3D-printed microrobots from design to translation

Abstract

Microrobots have attracted the attention of scientists owing to their unique features to accomplish tasks in hard-to-reach sites in the human body. Microrobots can be precisely actuated and maneuvered individually or in a swarm for cargo delivery, sampling, surgery, and imaging applications. In addition, microrobots have found applications in the environmental sector (e.g., water treatment). Besides, recent advancements of three-dimensional (3D) printers have enabled the high-resolution fabrication of microrobots with a faster design-production turnaround time for users with limited micromanufacturing skills. Here, the latest end applications of 3D printed microrobots are reviewed (ranging from environmental to biomedical applications) along with a brief discussion over the feasible actuation methods (e.g., on- and off-board), and practical 3D printing technologies for microrobot fabrication. In addition, as a future perspective, we discussed the potential advantages of integration of microrobots with smart materials, and conceivable benefits of implementation of artificial intelligence (AI), as well as physical intelligence (PI). Moreover, in order to facilitate bench-to-bedside translation of microrobots, current challenges impeding clinical translation of microrobots are elaborated, including entry obstacles (e.g., immune system attacks) and cumbersome standard test procedures to ensure biocompatibility.

Fig. 1. A schematic view of a microrobot from bench to bedside.

The design and material-selection process can be assisted by AI and PI to design an application-specific device. AI can also improve the 3D printing process by optimizing printing parameters to reduce printing defects. In the application phase, AI can help clinicians to track microrobots and enhance maneuverability by tuning actuation parameters to ensure proper functionality. On the other hand, PI enables microrobots to sense different stimuli in their environment and respond to those stimuli independently (e.g., drug release at a particular pH level in the target site). In order to translate proof-of-concept microrobots to clinical medical devices, new microrobots must undergo standard tests to ensure safety for short- and long-term uses in the human body. However, these tests require cumbersome and costly procedures, which delays the rapid translation of microrobots. Thus, besides developing new materials, fabrication methods, and actuation modalities, more straightforward test procedures should be proposed to truncate the current test process while maintaining safety factors. Some elements in Fig. 1 have been designed using resources from Flaticon.com.

Fig. 2. Schematics of the 3D printing technologies used for fabrication of microrobots.

A Stereolithography (SLA). B Digital light processing (DLP). C Continuous liquid interface production (CLIP). D Direct laser writing (DLW) or two- or multi-photon polymerization (TPP or MPP). E Laser-induced forward transfer (LIFT). F Selective laser sintering (SLS). G Microextrusion 3D printing. H Inkjet 3D printing. I Fused deposition modeling (FDM). Subfigures A, F, I are reproduced with permission under CC BY 4.0 licenses from ref. ; subfigures B, D, G, H are reproduced with permission from ref. , copyright 2020, Wiley-VCH GmbH; subfigure C is reproduced with permission under CC BY 4.0 licenses from ref. ; and subfigure E is reproduced with permission under CC BY 4.0 licenses from ref. .

Fig. 3. 3D printed microrobots for drug delivery.

A ZIF-8 coated, biocompatible, and pH-responsive drug carrier helical microrobots. Graphic representation of the production steps of ZIF-8@ABF microrobots. Reproduced with permission from ref. . Copyright 2019, WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. B, C Three-dimensional (3D) printed, magnetically actuated chitosan microswimmers with the ability to release drugs with light excitation. B Energy-dispersive X-ray spectroscopy elemental mapping showing the presence of iron atoms (red color) in the microswimmers. C Total DOX release from the microswimmers with time for 6.7 × 10⁻² and 3.4 × 10⁻¹ W/cm² light intensity. Higher light intensity was directly correlated to the release rate. Subfigures B and C are reproduced with permission from Bozuyuk, U. et al. Light-triggered drug release from 3D-printed magnetic chitosan microswimmers. ACS Nano 12, 9617-9625 (2018). Copyright 2018, American Chemical Society. D, E Characterization of the magnetic propulsion and drug encapsulation capabilities of biodegradable hyperthermia microrobots (DHM). D Velocity of microrobots in respect to RMF frequency. The “step-out” (i.e., the sudden plummet of swimming speed) happened in lower frequencies/speed for 15 mT RMF. Hence, in order to acquire higher speeds, higher FMF frequencies are required. E Green-fluorescence images of in vitro test of the hyperthermic effect of DHMs on HCT116 cells, confirming the potency of DHMs for targeted hyperthermia therapy. Control: HCT116 cells only; +MR/ + AMF: DHM with AMF. Scale bars are 200 µm. Subfigures D and E are reproduced with permission from ref. . Copyright 2019, WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fig. 4. 3D printing of more complex microrobots.

A–C Three-dimensional (3D) printed artificial fish propelled with catalytic impulsion. A Functionalization of microfishes. Platinum (Pt) nanoparticles were loaded to the tail of the fish using catalytic decomposition for propulsion. Subsequently, to enable magnetic actuation/control, Fe3O4 nanoparticles were loaded on the head of the fish. B Energy-dispersive X-ray (EDX) spectroscopy images of poly (ethylene glycol) diacrylate (PEGDA) microfish body, platinum tail, and the iron-oxide head (scale bar: 50 µm). C Velocity plots of microfishes with different shapes and Pt nanoparticle concentrations (5, 10, and 15% H₂O₂). Fish 1: common fish with 8.0 × 108 Pt particles per ml; Fish 2: manta ray with 8.0 × 108 Pt particles per mL; Fish 3: common fish with 4.0 × 108 Pt particles per mL. Subfigures A–C are reproduced with permission from ref. . Copyright 2015, WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. D–G Three-dimensional (3D) printed self-propulsive microswimmers. D Computer-aided design (CAD) and dimensions of a low-drag bullet-shaped microswimmer with an inner cavity to produce catalytic jet bubbles. E Microbubble generation from microswimmer’s inner cavity at a steady frequency, demonstrating continuous/steady self-propulsion ability of the swimmers. F CAD and dimensions of microflowers. G Scanning electron microscope (SEM)-image validation of separately patterned chemical sites on microprinted flowers by fluorescent dye-coupled particles that orthogonally reacted with their target sites. Subfigures A–C are reproduced with permission from ref. . Copyright 2016, WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fig. 5. Microrobots and microactuators.

A, B Two-photon-polymerization (TPP) three-dimensional (3D) printed iron platinum nanoparticle-based magnetic helical microswimmers. A Conceptual design of a trimethylolpropane ethoxylate triacrylate (PETA) magnetic helix with three turns and embedded FePt or superparamagnetic iron-oxide nanoparticles (SPIONs). B Swimming velocity of 30 μm long SPION/PETA and FePt/PETA magnetic helical microswimmers. FePt-based microswimmers were able to endure higher frequencies (with higher step-out frequency), reaching higher velocities compared to other microswimmers. Subfigures A and B are reproduced with permission under CC BY 4.0 licenses from ref. . C, D Three-dimensional (3D) printed soft microstructures that actuate upon water absorption. C Illustration of the actuation motion with hydration. The actuation was triggered by water vapor absorption. D The motion of a bilayer hydrogel structure during hydration with vapor for 360 s. Subfigures C and D are reproduced with permission from ref. . Open access, 2020, IOP Publishing Ltd. E, F Soft microrobotic grippers and microfluidic transistors fabricated by in situ direct laser writing (isDLW). E An integrated microfluidic system comprising of one microfluidic transistor and one soft microgripper. The grippers closed upon application of P_g to the transistor (right). According to the working principle of this soft microgripper, an applied input pressure (P_s) triggered the inward movement of grippers, while microgrippers remained open when the pressure was not present. Scale bars are 50 µm. F Experimental results of flow rates through a 25 µm disc transistor for varying P_g values and P_s values of 50, 100, and 150 kPa. For a constant P_g, higher flow rates were achievable using higher P_s. Subfigures E and F are reproduced with permission from ref. . Copyright 2021, IOP Publishing Ltd. Reproduced with permission. All rights reserved.

Fig. 6. Cargo delivery and dissolvable microrobots.

A–E Three-dimensional 3D-printed microrobot cell transporter (MCT) with the ability to deliver stem cells in vitro. A Computer-aided design (CAD) design was two-photo-polymerization (TPP) 3D-printed, and the inner surfaces of the structure were modified to increase stem cell bonding capability. B 3D confocal image of cell-loaded MCTs after 72 h of being in Matrigel (red: actin; green: RUNX2, osteogenic cell marker) (scale bar: 60 µm). C Image of an MCT with encapsulated cells during rotational actuation (propulsion) and steering in vitro with a 10 mT, 5 Hz magnetic field (scale bar: 50 µm). D Graph of the average speed of MCTs with respect to different frequencies of a 10 mT magnetic field. An increase in magnetic field frequency over 5 Hz resulted in a decrease in velocity since the MCT failed to convert the high-frequency rotational magnetic field to linear movement. E Out-migration of cells from MCT within 24 h period (scale bar: 20 µm). Subfigures A–E are reproduced with permission from ref. . Copyright 2019, WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. F–I Three-dimensional (3D) printing of sugar-based microrobots that can be moved magnetically. F, G Microscopy images of saccharide-based, selective laser sintering (SLS) 3D-printed structures. F A glucose-based helix (P = 22.5 W; V = 1.4 cm/s). G sucrose-based gears (P = 22.5 W; V = 1.4 cm/s). H Magnetic operation route of a sugar helix inside 30 wt% Water/Glycerol seen from the top. I Dissolution images of a sucrose-based slab in W/G at 60 and 600 s. Scale bars are 10 mm. Subfigures F–I are reproduced with permission from ref. . Copyright 2020, Wiley-VCH GmbH.