Hemdeep (00:12)
Welcome to Big Ideas in Microscale, the podcast where we explore groundbreaking research happening at the microscale where micro innovations makes a big impact.

We're excited to showcase the incredible work being done by our users from around the world who are pushing the boundaries of microfluidics, lab on a chip, organ on a chip and beyond. Through these conversations, we hope to learn from their experiences, uncover their insight and bring their big ideas to wider audience. So whether in a lab, on the go, or just curious about the future of microtechnology, join us as we dive into big ideas at Microscale.

Hemdeep (01:07)
So Robin, here we are again. We tried the first round and now this is the official launch of our podcast, Big Ideas at the micro scale. And when we last left off, we had said that we were going to start bringing on some really interesting teams. And I'm so happy to start off with the team out of Cambridge.

Philippe and Iwin were amazing when we first spoke to them, I think it was in 2018 or 2019. I got a chance to meet them in 2023 at their lab and the work that they've been doing has been quite amazing. I guess before I go any further, I'd like to introduce myself. I'm Hemdeep co-founder of Cadwix3D and I've got my co-host, Robin. Hello. How are you doing, Robin? You've been digging out of all this snow over the last, I guess, four days now.

Robin (02:00)
Yeah, there was really a lot of... It's not fun. My arms hurt. I think it was, was it? 30 centimeters of snow over two days, I think it was.

Hemdeep (02:13)
Yes. Yeah. Yeah. It was a real, it was a barn burner. It really was a lot of snow. let's start with this conversation. I'm happy to introduce Aywin and Philippe to our first inaugural podcast. And so here they are.

Iwan (02:30)
Thanks a lot for having us on. It's a great honor to be the first ones.

Filip (02:35)
Yeah, thank you very much.

Hemdeep (02:36)
I'm going to rewind this to some of the more important starting points for you guys. You know exactly what your backgrounds are, what your relationship is, and sort of where the connection point between the two of you started off.

Iwan (02:50)
Yeah, why not? We, mean, to be honest, a lot of the connection came through 3D printing. I started about actually in January of 2020 in our lab in the University of Cambridge. I started as a postdoctoral researcher, really looking at making electrical phantoms of the cochlea, which is a little structure, which looks like a snail in the middle of your inner ear. And basically the first week that I started, I was tasked by our supervisor to

buy a 3D printer like this week. So figure out which kind of printer you want to get. And then I met Philip who just started his PhD a few months earlier and we kind of went through and tried to really kind of look at what kind of printer we'd want to get.

which ended up being a longer process than one week because the structure of the cochlear is so small and intricate. We were really looking at prints that could replicate that really kind of fine anatomy and especially the small hollow channels. And that kind of snowballed over time to doing all sorts of weird and wonderful prints.

mainly related to the year anatomy and eventually kind of come into us, co-founding a company about a year and a half ago called Cosa, which specializes in 3D printing different sorts of anatomies and getting really fine structures.

Hemdeep (04:07)
And you Philip, how do you connect in with IWIN and what kind of specialty do you bring into this team?

Filip (04:13)
Yeah, I've met Ivan first time in a couple of months after starting my PhD. Ivan joined us also again, as he mentioned, first task was to get a 3D printer. And it's a bit funny because now looking in bags, like getting the task to select a 3D printer for very special use case and giving a time out of five days was bit crazy and ambitious, but...

During the PhD, which was in clinical neuroscience, I did an engineering degree back in Czech Republic, which was in nanomaterials and nanotechnology. It's basically the equivalent of master of science. And then I did master of philosophy or MPhil here in Cambridge, which was about micro and nanotechnology in enterprise. And it should have been like 50 % science, 50 % business.

but it ended up in good old 95 % science, five percent business. But I really liked the environment around Cambridge and the university itself. So I applied for the PhD and got in, worked with Manohar for a couple of months. And then Ivan joined in. We started working on selecting the 3D printer and then we start the actual work where, particularly my research, was a lot about 3D printing Proclea for the inner ear.

Specifically what I was looking at is that maybe I should introduce a little bit the cochlear implants because that was the core research and still is part of research in the lab. Cochlear implants are these devices which help people with tremendous hearing loss to hear again. It's a device which can bypass normal hearing. So how it works is that if you have very high level of hearing loss, so imagine no hearing.

You are a great adept for cochlear implants and you basically need to undergo a brain surgery where they cut the skin, open the skin or cut the skin behind the ear, drill into temporal bone, create mastoidectomy and then that creates an access to the inner ear where they then can put the cochlear implant, which is basically a wire with a couple of electrodes covered in silicon.

And this way you can directly stimulate the auditory nerves which are located inside of the cochlea, the spiral shaped like object. Even though this technology is incredible because it basically gives you ⁓ a sense which you might have lost over time or you were born without. There are a couple of problems. So one of problem is that if the patient has any residual hearing, there is a quite high probability they will lose it.

during the insertion. So because there are insertion forces that arise and then you can basically mess it up as you're putting in it because it's a very small object and quite fragile as well. And that was basically my research. So I was looking at how these insertion forces arise and how we can mitigate them to preserve the residual hearing of patients. So then the patient could sort of benefit from both type of hearings, the auditory one and the electric one.

Hemdeep (07:30)
The time that I was at your lab, you guys showed me that stage that actually measures insertion forces. Did that require a completely set of engineering in order to understand how to even measure those internal forces?

Filip (07:46)
Yes, Part of the work was to create this insertion setup where we use quite sensitive sensors to measure the insertion force. So it's a setup where you can load up a cochlear implant and on one sensor and on the other sensor, you can put 3D printed cochlear model. And then you can slowly insert the implant in while you have multiple cameras and all the recordings.

as it goes in and you measure the insertion force profile and then you can sort of look at how the geometry of or the anatomy of the cochlea could make a difference on these insertion forces.

Hemdeep (08:28)
Like how many specialties did you have to bring in in order to sort of develop? It sounds like even before you got to actually testing it, there was a set of protocols that you had to develop was involved a significant number of skills to and into place.

Iwan (08:43)
Yeah, so my background is...

a little bit strange in a way. So I originally did a masters in physics, so very pure physics, going into a little bit of biophysics, went more into the bio during my PhD in Manchester, UK, working in tissue engineering and regressive medicine, where we were looking at engineering effectively scar tissue and muscle tissue in a dish and looking at the mechanics of how that the cells would remodel the matrix or the materials that they sit in.

And then I went game kind of in this sort of interface between that with the postdoc work kind of going.

bridging the kind of electrical physics kind of aspects with the biomaterials kind of aspects. But it's a really good question, in terms of the, the multidisciplinary nature of our kind of work, because as well as us two, there's obviously quite a more of a team as well, which look at both the mechanical aspects for this, but also more biological aspects and also clinical as well. we have people on the coming from more of a clinical side. So.

ENT surgeons who come to do a PhD or different research projects with us, as well as people coming from more pure biology, looking at sort of a cochlear on a chip project that we've done that we can go into a little bit on the microfluidic side, as well as more on the computational aspects, where really trying to simulate both on a physical level and the computational level, especially electrical interactions.

between the cochlear implants and the nerves because that's kind of the key component here. Once you make sure you have a nice assertion, which makes sure it preserves the native neural population, you want to be able to most efficiently stimulate those nerves to give you the correct sound that you want it.

Robin (10:38)
Yeah, so I was kind of curious who actually brought both of you to cochlear implants? Like, was it one of your primary research topics or were you building on a different researcher?

Filip (10:49)
Yeah, so I knew nothing about cochlear implants before during the PhD. So that's also interesting because then from that perspective, the PhD was in clinical neuroscience, but I'm very much an engineer rather than ⁓ a clinician. But the way I joined is that when I was doing my MPhil here in Cambridge, I was working in the material and metallurgy department. My supervisor recommended me to Manohar and during the MPhil, I was working with a

a very special type of 3D printer called or printing technology called aerosol jet printing, which is this like unique type of technology. And I was working on a project to create like basically these flexible stretchable micro batteries, which could potentially power cochlear implants. And yeah, that's the first time I heard about cochlear implant. And after finishing up that project,

I started talking to Professor Manohar Bens, who then became ⁓ my supervisor on PhD.

Robin (11:51)
Speaking

of properties, I think that was part of your PhD project where I was focusing mainly on the material properties of like the implant arrays and how that affected the insertion forces. Is that right?

Filip (12:05)
Yes, partially. Basically, the PhD itself, what I was trying to investigate is that because there is a range of anatomies related to the cochlea, so generally speaking, there are different shapes and sizes of cochleas. every cochlea is like... Yes. One of the chambers. Yes, yes. So the cochlea itself is divided into these three chambers.

Robin (12:22)
Scarlet and Pani, right?

Filip (12:31)
And the one I was mainly interested in is the skeleton implanted one where the hip one actually goes. And these chambers could be of different sizes. And I was interested in how these might affect the insertion forces and if there is any sort of relation between if the insertion force is higher, if that results in ⁓ a higher probability of losing the residual hearing, or if let's say robotic insertion could help out.

with reducing the trauma, hence preserving the residual hearing. So PhD itself was about studying these forces, generally speaking. And part of that was to segment the shapes of the copias from micro CTs and create a workflow where we could 3D print these reliably with a certain level of deviation and then improve the properties of the prints to be representative.

of the insertion forces, which can be also measured in cadavers. So there was a lot of sort of work and side projects along the way. And part of that was also creating the insertion setup.

Hemdeep (13:43)
So in terms of your data set, then how big was this data set that you needed to work off for? You felt that you had a viable starting point and the insertion forces and the data that you were starting to obtain from all of your setup was now not only theoretical, but it actually was something you can derive an application from.

Filip (14:07)
So I also have to ⁓ add in that a lot of the work was a teamwork. So it wasn't just me working on this. There are people working on the scanning and characterization of the cochlear shapes. And we were able to get about 90 cochleas to be segmented out and fully characterized, which create the pool. And then out of the pool, we were able to

checked different properties and select the cochlea based on these extremes. So what I was interested in, you know, looking at, okay, average volume versus very big one, very small one, then other aspects. In one of the papers we published, we look at one particular shape of the cochlea and then we artificially change it so we could measure the specific parameter and it change on the insertion force. That's

Also, one of the things really like and I think it's important to mention about 3D printing is that it gives you ability to change just one parameter at a time and measure it multiple times. And then you create results which can be built upon because the problem is that if you start with complicated structure right at start and you get another complicated structure, is different in five different parameters.

It's difficult to then measure which parameter actually plays a significant role and makes the biggest difference. So one thing we explore is that we took one average gopher and then we artificially change one parameter at a time and measure the insertion force, I know, 10 times, 100 times to get reliable data. And then we change another parameter again. And then this way we were able to compare.

insertion forces between these different parameters and say which parameter is actually important.

Robin (16:07)
I was just curious, what are the main parameters that you guys identified?

Iwan (16:11)
Yeah. So there's a fair bit of characterization to do actually on the small cochlea. So we have some kind of small complex shape like this. Because it's a, ascending spiral complex shape, it's one of the worst kind of shapes to use it at engineering wise, because in every direction is kind of complicated. And we've got to shout out Chloe Swords, who is a PhD student coming from a clinical background, who did a ton of work on this in terms of cutting down samples and scanning and a lot of the characterization.

of these cochleas as well as 3D printing phantoms directly with them with which we collaborated closely. So there's kind of a workflow that we've developed which we're preparing some publications on as well now where we can take a...

template from a synchrotron micro CT, which is effectively a particle accelerator, which will generate really high power x-rays to conduct a very good micro CT effectively, where you have much better contrast. What that allows you to do is to see the individual chambers of the cochlea or the microstructure within the cochlea.

And using that template, we've worked with colleagues in engineering, such as Professor Andrew G to manipulate this template to fit other micro CT data, as well as clinical grade CT, where because you can see the outline of the shape, you can fit this template on. And what I did afterwards is to effectively

characterized from different landmarks that we have along this like spiral shape, characterized the cross-sectional area, the overall size, the volume, everything under the sun that we can think of to characterize this type of shape. Because a lot of people would say, ⁓ well, you want to compare.

what's the influence of the anatomy on different factors. But you need to know what the anatomy changes would be when you're actually doing this. Otherwise it can be in some, sometimes in the literature, quite vague. Like we've just chosen a big cochlear or a small cochlear, but it may be the curvature is quite different. And that might be the.

key determining factor in the forces, for example, or maybe the shape or the angle of approach, surgical approach might be quite difficult. So there's lots of different considerations to think about. And now we've generated this large data set of about 90 cochleas that Flip mentioned. We can then see what the population would look like and where that kind of average cochlea would be and see what the extremes then would consist on it.

One other thing that we found in the paper we recently published was that for, least on the insertion forces, when we made a mathematical model of how the insertion forces should change due to the anatomy, it really all boiled down to how many degrees you've went around the spiral, where it effectively comes in this stand model, which is actually, funnily enough, used for

like very old engineering principle of how many times you tie a rope around a bollard on the side of a dock. The force exponentially increases. But rather than going around the bollard, you go on the inside of a structure. You can use the same principles mathematically. It's kind of equivalent. So once we changed the size and shape actually, you accommodate for the angular insertion depth around this little structure.

then the force is all aligned even on a big bigger cochlear or a smaller cochlear.

Hemdeep (19:57)
So now, as you're doing the lab work, how frequently are you then reconnecting with clinicians or those that are on the surgical side in order to validate what it is that you're doing? Are surgeons looking at you and saying, okay, these are the steps or the angle at which we do our approach? And then how does that impact the type of research that you're doing on your side?

Iwan (20:23)
Yeah. So I think this is really key really is the validation of the work. And actually I think mentioned is Professor Manohar Bans who leads the academic lab is a practicing ENT surgeon. So he's been an ENT surgeon for almost 30 years now. So it's a wealth of experience and guides a lot of the research questions that we would try and engineer. So he gives us problems that we try to engineer solutions effectively. For example, Chloe, who I mentioned comes from an ENT background. So she really brought that insight as well.

And it's really interesting to see the different perspectives you get in terms of the practical kind of, how do I use this in my practice effectively versus, how do you then, how do you simplify that into really understanding on a mechanistic level, what the key influences are? For example, like we've got the

the very detailed work looking at the forces on the cochlear itself. But then we also need to look at how do you secure the lead during the, after you've put the cochlear implant in, you need to make sure the lead is secured. Otherwise that might actually lead to the cochlear implant coming out and actually destroy all the good work that you've done. So we've worked with Dr. Siddiqulack and Dr. Tom Hudson on quite a lot of work on that and seeing how.

You might do different drilling techniques or different ways that you might secure the lead to make sure that it's secure over long-term use and actually that you're not generating more trauma after you've been very careful putting it in and just like, okay, let me tie things up at the end and actually making the things work.

Hemdeep (22:03)
Amazing.

And speaking of tying things up, that's a wrap for today's episode of Big Ideas at Microscale. Huge thanks to iVintage Leap for sharing the beginnings of their groundbreaking work in 3D printed cochlear implants. The combined expertise in biophysics, tissue engineering, and clinical neuroscience is really driving real innovation in medical applications.

Robin (22:25)
If you enjoyed today's conversation, don't forget to join us next week as they return to discuss fabricating high-precision cochlear models, micro CT scans, and the challenges of replicating soft tissue. We'll also explore their exciting work on microfluidic cochlear chips. If you enjoyed the episode, make sure to follow us and stay up to date. You can listen on Apple podcasts and Spotify, or watch the full video on YouTube. You can also follow us for more updates and behind the scenes content on LinkedIn, Instagram,

Blue Sky, and X. We're Cadworx3D across the board. That's spelled C-A-D-W-O-R-K-S-3D. For show notes, paper references, and bonus resources on today's topic, visit our website, cadworx3d.com. That's spelled C-A-D-W-O-R-K-S-3D.com.

Hemdeep (23:21)
Thanks for tuning in and as always stay curious, keep exploring and never stop asking the big questions that are shaping our world. Whether you're in a lab, on the go or just curious about the future of technology, join us as we continue to dive into big ideas and microscale.