Microfluidic devices are compact test tools made of tiny channels etched onto a chip that allow biomedical researchers to test the properties of liquids, particles, and cells on a microscale. They are essential for drug development, diagnostic tests and medical research in areas such as cancer, diabetes and now COVID-19. However, producing these devices is labor intensive, with tiny channels and wells that often have to be manually etched or molded into a transparent resin chip for testing. While 3D printing has offered many advantages for the fabrication of biomedical devices, its techniques were previously not sensitive enough to build layers with the fine detail required for microfluidic devices. Until now.
Researchers at the USC Viterbi School of Engineering have now developed a highly specialized 3D printing technique that allows microfluidic channels to be fabricated on chips at a precise microscale never before achieved. The research, led by Daniel J. Epstein Department of Industrial and Systems Engineering Ph.D. graduate Yang Xu and Professor of Aerospace and Mechanical Engineering and Industrial and Systems Engineering Yong Chen, in collaboration with Professor of Chemical Engineering and materials science Noah Malmstadt and Professor Huachao Mao at Purdue University, was published in Nature Communication.
The research team used a type of 3D printing technology known as vat light-curing, which harnesses light to control the conversion of liquid resin into its final solid state.
“After the light is cast, we can basically decide where to build the parts (of the chip), and because we’re using light, the resolution can be quite high within a layer. However, the resolution is much worse. between layers, which is a critical challenge in building micro-scale channels,” Chen said.
“This is the first time we’ve been able to print something where the channel height is at the 10 micron level; and we can control it very precisely, with an error of plus or minus one micron. This is something that has never been done before, so this is a breakthrough in 3D printing small channels,” he said.
Vat photopolymerization uses a vat filled with liquid photopolymer resin, from which a printed article is built up layer by layer. Ultraviolet light is then shone onto the object, curing and hardening the resin at each layer level. When this happens, a build platform moves the printed element up or down so that additional layers can be built on it.
But when it comes to microfluidic devices, vat light-curing has some disadvantages in creating the tiny wells and channels needed on the chip. The UV light source often penetrates deep into the residual liquid resin, hardening and solidifying the material inside the channel walls of the device, which would clog the finished device.
“When you cast the light, ideally you only want to cure one layer of the channel wall and leave the liquid resin inside the channel untouched; but it is difficult to control the depth of cure, as we try to target something that’s only a 10-micron gap,” Chen said.
He said current commercial processes only allow channel height to be created at the 100 micron level with poor precision control, due to light penetrating too deeply into a hardened layer, unless you Don’t use an opaque resin that won’t let in so much light.
“But with a microfluidic channel, you usually want to look at something under a microscope, and if it’s opaque, you can’t see the material inside, so we have to use a transparent resin,” Chen said.
In order to precisely create transparent resin channels at a microscopic level suitable for microfluidic devices, the team developed a unique auxiliary platform that moves between the light source and the printed device, preventing light from solidifying the liquid in the walls of a channel, so that the roof of the channel can then be added separately to the top of the device. The residual resin that remains in the channel would still be in a liquid state and can then be discharged after the printing process to form the channel space.
Microfluidic devices have increasingly important applications in medical research, drug development and diagnostics.
“There are so many applications for microfluidic channels. You can run a sample of blood through the channel, mixing it with other chemicals so you can, for example, detect if you have COVID or high blood sugar,” Chen said.
He said the new 3D printing platform, with its micro-scale channels, enables other applications, such as particle sorting. A particle sorter is a type of microfluidic chip that uses chambers of different sizes that can separate particles of different sizes. This could offer significant benefits to cancer detection and research.
“Tumor cells are slightly larger than normal cells, which are about 20 microns in size. Tumor cells could be larger than 100 microns,” Chen said. “Currently, we use biopsies to look for cancer cells; by cutting an organ or tissue from a patient to reveal a mixture of healthy cells and tumor cells. Instead, we could use simple microfluidic devices to flow (the sample) through channels with precise height prints to separate cells into different sizes so that we don’t allow these healthy cells to interfere with our detection.”
Chen said the research team is now in the process of filing a patent application for the new 3D printing method and is seeking collaboration to commercialize the technique for manufacturing the medical test devices.