Honey I shrunk the particles!

CHRIS HATZIS
Eavesdrop on Experts, a podcast about stories of inspiration and insights. It’s where expert types obsess, confess and profess. I’m Chris Hatzis. Lets eavesdrop on experts changing the world - one lecture, one experiment, one interview at a time.

When we think of nanoparticles do we think about the potential advances in medicine with targeted cell-specific treatments? Or do we get all dystopian and become paralysed with anxiety at the thought of uncontrollable invisible entities taking over the world?

I’m leaning towards the former. Thankfully, though, we have somebody like Matt Faria to set our minds at ease.

Matt Faria - now bear with me - postgraduate student, Nanostructured Interfaces and Materials Science Group, Department of Chemical and Biomolecular Engineering, Melbourne School of Engineering at the University of Melbourne. Yes, he works on much smaller things than his descriptor. He chats to Steve Grimwade, with the even smaller descriptor of Eavesdrop on Experts reporter.

STEVE GRIMWADE 
I hear nanoparticles are mentioned around your name. Often they're congregating around you as we speak, I believe. This is part of your research?

MATT FARIA 
Yes, yeah. So I work with - I work in two labs. The Systems Biology Lab is my main lab. They're focused on computational biology - or systems biology, which is a branch of computational biology. They are looking at building computational models to solve problems around biological systems.

The other lab that I work with is the Nanostructured Interfaces and Material Science Lab. They make nanoparticles, make nanomaterials. So I'm kind of at the intersection of that of trying to find models that - computational models and mathematical models that can tell us something about how these new nanoparticles interact with biology. The interesting thing about nanomaterials is that we can engineer and control a vast number of properties and the lab that I'm part of that does that is focused on trying to make new types of therapeutic delivery systems.

So the ideal of nanotherapeutics is that you could design a medicine that goes to one part of your body, perhaps one cell in that part of your body, one type of cells in that part of your body, delivers medicine and changes it, fixes it. So, for instance, if you have cancer, you want to take something that goes directly to the cancer site, delivers the drug that kills the cancer cells and doesn't touch any other cell in your body. That's the ideal.

The reality is a little bit far from that. There's still a lot we don't understand about how they interact with cells, how cells are responding to them and about how our body reacts to nanomedicines. There's lots of - you know, so cancer is one example. Other examples are vaccines, right? So in a vaccine it's a similar problem where you want to go to a specific cell type and then do something to it. So you want to go to the immune cells of interest, you want to introduce something that causes them to respond to whatever you're trying to vaccinate against.

Right? So that's what I see the central problem as being, and then there's many different subproblems that are, of course, huge and extremely relevant to solving real problems.

STEVE GRIMWADE 
I want to get back to that small little thing, the nanoparticle. What on earth is it?

MATT FARIA
So a nanoparticle - I think the textbook definition would be something that is engineered on the nanoscale in at least one dimension. The truth is, is that nano is a little bit of a buzzword for like - everything has - we're all made of atoms, so everything has nanostructure, right? We're all - well, nano - I guess atoms are a little bit smaller than nano, but it's - so it's a little bit of a buzzword, but the idea is controlling properties at the nano level. So - and that turns out to be very interesting for a number of applications. So I was talking about healthcare before, but there's plenty of other applications that are heavily affected by being able to affect things at the nanostructure. So, for instance…

STEVE GRIMWADE
Well, I was going to say, like shrinking a spaceship until it's really, really small and then injecting it into someone's body, yeah?

MATT FARIA
Yes.

STEVE GRIMWADE
That's what we're talking about?

MATT FARIA
Yeah. well, that's the popular opinion. That - I mean, that's the happy opinion. The more troubling one are people who are worried about self-replicating tiny robots, like, destroying the entire earth. Right? The grey goo situation is what it's called. The truth is, is that we're very, very far from both of those things. It's more about understanding how to make - to have any kind of property at a very small scale. So, for instance, one of - the - in the skydiving experiments that I think brought you to my - brought me to your attention, we were looking at a type of material called a MOF, a metal organic framework. And they're very interesting, because they're have - they're very, very porous. Well, they're interesting for a number of reasons, but one of the reasons is that they're incredibly porous. An incredibly porous thing. So think of a sponge. Now, if you can - if you compare a sponge to a block of whatever a sponge is made of that isn't spongey - no. That's not a very good analogy.

A sponge to - compare a sponge to the same thing, but it's wood, instead of a sponge. The wood doesn't absorb water very well, right? It's terrible at it. You take a block of wood. You put it on a puddle, it's not going to do a good job at all. I mean, I've never done it, but I'm very certain of that. Now, you take a sponge and it's great. It sucks up tons of water and it can hold it. That's very analogous to what happens with these MOFs, is that they can absorb a tremendous - because they have so many pores and it's at a degree of magnitude greater than a sponge, because the pores are not only on the physical macroscopic level, they're on a nano level. So they're among the most porous materials that there are that we know of. So they can absorb all kinds of things, which makes them very useful for a lot of chemical applications.

STEVE GRIMWADE
This is where I come to that point where science equals freak out for me. Like - and I read that basically a - I mean, I did read about these nano sized synthetic structures, but they're, as you say, riddled with molecular holes, but their huge surface areas mean that a teaspoon of MOF can have the same surface area as a football field. It begins to freak me out just a little bit. It's kind of like - yeah, I'll - how do you explain that further? Are you saying they're porous, they have holes? How can something that small have such great area?

MATT FARIA
Well, I think it's maybe challenging our intuitions about what surface area means a little bit, so I think for most of the things we're used to, the surface area of something not being - so the surface area of a sponge you could consider being - it's much greater than the actual surface area of the equivalent block of wood, because of the holes, right? So holes essentially add surface area without taking away - without needing more mass. In fact, they need even less mass. Right? By taking something out, you've added to the surface area and you haven't - and you require less material to make that thing. Right? So that's how you get massive, massive surface areas without needing a ton of material.

So, right, these are so holey essentially that there's very, very little material, but they have so much area available to them.

STEVE GRIMWADE
If you continue to get smaller and smaller and are able to manipulate the surface area at a tiny level, you're exponentially increasing the size or the surface area as you go up, yes?

MATT FARIA
Sorry. I'm not quite sure that I understand that. Sorry. So…

STEVE GRIMWADE
So let's turn to my silly question…

MATT FARIA
Yep.

STEVE GRIMWADE
…because this is related.

MATT FARIA
Yep.

STEVE GRIMWADE
Bear with me.

MATT FARIA
Yep.

STEVE GRIMWADE
I try and think of the - let's say, the coast, the coastline. I look at a map every now and then and I see the coast.

MATT FARIA
Yep.

STEVE GRIMWADE
I see this line that waves, that is scratchy. I can get closer and I get more detail as to what the actual line means and the length and area around that line. So from a top level, as the crow flies, as I might think, the coast is 1000 kilometres long.

MATT FARIA
Yep.

STEVE GRIMWADE
But as I go down, the coastline is actually maybe twice as long as that, because it's actually going from side to side. The more and more I zoom in it and get closer to the small intricate wiggles on that line, the length of that absolute line gets bigger and bigger. Is that the same case with nano particles? The smaller you get and the more you can actually open up that space, the larger the area is?

MATT FARIA
Yeah. I think that's a good analogy. I'm thinking about it now and I think that maybe with lines, it might break - I think it's a little bit different in three dimensions than in two or in one. I think that there are some - I think the way that it - it's more of a mathematical question at that point. I think that the way it works is with - you can have a limit in two dimensions that isn't infinite. I have to think about it. In any case, I think that is a good analogy. So it - but - so the…

STEVE GRIMWADE
Matt's being very kind. Matt's being very kind right now. I…

MATT FARIA
No. I'm thinking about it. No. I do think it's a good analogy. I just - I feel like maybe in three dimensions things work a little bit differently in terms of that, but, of course - so the difference is in - from your analogy is that what you're describing is how things really are, right? So you're going from an approximation that we use for a map to how things really are. Now, we're going from how things are really are to a different way that things really are, right? So if you can - again, if you go - use the sponge analogy, which I like, if you look at the block of wood, the block of wood really has a surface area that's a lot less than a sponge, right? There's a lot less area involved. Why is surface area important? That's another thing I should probably address. So a lot of chemical reactions, they are faster or more efficient when you have a larger surface area. So there's a lot of interest in having materials that have a high surface area.

Traditionally one of the ways that we got surface area was really to make holes in things and that makes the reactions faster, because there's just more - there's - you can think of it as there being more material available for reaction at the same time, so - and there is, of course, a limit of how much surface area a material can have. So I - graphene is a 2D material essentially. It's one sheet of atoms. So you can't have more surface area than that, because if you take away that atom - you put holes in that, there's no more atom space, right? There is a limit in terms of how little surface area you can have. I think MOFs get close. I should probably check for a reference on that.

[Laughter]

CHRIS HATZIS
I hope you’re getting all this. Matt Faria and his colleagues certainly talk the talk, but they also walk the walk. He and several of his post-grad colleagues undertook experiments while actually skydiving from 14,000 feet above Melbourne. The intention was to release metal and organic particles into a solution using a syringe where they would mix and form crystals in the temporary low-gravity generated by free-falling. That's right, they jumped out of planes with syringes.

STEVE GRIMWADE
Why on earth were you and three of your scientific buddies falling at 9.8 metres per second squared doing a scientific experiment?

MATT FARIA
So we were looking at how the crystals of these MOF structures form.

STEVE GRIMWADE
Can we clear here: you jumped out of a plane for science.

MATT FARIA
That's correct. It's also been described as a leap of faith [laughs]. We - so it wasn't our first step. So we wanted to look at how low gravity impacted the crystal formation and there was some studies back, way back when, looking at crystal formation that showed that lower gravity seems to result in higher - in larger crystals. So first we thought, oh, how can we get this to have low gravity? How can we - so high gravity. So varying gravity is easy if you want to get heavier. The way you do that is you spin something. So spinning something makes it feel - makes it seems like it's feeling a force that's much greater than gravity in the direction away from the middle of the spin.

STEVE GRIMWADE
Hence, the Gravitron.

MATT FARIA
Yes. Exactly. The classic carnival ride [laughs], which I actually loved as a kid. That was my favourite ride. It felt like you were heavier. It felt like you were getting stronger.

STEVE GRIMWADE
I was horribly sick every time I rode it, so it was only twice.

MATT FARIA
It made you really appreciate the gravity of Earth, that you were generally exposed to, for sure. But - so it's easy to get higher gravity, but lower gravity is much harder. You have to be falling - you have to be accelerating essentially without - you have to be accelerating without having reached terminal velocity. So we thought, well - so the first thing we did was we chucked it off a tall building to see - and that gives a few seconds of low gravity, low G. Then - but it's not very much, so you could see an effect, but it was quite small, so it's hard to tell if it's maybe you're just seeing what you want to see; maybe it's not - you just want - you want a bigger effect to be sure that you're seeing what you think you're seeing. So then we thought, oh, maybe we could use drones or rockets, just get it up high, but, of course, recovery is going to be a bit of an issue, plus I'm pretty sure you need permits for those things and it's not like it's inexpensive to buy a drone.

The classic way that this was investigated was on the Space Station, which is also way out of budget [laughs]. There was no way we were going to get time on the Space Station or be able to pay for it, even if we could get time. And the other way this is done is through these fancy parabolic flights where an aeroplane flies in a special up and down orbit and a bit snakelike, parabolic, it simulates low G as well; also totally not possible for us.

So we thought, oh, well, we'll jump out of a plane and see if - we'll be experiencing it, so if we're carrying something, it will be experiencing the same forces that we are. So we did it. It was a great - it was a collaboration with a couple of people from CSIRO. Joseph Richardson was the lead guy at CSIRO on this and a few of us from the University of Melbourne as well.

STEVE GRIMWADE
I love - having read about this, the jumpers had all be nervous about parachuting. This is a quote: "but like true scientists, the fear of the experiment backfiring was greater than the fear of jumping out of the plane," which I kind of love. Except, I - that moment that you jump, I expect that actually trying to remember to inject the fluid or the metal into the fluid or whatever it was…

MATT FARIA
Yep.

STEVE GRIMWADE
…that would have been the freak out thing. I've got to jump and remember something. I - yeah.

MATT FARIA
Yeah.

STEVE GRIMWADE
[I couldn't remember] my name. I'm interested in this idea that nanoparticles are engineered. So nanoparticles are not organic or natural to the world?

MATT FARIA
Well - so I think we should all be careful when we use the terms natural or not natural to the world, but I think that they've become kind of loaded terms and people have started to believe that somehow something being natural is better in some way or another. They can be natural - they can be made out of natural materials and there's plenty of people doing that. It turns out the natural materials are frequently cheaper or easier to obtain, which is why that's an advantage. But I think, let's be clear, something being - so, in my opinion, and I'm sure people would debate me about this, but I think something being natural is of no advantage particularly. But you're right, we typically engineer them. So we purposely create properties that they have. Well, we try to make them have specific properties of interest for us.

I think one of the problems with the nature versus - the natural versus non-natural thing - and one of the things that drives it is that we want things to be simpler than they are. I think most people want the world to be simpler maybe than it is. I think humans have a very deep-seated need for simplicity, which is good. We simplify things. It makes them - it makes it possible for us to understand. I mean, the truth is is that most of the world is so complicated it requires a lot of work to understand even an area of it, right? This is across science, across everything. It's not just science that's complicated. Any human endeavour is. For nature - for natural things, I think there's a feeling that it's somehow less complicated. So you see that a non-natural - and I'm putting - I'm using air quotes as I say this - a non-natural thing is - has a lot of complicated looking things in it and people - oh, it's made of chemicals.

Well, everything is chemicals. So - and I think the idea is that, oh, but just an apple doesn't have very much in it. It's just an apple, but the apple has thousands, if not millions of different components and chemicals. If you could list out everything that was in a particular natural thing, you would realise it was just as complicated, if not much more. In most of the cases, it is much more complicated. So this idea that something is natural, I think, comes from the idea that we want things to be simple and easy to understand.

STEVE GRIMWADE
So the man that says that natural things shouldn't be number 1 is also the man that is creating the killer robots, but that's okay.

MATT FARIA
[Laughs]

STEVE GRIMWADE
We'll deal with that. When we speak about directing a nanoparticle or when you speak about directing a nanoparticle to provide a certain function, how can you be assured it does what you want it to do?

MATT FARIA
So that is the question. So it's much more likely, in my experience, that it does nothing than it does what you want it to do. I think that the killer robot situation is people are worried about it doing something that you didn't expect it to do. So first off, not only would it have to not to do something you expect it to do, it would have to do something much more complicated and much more interesting than you would have ever designed or expected it to do, which is not - it's not really going to happen, something like that.

Something doing - something reacting in a way that you didn't expect that is undesirable, that's very common, right? So it doesn't do what you want or maybe it does something else. Very commonly you might design something, hope that it does a specific thing to a cell and then unfortunately the cell doesn't like the material that you're using and the cell can die. Yeah. So that's common.

And knowing whether or not it's going to do the thing that you want it to do is the central question in the science, right? So we try with cell studies, in vitro studies and then we gradually - when we have something that we think is promising we go to in vivo, so use rats or mice. Some people use things like zebra fish to see if things will happen in animals, because of course this - all of a sudden, the system is a lot more complex than cells on a plate. Then eventually, just like any other therapeutic, you move into human trials to make sure that what you're doing is safe before you try and introduce it to the broader public.

STEVE GRIMWADE
When we speak about nanoparticles being these tiny little objects and they're porous, I mean, we're using them as - sorry - you're using them as a delivery device, yes?

MATT FARIA
Yes. Well - so my research is more about finding models of how they're interacting with cells, but, yes, we're essentially - we're very - so our group is very often interested in using them as a delivery system for drugs. Now, sometimes we do that by forming the particle out of the drug of interest, right? So you could imagine that you could somehow make sort of a more concentrated form, that's a bunch of the drugs stuck together, and then once the cell takes it up, it gets - it disassociates and then there's a big amount of drug all at once in that cell. Or you could think it more as an envelope, so you have the drug, you put it inside and then once it gets in, it opens up and releases the drug. Now, of course, the central - one of the big problems is making sure it opens up and lets the drug go that you're trying to deliver and making sure it only opens up within the cell and making sure it gets to the cell.

In the case of the envelope, making sure you have the address and it's actually getting to the cell and the cell's doing something with it. That's one of the - those are the big problems in the field of nanotherapeutics; some of the big problems.

STEVE GRIMWADE
When we talk about your role in nanotherapeutics, I mean, let's say we've met at a barbecue and you've met some rube like me who actually says, what is it that you do? What is your role to play? When you talk about computational modelling, what is your role to play in delivering nanoparticles to parts of our body?

MATT FARIA
So I think that the field that I'm in - one of the problems that I'm very passionate about is that we don't do a very good job of comparing new particles to existing particles. So - and part of the reason is that we don't have very good ways to do that. So people make very interesting new things. They show them doing very interesting new things, but it can be quite difficult to know which one's working better or how it's working better. One of the reasons for that is a lot of the methods that we use is a little bit qualitative. So what I mean by that is that it's hard to get a hard number on how well something's doing, how well it's delivering the drug. Part of that is that you need to carefully think about what it means to be doing something well. You define what doing something well or what better means. Part of the reason is just historically people have - are used to designing new systems and comparing them against the - a control of their choice.

So that's something I'm very passionate about, is finding ways to compare particles. Part of that is defining what comparing means or - and not just particles. There's different - people say particles, capsules. I use the term particles to mean sort of any nanotherapeutic. But finding ways to compare them and I feel that by finding a way to compare them, that points the way to how to make better ones, right? Because if you know it's working, then you know what you should work on, right, what you can improve.

STEVE GRIMWADE
So your modelling is modelling of big data that's come out of experiments as to the success of the particle itself?

MATT FARIA
It's not big data. It's more low to medium data. I would love to work with big data. I would love to have a ton and ton of experiments, but the truth is is that we just don't have that volume of data coming out. Usually to get big data you need massive investigations that require millions and millions of dollars and automated or somehow systematic ways of investigating things.

STEVE GRIMWADE
Four guys jumping out of a plane wasn't the same thing?

MATT FARIA
Not quite [laughs]. We're not really getting there. It's more taking - the scale of data that we're getting on is individual experiments. So it's not millions and millions and millions of experiments, which is what people would conventionally mean when they say big data. But there's still plenty of very interesting challenges in figuring out how to use the data that we do have and maximising its value.

STEVE GRIMWADE
What's the greatest personal challenge or scientific challenge for you right now?

MATT FARIA
So I'm from a very computational background and as I've been here I've been trying to learn more about the experimental sides and doing more experimental things, clearly, as the skydiving experiment shows. So for me, learning how to do a lot of these in the lab type experiments has been a big challenge. Of course, I'm also learning stuff, totally - new areas of mathematics to myself, which is always hard and always fun, but, yeah, I think the learning the experimental side and just really coming to terms with a lot of the techniques that we use and figuring out the assumptions behind them, because almost everything that we measure, almost everything that we do in science or really anything that people do, there's a lot of assumptions underlying any particular piece of data or information that we come up with and understanding those makes you able to react and plan appropriately.

STEVE GRIMWADE
Sometimes I think of lab scientists as being people who have got to be incredibly calm and resolved to sit there and conduct an experiment over time and over time and over time and doing it again and again and again. Is there something of a personal challenge to you and the way you work?

MATT FARIA
Yeah, I think there's definitely a discipline aspect of it, where you have to separate your own personal feelings from what you want and how you want an experiment to go from what you're actually doing, right? So you need to remove as much as possible any kind of bias that you have. So you want to - you don't want to be doing something different because you want a particular outcome, right? So there is that - there's a sort of a discipline, a separation of stepping back and analysing things clearly without involving your own personal bias. I think that's a very, very important skill for all scientists to have. Really, I mean, I guess, everyone to have, right? You should be trying to think rationally about things, even if they're not science things, right? You come home and your house is robbed. You should - you don't want your house to be robbed, but you should analyse the situation and realise what's going on. Right? Maybe I should change my locks.
That's not a very good example [laughs] at all.

STEVE GRIMWADE
I think we should give you a PhD right now, just on that.

MATT FARIA
[Laughs]

STEVE GRIMWADE
Is there something about conversion science that is now? Is this a new field is this - have we just changed our perspective on science?

MATT FARIA
There's a lot of interest in doing interdisciplinary or convergent things. I think part of the reason for that is that people see that there's a lot of opportunity to take skills or interest in one area and you go to a new area and then do new and exciting things in that new area, because you have a very different perspective. That's the dream of it, right? I certainly believe that as well. Like, that's kind of what I've been playing at really is I think that because I have this computational background, that going into this - the nano side of things, I can offer a perspective that's a little bit different, that's - I'm not better in any way, but just different from what other people have done and then by working with other people that have different perspectives, we can do better work than we would have alone.

The problem with that is that moving into a totally new area that you don't know anything has the result that there's a lot of work to learn a new area and there's also the possibility that you'll misunderstand something, which is why it's very important to work with good people, I think; work with people who are experts and make sure that you're talking and communicating and having a team. That's why interdisciplinary research, I think, has become a big thing, because people see these opportunities and they want to do something about them.

STEVE GRIMWADE
Finally, what would you like to think about when we think about very small things?

MATT FARIA
About nanomaterials? Everything is nanomaterials, I think. I have an uncle who's very worried about the grey goo situation of something getting in and causing problems. That's not going to happen. That's - there's not a reason to be - there's - obviously, we should always be worried about problems that could arise in any discipline, any field, any science, but that concern is coming from science fiction, right? We're worried about a situation where tiny robots - we're not making tiny robots. We're making materials - things that are much more passive. There are few very small groups that are making something that can move just a little bit, maybe it can open and close an arm, but it's not a…

STEVE GRIMWADE
Like a tiny killer robot?

MATT FARIA
[Laughs]

STEVE GRIMWADE
You had to see Matt's hands there, clipping together like a crab, a very dangerous crab.

MATT FARIA
It's not killer and it's stretching it to call it a robot. I think a lot of people would like it to be a robot, right? We would like to - I mean, I would love to have a tiny robot that could do amazing things, right, but we can't even make a thing that passively opens and closes something, right? It's - that's very challenging. So I think the take home message is that this is an area that has tremendous promise and, to be honest, not a lot of downside, it seems. We're really engineering things and controlling the creation of new materials in a way that hasn't ever really been done in human history and I think that that's incredibly exciting. I think that there's so much potential and so much promise that nanomaterials have for the world.

STEVE GRIMWADE
A perfect end. Matt, thanks very much for joining us.

MATT FARIA
Thank you very much for having me.

CHRIS HATZIS
Thanks to Matt Faria from the Melbourne School of Engineering, University of Melbourne, for his insights into very little things. And thanks to our reporter Steve Grimwade.

Eavesdrop on Experts - stories of inspiration and insights - was made possible by the University of Melbourne. This episode was recorded on Aug 12, 2016. You’ll find a full transcript on the Pursuit website. Audio engineering by Arch Cuthbertson. Co-production by Claudia Hooper.

Still curious about the world? Visit our sister podcast Up Close which features in-depth and long-form conversations with seasoned researchers across many fields. Don't forget to check out the rest of the amazing content on the Pursuit website. And if you're listening to this on iTunes, why not drop us a little review? I’m Chris Hatzis, producer and editor. Join us again next time for another Eavesdrop on Experts.