Jie Xu

Hollow microneedles (HMNs) offer a transformative solution for topical diagnosis and therapeutic applications due to the unique challenges addressed by their ability to adjust dosing and their integration capabilities in the context of microfluidic and microelectronic devices. To fabricate HMN devices, 3D printing has been introduced as an advanced manufacturing technology in fabricating high-resolution micro- and nanofeatures overcoming the inferior capabilities of traditional manufacturing technologies such as lithography, etching, and laser fabrication in producing sophisticated devices. In this paper, a comprehensive review of recent advancements in the utilization of 3D printing technology for developing HMN devices is provided. The current fabrication technologies are summarized. In addition, design, fabrication, and testing considerations for generating HMN devices are summarized. Various applications, including drug delivery, sensing, and recording, along with integrated devices necessary for these applications are highlighted. Finally, the limitations of the current approaches are discussed, and the future of HMN devices fabricated by the 3D printing technology is proposed. In summary, this Review provides insight into the current status of 3D printed HMN devices and a roadmap for developing HMNs including design criteria, fabrication considerations, postprocessing approaches, and required testing for device functionality evaluation.

A 3D‐printed array of hollow microneedles (HMNs) is designed and fabricated using a high‐resolution stereolithography 3D printer and assembled with a 3D‐printed reservoir that incorporates a Luer lock mechanism, ensuring standard and secure connection to syringes. The proof‐of‐concept needle designs consist of half‐eccentric and concentric conical tip shapes, each arrayed with two different interspacing values. After the geometrical features of the devices are characterized, the devices are tested ex vivo in porcine skin to evaluate the impact of tip shape and interspacing on the depth of penetration and the efficacy of the devices in delivering fluids (such as tattoo ink) into the dermis. Overall, the 3D‐printed HMNs can deliver fluids into the target layer of skin. Refinement of the design is ongoing with the ultimate aim to provide alternatives for intradermal drug delivery and diagnostic imaging, such as superficial lymphography.

We derived equations and closed-form solutions of transit time for a viscous droplet squeezing through a small circular pore with a finite length at microscale under constant pressures. Our analyses were motivated by the vital processes of biological cells squeezing through small pores in blood vessels and sinusoids and droplets squeezing through pores in microfluidics. First, we derived ordinary differential equations (ODEs) of a droplet squeezing through a circular pore by combining Sampson flow, Poiseuille flow, and Young–Laplace equations and took into account the lubrication layer between the droplet and the pore wall. Second, for droplets wetting the wall with small surface tension, we derived the closed-form solutions of transit time. For droplets with finite surface tension, we solved the original ODEs numerically to predict the transit time. After validations against experiments and finite element simulations, we studied the effects of pressure, viscosity, pore/droplet dimensions, and surface tension on the transit time. We found that the transit time is inversely linearly proportional to pressure when the surface tension is low compared to the critical surface tension for preventing the droplet to pass and becomes nonlinear when it approaches the critical tension. Remarkably, we showed that when a fixed percentage of surface tension to critical tension is applied, the transit time is always inversely linearly proportional to pressure, and the dependence of transit time on surface tension is nonmonotonic. Our results provided a quick way of quantitative calculations of transit time for designing droplet microfluidics and understanding cells passing through constrictions.

Three-dimensional printing technology has been implemented in microfluidic mold fabrication due to its freedom of design, speed, and low-cost fabrication. To facilitate mold fabrication processes and avoid the complexities of the soft lithography technique, we offer a non-sacrificial approach to fabricate microscale features along with mesoscale features using Stereolithography (SLA) printers to assemble a modular microfluidic mold. This helps with addressing an existing limitation with fabricating complex and time-consuming micro/mesoscale devices. The process flow, optimization of print time and feature resolution, alignments of modular devices, and the advantages and limitations with the offered technique are discussed in this paper.

A simple, low‐cost, three‐dimensional (3D) lab‐on‐a‐foil microfluidic device for dielectrophoretic separation of circulating tumor cells (CTCs) is designed and constructed. Disposable thin films are cut by xurography and microelectrode array are made with rapid inkjet printing. The multilayer device design allows the studying of spatial movements of CTCs and red blood cells (RBCs) under dielectrophoresis (DEP). A numerical simulation was performed to find the optimum driving frequency of RBCs and the crossover frequency for CTCs. At the optimum frequency, RBCs were lifted 120 µm in z‐axis direction by DEP force, and CTCs were not affected due to negligible DEP force. By utilizing the displacement difference, the separation of CTCs (modeled with A549 lung carcinoma cells) from RBCs in z‐axis direction was achieved. With the nonuniform electric field at optimized driving frequency, the RBCs were trapped in the cavities above the microchannel, whereas the A549 cells were separated with a high capture rate of 86.3% ± 0.2%. The device opens not only the possibility for 3D high‐throughput cell separation but also for future developments in 3D cell manipulation through rapid and low‐cost fabrication.

We report a microfluidic droplet generator which can produce single and compound droplets using a 3D axisymmetric co-flow structure. The design considered for the fabrication of the device integrated a user-friendly and cost-effective 3D printing process. To verify the performance of the device, single and compound emulsions of deionized water and mineral oil were generated and their features such as size, generation frequency, and emulsion structures were successfully characterized. In addition, the generation of bio emulsions such as alginate and collagen aqueous droplets in mineral oil was demonstrated in this study. Overall, the monolithic 3D printed axisymmetric droplet generator could offer any user an accessible and easy-to-utilize device for the generation of single and compound emulsions.

We present a novel acoustic bubble-based tumor-on-a-chip platform (ABSTRACT) for multi-step CTC processing on a chip (spheroid trapping, rotation, and culture).

Constrained-surface-based stereolithography has recently attracted much attention from both academic and industrial communities. Despite numerous experimental, numerical and theoretical efforts, the fundamental need to reduce the separation force between the newly cured part and constrained surface has not yet been completely solved. In this paper, we develop a fluid dynamics approach, proposed in our previous work, to theoretically model the separation force in 3D printing of a cylindrical part for flat and patterned windows. We demonstrate the possibility of separation force reduction with an accelerated movement of the printing platform. In particular, we investigate behaviors of transient parameter, its reduction rate, and separation force reduction with respect to elevation speed and time. The proposed approach involves deceleration and acceleration stages and allows to achieve the force reduction for the entire printing process. Finally, we provide implicit analytical solutions for time moments when switching between the stages can be done without noticeable increase of separation force and explicit expression for separation force in case of patterned window.

Highlights• Perform traveling-wave dielectrophoresis cell separation on a lab-on-a-foil microfluidic device• Study Z-axis movement of CTCs (A549 cells) and red blood cells under traveling-wave dielectrophoresis• Provide a novel fabrication method for multi-layer flexible electric microfluidic devices• Optimize cell label-free separation performance with driving voltage and frequency