Researchers from Drexel and McGill Universities have developed a method for using the feeding tube of mosquitoes, called a proboscis, as a dispense tip for high-definition 3D printing.
In a redeeming development for one of nature’s most universally denounced pests, researchers from McGill and Drexel Universities have discovered that mosquito stingers might one day be used for high-definition 3D bioprinting. Reported in the journal Science Advances, the findings demonstrated how the needle-like structure, called a proboscis, that mosquitoes use to extract blood, when repurposed as a tip for a 3D printer, can extrude lines finer than a human hair — surpassing commercially available 3D printing tips.
The discovery could ultimately enable precision fabrication of microscopic structures and tissue samples used in regenerative medicine, drug screening and cancer treatment. And do it at a fraction of the cost of top-of-the-line tips.
“Mosquito proboscides let us print extremely small, precise structures that are difficult or very expensive to produce with conventional tools,” said Changhong Cao, PhD, an assistant professor at McGill and Canada Research Chair in Small-Scale Materials and Manufacturing, who was a co-author of the research. “Since biological nozzles are biodegradable, we can repurpose materials that would otherwise be discarded.”
The study, which laid out a process the researchers call “3D necroprinting” — using a non-living biological structure as an advanced manufacturing tool — was led by McGill graduate student Justin Puma. He was also involved in a previous study using a mosquito proboscis for biomimetic purposes that established a foundation for this research.
Building Better Models
One of the most promising applications of 3D printing, or additive manufacturing, that has improved over the last decade is printing biological structures.Researchers at Drexel pioneered the process, creating a device that could print tumors for cancer treatment. But to advance the field, researchers have been refining various components of the process to capture the subtle differences in healthy tissues and cancerous tumors at the cellular level.
“Evolutions in bioprinting are helping medical researchers develop unique approaches to treatment,” said Megan Creighton, PhD, an assistant professor in Drexel’s College of Engineering, who was a co-author of the paper. “The more precisely we can make these samples to mimic biological tissue and structures with improved 3D bioprinting, the more accurate our testing and ability to design more effective treatments. This is an exciting, if unexpected, development that could help to advance this line of research in interesting new directions.”
To produce the tissue samples — which are being designed to model biological structures, from tendons to tumors, right down to the cellular level — researchers primarily use 3D printing nozzles, called dispense tips, made from glass that has been heated and drawn into a fine point. These tips can extrude a line as thin as 40 microns, but they are quite fragile and cost as much as $80 per tip to replace. The researchers estimate that more than 4 billion dispense tips are used in the United States each year.
By comparison, proboscides from deceased mosquitoes can be procured and repurposed for about 80 cents. They are quite durable and have the added benefit of being fully biodegradable, according to the report.
A Natural Solution
“Nature offers a diverse array of micro dispense tips with intricate structures and excellent performance, such as insect proboscides and plant xylem vessels,” the researchers wrote. “The unique combination of mechanical, geometrical and structural properties makes the female mosquito proboscis appealing for dispensing applications.”
The same rigidity and vibration-assisted mechanism that enables the mosquito’s feeding tube to pierce skin with minimal force and access blood vessels with precision, also give it the durability to withstand the rapid extrusion of printing materials.
Under a microscope, the McGill researchers carefully removed the structure and attached it to a standard plastic dispenser tip using a small amount of resin. The researchers characterized the tips’ geometry and mechanical strength, measured their pressure tolerance and integrated them into a custom 3D-printing setup.
They then tested the tips’ ability to print high-resolution microscopic structures — in the shape of a honeycomb and maple leaf — using a common filament and two different types of bioink.
A scanning electron microscopy image of the honeycomb — measuring just 600 by 600 by 310 micrometers thick — revealed a stable structure with constancy between printed layers, each 22 micrometers thick.
The second demonstration, a maple leaf structure, exhibited even greater fidelity in printed lines between layers — 18 micrometers thick — with each filament clearly defined in the sidewall, they reported.
The proboscis tip also successfully printed a high-density microscopic structure containing red blood cells with a bioink, a test that indicates its utility for printing tissue scaffolds to test responsiveness to drug therapies.
In a final test, the dispense tip also proved to be adept — perhaps not surprisingly — at piercing pig skin to deposit hydrogel as a model of a drug carrier, mimicking therapeutic drug delivery in live tissue.
More than 100 million years of evolution have endowed the proboscis with two traits that give it a distinct advantage over synthetic dispense tips: its intrinsic elasticity prevents the tip from damaging the substrate on which its printing; and the narrow gauge of the tube limits the force that can be exerted during the process, which acts as a natural safeguard against breaking or springing a leak during extrusion.
The Path to Redemption
The unexpected biological inquiry came about when Creighton — a chemical and biological engineering researcher, with industry experience in additive manufacturing — was developing a topical application to prevent mosquito bites
Their exploration of the proboscis’ unique structural properties led to a conversation about potential uses for it — aside from sucking blood. And the idea of using it as a disposable 3D printer tip emerged.
"The discovery was made possible by combining perspectives across biology and engineering to think about the same problem in different ways,” Creighton said. "Thanks to this collaborative effort we now understand that the biological adaptations that make mosquito bites so difficult to prevent are the same traits that may enable exciting new possibilities for additive manufacturing."
To source the proboscides, Creighton turned to her colleague Ali Afify, PhD, an assistant professor in Drexel’s College of Arts and Sciences, whose research examines mosquito behavior in hopes of repelling or directing them away from humans to prevent the spread of malaria.
“I see mosquitoes as both a model organism which we can use to ask basic questions on sensory neurobiology and also as a disease vector that we try to develop methods to control, so approaching mosquitos as a ‘material’ used in an application is a completely different idea for me,” Afify said. “I think this collaboration between biology and engineering has discovered a beneficial use for mosquitoes for the first time.”
Afify provided the group with deceased female A. Aegypti mosquitoes sourced from ethically approved laboratory colonies used for his biological research. He suggests that the proboscis of most mosquito species could function well as a dispense tip.
Future research could explore this, looking into other candidate biological structures, such as snake fangs, centipede claws and scorpion telsons. The researchers also suggest that important information could be gleaned from testing the tips in more extreme conditions and closely investigating the role of surface roughness in fluid flow performance.
The research was supported by the New Frontiers in Research Fund Exploration program, the Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery program, Fonds de recherche du Québec Nature and Technologies. (FRQNT) New Academics program, and the Canada Foundation for Innovation John Evans Leaders Fund, the Canada Research Chair Program and an NSERC-FRQNT Nova grant.
In addition to Cao, Creighton, Afify and Puma; Zhen Yang, Evan Johnston, Zixin Zhang, Xiaoyi An, Lingzhi Zhang, Hongyu Hou, Zixin He, and Jianyu Li, from McGill, contributed to this research.
Read the full paper here: https://www.science.org/doi/10.1126/sciadv.adw9953