Overview." Micromachines 15, no. 9 (2024): 1137. http://dx.doi.org/10.3390/mi15091137.
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This review explores significant advancements in polymer science and fabrication processes that have enhanced the performance and broadened the application scope of microfluidic devices. Microfluidics, essential in biotechnology, medicine, and chemical engineering, relies on precise fluid manipulation in micrometer-sized channels. Recent innovations in polymer materials, such as flexible, biocompatible, and structurally robust polymers, have been pivotal in developing advanced microfluidic systems. Techniques like replica molding, microcontact printing, solvent-assisted molding, injection molding, and 3D printing are examined, highlighting their advantages and recent developments. Additionally, the review discusses the diverse applications of polymer-based microfluidic devices in biomedical diagnostics, drug delivery, organ-on-chip models, environmental monitoring, and industrial processes. This paper also addresses future challenges, including enhancing chemical resistance, achieving multifunctionality, ensuring biocompatibility, and scaling up production. By overcoming these challenges, the potential for widespread adoption and impactful use of polymer-based microfluidic technologies can be realized.
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Lee, Somin, Jungeun Lim, James Yu, Jungho Ahn, Younggyun Lee, and Noo Li Jeon. "Engineering tumor vasculature on an injection-molded plastic array 3D culture (IMPACT) platform." Lab on a Chip 19, no. 12 (2019): 2071–80. http://dx.doi.org/10.1039/c9lc00148d.
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Marcos, Luis F., Samantha L. Wilson, and Paul Roach. "Tissue engineering of the retina: from organoids to microfluidic chips." Journal of Tissue Engineering 12 (January 2021): 204173142110598. http://dx.doi.org/10.1177/20417314211059876.
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Despite advancements in tissue engineering, challenges remain for fabricating functional tissues that incorporate essential features including vasculature and complex cellular organisation. Monitoring of engineered tissues also raises difficulties, particularly when cell population maturity is inherent to function. Microfluidic, or lab-on-a-chip, platforms address the complexity issues of conventional 3D models regarding cell numbers and functional connectivity. Regulation of biochemical/biomechanical conditions can create dynamic structures, providing microenvironments that permit tissue formation while quantifying biological processes at a single cell level. Retinal organoids provide relevant cell numbers to mimic in vivo spatiotemporal development, where conventional culture approaches fail. Modern bio-fabrication techniques allow for retinal organoids to be combined with microfluidic devices to create anato-physiologically accurate structures or ‘ retina-on-a-chip’ devices that could revolution ocular sciences. Here we present a focussed review of retinal tissue engineering, examining the challenges and how some of these have been overcome using organoids, microfluidics, and bioprinting technologies.
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Chang, Ning, Jingyan Zhai, Bing Liu, Jiping Zhou, Zhaoyu Zeng, and Xiangwei Zhao. "Low cost 3D microfluidic chips for multiplex protein detection based on photonic crystal beads." Lab on a Chip 18, no. 23 (2018): 3638–44. http://dx.doi.org/10.1039/c8lc00784e.
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Gupta, Sharda, Lavish Patel, Kunal Mitra, and Arindam Bit. "Fibroblast Derived Skin Wound Healing Modeling on Chip under the Influence of Micro-Capillary Shear Stress." Micromachines 13, no. 2 (2022): 305. http://dx.doi.org/10.3390/mi13020305.
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Fibroblast cell migration plays a crucial role in the wound-healing process. Hence, its quantitative investigation is important to understand the mechanism of the wound-healing process. The dynamic nature of the wound-healing process can be easily implemented using a microfluidic-based wound-healing assay. This work presented the use of a microfluidics device to simulate traumatic wounds on fibroblast cell monolayers by utilizing trypsin flow and PDMS barrier. In this study, a microfluidic chip with a transparent silk film is reported. The placement of film provides 3D cell culture conditions that mimic a 3D extracellular matrix (ECM) like environment and allows real-time monitoring of cells. A numerical study was conducted to evaluate the influence of dynamic medium-induced shear stress on the base and wall of the microchannel. This could facilitate the optimization of the inlet flow conditions of the media in the channel. At the same time, it could help in identifying stress spots in the channel. The scaffolds were placed in those spots for evaluating the influence of shear forces on the migratory behavior of fibroblast cells. The in vitro microfluidic assembly was then evaluated for cell migration under the influence of external shear forces during the wound-healing phenomena. A faster wound healing was obtained at the end of 24 h of the creation of the wound in the presence of optimal shear stress. On increasing the shear stress beyond a threshold limit, it dissociates fibroblast cells from the surface of the substrate, thereby decelerating the wound-healing process. The above phenomena were transformed in both coplanar microfluidics surfaces (by realizing in the multichannel interlinked model) and transitional microfluidics channels (by realizing in the sandwich model).
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Chen, Li, Xing Liu, Xiaolin Zheng, et al. "Dielectrophoretic Separation of Particles Using Microfluidic Chip with Composite Three-Dimensional Electrode." Micromachines 11, no. 7 (2020): 700. http://dx.doi.org/10.3390/mi11070700.
Full textAbstract:
Integrating three-dimensional (3D) microelectrodes on microfluidic chips based on polydimethylsiloxane (PDMS) has been a challenge. This paper introduces a composite 3D electrode composed of Ag powder (particle size of 10 nm) and PDMS. Ethyl acetate is added as an auxiliary dispersant during the compounding process. A micromachining technique for processing 3D microelectrodes of any shape and size was developed to allow the electrodes to be firmly bonded to the PDMS chip. Through theoretical calculations, numerical simulations, and experimental verification, the role of the composite 3D microelectrodes in separating polystyrene particles of three different sizes via dielectrophoresis was systematically studied. This microfluidic device separated 20-, 10-, and 5-μm polystyrene particles nondestructively, efficiently, and accurately.