Why's Graphene Great?

Ben -   Alzheimer's disease is a common cause of cognitive decline amongst elderly people.  An estimated one person in every five over the age of 80 is affected, and develops a range of symptoms including memory loss.  The cause of the disease is a build up in the brain of a protein called beta amyloid which damages nerve cells, but why does this happen?  Chris Smith spoke to Randy Bateman, a neurologist at Washington University in St. Louis...

Randy -   So, there was a basic question which we began to consider about four or five years ago, and the question was, what causes Alzheimer's disease?  And that question has been asked for a long while, but this was more directed at the current thinking about what causes Alzheimer's disease in relationship to what's known scientifically.  There's an amyloid hypothesis which specifies that build up of a protein called amyloid beta, which is normally made by our brains, that this increase in this protein in the brain leads to damage that causes the symptoms of Alzheimer's disease.  Now the basic question that we were asking was in Alzheimer's disease, does the amyloid beta build up there because it's being produced too much, or made too much in the brain, or is it there because once made, the brain has a problem clearing it away?  Some of the basic information about amyloid beta is that the brain normally makes this, the neurons or the thinking cells of the brain normally produce this amyloid beta protein in the brain, and it's normally cleared away and it doesn't build up into very high amounts.  But what we also know is that in patients that have Alzheimer's disease, their brains are filled and littered with this substance up to 100 to 1,000 fold normal levels.  So it builds up at very high levels and this is thought to be toxic to the brain and cause damage, ultimately culminating in dementia of the Alzheimer's type.

Micrograph showing amyloid beta (brown) in senile plaques of the cerebral cortex (upper left of image) and cerebral blood vessels (right of image) with immunostaining. © Nephron @ Wikipedia

Chris -   So you've got two problems there.  One of them is, that there's too much being produced or is it that it's not being dispensed with, dealt with by the brain as it is in a healthy person's brain?  So how can you try and disentangle those two?

Randy -   That was the challenge and that's where the technique was actually developed to answer this question.  Essentially, the way to do this is to label the proteins as they're being made so you can track them.  And then once a protein is labelled then you can track how fast it's being produced, how quickly it's being cleared away.  The first publication of the method itself was in 2006 where we reported what normally happens in young healthy people with amyloid beta in the brains in terms of its production and its clearance rate.  And often, I use an analogy that this labelling system - imagine that you have a single water and you have a faucet on with water coming into the sink, and you have a drain that's draining the sink at the same time.  If you just look at the sink and you don't look at the faucet or the drain, you only see a level of water in the sink, and that's what we normally measure when we sample the fluid that surrounds the brain.  We measure how much of that amyloid beta protein, or the water level, is there.  One way to track how fast it's coming in is, you can imagine that if you dyed the water coming out of the faucet a certain colour, say blue, that the water in the sink would turn bluer and bluer over time, the more blue water came into it.  And if you watch over time, how much of that water has been labelled with that - in this case, a colour label.  In the case of the amyloid beta protein, we're using a label that's just slightly heavier for the protein then we can estimate how fast the production or the rate of water coming in to the sink is.  And by the same token, if you stop labelling and then you watch the water as it's cleared away, new fresh clear water comes in and the blue is cleared away, you then have an estimation of how fast the sink is draining that water.  And so, this is what we do.  We take a label that incorporates into the protein, it's an amino acid which is a building block of proteins which our body normally makes, and it's slightly heavier than normal amino acids.  We infuse that into the bloodstream of the person and all the proteins that person is making can be tagged with this label, marking it as newly made.  Then we sample over time the fluid that surrounds the brain, it's called cerebrospinal fluid and we watch the appearance of this newly labelled amyloid beta protein, and then we stop labelling and we watch how that labelled amyloid beta is cleared away over time.

Chris -   And you did this in healthy people and you did this presumably in a group of Alzheimer's patients to compare the rate of production and removal of the beta amyloid in the brains of both?

Randy -   Exactly.  And so, in this study, what we did is we compared 12 people who have Alzheimer's disease to 12 people who don't have Alzheimer's disease, but are about the same age, and we compared the two to find that there was a significant decrease in the clearance of amyloid beta.  But on average, there was no significant change in the production rate of amyloid beta.

Chris -   The only problem with this study is that it tells you about people who've already been diagnosed and it would be very interesting to wind the clock back in their lives, or look upstream - look in people who are going to develop Alzheimer's disease or just look in people who are viewed as healthy, and then follow them up, and then see who does get Alzheimer's disease and see if there's anything lurking upstream in those people.

Alois Alzheimer

Randy -   That's exactly right.  That's an insightful point and one which we're planning on doing as the study goes on and participants come in to the study.  We're in fact following each individual over time clinically so that the cognitively normal people that have done this study, they don't all have exactly the same production in clearance rate.  Some are faster and some are slower and so, the basic question is, are the people who have slightly impaired or impaired clearance but are cognitively normal now, are those people with increased risk of getting the disease at some point in the future?

Chris -   How do you know that the people who have got Alzheimer's disease now haven't just got a reduced clearance because the disease has in some way damaged the brain, and the reduction of nerve cells that is associated with Alzheimer's disease has just impaired their ability to get rid of it? And that's why you're seeing that;  As a consequence of the disease process, not so much as a consequence actually of having caused the disease.

Randy -   With its current data, there's no way to distinguish between those two possibilities.  And although we may hypothesise that for example, decreased clearance may lead to increased levels of amyloid beta and plaques, that's not demonstrated in this particular study.  That's the point of doing the ongoing research, to determine if that's correct or not.

Ben -   Randy Bateman, a neurologist who's looking for a way to knockout Alzheimer's disease on the head.  He was talking to Chris Smith and has published that work this week in the journal Science.

Observations made by the Keck telescope in Hawaii have confirmed a fourth planet orbiting a nearby star but have thrown current theories of planetary formation into doubt.

Publishing in the journal Nature this week Christian Marois, from the Herzberg Institute of Astrophysics in Canada, and colleagues in the United States analysed near infra-red images of the star HR 8799 and found a new exoplanet to add to the three previously discovered.  These planets have particular properties that make this sort of imaging possible:  They're very massive, the new one is somewhere between 7 and 10 times the mass of Jupiter; they're a long way from the star itself, over 25 times the distance between the Sun and the Earth; and they're relatively young, less than 100 million years.  Younger planets are still hot from their creation, which makes them glow brightly in these frequencies.

Finding new planets is always fascinating in itself but the really interesting thing about this system is that it doesn't fit with current models of planetary formation.  There are 2 models that describe the formation of giant planets like this. There's the core accretion model, where small bits of rock collide and gradually clump together until the planet has enough mass and, therefore, gravity to hold on to an atmosphere. Then there's the disc instability or the gravitational collapse model, where variations in the disc of material around the star, the protoplanetary disc or proplyd, will condense out into balls of gas that gradually collect dusty matter at the core.

In the case of the HR 8799 system, the innermost planet could have formed by core-accretion, but those further out would need far longer; in fact, more than the age of the star itself.  However, If we look to the disc instability model, the protoplanetary disc would not have been in the right condition to allow the innermost planet to form when it did.

So how did these planets get there?  Right now, we can't be sure.  The authors say that "a hybrid process with different planets forming through different mechanisms cannot be ruled out, but seems unlikely with the similar masses and dynamical properties of the four planets."  The other option is that the planets formed elsewhere and then moved into their current locations, but until we find more systems like this one we simply don't have enough information to make a decision.  But, with exoplanets being discovered at an astounding rate, we may find more of these planetary families soon.

Ben -   In this week's episode of Planet Earth we're looking at one of Britain's best loved mammals, the elusive red squirrel.  They've been under threat from a squirrel pox for a number of years and in 2008, the virus decimated numbers of one of the few remaining reserves at Formby, near Liverpool.  Sue Nelson visited the reserve to find out more about a four year scientific project, aimed at understanding squirrel immunity and improving red squirrel conservation.  There, she met Julian Chantrey from the University of Liverpool School of Veterinary Sciences and Researcher Tim Dale, who was carrying a bunch of very long wire cages.

Tim -   We've got four of the traps we use for the squirrels.  They are in fact, mink traps but they generally use the same principle.

Sue -   So they're basically just a long rectangular wire cage, aren't they?

Tim -   That's right.  With a pressure plate in the back that has a trigger that allows the door to spring shut when that pressure plate goes down.  We usually bait the back of the trap with peanuts, maize and black sunflower seeds are quite favourable.

Sue -   Where do these go?

Tim -   We've got two tactics for catching the squirrels.  One goes on the floor and the other one goes on the tree trunk vertically.  They tend to work better for red squirrels whereas the ground traps work better for greys.

Sue -   And once you've trapped the squirrels, what do you do then?

Tim -   The first thing to do - because our first concern is the welfare of the squirrels - is just cover the trap.  It tends to calm them down, they don't feel as frightened then and then we'll get all set up with this equipment and sample the squirrels.

Sue -   Julian, once you've got a sample of blood from a red squirrel, what are you looking for?

Julian -   We're looking for antibodies to the squirrel pox virus which shows that these squirrels have survived the epidemic back in 2008 and now have antibodies, a degree of immunity to this virus.

Sue -   And so far Tim, what have you found?

Tim -   We've found a small number of the population that do seem to have antibodies to the pox virus, which is certainly promising news because it does say that vaccine might be a viable option.  In terms of numbers, it is a very, very small percentage and so, it isn't the answer to the red/grey squirrel disease problem.

Sue -   When you say red/grey squirrel disease problem, is this because a grey squirrel's immune to this virus?

Tim -   Effectively, yes.  It seems that the grey squirrels brought the squirrel pox with them, when they came over from America.  And because the grey squirrel has evolved with that virus for a long time, it doesn't cause any clinical disease.  So, they're able to carry on a normal life without it affecting them.

Sue -   It sounds as though this is potentially good news for the red squirrel population Julian, but I do sense, particularly from Tim, a touch of caution there.

Julian -   Yes, you're perfectly right.  You've got to be a bit cautious when you interpret these blood results.  It's good that some of the squirrels have encountered the virus and survived, and now have antibody, but that doesn't necessarily mean that they are immune.  All we can do is monitor the population as we are trying to do, making sure that their body conditions, their weight, their fat reserves are up to standard for them to survive through the forthcoming season.  If another outbreak occurs, you'd hope that these squirrels will be the ones that survive and their offspring.  But we just don't know without monitoring the group.

Sue -   Tim Dale, you've got a brown cardboard box here at our feet.  What's inside?

Tim -   What we've got here is one of the red squirrels that we've chipped and sampled.  When I say chip, that's an identichip so we can identify each individual squirrel that we've caught in the past and we're about to release it after its experience with us.

Sue -   Okay.  All right, are they quite shy creatures?

Tim -   Definitely.  We'll have to be reasonably quiet now...

Sue -   Okay, you're opening the box.  It's got lots of dried hay and straw in there, gently moving it.  Oh my goodness!  It is small, isn't it?  There it went, up a tree.  That gave me quite a fright there.  It suddenly scarpers, doesn't it?  Yes.  Wow!

Tim -   Yes, they don't hang around.  They're fast little creatures.

Ben -   Tim Dale and Julian Chantrey from the University of Liverpool, celebrating the release of a healthy red squirrel with Sue Nelson. 

Ben -   Using sticky tape is just one way of getting some graphene and it is not likely to be much use, as Andrea was saying, for Samsung making television screens.  Exactly how graphene is made may well depend on what it is that you intend to use it for. So to explain more, we're joined by Dr.  Karl Coleman.  He's from the Department of Chemistry at Durham University.  Karl, thank you ever so much for joining us.

Karl -   Pleasure.

Ben -   How do we make graphene in larger quantities?  Sticky tape is all well and good for doing physics on graphene but how do we make it in bigger quantities, in bulk?

Karl -   Yes.  I mean, as you can imagine using sticky tape is a bit labour intensive if you wanted a large volume of the material.  There are a number of ways to make it and we categorise those I guess into two camps. A top down approach, the sticky tape method would be a top down, so that's starting from graphite to the thin layers and then a bottom up approach.  So top down, you can actually use a chemical method to really replace the using of the sticky tape.  So there are people out there who basically take graphite and they do a rapid thermal expansion in the presence of an oxidising acid such as sulphuric acid.  That breaks away, breaks apart those layers, and that also gives you the single sheets.  So that's another way of producing it and of course, you can sort of imagine that being a little bit more scalable.

Ben -   So effectively, by superheating a block of graphite, rather than peeling layers off, you're causing the layers to break apart spontaneously.

Karl -   Exactly.  So, just give it a big kick in energy, through oxidising acid, split those layers apart and then you'll get some single sheets.  It's a little bit more difficult to separate of course if you have lots of graphitic impurities in there as well.  So there's lots of processing that's necessary, so lots of centrifugation, dispersing in solvents.  There are other hurdles to overcome using that method.  If you go for more of the bottom up approaches, which you can potentially see as more scalable, then we are talking more or so CVD,  that's chemical vapour deposition approach.  And there, you can actually decompose pretty much any hydrocarbon containing gas that you like; methane, ethane, propane, et cetera.  People tend to prefer methane, but you can use a mixture of methane to hydrogen, and literally flow it over the top of a metal catalyst, and what the researchers in graphene like to do at the moment is use nickel or copper - copper being perhaps the most prominent.  And you can grow a graphene film by the decomposition of the methane hydrogen on top of the copper, and I believe that's what Samsung are using, the Korean scientists, to grow very large tens of centimetre graphene films.  So that's a little bit more scalable and easy to use than sticky tape.

Ben -   And rather than using something that's becoming relatively rare as it gets used too much, the indium that we are seeing in current screens, using copper which is quite common and still relatively cheap, and something like methane or any hydrocarbon, of which the prices are slowly going up, but we do still have plenty.

Karl -   We do still have plenty.  I mean, that's another issue about using fossil fuels, I guess.  But yes, we do have plenty of natural gas kicking around.  So using natural gas, you need hydrogen in there, you need a reducing atmosphere, and that's the key.  And copper is perhaps the most useful because the solubility of carbon in copper is quite low.  This is one of the reasons why you tend to grow only one or perhaps two layers on top of the copper substrate.  It's not without its own difficulties, of course, because you'd have to remove the copper because the whole idea of replacing indium tin oxide, ITO of course, is to have a transparent electrode and copper isn't transparent, so you'd need to remove that copper and so it's usually an etch to remove the copper and then you can transfer the graphene film onto your plastic to assemble your plastic electronics.

Ben -   So, there are still fairly complicated methods that we have to create it.  Is there one great way of doing it and several not so good ways or do they each have advantages over the other, depending on what product you actually want?

Karl -   Yeah.  It really depends on what you want to do and that will really dictate what method you want to use.  The micromechanical methods, i.e. the scotch tape, sticky tape is very good for physicists, they need a small little chunk of the graphene, or a small sheet and they can study it, measure it, and do lots of different things.  The display is obviously a little bit different so you are going to need something like a large piece of copper foil to grow your film on, but then you have to transfer it from that copper onto your plastic and remove the copper.  So yeah, I mean if you want the ITO replacement, that would be the method you would use.  But if you were to use it in say, composite materials, there's a lot of work going on at the moment about using graphene in composites so as a nanofiller.  Then of course, neither of those methods would be suitable and so we need another method to make the graphene.  There are variations on CVD to do that, so where you don't actually use a copper foil, you use other metal catalysts or you use a spray pyrolysis type approach to get basically graphene powder that you would then be able to disperse in your polymer matrix to make your composite material.  So it does really depend on what you want to do with it.

Ben -   Composites are relatively new, we haven't been using them for that long, but they've made huge waves in the aerospace industry.  We've had a question from David Whalley who got in touch via Twitter.  He wants to know if graphene is likely to be used in spacecrafts.  I would imagine it's composites we'd be looking at there.

Karl -   There definitely would be composites.  On its own, it would be difficult to use in aerospace.  So, it would be incorporated into some sort of polymer matrix.  So yes, there's lots of carbon based nanofillers.  So of course, we are all familiar with carbon fibre which is perhaps the most common one that's out there at the moment, and carbon nanotubes which have been making some headway, but of course, there are some problems associated with that.  I think really, people have been looking there at these one dimensional, high aspect ratio materials as fillers.  And then graphene has come along and challenged carbon nanotubes in the prospect of being a carbon fibre replacement.  So, you'd have to get it into some sort of polymer matrix, so a resin or a thermo plastic, and really, the difference I guess with the nanofillers is you require much less of the nanofillers compared to say, carbon fibre.  And so, that opens up a whole new game for the guys dealing in composites, and how they process the materials, how they mould complex shapes, et cetera.  So it opens up new doors perhaps that you wouldn't get with carbon fibre, but you'd still get the high strength:weight, at a ratio that you would need from a composite material.

Dave - I'll start off with diamond and graphite, the large scale structures - three dimensional structures. Graphite and diamond have got incredibly different structures even though they're both just made out of carbon atoms. In graphite, you've got a whole series of planes made up of hexagonally arranged carbon atoms, all tesselating together with an atom where all the hexagons meet. Whereas diamond is this tetrahedral structure with each carbon atom being bonded very strongly to four others at the corners of a tetrahedral pyramid or triangular based pyramid. This is the reason why diamond is incredibly strong. It bonds in every possible direction whereas graphite is very strongly bonded inside the plains, but very weakly between them, so they slide across each other, and it's quite a good lubricant.

Ben - So, if you wanted to convert between the two, you actually have to break and then remake quite a lot of bonds, so it must be quite an intensive process?

Dave - Yes, that's right and diamond is only actually stable under very, very high pressures. The stable form of carbon at room temperature and pressure is graphite. So, in order to convert graphene or graphite into diamond, for a start, you'd have to use incredibly high pressures. And also, diamond is an intrinsically three dimensional structure so a single plain of it, equivalent of graphene, wouldn't really make sense. It will be incredibly unstable and it would immediately convert back into something like graphene or just fall apart.

Ben - So, graphene itself is not a better source for making something like a flat sheet of diamond. You may as well just use any old carbon kicking about.

Dave - Yeah, that's right and it's probably a lot easier to get it from some kind of gas like methane or something in a CVD process like they've talked about earlier.

James - So, if you have a bucky ball, that is considered zero dimensional. Even though it does have dimension - it doesn't reach out in different directions. If you have a nanotube, that's considered one-dimensional. It is extending in one direction and in the other direction, it's only about a nanometre wide. But fundamentally, it's considered one-dimensional whereas graphene is like a sheet, it's 2-dimensional. The fullerenes turned out in high compressive operations, they would actually tend to decompose in many structures and that's why they turned out not to be very good lubricants. Whether graphene is going to be a great lubricant, I don't know. Graphite, a 3-dimensional structure, is a good lubricant because it's able to shear off lots and lots of sheets of graphene which is really what makes it slippery.

Ben - So, the sheets themselves slide past each other, which is also why they make good pencil lead.

James - Correct, and whether a sheet of graphene would make a good lubricant, I'd rather doubt it in the sense that it does not have that ability to slide past itself. It is only one atom thick.