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3D Printing MICROFLUIDICS:
This is the result of my work with Professor Natalie Artzi’s lab (MIT Institute for Medical Engineering & Science). We created a platform to extract interstitial fluid from patients and analyze it to diagnose cancers. 3D printing the devices allows us to accomplish this at a low cost. I worked on the parts highlighted in green.
Interstitial fluid is the fluid that fills the spaces between an organism’s cells. Although it lies outside of blood vessels, it contains many dissolved biomarkers that make it almost as effective a diagnosis tool as a blood sample. The major advantage of using interstitial fluid for this purpose is that it can be extracted painlessly.
Closeup picture of the 3D printed microfluidic pieces
Here are the steps in our diagnostic platform:
Prepare a microneedle patch
Administer the microneedle patch to the patient
The microneedle patch acts somewhat like a sponge, soaking up the interstitial fluid and some of the surrounding cells
Remove the patch
Digest the patch using enzymes, leaving only the interstitial fluid and the biomarkers the microneedles picked up
Introduce microscopic ferromagnetic particles into the solution, which adhere to the cells.
Separate the cells from the other molecules in the fluid using a magnet
Run the cells through a microfluidic device, which contains a variety of antibodies for the cells to interact with
The cells will attach to certain antibodies and become trapped in the microfluidic device
Observe the cells and the antibodies they are attached to under a microscope.
MiCRONEEDLE PATCH
This one of the two 3D printed devices I worked on. The microneedle patch is used to extract the interstitial fluid. It is pressed against the skin, and the tiny (0.6mm tall) needles penetrate the outer layers, reaching the interstitial fluid.
Since the needles are so short, they do not pierce any blood vessels, or reach any pain receptors. The patch feels only like a rough piece of sandpaper, thus making it easy to use and painless.
I designed all of these parts in Fusion 360 and 3D printed them on an Elegoo Mars Pro. This printer is different from the traditional filament-based 3D printers. It selectively cures a liquid resin using ultraviolet light. The light is masked by an extremely high resolution LCD screen, thus allowing for very fine detail prints.
Here are some microscope images of the printed microneedle patches: The entire patch is about the size of the nail on your thumb.
Nanowell ARray
This is the device used to analyze the cells within the interstitial fluid. It contains 5 independent narrow channels which the fluid can be run through. The different channels can be preloaded with different antibodies, thus allowing each channel to test for different characteristics.
Each channel contains 250 “nanowells”. These are microscopic (0.05 mm wide) square indentations that trap the cells if they attach to the antibodies. The nanowells are small enough that they can only hold up to 3 cells.
The entire device is transparent, so that the cells can be labeled with a fluorescent protein, and then observed under a microscope by shining an ultraviolet light through the device.
This was printed as two parts, with the top and bottom part prepared independently, and then fixed together using screws.
Even with the SLA printer, it was very difficult to get the nanowells to print properly, because they are right up against the minimum feature size the printer is able to achieve. I had to do a lot of experimentation with the printer settings, and the process of cleaning up the prints afterwards to get them to come out right.
Presentation of INitial Results AT LAB MEETING
Due to the pandemic, I wasn’t able to come in to the lab to do any work on the project. I instead designed and printed the parts at home, then sent them to the lab. Here are some screenshots of our weekly lab meetings where one of the other lab members presented the results of their experiments using my devices.
