A 4D printed microrobot integrates magnetic actuation, optical pH readout, and pH-triggered morphing to link navigation, measurement, and on-cue drug release.
(Nanowerk Spotlight) Tiny changes in body chemistry can flag where disease hides. Tumor tissue often sits in slightly acidic pockets while nearby healthy tissue stays closer to neutral. A device that could notice those shifts on the spot and respond with a measured dose would change how clinicians think about precision therapy inside narrow biological channels.
The parts exist in isolation. Magnetic fields can pull small objects through fluid with fine control. Smart gels expand or contract when acidity changes and can act as soft hinges or gates. Optical microstructures turn geometry into color that any microscope can read.
What has been missing is a way to fuse motion, sensing, and action inside one microrobot without bulky add ons, fragile wiring, or complex assembly that fails at the scale of a grain of sand.
Manufacturing is catching up to the ambition. Multimaterial microprinting places different substances within the same tiny body with sub micrometer accuracy. Iron oxide mixed into light cured resin gives reliable magnetic steering. pH responsive hydrogels bend predictably and can open or seal a small chamber. Four dimensional printing treats time as part of the design so a printed part changes shape or function when a trigger appears, such as acidity.
The authors present a fully printed device about the size of a grain of sand that combines magnetic motion, optical readout of acidity, and shape change that opens or closes a small cargo chamber. Its importance lies in integration. The same 4D-printed body that moves under a magnetic field also reports a chemical cue and controls release. There is no separate sensor package and no external valve. That reduces complexity and size and creates a direct loop from sensing to action.
Schematic illustration of 4D-Printed Microrobots with Multimodal Synergy. i) Multi-material two-photon polymerization enables the fabrication of microrobots. ii) Gradient magnetic fields control the navigation of microrobots. iii) A head-mounted optical diffraction module enables pH sensing. iv) The end-effector joint opens in abnormally acidic environments. v) Drugs are slowly released from the porous structure. (Image: Reprinted with permission from Wiley-VCH Verlag) (click on image to enlarge)
The robot has the outline of a small fish about 150 micrometers long. The head carries an optical sensor built as a diffraction grating, which is a regular set of fine lines that split light into colors. When the spacing between lines changes, the observed color shifts. The abdomen contains a magnetic composite formed by dispersing iron oxide particles in a laser cured resin. This region couples to a magnetic field gradient. A magnetic field gradient is a change in field strength across distance that produces a force on magnetic material. The tail is a joint made from two bonded layers. One layer is a rigid resin that barely changes size in water. The other is a hydrogel that expands in acid and contracts in alkali. Because the two layers change size by different amounts, the joint bends. In neutral or alkaline liquid it closes and forms a pocket for cargo. In acidic liquid it opens.
All parts are produced and aligned with two photon microprinting. In two photon printing, a tightly focused laser hardens a resin only at the small point where two photons are absorbed at the same time. Because the reaction is confined to that tiny focal volume, the printer can create features below a micrometer and place different materials with high precision.
The team used small internal markers so each print step could align to the last one. They confirmed the planned material layout by mapping element specific X ray signals using energy dispersive spectroscopy, which detects the characteristic X rays that elements emit under an electron beam. They also used fluorescence imaging to see how the materials were distributed within the structure.
Motion comes from an external permanent magnet that provides both a field and a gradient. Under that drive the fish shaped body follows set paths with high repeatability. The study reports travel through artificial vascular networks made from cured adhesive with channel widths close to the robot length. A maze with tight turns confirmed that the streamlined body helps the robot slip through confined paths.
Comparisons showed that the fish form moves faster than a circular form under the same field conditions. The team measured how closely the robot could approach a target and found errors on the order of tens of micrometers, precise enough to reach small features within complex networks.
The optical head reads acidity through structural color. Structural color is produced by the interaction of light with repeating patterns rather than by dyes. The researchers printed a grating with a chosen spacing and attached it to a small joint that changes distance between lines as the hydrogel swells or shrinks.
Viewed at a shallow angle under a lens with low numerical aperture, the head displays colors that shift with pH. Numerical aperture is a measure of how much light a lens can collect and how fine a detail it can resolve. Through design tests they selected a grating spacing that produced visible color transitions across a useful pH range.
The device relates hue to pH with a simple mapping. Hue is the angle on a standard color wheel that represents the type of color such as red or green. The relation follows an S shaped curve that the team fit with a standard Boltzmann model, which is a mathematical function often used to describe smooth transitions. This lets an operator estimate local acidity from a single image.
The tail handles cargo. It is a bilayer hinge in which the hydrogel changes size with acidity while the resin remains almost constant. When the liquid is neutral or alkaline the joint closes and forms a pocket roughly the size of a red blood cell. When the liquid becomes acidic the joint opens and exposes the pocket. The response time is short for a structure at this scale.
In tests the joint reached a new position within seconds after a shift in acidity and relaxed even faster when the medium returned to alkaline conditions. The bond between hydrogel and resin remained intact across repeated cycles. That bond is crucial, since any delamination would degrade bending and defeat the gate like function.
To demonstrate drug handling, the team used doxorubicin, a standard cancer drug that glows red under blue light. They prepared two tail materials. One was a continuous hydrogel. The other was a porous hydrogel with small holes that increase surface area and give molecules more paths to move. They pulled drug solution into each material under vacuum to achieve consistent uptake.
Under the microscope the porous gel showed an even red glow across the volume, which signals uniform loading. The continuous gel displayed brighter edges and dimmer centers, which signals less uniform loading. Pooled measurements over large batches provided a total drug mass from which loading per device can be inferred, given that each microrobot carries two drug modules.
Release tests showed a clear role for acidity. In strong acid the porous gel released drug much faster than the continuous gel. Under neutral conditions the release was small. In cell culture medium the tail opened over time, which created a two stage release profile that matched the mechanical opening of the pocket.
Integration during operation was the crucial test. The researchers steered the robot through patterned channels that mimic small vessels while the head reported local acidity through color. In one region the hue indicated an alkaline pocket. In another it indicated conditions closer to neutral.
This kind of live chemical feedback during motion gives an operator a straightforward way to locate areas that match a chosen target chemistry and to decide when to open the cargo pocket.
The team also studied biological effects using human gastric cancer cells in vitro. They used the MGC 803 line and compared robots with and without drug cargo across different pH conditions. In a large field, a single robot affected only a small fraction of cells because the drug spread across a wide area.
In a tight zone near the robot, the effect was pronounced. Within about half a millimeter around a loaded robot, the measured fraction of dead cells was high. Robots without drug left cells largely intact over the same period, which supports the view that the printed materials and the magnetic actuation do not harm cells under the test conditions.
Alongside performance data, the paper describes production steps that support repeatable results. Magnetic resin layers were made thin enough that the laser could cure features through them without losing too much energy to the particles. Alignment relied on printed markers and image based registration at each step so that head, abdomen, and tail lined up as intended. Material interfaces were chosen to bond under the same printing chemistry.
Tests of different body shapes confirmed that a streamlined form reduces drag and increases speed under the same magnetic drive. Path following exercises that traced set patterns and navigated mazes validated control. Placement tests yielded small errors close to a few tens of micrometers.
The authors are clear about limits and next steps. The color signal used for pH readout is easy to see under a microscope but does not travel far through tissue. That makes deep use inside the body difficult unless an optical path such as an endoscope is available. The team proposes acoustic feedback as an option. They suggest the use of phononic structures, which are patterned materials that guide sound waves, to transmit signals through tissue where light fades quickly.
The materials in the current device are not degradable. For medical use, the microrobots should either leave the body safely or break down into harmless pieces after a planned time. The tests involve single robots or small sets in lab dishes. Moving toward practical therapy will require coordinated groups, better imaging to track them, reliable control to avoid clogging narrow channels, and methods to manage dose and clear devices after use.
Seen together, these results show a single printed body that performs three essential jobs. The head senses acidity and converts it to color for a simple optical readout. The abdomen couples to a magnetic field gradient and gives the operator precise control of motion. The tail turns acidity into movement that opens or closes a pocket and controls release. The device moves through confined networks, measures a relevant chemical signal, and acts on that information.
The specific materials and geometries can change. The optical head could be paired with a different responsive element to sense glucose or oxygen. The hydrogel tail could be tuned to respond to temperature or enzymes. The central idea is the integration strategy. By assigning jobs to regions during printing and aligning them with care, the structure becomes the controller. This approach offers a clear route to microrobots that do not only move but also measure and respond within complex biological environments.
For authors and communications departmentsclick to open
Lay summary
Prefilled posts
Nanowerk Newsletter
Get our Nanotechnology Spotlight updates to your inbox!
Thank you!
You have successfully joined our subscriber list.
Become a Spotlight guest author! Join our large and growing group of guest contributors. Have you just published a scientific paper or have other exciting developments to share with the nanotechnology community? Here is how to publish on nanowerk.com.
