3D-printed devices could streamline the production of drug-delivery microparticles

MIT researchers have demonstrated a low-cost design of specialized electronic nozzles, called triaxial electrospray emitters, that could be used to manufacture time-release drug-delivery particles or self-healing materials efficiently and at scale.

Triaxial electrospray emitters use electricity to precisely dispense three liquids from microscopic nozzles to generate a steady stream with three distinct fluid layers. The liquid forms multilayered droplets, which can solidify into layered microparticles.

For instance, an array of triaxial electrospray emitters can be used to make three-layer drug-delivery nanoparticles. The outer layer might slowly erode in the stomach, revealing a second material that controls the release of a core material, which delivers medicine to a specific area of the intestines.

Developing a tiny array of electrospray emitters typically requires expensive and time-consuming microfabrication processes inside semiconductor cleanrooms, which limits their use. To overcome these drawbacks, the MIT researchers 3D-printed arrays of triaxial electrospray emitters that have 16 nozzles in an area of about one square centimeter. Each device contains an intricate network of three-dimensional microchannels that uniformly supply liquid to the nozzles. 

Their one-step fabrication process takes only a few hours to produce complex emitter arrays. 

When tested, the 3D-printed arrays generated uniform, three-layered droplets at scale. Such uniformity is key for high-throughput manufacturing of layered microparticles for applications like biosensors that detect chemical substances or artificial cells to aid in tissue regeneration.

“We couldn’t make a device like this in a semiconductor cleanroom. This is only possible because they are 3D-printed,” says Luis Fernando Velásquez-García, a principal research scientist in MIT’s Microsystems Technology Laboratories (MTL) and senior author of a paper describing this advance. “The particles these devices generate, whether they are used for a self-healing composite or to deliver medicine, can have a big impact in many applications. We want to democratize this technology so the benefits can touch many more people.”

Velásquez-García is joined on the paper by lead author Bryan Ivan Quintanar-Abarca of the Technological Institute of Monterrey in Mexico. The research appears in Virtual and Physical Prototyping.

A precise process

Electrospray emitters apply a high voltage to a liquid as it exits the device’s nozzle, producing a steady stream of extremely tiny droplets. 

Triaxial devices contain arrays of three concentric nozzles that emit three immiscible, or non-mixable, liquids simultaneously into layered droplets, which can be used to generate compound microparticles with distinct layers.

For instance, one could use a triaxial electrospray emitter to create a biosensing particle that contains three different chemical markers, one in each layer. Electrospray emitters can make smaller microdroplets much faster than other techniques.

Miniaturization is key for electrospray devices, since the smaller the emitter, the lower the voltage required to generate droplets. The output of a single electrospray emitter is modest, so arrays of emitters are required to boost droplet production without sacrificing uniformity. 

Multi-emitter electrospray devices are typically manufactured in semiconductor cleanrooms, but traditional processes limit the shapes and sizes of device components. The researchers could not find any previous reports of a miniaturized triaxial electrospray array in the open literature, highlighting the novelty of this work.

“When you build a triaxial array, you need to find a way to create geometries that have many integrated parts and extremely fine structures in the smallest footprint possible. And you need to ensure the devices will work uniformly,” Velásquez-García explains.

To do this, he and his collaborators used a 3D-printing technique called vat photopolymerization, which utilizes light to solidify extremely thin layers of liquid resin, fabricating a complex device one layer at a time. 

This extremely precise process enabled the researchers to print layers that were only 25 micrometers tall, just a fraction of the width of a human hair. In this way, they could generate the complex internal geometry needed for a triaxial electrospray emitter.

Refining the design

The array, which is slightly larger than a U.S. penny, contains a network of internal coiled channels that carry liquid to 16 nozzles. These helical microchannels help maintain a uniform spray of microdroplets across all nozzles, while keeping the device as compact as possible. 

“In a sense, the emitters in the array never learn they have company, or otherwise there would be cross-talking and causing interference between them. We achieved uniformity because of the work that went into our designs,” Velásquez-García says.

They also needed to fabricate extremely tiny channels without support structures, which could clog the device, and ensure all uncured resin was removed before the array was used.

The microchannels funnel liquid to the concentric nozzles, which must be perfectly aligned to properly emit microdroplets in a consistent manner.

“We were able to aggressively optimize the design because we could iterate in a much timelier manner. This ability to exquisitely refine designs is a key advantage of 3D printing,” Velásquez-García says.

The researchers tested multiple architectures to determine the ideal combination of liquid flow rates to maximize the stability and consistency of emitted microdroplets. They were surprised to find that the viscosity of the middle liquid plays the most important role in achieving stability in a microdroplet, since it preserves the thickness of each layer. 

In addition, the researchers found that by adjusting flow rates and voltages, they could precisely tailor the thickness of each microdroplet layer. This would allow scientists to design drug-delivery particles with ideal layers so medicine releases at exactly the right time.

“By making such intricate devices more practical, we can empower others to pursue entrepreneurial and scientific advances,” Velásquez-García says. 

In the future, the researchers want to continue refining their fabrication process and designs to achieve even smaller dimensions and integrate conductive or dielectric materials to the devices to make more advanced electrospray emitter arrays.

This research was funded, in part, by the Tecnológico de Monterrey – MIT Nanotechnology Program.