Nanotechnology: Tiny science, huge possibilities

Ferdouse Akhter  00:05

Hi and welcome to health in a handbasket. I'm your host, Ferdouse, Marketing and Community Manager at UCL's Institute of Healthcare Engineering. In this podcast, we sit down with an expert to learn about all the wonderful and impactful things happening in Healthcare Engineering. Today we're picking out the topic of nanotechnology. Nano means very small or microscopic. So how are we using this to improve our lives? Well, I'm here with Alessandro Rossi to tell me a bit more about this. Alessandro is a PhD student currently on his last year. So wish him good luck! He's at UCL department of Electronic and Electrical Engineering. He works in the nano fabrication field, especially for applications in X ray imaging. So hi, Alessandro. So let's start off with an easy question. What is nanotechnology?

Alessandro Rossi  00:48

Not an easy question, but I'll do my best. Yeah. So the term nano is usually used for something that is very small. Technically, the prefix nano means a billion times smaller. So a nanometer is a billion times smaller than a meter. To give you a sense of what there is, a nanometer is 20 to 200 times smaller than human hair. And I know it sounds like sci fi, but actually now we are able to pattern features on substrates that are that small on the order of the nanometers, 10s of nanometers and so on.

Ferdouse Akhter  01:28

Where would we see stuff like that?

Alessandro Rossi  01:30

Nanotechnology is now a pervasive field. It is basically in everything around us, in phones, in batteries, in drugs. I struggle to think of examples where nanotechnology is not present. So how do you see the small stuff? That's a very good question, because for everyone working with these sizes and these dimensions, a big part of the of the job is actually managing to see what we did. It's, as I said, these dimensions are too small to be seen with visible light, so with our eyes or even using optical microscopes, which is the microscopes that usually people think of when they think of a scientist. We use usually different probes or mechanisms to see these features, such as electrons or even mechanical probes. Basically, we use something called atomic force microscope, which uses a small diamond tip, and it scans over the surfaces of our substrates and samples. My favorite is the electron microscope. It's big. You have to imagine this big vacuum chamber, and you place your little sample scene, and there's an electron gun that shoots electrons at it, and you are then able to see, by the response that you have from your sample, how your sample is made, to a very small scale, down to the nanometers, again. So it's very cool, very you have very clear images, and you can have images on all angles from your sample. So yeah, that, if I have to say that's my favorite.

Ferdouse Akhter  03:05

So how do you see the muscle and the skin?

Alessandro Rossi  03:08

We have to go a bit back now to GCSE physics, you might remember what refraction is, or at least looks like. Refraction is what happens when you put up straw in a glass of water and you see that it looks like broken because the light actually deviates from its straight trajectory. When it changes medium, it goes from water to air and vice versa. These deflection of light happens also for X rays, also X rays can be refracted, but they're refracted by a very, very small angle. We're talking again, micro angles. So it's very hard to pick up, but then when you manage to pick up, it makes visible what usually is not visible, so you focus on these refractions instead of absorption.

Ferdouse Akhter  03:58

And how will that impact healthcare?

Alessandro Rossi  04:01

Well, it is probably going to be a change of paradigm in how we use X rays. Maybe I'm too optimistic, but there definitely are some interesting applications that can be very effective as of now, especially our group is working on applications that can be, yes, very effective. For example, one application that seems very promising is the what is called intra operative imaging. Very often, when there is a tumor is detected. As of now, in cases, like in breast cancer, they're trying not to have a full mastectomy, but to remove just a part of the of the breast to contain the the tumor, the possibility of enhancing contrast for soft tissues is incredible. For example, you would be able to see smaller and thinner tumors and anticipate the diagnosis for it. In many cases, this Saves lives. You can see metastases and carcinogens that you wouldn't be able to see usually. You can see ligands and damaged ligands that are usually invisible to X rays, entire organs, like the esophagus, have very poor visibility with conventional X ray imaging. Using face contrast imaging would be the key to allow superior contrast and then visibility for all these types of soft tissues like or organs like the esophagus. Therefore, there is plenty of applications for this in tumor detections. One of the very cool applications this could be used is, for example, intra or what is called intraoperative imaging. It happens very often now that when tumor is detected, the operation tries to preserve the the organ the tumor is in, and just extract a part of the of the tissues, hoping that this would be enough to take away the whole tumor. If that doesn't happen, then the patient has to go back in surgery, and by then, things can get can get worse. Then, very often, then the removal of the whole organ is the only option. It happens a lot in breast cancer, for example. But using x ray imaging while the patient is still under surgery could help the doctors to see not in real time, but after just 10 minutes, if the operation worked and the tumor is actually, has actually been removed completely. If I'm not mistaken, this would reduce the percentage of second surgery by 20 or 25% with incredible, of course, benefits for the patients, but also for the healthcare system.

Ferdouse Akhter  06:51

Would you be working with stuff like cells?

Alessandro Rossi  06:53

Cells are usually seen using optical microscopes. I'm not an expert in biology. I think that's what is usually done, we go down to even 100 times smaller than that. What does a day to day life look like for you? It's not just looking at gratings and stuff like that, because I imagine people working in labs, they wear a white coat and they, you know, look into what did you say the traditional microscopes were called?  yeah, the optical, optical micro

Ferdouse Akhter  07:18

yeah, that's what I just imagined.

Alessandro Rossi  07:19

What I do usually is to work in a clean room. A clean room is one of those very super duper clean labs where you get in dress like an astronaut and you can't sneeze or cough to maintain a sort of cleanliness and contamination free environment for your samples. And what I did was to basically pattern and process this silicon subset in order to create what they're called gratings, usually in a way, similar to what old CDs were. What I do we on on my gradings is more or less what it was done on CDs, old CDs. Do you remember how when they were facing the light, they would show, you know, rainbow colors and stuff. This is because on this surface of the CD, the shiny side of the CDs, there was actually a pattern of, you know, heights and valleys that then would be read by the CD readers. But you can't see that. But you can't see that because it's too small. In my case, I have to go actually smaller than that to let that work for X rays, basically create a sort of, well, I'm just repeating myself now, but a pattern on of heights and valleys on my silicon sub to manipulate the X ray fronts to then perform imaging. That would be the second part of my my work, which is the testing and the application for this.

Ferdouse Akhter  08:47

How do you link the grating with X ray? Because it seems like two different methods or two different parts.

Alessandro Rossi  08:52

Yes, I agree. The link can be obscure, but basically, without going too much into details, in order to detect that very small refraction X rays undergo while traveling through soft tissues, tumors and etc. You need some devices that manipulate and interact with the X rays. And these devices are called gratings, and it is what I do. So what usually happens is that between the x resource and the detector, there is a set of gratings are placed in appropriately so that the access would be would interact with the gratings, first the patient, second, and then again, the detector.

Ferdouse Akhter  09:37

So the gratings are kind of like our bones, like, you know, the way that they absorb the Xray.

Alessandro Rossi  09:43

They absorb the refract in a way, in a, let's say, in a clever way, so that then we could create a signal on the detector that it can be resolved and studied and analyzed to then retrieve the face image.  What do the chemicals do  at different stages of this process. This, you want to differentiate things from basically from your chemicals. So at this, at the start, what I usually do is to coat and cover the silicon wafer with a photo sensitive chemical so that then I can expose only where I want this photosensitive layer with light these exposed areas will be kept or removed. Whatever part of this layer is still on my silicon wafer will act as what we call a mask, so that whatever is beneath this layer will be preserved. What's not covered by the this layer, by then, will be actually exposed to the second round of chemicals. Let's call it in a chamber that will try to dissolve the silicon. That's how you get the the peaks and the and the valleys on my silicon wafers. And all of this has to be perfectly optimized. Is quite a headache, if you ask me, so that a lot of work has to be put into the optimization of timings and proportions of these chemicals and how long you want to expose them for and use them for, etc, etc. So it can be quite a long and time consuming process, the optimization process of all this. That's why, when at the end of the day I get out of the clean room and go to look at my little samples, at the electron microscope, I really cross my fingers very tight that things worked out well.

Ferdouse Akhter  11:32

So you get this silicon wafer, or this little slab of silicon, and then you do like...

Alessandro Rossi  11:38

magic, the Nano fabric, nano processes.  Let's say I do a series of physical and chemical processes to selectively let's say the technical term is etching.

Ferdouse Akhter  11:50

So you sketch like peaks and troughs on it exactly, but you can't see that with the naked eye. And then that's called gratings. And then you use that for your X ray bit, yes. So that's the second bit, yes. Okay, what's the second bit? Tell me

Alessandro Rossi  12:02

the second bit is X ray imaging. We all went to the doctors, the dentist, to get an x ray radiography. And we know how, We know what those show up. The bones are very clear. The teeth are very clear. We can remember, I think, that all the tissues around were basically invisible. So this is because X rays get absorbed easily by bones and teeth, but they don't by soft tissues. And basically, when we make a radiograph of ourselves, we see a contrast between bones and soft tissues, and that's what conventional X ray imaging is. So it works well, it has been working for 120 years. Contrast with by absorption works, but again, you don't see any soft tissues. What if we want to see soft tissues? We go to MRIs, ultrasound, other imaging techniques that are usually a bit more complicated. It would be much better if we could extend the X ray capabilities into imaging and create contrast also for the soft tissues. And this is what our group and others in the world are working towards by shifting the paradigm. Instead of using absorption, we use what is called phase shift and to create contrast between soft tissues. You might know what phase shift is without knowing the world. This is called a refraction and it's a phase shift effect. If you manage to do that with X rays, then you would be able to increase the contrast among soft tissues and stuff that usually are invisible to X rays, conventional absorption X ray imaging. Once migratings are ready, it's time for testing and see their applications for X ray imaging. Now everybody knows how x ray imagings are, or at least look like when we go to the dentist or to the hospital for the Radiography of our broken arm or our teeth. We all know that the contrast is between the bone and the soft tissues, or the teeth and the soft tissues, because they are made by different chemicals, the components by different elements that absorb more or less X rays. But again, we see the bone, we see the teeth, we don't see the soft tissues, so we are missing information there that we cannot see with X rays. What our group works on, and many other groups around the world, is to shift in the paradigm and trying using other mechanisms to actually be able to see the soft tissues using X rays.

Ferdouse Akhter  12:21

So what are you currently working on there?

Alessandro Rossi  14:39

I'm currently on writing my thesis. At the moment

Ferdouse Akhter  14:42

how long is that?

Alessandro Rossi  14:43

So far? Two pages going well, right? Yeah, not too bad. Can complain.

Ferdouse Akhter  14:50

So when is your thesis due?

Alessandro Rossi  14:51

Then there's no hard deadline with what usually happens with PhDs is that we receive a scholarship. Cheap salary, and it is limited in time for usually four years.

Ferdouse Akhter  15:05

So you get paid every year like a proper salary

Alessandro Rossi  15:07

every month!

Ferdouse Akhter  15:09

And what happens if you don't finish your thesis by the end of the four years?

Alessandro Rossi  15:13

Well, nothing, really. I think there is a limit at some point, but it's very loose, and you have some more time to even up to a year where you can focus and write or very often, it happens that people find the job and so the finishing the thesis might, you know, take a bit longer, because then they're also working. This is very common, and it's not the end of the world, but what people usually tend to do is try to save a few months at the end of the their PhD to write that, yeah,

Ferdouse Akhter  15:48

so in that four years journey, or whatever it is, you're kind of like getting all the research and the information to be able to write that thesis, basically, and then that becomes like a published paper, or...

Alessandro Rossi  15:59

It is up there. It is official published document. It is published basically by the university, whereas usually publications and papers are published by external entities, external bodies, which are the journals, you know, magazines.

Ferdouse Akhter  16:13

Can it be published by UCL and then say, if it's like really interesting to a certain journal, they then pick her up, or after it's been published. That's it.

Alessandro Rossi  16:21

Usually it is the opposite the other way around. You try to publish your results first through journals. This is quite kind of one of the main goals of your PhD. Also now the there's a lot of debate, because the old scientific community is publication driven. There is a sentiment in academia where this is detrimental for the research, because people go for things that would be popular, yeah, exactly any easier publication, instead of thinking maybe of a bigger pictures or a bigger work. Because at the time as of now, the your publication records, basically is your best way to find a career, find the next job, find a permanent position. And so this is kind of like starting some debates in the community. We are maybe forgetting about science itself and just thinking about publications, but it is a metric we have now, and it is, I guess, the best we have. So what happens? To get back to your question, what happens usually is that they PhD years, and with their supervisor, when they find when they have some relevant result, they try and publish it, so that result can then also quit in the and reported in the thesis as well.

Ferdouse Akhter  17:39

Does anyone you know, at the end of, normally, dissertation, or whatever it is. So I only went up to undergraduate, so I only did a BA, but so does someone mark that work? Or how does that work?

Alessandro Rossi  17:51

Yeah, so these changes between, you know, different countries. There is a two examiners in the UK

Ferdouse Akhter  17:58

that, well, not two people, two examinations, two examiners?

Alessandro Rossi  18:03

like you go into the and then defend your thesis in front of, I think, two, oh, I should know it by now, but yeah, I think it's two examiners basically asking you question, kind of like probing you and discussing about your work, basically where that you have to defend, and you then, very quickly after that, know whether you are basically a doctor or not, there isn't an a grading system like ABC or first second, but you can receive some marking of this sense of okay, you you passed and there's no correction at all, or you passed with minor corrections. So you're a doctor with minor corrections, and that is the majority of the cases where you basically have to go back to the thesis and change a few bits. This is usually what happens if everything went well. Sometimes you can be they give you major corrections, and that's more of a problem, because that means that means that there is some lacking in your the science of your dissertation, so you might have to go back and do some more experiments and do some more actual some bigger work. I can appreciate that this might be quite scientific centric. I don't know how that works in, I don't know, the humanistic area or other fields, but this is what happens in engineering and physics, usually.

Ferdouse Akhter  19:28

So, normally it's kind of like two academics who are, like, very intimidating academics,

Ferdouse Akhter  19:34

 two very knowledgeable, I guess, academics. I mean, everyone's knowledgeable, in some sense, but two very knowledgeable academics in that field, so like you, do nanotech, so it'd be two academics working in nanotech.

Alessandro Rossi  19:46

 As we said, I do nanotech for X ray imaging. So we'll probably be one. I'm just guessing here, but they will probably be one nanotech expert and a. X ray expert.

Ferdouse Akhter  20:00

So what's your thesis on what you working towards right now?

Alessandro Rossi 20:03

Well, now I am basically collecting all the results and the ideas we worked through these last four years. Mainly I've been working on, as you know, on nano fabrication for X ray imaging. So there will be a big part talking about the fabrication side of my work, and then how I tested it in X ray systems, the imaging side, and what the applications of that could be.

Ferdouse Akhter  20:34

So what's the nanotechnology bit of your work?

Alessandro Rossi  20:37

In my case, nanotechnology means mostly nano engineering on silicon substrate, substrates just like materials. Yeah, you buy these wafers of silicon, and they arrive to your lab, and then you start playing around with that.

Ferdouse Akhter  20:52

So that's not the only bit of your work. So that's probably like half your work, dressing like an astronaut and doing that kind of stuff. And then the other half?

Alessandro Rossi  20:59

other half consists in using these samples in X ray systems. So they can be X ray systems in our labs, or sometimes we go to a very fancy facilities called a synchrotron. Usually, these are facilities as big as Wembley Stadium, more or less there is one, roughly, in every country. And what they do is they create very high quality X rays so that we can do, usually, proof of concept experiments there with the purest, most perfect x's we can have, and then try to replicate them in the lab. After that is done, we go back to UCL with our data and try to make sense of it. So the other half of my job is mostly sitting on the in front of a computer and analyze the data until they make some sort of sense.

Ferdouse Akhter  21:54

It's a lot of back and forth. I'm guessing there is trial and error

Alessandro Rossi  21:58

and ups and downs.

Ferdouse Akhter  21:59

Yes, that's it. Thank you for speaking to me today.

Alessandro Rossi  22:03

Thank you for having me. Yeah, thank you.

Ferdouse Akhter  22:06

I learned a lot today. Learnt a lot about Nanotech and how it's used in everything, and how it can help with cancer and maybe finding solutions to problems that we have right now. So thank you.  This has been held in a hand basket produced by UCL Institute of Healthcare Engineering and edited by Shakira Crawford from Waltham Forests Future formed. What's the Institute of Healthcare Engineering? Well, let me tell you. The Institute brings together leading researchers to develop the tools and devices that will make your life better. We're using this podcast to share all the amazing work taking place, but there's so much more going on, so please check out our website@ucl.ac.uk forward slash health dash in dash a dash hand basket to find out more, and please share with your friends and family. If you found this interesting, we're available everywhere, especially where you've just listened to us.