Hemdeep (00:13)
Welcome to Big Ideas in Microscale, 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 (01:11)
Welcome to Big Ideas at Microscale. I'm your host, Hemdeep, co-founder of Creative Cadworks, Cadworks 3D, and Resinworks 3D.

Robin (01:19)
Robin, co-host and also the technical writer within the marketing team.

Hemdeep (01:24)
Last week we spoke with Irwin and Philippe from the University of Cambridge to introduce their groundbreaking work in 3D printed cochlear models and how their expertise is advancing cochlear implantation techniques. If you missed it, be sure to check out that episode.

Robin (01:39)
This week we're diving deeper. Iowan and Philip return to discuss model accuracy, micro CT scans, and the challenges of replicating soft tissue. We'll also explore their development of microfluid cochlear chips and the role 3D printing played in shaping their research. Let's jump in.

Hemdeep (01:57)
Was there an actual aha moment, a moment where you're just like, think there's traction in what you're doing and there's the feedback that you're getting from clinicians seem to indicate that you are sort of moving in a fairly positive direction?

Filip (02:12)
Yes, like in terms of the research itself, the advantage there, I mean, we were discussing this, the ENT surgeons here in Ellenbrook's hospital, is hospital at the biomedical campus of the University of Olze. And it wasn't an aha moment rather than like a disbelief that the model could actually follow up, let's say the Kapstan equation. And that, you know, that's fairly simplistic.

solution could actually work out for to describe the insertion forces in Cochlear. So we spent a lot of time to prove that that works and then there was a lot of back and forward regarding publishing the paper as well because there was this belief that the black portion could gripe the insertion forces. The thing that the real surprise was when we

3D printed the models and treated them in the way that the insertion forces started to look similar to the one in cadavers. Because we knew from literature and from experience what the insertion forces should be and once we find the solution to treat the inside of the luminal, inside of the channel in a way that the insertion felt and behaved as during the cadaveric work.

Then we thought that we are on something. And then once we start looking at, because we were worried that this treatment could actually change the accuracy of these models. So we spent a lot of time to create a technique to double check that the models are still fine and they are within a certain deviation. Once we got all this work done, then we were sort of sure that we have one of the best models.

to describe Cochlear and to do this type of work.

Hemdeep (04:08)
If you're telling me that the development of the internal model was the actual aha moment, can you describe what steps you needed to do in order to start developing an accurate internal model? what was the work that you guys had to do before you got to that point?

Filip (04:24)
First of all, you really need to start with a good micro CT scan. Quickly realize that CT scan is simply not good enough to create a great segmentation, just so you can sort of understand what I'm trying to say. Cochlear is so small, is that if you take a normal hospital CT scan, you will have about seven scans where the cochlear actually is shown. So seven slices.

Whereas if you use Micro CT, it's about 700. So then you can really pick up all features and you can create a high resolution model. And that's very important for any 3D printing, I would say.

Hemdeep (05:08)
And what was the scale at which some of the features were at in terms of a millimeter or micron? What sizes were you working with?

Filip (05:16)
entrance. So let's say the round window, which is the entry point for the cochlear implant, is about 1 1.5 millimeters. And then as you follow up the channel and it starts to spiral up a little bit, it becomes smaller and smaller. By the end, we're talking about 300 micrometers, I would say. 200, 300, depends. It sort of changed the shape a little bit as well.

But yes, the channel is very small. The spiral shape is the cockpit. Then the entry.

Iwan (05:54)
So it's about the size of a pea, we like to say. So it's a very small kind of tiny structure. So there's a lot of work in also thinking how you, about the design as well, because once you've got the cochlear, it's in a kind of a strange orientation or it's in its natural orientation. But in terms of

understanding what the forces in different relevant directions, we'd have to correct for that within the, kind of processing pipeline. So we built a whole pipeline within Matlab where we would take all of these micro CT scans, segment them with this template assisted segmentation. Then go into a Matlab implementation of slicing the cochlea, understanding the cross sectional area, understand making equation effectively for this like characteristic spiral.

And then correcting that and making it directly into a print. So we could get at the end, a STL file we can directly send to the printer. So then we can have everything very consistent and ensure we're accommodating for things in the right way. Because depending on how you slice things, for example, we'd have to take away the little membrane you'd usually insert the cochlear implant because it has a bleak angle where that would also play a role where if we want to look at just the shape.

of the cochlea, want to isolate all these different variables and increase the complexity as we go, effectively. One of the key pieces of post-processing we were looking at also improving the transparency of the models. So then we could understand where the positioning of the implant would be and relate that to the force as well. So otherwise, it's to know within the actual...

normal anatomy or cadaveric specimens, you're putting it into a small bony channel and you have no idea what's happening inside. So the beauty of a 3D printed model is that you can actually see what's happening to the implant. Is it bending over on itself? Is it buckling? And try to relate that to any features you see in the force, but also in the kind of electrical modeling as well.

Hemdeep (08:01)
And then you also mentioned that you had to do some sort of coating so that the internal surface can closely mimics the internal surface of the skin. How did you guys accomplish that with your printed models?

Filip (08:13)
So we tried a couple of different coding techniques. we used, you know, soap, the solution of soaps. tried medical oil, like silicon medical oil. We tried lots of different things. And then we tested out Pluronic, which is a polymer based, right? Which we had really good results with.

Iwan (08:34)
Yes, a peg-based surfactant, effectively.

Filip (08:39)
and it helped out to create a very thin, nice layer, which then resulted in a solution very similar in search and force profile as in Kadar.

Robin (08:48)
Did you test other fabrication methods besides 3D printing?

Filip (08:52)
We were interested in casting. There was a time where we were interested in casting and there were papers discussing the casting. What I quickly disliked about that is that it just takes a lot of time. The problem there is that you cast material within the temporal bone into the cochlear channel and then you dissolve the bone itself and then you take that part and then you cast around that part again. And so it's a bit more...

hands-on, than 3D printing. And that also introduced a lot of variability. So the problem is that then, you know, creating the same model 10 times could create deviation because there is lots of manual work. So that's one thing which we were a little bit worried about post-processing or specifically the coding because the coding was done manually. But then we did lots of analysis using micro CT again.

to rescan what we already printed with the coating in and compare it to the original CAD model to see what is the actual deviation. And we are pleased to see that the deviation was minimal for our use case.

Iwan (09:59)
Yeah. And I guess the issue with the casting techniques is this is destructive, right? So once you make that one model, then that's it. Where with the beauty of 3D printing is once you have the file, you can manipulate it. You can add different channels for flushing water or whatever you need as many times as you want. So you can replicate that file and using that nominal actual analysis, Philip showed, we could get down to

about 30 microns of deviations of the surface, which is the resolution of the printer that we were using, the Cadowix printer. So we were very happy with that. We could get down to that level of resolution ⁓ or accuracy of the surface, I should say. In terms of other techniques, also looked at stelar lithography, like classical stelar lithography techniques, more to make a cochlear ownership model.

So this is more of a microfluidic version of the cochlea that we've also worked with, where we'd want to make a flat cochlea where we could inject cells, have them inhabit the model as they would in the real anatomy, then look at how they electrically behave when you stimulate with cochlear implant. But the issue with that was, although it could probably get you smaller, very fine features.

You couldn't get the size of the, like a one millimeter high channel because that's very difficult to make with those. So it's kind of strange actually for this. It's a hard scale to work with because it's not small enough for a lot of microfabrication kind of techniques, but it's not big enough for lot of kind of standard 3d printers or other kind of fabrication techniques. So it's kind of this middle scale, which is very hard to engineer with, it's a, it's an interesting challenge.

Filip (11:50)
We also tested out the SLA printers and to a certain degree it worked. Funny enough, with the CADWORKS one we were able to achieve like, even though the resolution on paper was higher or lower, mean, comparing let's say 20 to 30 microns, we are still able to achieve better overall deviation from the model. So the deviation over 90 % of the surface of the model.

was actually lower with the Catwalks printer compared to other SLA printers. And we were also studying why is this happening and like, how is it possible that DLP achieves better resolution? So yeah, it was a lot of interesting things. And I think one part of it is also the material itself. So we're using the microfluidic one, the Catwalks microfluidic. And what we like there is that the viscosity of the resin is

actually lower, it's easily flush out from the channels as they're being printed because what we found out is that the viscosity of the material itself is higher than the resin is trapped inside during the printing. And then when you create another layer and another layer, let's say in a channel, then as the resin is trapped inside, the curing actually penetrates also a little bit inside of the channel, which creates the deviations. So...

Yeah, that was one of the things we discovered and we're to publish.

Hemdeep (13:23)
I think there are two things that I wouldn't had said that were really ⁓ piqued my interest. One was the fact that you guys had attempted to sort of do the modeling on stereolithography. I understand that you weren't able to get the size that you wanted to work at. Like, would you have been able to duplicate the work that you did on the 3D model? Like what part of the work would have been translated onto that platform? What was it that you were trying to do on that one?

Iwan (13:49)
Yeah. So I can maybe explain a bit more about the, the cochlear chip that we were looking to make for that. effectively we needed a PDMS microfluidics chip that we could put then on a glass substrate, ideally a microelectrode array, which is effectively a bunch of electrodes, which is patterned on a glass substrate, which can then connect to a, an MEA rig, which can record from all of those little electrodes and record the

action potentials from individual auditory neurons in that case. Actually embedding lot of electrodes within and culturing cells within the 3D prints is quite difficult and if you can use glass substrates where everything is already well established then it makes it much easier because you need every chance you can get with these types of cells because the extraction of the cells from these auditory neurons is very delicate and

you need to be able to handle them correctly and culture them into the correct conditions. So we were able to get the, ⁓ slightly simplified version of the structure of the cochlea within a microfluidic chip and actually embed small channels that replicate some of the, porosity of bone that we have in the real cochlea between that channel and the channel which could contain the cells. with putting a real cochlear implant inside of this microfluidic chip.

we could see how the cells would react to it. So how they would electrically respond. And it turns out that like we actually focused a bit more on patch clamp electrophysiology, which effectively stabbing a single neuron with a small needle and delivering a very defined amount of current or different current patterns, which other members of our lab. it comes with Gillies. She did lots of the work in terms of.

extracting the cells and culturing those and Paul Galsworth, he worked a lot on, there's a wealth of experience in patch confidence physiology. He comes more from a kind of bit of bioengineering background as well as Sarantos who did a lot of work on purely kind of computational work and lots of more engineering work, could still make all of these different paradigms of different electrical pulses effectively. It was really good collaboration between us.

to see how you could deliver all these different types of patterns in a really high throughput format to understand how the cells would react to these different electrical impulses, to see how you can make that interface as efficient as possible. It was a really interesting kind of multi-disciplinary project and interleaved with ⁓ some of the more accurate cochlear models that we've had, which we introduced pores into the full cochlear shape to...

mimic the electrical properties of the cochlea. So we designed different pore structures directly with it, actually within MATLAB again, to basically have voids within the model. And by filling that with saline, which is conductive and the resin plastic, which is non-conductive, then we can tune the electrical conductivities of different parts of the structure around the cochlea and mimic the real patient.

electrical profiles. And as I mentioned, the lot of Chloe Sorts's work was looking at making specific phantoms that match the cadaveric specimens. So she did a lot of work between cadaveric human tissue and these 3D printed equivalents.

Filip (17:26)
Basically by tuning the size of the channels, we could change the current spread within the model. So one part of the research, what is interesting is to see how the implant stimulation spreads through the viral shape. Because as you have the implant inside and that it has 16 to let's say 22 electrode plates.

Each plate is being stimulated at a certain frequency. So basically you stimulate the plate and that stimulates a certain amount or like, yeah, certain degree of neurons, which then transfer it into a specific frequency. So this way, what we were studying is that if you put the implant in and you stimulate electrode number 13, how does the current spread and does it also affect different neurons that it should? in a certain way.

Hemdeep (18:19)
Where's that research right now? Has there been a publication of that or is that ongoing right now for you guys?

Filip (18:24)
So Chloe finished her PhD this year or ending of last year and this is being published as we speak about it.

Hemdeep (18:35)
great. Amazing. Considering that you've been able to do such amazing work over the many years using 3D printing, there must have been some significant gaps or at least minor gaps in the use of 3D printing that you would have felt that, if we had this in place, it would have been either better or the data set would be a lot more clear without any outliers or anything like that. How would you guys address that?

Filip (19:02)
One of the key drawbacks, at least in my research, was that the cochlea or the spiral shape like object, the calatimpane itself, it has this very thin layer of soft tissue inside, which changes the insertion ever so slightly. And what would be amazing to have a model where you could replicate that soft tissue inside of the model. But at the moment,

We might try to replicate this with multi-jet printing technology, but the problem is that the channels are so small is that it will probably result in ⁓ significantly higher deviations. So there was one thing. So looking at the multi-material properties, being able to print conductive material, that would be very interesting for lots of reasons, specifically with the research about...

cochlear implant stimulation, looking at where the current spreads during the stimulation. will be interesting.

Iwan (20:03)
So to pick up on that point specifically, like to look at the kind of electrical spread, we've actually focused a lot on the kind of designing small channels to just manually feed wires into the models and then doing post scans to understand like exactly where those wires are. But if you could make electrical tracks within a 3d structure that small, then it would be, it's a significant challenge. So it's completely understandable why it's.

not really possible with any technology, even multi-jet technologies now.

Hemdeep (20:35)
On our side, always find the hardware side is one that has a very defined trajectory, meaning in terms of pushing scale to its limit. The material side is almost a blend of chemistry and a fast order chef at a fast food restaurant. Because the user base, especially amongst biotech and the larger biology base, I think.

need for a wide range of very unique materials is immense. ⁓ pretty much anything that conductive material, I think has become one of the most sought after material. But what you're asking for is not broad conductivity, you're asking for being able to embed a thin line or a conductive material within a larger matrix, which...

It'd be nice to have something like that. I wish I could do that. That would be really nice.

Iwan (21:33)
Yeah. Yeah. But even just having good flexible materials that replicate the kind of small membranes within the cochlea is like very important question that we've really struggled to fabricate. we've made a lot of this stuff you can actually mitigate with design considerations. So we've looked at different effectively sandwiching different membranes between different prints.

having smaller channels that you can feed wires in, for example, or feed conductive material in, or even for example, for some of like adding colors to make like a, a nerve so you can identify where the nerve would be within a clear model. We've found ways to kind of get around the kind of limitations and a lot of that has just been in the geometrical design. So even in the pore structures I mentioned before, really we've made it so

Okay, you've got this non-conductive material by the way that you construct the actual layout of the material, we can actually play with electrical properties. Most of the time you can find ways to get around things just with some ⁓ creative.

Robin (22:40)
When did 3D printing actually become prominent in cochlear research? I assume it's more of like an emerging technology or has it been kind of?

Filip (22:49)
literature like a couple of years ago they started experimenting 3d printing models, testing different technologies. The problem is that they didn't really check what's the deviation from the real model, so from cadaver. So then it's difficult to see like if that technology worked well or if it didn't work well. So 3d printing started a couple of years back like basically with the first SLA printers. So let's say

It was like around 2015 or things like that. Creating a model which is fully characterized and so everyone else can print it, the deviation using the nominal actual analysis as a proof that's fairly unique. It's been done for different ⁓ use cases, but as far as we know, not for Cochlear.

Robin (23:38)
What were the models look like before 3D printing? Was it primarily physical? Was it like animal?

Filip (23:44)
⁓ Yeah, exactly as what you just said. So was cadavers, so cadaveric temporal bones. was one thing. The problem there is that there is a difference between fresh cadaver, the freshly frozen or fixed cadavers. These models, then there were models which were casted. So as we discussed before, there was the technique there and they were also milling.

One of the techniques they were using is instead of creating a 3D model, they created either a 2D model where they cast, let's say they have a 2D spiral and then they cast acrylic around it and then just pull out the material itself, which create a spiral, but it wasn't rising spiral, it's just 2D spiral. The problem with Cochlear is that it's too big for microfabrication, but too small for...

for normal type of 3D printing. We were also checking out FGM printing, we were checking out ⁓ SLA. We also checked two-photon polymerization, which is a very high-end micro- fabrication technique. I mean, again, the problem is that the cochlear itself is too big for that type of technology. So you can create like nano lenses and things like that. But it's exactly the range where you need to have.

something which can create something, let's say in centimeters, but on the resolution of below, let's say 50 microns. So it's yeah, it's a challenge.

Robin (25:20)
out of curiosity, did you both have experience with 3D printing before you started working on Cochlear Implant?

Filip (25:26)
I had about a year with the RSOJet printer, which was very specific. And during that year, I was also testing out SLA printer, but not... expensive.

Robin (25:37)
Not

so much.

Iwan (25:39)
Yeah, so I collaborated quite closely with a friend who was doing a lot of bioprinting at the time. So he was using more extrusion based printing for like polymers as well as gels embedded with cells. So I helped out a little bit in terms of imaging those like playing around effectively. And we also at the time.

had a startup idea, was mainly for like competitions and learning, where we'd look to make a 3D printed nerve based conduit, which would help the bridging of nerves that suffered from traumatic injury to regrow effectively. So I was looking at more of the gels and the biomaterials aspect. He was looking at the 3D printing aspects and other people looking at the neuron kind of outgrowth as well.

That's a quite interesting project, but so that kind of sparked my interest into 3D printing and actually when this opportunity came along as well as my interest in kind of neurotechnology, kind of as a good combination of those interests really.

Filip (26:38)
I always found that 3D printing allows you to create something in CAD and then just have it physically in your hands. And it was like one thing I really like about my PhD is like it was applied research. So like we designed something, you know, the next day or in a couple of hours we had it physically and we could like see what it actually is and how it works. Because it's also difficult to appreciate like how things work.

specifically in inner ear and how small they are because if you work in cats, you know for hours You've got everything like 200 times scale Everything is huge, you know, and you're like, yeah And then once you 3d print and see it one-to-one then then you actually appreciate like how delicate the structures are and how Amazing is the anatomy of human ear

Robin (27:14)
and then then and

Iwan (27:32)
That's one thing we found with the anatomical models that we've been making for more education purposes is that there's been a huge growth in terms of virtual models, VR, AR models to understand kind of the anatomy, which especially for like surgeons, it's really important to know the visual spatial kind of way, how they relate to each other or the size and shape, but there's nothing quite like having something in your hand that you can actually turn around and...

I really appreciate it really see the scale because as Philip says, you can zoom in as much as you want on the virtual model, but you sometimes kind of can miss the scale. I know like a lot of the times I'll make something in CAD, but actually it's like, they're small rather than like I think about it's this big.

Hemdeep (28:18)
Yes, you

do get tunnel vision. The blinders go on and you forget scale at that time and until you print it out, do you realize that really I thought it was a lot bigger than this and I can't see it or I just broke it and that usually is either one of the two. Amazing. So that's a wrap for today's episode of Big Ideas in Microscale. We hope you enjoyed this deep dive.

Robin (28:41)
Huge thanks to Iowan and Philip. If you're excited for what's coming next, don't forget to join us next week where we explore the next step in Iowan and Philip's research. From expanding their work to accommodate a wider range of cochlea shapes to improving surgical techniques for implant insertion. We'll also discuss their company, COSA LTD, and how they are creating realistic anatomical models for surgical training.

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. Let's spell C-A-D-W-O-R-K-S-3D.

For show notes, paper references, and bonus resources on today's topic, visit our website, catworks3d.com. That's spelled C-A-D-W-O-R-K-S 3D.com.

Hemdeep (29:45)
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 at Microscale.