Thursday 24 December 2015

Microcannons firing nanobullets

Sometimes I read papers that enhance my understanding of how the universe works, and sometimes I read papers about fundamental research leading to promising new technologies. Occasionally though, I read a paper that is just inherently cool. The paper by Fernando Soto, Aida Martin, and friends in ACS Nano, titled "Acoustic Microcannons: Toward Advanced Microballistics" is such a paper.

The grand scheme of this research is developing a tool that can selectively shoot drugs into cells at a microscopic level. This is hard because everything happens really slowly at the  microscopic scale in a liquid, in ways that meter-sized beings who live in air would not necessarily expect. For example, it is impossible for small organisms to move through a fluid using a repetitive motion that looks the same in reverse. For example, the way we move our feet back and forth to walk would not work for a tiny aquatic human, because the forward motion in the first phase of movement would be nullified by backwards motion in the second phase. This is why bacteria use things like rotating flagella to move*. Digressions aside, if you tried to shoot a tiny bullet through a cell wall, it would halt really quickly and diffuse away. Soto, Martin, and collaborators wanted to beat this.

They developed a "microcannon," starting with a thin layer of polycarbonate  plastic studded with small pores, which is a thing you can buy and don't have to make. They deposited graphene oxide onto the inside of pores in polycarbonate using electrochemistry, and then sputtering gold onto the inside of the graphene layer. The polycarbonate could be washed away with acid, leaving free-floating carbon and gold cannon barrels a few microns in size. While they were still in plastic membrane, the cannon pores were filled with a gel (literally gelatin from the supermarket) loaded with micron-sized plastic beads to act as bullets, and the "gunpowder."

The microcannons, loaded with nanobullets before and after firing.

Regular readers of my blog will remember that bubbles are somewhat of an exception to the small+water=slow rule, and that when they collapse it can lead to very fast motion on very small scales. So, the authors of the paper used perfluorocarbon (same structure as a hydrocarbon but with fluorine instead of hydrogen) droplets as a propellant, which they turned into bubbles with an ultrasound-induced phase transition. The bubbles collapse, leading to a pressure wave which drives the nanobullets out of the barrel towards their target**.

Composition and operation of the microcannons.
The authors wanted to characterize how powerful these things were, so they did two relevant tests. First, they embedded the cannons in an agar gel and loaded them with fluorescent beads. They looked at where the beads were before firing the ultrasound trigger at the cannon, and after. It was observed that they penetrated an average of 17 microns through the gel. I don't have much context to gauge whether this is a lot or a little.

The bullets were too fast to record with a microscope camera, so their second test involved recording the motion of the cannon after it fired the bullets. Naively one would expect to be able to calculate the bullet speed with conservation of momentum from knowing the cannon's speed, but momentum isn't conserved in a noisy viscous environment. They modeled the fluid dynamical forces acting on the system, measured that the terminal speed of the cannon was about 2 meters per second, and concluded that the initial speed of the bullets is 42 meters per second or 150 kilometers per hour. Pretty fast, especially for something so small in a draggy environment.

I don't know if this technology will succeed in the authors' goal of localized drug delivery to cells, but I think it's awesome that they made a functioning microscale cannon.
Oh the humanity.

*I recommend reading Life at Low Reynolds Number if this interests you.
**Or just in whatever direction it was pointing, I guess.

10 comments:

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    1. https://s-media-cache-ak0.pinimg.com/736x/0e/6c/12/0e6c12e42465076d0afce605098fc4aa.jpg

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  2. This is very interesting. If the strength of the shot manages to cross the cell membrane without destroying it or damaging the organelles it could be used for drug delivery.

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  3. Thank you for sharing this paper. I came across it on reddit and it has been in my mind ever since.
    I'm curious: where does the motivation for this research come from? In my experience, you start with a problem and design an experiment to solve said problem. It seems like that isn't the case here.

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    1. I think the motivation (from the funding agencies' perspective, at least) has to do with drug delivery, where you can transport things across cell membranes by applying ultrasound to specific body parts. This can be used for example to only deliver chemotherapy drugs to affected organs and not to the whole body. I used to work on a project using bubbles for this purpose (I discuss it here: http://klotza.blogspot.com/2015/11/bursting-bubbles-breach-blood-brain.html). However, as useful as a project can be, sometimes you just want to work on something that is cool.

      Generally to figure out why a given group does a given experiment, you can track their publications over a few years to see what direction their work goes in (e.g. here: https://goo.gl/7xaNOp). Looks like a lot of papers about ultrasound-driven micromachines.

      I actually emailed the author of the study after I wrote this article. He referred it to a "sci-fi nanodream."

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    2. Argh how do I make links link.

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    3. Hi, my name is Fernando, i am one of the authors of the article,

      The main motivation to peruse this kind of more "sci-fi concepts" is that there are not really that many tools at the micro/nanoscale, and most of the the tools we use in medicine are not in the same scale, most cells and bacteria are around 1-20 micrometer in size, but catheters are and scalpels are in the macroscale,

      this in some ways is like trying to kill a cell with a hammer!

      We work developing other kind of nanomachines, but they are not powerful enough to try doing some nanosurgery or deep penetration, so the starting problem we wanted to solve was to juice up the power considerably.

      There are a lot of ancient man made nanomaterials (Lycurgus Cup, Mayan blue), but until we developed Electron microscopy and other characterization tools, the field of nanoengineering took off, in some ways,we hope we are helping to do something similar with medicine, by creating these nanotools.

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    4. Here are other cool nanomotor related news if you are interest in the subject

      http://www.cnn.com/2014/02/12/health/nanomotors-cells-science/

      http://www.techtimes.com/articles/29134/20150128/micromotor-drug-delivery-method-gets-tested-in-mouse-for-the-first-time.htm

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    5. Thank you for your responses. This research tells a very interesting story!

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