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Tiny technologies for high-impact medical applications 

The universities and companies exploring the frontier of nano and micro 3D printing for medical applications

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Nano 3D printing, with its incredibly high-accuracy parts measuring less than 100 nanometers, and micro 3D printing (a micron is a thousand times larger than a nanometer but is still just one thousandth of a millimeter) 3D printing have the potential to radically disrupt the medical device industry—more precisely, and less invasively. Devices for surgeries and laboratory equipment, which require high levels of detail, are often demanded in small batches. Over the past few years, many have leveraged this technology for just that. Let’s take a look at the companies and technologies that are leading this disruption, and what it means for the future of medical care.

Leading university research

Nano 3D printing technologies such as 2PP (Two-photon polymerization) and high-precision stereolithography have all seen great advancements through university research and via systems developed by academic teams, that often lead to a commercial spinoff company. As many will remember, one of the very first high-profile projects in nano 3D printing was a Formula 1 car produced via internally developed 2PP technology at the University of Vienna in 2012. The F1 car measured 285 microns in length, about the size of a grain of sand. Photographed with an electron microscope, the model was created using the latest version of two-photon lithography or 2PP, a 3D-printing technique in which highly focused laser beams manipulate liquid resin into detailed solid structures. Molecules in the resin, which induce polymerization to make it hard, are activated when they absorb two photons at once – that happens only at the center of the beam, hence the precision. It’s fast, too. The car, made up of 100 layers, was printed in just four minutes.

Tiny technologies for high-impact applications - the frontier of nano 3D printing and micro 3D printing
One of the first 2PP experiments to receive global visibility. Image: University of Vienna

Purdue University

In 2021, a team of researchers at Purdue University developed a way for rapid nano 3D printing of complex resin objects with smooth features by combining multi-photon lithography with spatiotemporal focusing of femtosecond laser pulses. The researchers’ goal was to speed up and scale up multi-photon lithography. In one print, the team produced more than 74,000 small units into a 42 x 42 x 42 unit cube, measuring nearly 1 millimeter in width. This technology can be used by doctors to quickly produce a bio-engineered scaffolding—built by combining multiple 3D printed nanostructures—for tissue cells to grow on.

Georgia Tech

Early this year, researchers at Georgia Tech developed a light-based nano 3D printing technique to produce metal structures. The technique is reportedly 480x faster and 35x cheaper than other conventional methods, thanks to the use of commercially available superluminescent light emitting diodes (SLEDs), instead of the typically used femtosecond lasers. When the light from the projection system hits the clear ink solution (made of metal salt and other chemicals) it causes a chemical reaction that converts the salt into metal. The researchers expect their technology to enable the development of electronics and optics, among other things, thanks to the significantly lower costs to entry.

Stanford University and the University of North Carolina at Chapel Hill

In 2021, researchers from Stanford University and the University of North Carolina at Chapel Hill developed a microneedle vaccine in the form of 3D printed microneedles lined up on a polymer patch. According to the universities, the resulting immune response from the vaccine patch was 10x greater than a vaccine delivered into an arm muscle with a needle jab. The 3D printed microneedles, which were produced on a CLIP prototype 3D printer developed by Joseph DeSimone, founder of CARBON and lead author of the study, can be easily customized to develop various vaccine patches for flu, measles, hepatitis or COVID-19 vaccines.

Image: Purdue University.

Micro 3D printing and nano 3D printing companies

Many university projects spinout into commercial companies and the number of technology providers for micro 3D printing and nano 3D printing hardware has been steadily increasing. In many cases, these companies sell systems to academic teams that want to focus their efforts on pure research rather than on developing their own systems. Some, like Boston Micro Fabrication and Fabrica (part of Nano Dimension), have already achieved very significant commercial success since they provide the ability to build parts that simply cannot be manufactured using traditional methods.

Tiny technologies for high-impact medical applications - the frontier of nano 3D printing and micro 3D printing for medical applications.
Image: Microfabrica

Microfabrica

Microfabrica was acquired by Technoprobe, an Italian microelectronics/semiconductor testing company, in 2018. By integrating advanced 3D printing with semiconductor manufacturing techniques, the company can fabricate microscopic, highly precise, and complex multi-part instruments from biocompatible materials. A notable innovation includes the development of submillimeter forceps, in partnership with US Endoscopy. These forceps are created for intricate tissue biopsies within the gastrointestinal tract, showcasing a significant leap in minimally invasive medical procedures.

Nanoscribe

Nanoscribe, a German 3D printing pioneer, in collaboration with KU Leuven scientists, has utilized Two-Photon Polymerization (2PP) to create synthetic microvessels for potential use in regenerative medicine and drug discovery, offering an alternative to animal testing. Additionally, a Boston University team employed Nanoscribe’s technology to construct a miniaturized human heart chamber model, advancing disease research and the development of chip-based organs. Nanoscribe’s introduction of Two-Photon Grayscale Lithography (2GL) has enhanced the production of high-precision optics for medical imaging devices like miniature endomicroscopes. 2GL, the fastest microfabrication technology based on 2PP, is breaking new ground in microoptics and photonics. The company was acquired and is now part of the BICO group of companies (together with bioprinting specialist Cellink).

Boston Micro Fabrication (BMF)

BMF, the developer of the microArch series of 3D printers for micro 3D printing applications, has enabled the production of RNDR Medical’s single-use endoscope, with a distal tip housing all components within a 3.3 mm diameter liquid-tight profile. The scope was designed for the direct visualization and navigation of disorders within the urinary tract. The company’s Projection Micro Stereolithography (PµSL) technology offers a resolution in the range of 2 µm to 25 µm, and tolerance of +/- 10 µm to 25 µm. The impact of BMF’s technology on RNDR Medical has cut development time by up to 50%. Other medical applications for BMF’s PμSL technology include cardiovascular stents and blood heat exchangers. The company has also 3D printed a spiral syringe needle for minimally invasive surgery, a 3D printed valve for a gene sequencer, and lab-on-a-chip (LOC) devices.

Tiny technologies for high-impact medical applications - the frontier of nano 3D printing and micro 3D printing for medical applications.Fabrica and Nano Dimension

Founded as Nanofabrica and later rebranded to Fabrica Group, this Israeli company was acquired by Nano Dimension, a producer of additively manufactured electronics (AME). Today Fabrica offers two micro 3D printing systems based on DLP technology, the Tera and the Giga, which deliver 1-5 micron additive layers for the highest precision 3D parts. The company also offers a range of compatible materials optimized for high resolution and repeatable micro-level accuracy and precision. Nano Dimension is also directly producing wearable medical devices, such as 40 μm-thick wearable piezoelectric antennas, using its DragonFly 3D printer and custom flexible materials. The company’s technology also enables the production of implantable optoelectronic probes that combine light delivery with electrodes for the readout of electrochemical signals, and lab-on-a-chip devices, as well as the miniaturization of micron-level mechanical plastic parts.

UpNano

UpNano, a high-resolution nano 3D printing technology developer based in Austria, uses its 2PP solution to produce biocompatible structures and surface textures that mimic the microenvironment of cells, the results of which play an increasingly important role in medical research. The non-cytotoxicity and high biocompatibility of the company’s UpPhoto and UpOpto materials have been certified according to EN ISO 10992-5:2009. The company also uses its technology to produce microstructures directly onto a microfluidic chip, with internal elements such as separators, channels, or membranes being fabricated directly within a commercially available or custom-made microfluidic chip.

Exaddon

Exaddon, a provider of microscale metal additive micromanufacturing (µAM) (a metal micro 3D printing process) produces and repairs microscale metal objects at room temperature with no need for post-processing using its CERES 3D printing system. One way the company uses this technology is in the manufacturing of tiny electrodes for implant into the brain (think Neuralink). These brain-computer interfaces connect external computing power to the brain via electrodes or implants and are expected to significantly change the lives of those suffering from conditions such as Parkinson’s or Alzheimer’s. The necessary micropillars can be printed with biocompatible materials with diameters as small as ~1 µm and in arrays with customizable pitch. Exxadon also produces transdermal microneedle arrays for drug delivery. The use of these hollow, non-brittle needles is painless and does not cause bleeding.

Tiny technologies for high-impact medical applications
Image: Incus.

Incus

Austrian company Incus leverages its lithography-based metal manufacturing (LMM) technology, rooted in the principle of photopolymerization, and biocompatible materials for groundbreaking medical and dental applications. This approach enables micro 3D printing production of high-precision components with intricate details. Typical applications extend to the creation of custom dental brackets, crowns, bridges, implants, and specialized surgical grippers, offering solutions that are tailored to meet the unique anatomical requirements of individual patients, and improving efficacy and comfort of medical treatments.

Heidelberg Instruments

Heidelberg Instruments, which merged with Multiphoton Optics in 2021, produces nanofluidic and microfluidic devices. The company’s nanofluidic devices, which handle very small volumes of liquid, are produced using the grayscale patterning capabilities of the NanoFrazor system. Applications for the technology range from DNA sequencing to sorting, assembling and manipulating nanoparticles, proteins, enzymes, viruses or angstrofluidics. The microfluidic applications include the development of lab-on-a-chip devices (which provide a miniaturized platform for performing chemical or biological reactions) used in fields such as drug discovery, point-of-care diagnostics, and environmental monitoring. The company’s MPO 100 2PP nano 3D printing system is used to create more complex 3D structures.

Tiny technologies for high-impact medical applications - the frontier of nano 3D printing and micro 3D printing for medical applications.
3D MicroPrint

3D MicroPrint

Germany’s 3D MicroPrint utilizes Direct Metal Laser Sintering (DMLS) to achieve resolutions and details that are critical for manufacturing the intricate parts needed in medical devices, such as surgical tools, implants and laboratory equipment. The company’s unique micro 3D printing capabilities is based on extremely fine powders. The ability to produce parts with features in the micrometer range allows for the creation of components that can be used in minimally invasive surgery techniques, improving patient outcomes by reducing recovery times and the risk of complications.

Microlight3D

Microlight3D, a Grenoble Alpes University (UGA) spin-off, specializes in producing intricate microscale and nanoscale medical components using 2PP technology. The resulting geometries are biocompatible, making them ideal for applications in tissue engineering, microfluidics and cellular scaffolding. The company’s solutions are instrumental in advancing personalized medicine, drug delivery systems and the development of lab-on-a-chip devices, as well as enhancing cellular research methodologies.

FEMTIKA

FEMTIKA, a provider of laser technology solutions in multiphoton polymerization and selective laser etching, also produces micro-fluidic devices from fused silica glass, for many scientific applications including biochemical research. The company’s lab-on-a-chip devices, made through a hybrid-fabrication approach using femtosecond laser ablation and multiphoton polymerization, offer the ability to combine ​​glass and polymer components. For example, the company produces microfluidic macromolecule separators for new drug development and production and liver-on-chip devices as in vitro liver models. The devices can be used in biomedical research to form complex cellular architecture and manipulate cell-to-cell interactions.

This article was originally published in VoxelMatters’ VM Focus Medical eBook. Read or download the full eBook for free at this link.

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Composites AM 2024

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Edward Wakefield

Edward is a freelance writer and additive manufacturing enthusiast looking to make AM more accessible and understandable.

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