Organ-on-a-chip (OOC) facilitates precise manipulation of fluids in microfluidic chips and simulation of the physiological, chemical, and mechanical characteristics of tissues, thus providing a promising tool for in vitro drug screening and physiological modeling. In recent decades, this technology has advanced rapidly because of the development of various three-dimensional (3D) printing techniques. 3D printing can not only fabricate microfluidic chips using materials such as resins and polydimethylsiloxane but also construct biomimetic tissues using bioinks such as cell-loaded hydrogels. In this review, recent advances in 3D-printing-based OOC are systematically summarized based on materials used for direct or indirect 3D printing of OOC, 3D printing techniques for the construction of OOC, and applications of 3D-printing-based OOC in models of the heart, blood vessels, intestines, liver, and kidney. In addition, future perspectives and challenges in this area are envisioned to inspire researchers to employ 3D printing techniques to accelerate OOC development. 

Recent Advances in 3D-Printing-Based Organ-on-a-Chip

Compound eyes are high-performing natural optical perception systems with compact configurations, generating extensive research interest. Existing compound eye systems are often combinations of simple uniform microlens arrays; there are still challenges in making more ommatidia on the compound eye surface to focus to the same plane. Here, a biomimetic gradient compound eye is presented by artificially mimicking dragonflies. The multiple replication process efficiently endows compound eyes with the gradient characteristics of dragonfly compound eyes. Experimental results show that the manufactured compound eye allows multifocus imaging by virtue of the gradient ommatidium array arranged closely in a honeycomb pattern while ensuring excellent optical properties and compact configurations. Thousands of ommatidia showing a gradient trend at the millimeter scale while remaining relatively uniform at the micron scale have gradient focal lengths ranging from 260 to 450 μm. This gradient compound eye allows more ommatidia to focus on the same plane than traditional uniform compound eyes, which have experimentally been shown to capture more than 1100 in-plane clear images simultaneously, promising potential applications in micro-optical devices, optical imaging, and biochemical sensing.

Biomimetic Compound Eyes with Gradient Ommatidium Arrays.

Although the enormous potential of droplet-based microfluidics has been successfully demonstrated in the past two decades for medical, pharmaceutical, and academic applications, its inherent potential has not been fully exploited until now. Nevertheless, the cultivation of biological cells and 3D cell structures like spheroids and organoids, located in serially arranged droplets in micro-channels, has a range of benefits compared to established cultivation techniques based on, e.g., microplates and microchips. To exploit the enormous potential of the droplet-based cell cultivation technique, a number of basic functions have to be fulfilled. In this paper, we describe microfluidic modules to realize the following basic functions with high precision: (i) droplet generation, (ii) mixing of cell suspensions and cell culture media in the droplets, (iii) droplet content detection, and (iv) active fluid injection into serially arranged droplets. The robustness of the functionality of the Two-Fluid Probe is further investigated regarding its droplet generation using different flow rates. Advantages and disadvantages in comparison to chip-based solutions are discussed. New chip-based modules like the gradient, the piezo valve-based conditioning, the analysis, and the microscopy module are characterized in detail and their high-precision functionalities are demonstrated. These microfluidic modules are micro-machined, and as the surfaces of their micro-channels are plasma-treated, we are able to perform cell cultivation experiments using any kind of cell culture media, but without needing to use surfactants. This is even more considerable when droplets are used to investigate cell cultures like stem cells or cancer cells as cell suspensions, as 3D cell structures, or as tissue fragments over days or even weeks for versatile applications.

Flexible Toolbox of High-Precision Microfluidic Modules for Versatile Droplet-Based Applications

The paper demonstrates an adaptation of a 3D printer (Prusa Mini+) with novel modules to develop a droplet generation system that generates combinatorial droplets from a standard 96 well plate....

Automated Dynamic Inlet Microfluidics System: 3D Printer Adaptation for Cost-Effective, Low Volume, On-Demand Multi-Analyte Droplet Generator

Concentration gradient generation and mixed combinations of multiple solutions are of great value in the field of biomedical research. However, existing concentration gradient generators for single or two-drug solutions cannot...

High-throughput 3D microfluidic chip for generation of concentration gradients and solution combinations

Abstract Reconfigurable modular microfluidics presents an opportunity for flexibly constructing prototypes of advanced microfluidic systems. Nevertheless, the strategy of directly integrating modules cannot easily fulfill the requirements of common applications, e.g., the incorporation of materials with biochemical compatibility and optical transparency and the execution of small batch production of disposable chips for laboratory trials and initial tests. Here, we propose a manufacturing scheme inspired by the movable type printing technique to realize 3D free-assembly modular microfluidics. Double-layer 3D microfluidic structures can be produced by replicating the assembled molds. A library of modularized molds is presented for flow control, droplet generation and manipulation and cell trapping and coculture. In addition, a variety of modularized attachments, including valves, light sources and microscopic cameras, have been developed with the capability to be mounted onto chips on demand. Microfluidic systems, including those for concentration gradient generation, droplet-based microfluidics, cell trapping and drug screening, are demonstrated. This scheme enables rapid prototyping of microfluidic systems and construction of on-chip research platforms, with the intent of achieving high efficiency of proof-of-concept tests and small batch manufacturing. 

3D free-assembly modular microfluidics inspired by movable type printing

As an important strategy to mitigate severe accidents, the in-vessel retention (IVR) technique has been applied to the new generation of pressurized water reactor (PWR). However, under IVR conditions, the decay heat distribution in the molten pool is very uncertain because of the complexity of the molten pool and the calculation method limitations. To explore the calculation method and distribution of the decay heat of lower head molten pool under IVR conditions, the decay heat calculation method is developed based on Reactor Monte Carlo Code (RMC). The verification results show that the relative error of calculation result is generally within ±0.25%. In addition, geometric modeling for lower head molten pools has been carried out, and space-time distribution of the decay heat in two-layer and three-layer structures has also been accurately calculated. The calculation results indicate that the decay heat power spatial distribution is relatively uniform in the two-layer molten pool structure. The decay heat power at the center of the lower head decreases from 0.71 W/cm2 to 0.023 W/cm2 within 1d-5d. In the three-layer molten pool structure, the spatial distribution of the decay heat power is severely uneven due to the precipitation of heavy metal uranium. Besides, in actual engineering calculations, it should lay emphasis on the heat transfer characteristics and design margin of the upper part of the heavy metal layer and the lower part of the oxide layer because the maximum decay heat power appears at these two positions.

/pdf/study-on-the-calculation-method-of-molten-pool-decay-heat-1ygxgulhcc.pdf

Study on the Calculation Method of Molten Pool Decay Heat Distribution under IVR Condition

3D printing has been widely used in the micromachining fields due to its flexibility in design and fabrication. However, due to the presence of undulations on the surface of the finished part, the 3D printing has hardly been employed in the optics manufacturing. In this study, we propose a manufacturing method for optical splitters based on 3D printing and microfluidic abrasive machining. We simulate the effect of microfluidic abrasive machining on microchannels, that helps mitigate the impact of undulations. The 3D printed optical splitter using microfluidic abrasive machining presents high efficiency in optical propagation and high uniformity. We believe that the 3D printing accompanied with microfluidic abrasive micromachining would be a promising technique in the optics manufacturing fields. 

Fabrication of a 1×4 optical splitter by 3D printing and microfluidic abrasive micromachining

/pdf/a-3d-printed-standardized-modular-microfluidic-system-for-1jkqevtl.pdf

A 3D-Printed Standardized Modular Microfluidic System for Droplet Generation

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Papers

3D free-assembly modular microfluidics inspired by movable type printing

Study on the Calculation Method of Molten Pool Decay Heat Distribution under IVR Condition

Fabrication of a 1×4 optical splitter by 3D printing and microfluidic abrasive micromachining

A 3D-Printed Standardized Modular Microfluidic System for Droplet Generation