Episode #82 | Advancing Microfluidic Technology Through 3D Printing (Virtual Event Recording)

Peering into the microscopic world of fluid channels just got a revolutionary upgrade. At this 3DHEALS event, we explore the transformative impact of 3D printing on microfluidic device development with industry experts and researchers at the cutting edge of this technology convergence. Our speakers share how specialized 3D printing systems are overcoming traditional fabrication limitations, enabling rapid prototyping and the creation of revolutionary new designs. 

Summary: 

• Hamdeep Patel from CatWorks3D discusses a specialized 3D printing system optimized for microfluidics with unbeatable feature resolution.
• CatWorks3D’s CytoClear material achieves 90% cell viability with optical transparency for direct microscopic analysis.s
• Paul Marshall from RapidFluidics provides rapid microfluidic prototyping services for researchers and companies worldwide.
• Professor Christopher Moraes from McGill University utilizes 3D-printed parts combined with biocompatible materials for advanced organoid culture applications.
• Jeff Schultz from Phase AM is developing technology to directly 3D print PDMS (Silgard 184) without modifications.
• Key adoption factors include leveraging 3D printing's unique capabilities rather than replicating 2D designs.
• The integration of world-to-chip interfaces, such as Luer locks, significantly improves device reliability.
• Creating truly 3D structures with complex internal geometries represents the future of microfluidics.

The consensus is clear: successful adoption requires leveraging 3D printing's unique capabilities rather than simply replicating 2D designs. As these technologies mature, we are witnessing the emergence of truly three-dimensional microfluidic systems with integrated functionality that promises to revolutionize diagnostics, drug development, and biological research.

SUBSCRIBE to join us at future 3DHEALS conferences to connect with innovators and investors in the rapidly evolving field of 3D printing for healthcare applications.

Watch this event recording on demand.

YouTube Event Highlight Playlist.

Podcast engineer: Faith Fernandes

Chapters

• 0:00 Introduction to 3D Heels and Microfluidics
• 3:37 CatWorks3D: 3D Printing for Microfluidics
• 22:08 RapidFluids: Rapid Prototyping Services
• 45:54 McGill University: Academic Research Applications
• 1:13:42 Phase: 3D Printing PDMS Materials
• 1:30:54 Panel Discussion and Q&A

Transcript

Speaker 2: 0:02

Good morning everybody. I'm going to let people to trickle in. Thanks for joining us. I know it's very early in the morning on the West Coast and sometimes in the middle of the night across the globe, so thank you very much for joining us. We have quite a large audience today. Hopefully, we will deliver the knowledge that you're looking for and also a very engaging and exciting conversation among the speakers and you.

Speaker 2: 0:27

My name is Jenny Chen, founder and CEO of 3D Heels. We're a small media company and we have three missions. One is to educate everybody. 10 years ago, when I started got interested in 3D printing, I realized my understanding of 3D printing was very shallow and I wanted to learn more, and then realized everybody else's knowledge is equally shallow. So it's time to learn about this technology, and it is constantly evolving. We have new things coming up, new founders, new technologies invented every day, and I think it's a great platform here for us to learn about them.

Speaker 2: 1:02

Number two is networking. We used to host a lot of in-person events. In fact, in 2018, I just realized we hosted 38 in-person events all over the world with the help of community managers, but that was the glorious day before COVID. And after COVID we're almost entirely virtual, although occasionally we do organize in-person events as well. However, the way that you can network here on the virtual platform is to input your social link in the chat and obviously you can tell people who you are, your name, where you're from, and typically we have 30 to 40 countries around the world who are either watching this live or on demand, so it's quite a vibrant community every time. So do that. And number three is we have a program called Pitch3D. We help early stage startup, which means up to series A, with fundraising, and this program is entirely free to you. I spend my free time to do this, so if you're in that category, feel free to reach out to me, and we have I can send share a link for you to to understand what that program is about. But without further ado, our topic today is quite popular and we host this once a year, every year.

Speaker 2: 2:23

I think that's a redundant description, but anyhow, you know, I know about microfluidics at the same time as I knew, or started to learn about 3D printing about a decade ago, and I learned. I actually went to Dr Ali Kudhasani's lab I don't know if you know him and he was showing me how he makes these microfluidics chips himself or his team in the lab, and it's quite an elaborate process, a lot of arts involved, and he's telling me that 3D printing, while very ideal in theory to make a chip, it's really challenging and we were just not there. And after all these years, it is really pleasant to see that we now have more options to do this with 3D printing, and everybody is recognizing the power. So the first speaker today is also Hamdeep Patel, and he's also the founder CEO of CatWorks3D, who is also the sponsor for this event. So thank you very much for the support. Without you guys, the supporters, we could not host this on a regular basis. So thank you very much, but without further ado, please share with us what you're working on.

Speaker 1: 3:42

Yeah, thank you very much, Jenny, for that introduction and let me just launch my presentation here. I am, my name is Hemdy Patel. As Jenny said, I am the co founder and CEO of Cadwork City. We are a 3d printing company and solution provider for microfluidics. Let me, I guess I can touch on what Jenny had just said.

Speaker 1: 4:09

In terms of the available technology for microfluidics, there have been quite a number of them and all of them had a very unique set of deliverables which was very, very important for researchers around the world. There was the soft lithography that Jenny had spoken about, the CNC milling and polyjet. There's injection molding. All of them had a really strong set of deliverables for microfluidics at the microscale. And then, around eight to 10 years ago, 3d printing made its way into microfluidics and at that time what the technology was was that printers were providing solutions for macro scale printing and then they were trying to adopt or modify that solution in order to reach the microfluidic or micro scale that is needed for microfluidics Now, right across the platform. All of these technologies have their barriers or at least their pain points. In terms of the first three that were traditionally used, pain points usually meant messy or very difficult technology to work with. It was expensive or the length of time. When it came to 3D printing at least the first and some of the more commercial available printing you're noticing that there is pixelation, there isn't a clear-cut device strategy, there are issues in terms of surface roughness, and those are the things that we're trying to address with our platform. To address with our platform, 3d printing, I think as everyone now has become aware is the fact that it does allow users, researchers and engineers to go from concept to commercialization a lot more faster. This iteration and design cycle gets a lot more quicker. In most cases, you're able to find iteration cycles are speeding up this design process by nearly 80% or more.

Speaker 1: 6:12

In terms of our company, and the focus of what we're doing right now is that we've sort of looked at microfolios in these two unique areas. One is the need to be able to cast PDMS, and we've got a master mold material that users are able to print and it's as simple as pour, print and cast In this case in terms of the cleaning stage. Really, these molds are ready to use right off the printer, where you don't need any release agents or any sort of post-processing of the actual device itself other than being able to cast Eupedemus or any like a silicone or agar-gar right on the actual mold itself. The second batch of users that we have is those that are looking at printing out monolithic devices. Again, the process is quite simple using our technology, pour, print and clean, and this cleaning process is as simple as it's noted. You clean it in IPA compressed air. You don't need to polish your surfaces, you don't need to coat it. It is optically clear directly out of the printer itself.

Speaker 1: 7:35

We are located in Canada and our client base is worldwide. We've got research teams around the world that are using our platform, along with Big Pharma and government agencies and really the thread that connects all of these entities together. In terms of what they were looking for, they were looking for a complete 3D printing system that was optimized for microfluidics, materials that were made specifically for microfluidics itself, and also a methodology that was made specifically for microfluidics and delivering the needs of microfluidic users. We were aiming to take them out of the clean room, take them out of expensive and long drawn out processes and then do everything at bench side. The one key fact and this is the overarching mandate and the mission of our company is to actually focus on deliverables undebeatable deliverables that our users expect when they're using traditional methods. They are wanting to be able to duplicate that on a 3D platform, and that's what we are aiming to do with our platform.

Speaker 1: 8:57

So if we were to do just a very simple cross-comparison between what you design and what you're getting, if you take a simple Y-channel design here, this Y-channel has a series of herringbone patterns down the center and if you were to print it on a commercially available printer using high-resolution, commercially available material and then compare that with our platform that has been optimized for microfluidics. This is what you get, so visually, when you expect, inspect it, you don't see much different. It seemed to be very similar to what your CAD file it's. It's when you sort of start taking a much more closer examination of your printed file and take a look at what those herringbone patterns do look like Now off of a commercial printer. As you can see, this is where it starts to.

Speaker 1: 9:51

The issues are very prevalent. You're starting to see pixelation, this sort of boxing pattern, as it's trying to make the actual herringbone, whereas our device is now really outlining the intended design of the researcher. If we take a further look at another feature and this is the Y junction, that happens again, that same pixelization that you can see on the channel walls, and this also impacts everything down the line. So if you're using this as your master mold and you're going to cast PDMS, this defect now translates onto PDMS and so, effectively, you end up with a PDMS that doesn't do or function the way that you would expect. Another type of file that would be expected by most users is this simple straight line with serpentine. Again, if we do just a very simple comparison, visual comparison, they look fine.

Speaker 1: 10:52

It's when we start scanning under a digital microscope and that's where the differences become very apparent. At 50 microns you are starting to test the limits of the material and the machine itself, whereas on our platform you can still see a very clean straight edge on this raised channel and really the big comparison happens in the serpentine. These are features that are very difficult to reproduce on a printer. If you look at the commercially available printer with their material set, you can start noticing that pixelization, or the noise that you're going to add to your design, is now very much prominent there, whereas if you look at our platform, it has a very distinct channel shape and the rounding of the corners are very distinct as well. If we take a look at our clear material, this has become one of our strongest materials out there because there are a lot of users who are trying to move away from PDMS onto a clear material and we use a very simple channel structure 80 microns wide, with three ports commercially available printer. There's always a distinct yellowing of the device and there's a frosted finish on the surface, whereas using our platform with the clear microfluidic material, you've got a very clear, distinct, transparent material and then, if we take a real closer look at the actual channel, you're off of the commercially available 80 microns. It was not, it didn't come out at all, whereas on our platform, you're able to form this channel. To form this channel.

Speaker 1: 12:46

Now the question that I always get at this point of any conversation is what's the difference between commercially available printers and what is it that you have you done on your side that allows you to do and deliver these type of features and products? And that is we knew right off the get-go is the fact that if you're going to be printing microfluidic parts or devices or features, you had to really deconstruct your printing functionality down to this most basic part, and that was actually each layer that was printed. So you're now needing to optimize each layer that's printed on your device and then that is the foundation of the next layer that's actually printed. So if we take a look at what a commercially available printer with high resolution materials, this is what the surface actually looks like.

Speaker 1: 13:37

This is a typical pixelation sort of checkerboard pattern that you see. If you compare it to ours, you see a much more smoother finish and just on the visuals you see that there is a significant difference between the two and this is more of a qualitative analysis. But if we're going to do a much more quantitative analysis and do a surface roughness analysis between the two, this is what you get off of a commercial 3D printer. The pattern that you see, the series of troughs and peaks, actually align with the actual pixelization of the checkerboard pattern that you see there. The same analysis. When you do it off of our platform, you see a much more smoother finish. Off of our platform, you see a much more smoother finish and if you were going to look at numbers, you would be looking at a roughness and RA value of anywhere from 1.5 to 11.5 microns for a commercially available 3D printer, whereas on our platform we've been able to reduce that down to 0.18 microns. So that's an improvement of nearly 85%.

Speaker 1: 14:51

So, when it comes to our tech and what we want to deliver, there are some very simple things that we want to deliver. We want to help researchers get out of the clean room and bring out most of their research, or at least their iteration cycle at BentSight. We want to ensure that the setup is very easy. We want to bring down their fabrication time from weeks and months down to a single day. Since we manufacture our own materials and reformulated ourselves, we're able to monitor the type of raw materials and raw products that we're starting with, so to ensure that for enclosed spaces where we're not going to be, none of our materials have odors in it. The fact that you're using a 3D printer allows you to fully customize your devices in all different areas and, lastly, the machine is fully open source, so it is open to any third-party material without the need for any licensing. We are more than happy to help researchers or any teams you know set up profiles for third-party materials as well, and that sort of sets up what the machine and our setup has been up until today. In fact, we're proud to launch that, and this is some of the articles that were written.

Speaker 1: 16:15

I think I just jumped ahead there. Let me just jump ahead right now. This is a launch of a new material that we're going to be bringing to our users on May the 8th. It is a material that's been in the works for quite a while. Take a look, thank you. So some of the key features of this new material is that we have had it validated over a broad spectrum of cell lines of over 90% cell viability.

Speaker 1: 17:31

It is optically clear, very, very optically clear, to the point where you can actually do microscopic analysis directly on chip itself. And it is inert under UV light, so you can start doing your analysis under fluorescent light without any issues. And this, as I said, has been a material in the works for quite a while. And here's some links that you guys can take a look at if you can get updates, white paper on this material. If you want to book a meeting with us and get more information, you can scan this, and these links will be available after the show as well, thank you. Oh, before I go any further, the optical transparency is very important to us. The optical transparency is very important to us, and so, for this actual presentation, you've been viewing this right through that chip that we had designed and that was on the video. So that is how optically transparent the actual material is, and this is unpolished. It hasn't been processed other than using IPA and a compressed air.

Speaker 2: 18:45

That is more clear than my glasses lens, to be honest. Thank you for showing us a great, great presentation, md. We have one question from the audience, but I highly encourage people who have questions to put it in the QA box. I can't follow the chat. Chat is for social and if you have questions, please put them in the QA box, and your questions are way better than mine, trust me. So we have one question from Luciano. I don't know, I feel like you already kind of addressed it. It says pixelated edges and uneven surfaces. In that context, which approach or process would you recommend when working with chips that involves optics?

Speaker 1: 19:31

That involves optics Like I can only base it on our knowledge. If you're using domed shapes, I guess they would need to answer is it domed shapes or is it flat structures, pixelations you're going to find right across the board. On our platform, we have been able to minimize all of that, so that would be like you'd have to get our system in order to minimize that type of stuff. Cause this our system is set up with, where we've optimized the actual printer platform, the material and the methodology in order to deliver what you're able to see.

Speaker 2: 20:10

Great, we have another question from Yan Liu. He said I don't think you had talked about it. He said what wavelength is the printer? Is it 405 or 385?

Speaker 1: 20:24

Oh, I guess 3D printing in general is available in a wide range of wavelengths. Ours is set at 385. We find that the available photopolymers are I guess our CTO, who manufactures all of our photopolymers, loves 385. And so we built our platform on 385 nanometers. Got it?

Speaker 2: 20:48

Okay. Julie asks were neural lineage cells viable on this material Very specific?

Speaker 1: 20:55

Very specific. I think it might be something you might want to sign up to our white paper. I don't think we did any neural lineage cells. There were. We did a variety of adherent cells and suspension cells. I can't remember the exact details of which ones they were, but while we're conversing I'll see if I can pull up that information for you and I can share it.

Speaker 2: 21:22

I mean. Another quick question, since this is a more general question, is how do you work with you guys if they're not sure if their cells are going to work with you? I mean, how do you work with researchers who are not sure if your system is going to work for them?

Speaker 1: 21:34

Well, I guess the first thing that we always do is that we ask that we first, during our first conversation, we try to figure out exactly what they're doing and what we're doing and if it is actually a match. The next stage of that would be trying to find out if they're doing cell lines, any particular cell lines and they want to evaluate the material. We're more than happy to print out a sample for them so that they can evaluate it on their side, and then we can proceed and have a conversation further at that point, Great.

Speaker 2: 22:05

Okay, let's take a look. We have more and more questions. This is like explosion of questions. I'm not sure I can address all of them, guys, so hold on one second, let me just take a look. Okay, what is the smallest channel, height and chamber you can achieve?

Speaker 1: 22:22

So right now we have. So this trip here, we've got that one there, I believe is 114 wide by 150 tall. We have done 60 microns wide at, I believe, 300 microns tall, like. The one thing that I guess people fail to understand is that as you get smaller and smaller, it isn't. You're now trying to. You're challenged by optics of everything. So there's your light. Your UV light is passing through a series of membranes and glass and surfaces, which causes defects and diffractions that will cause deviations on your size. You're also trying to optimize your materials in order to print at that scale as well. So it is a work in progress. Right now, the newest material that we have, we know that we can go down to a width of 60 microns and if we're able to share, in fact I do have that document. Yesterday I just got an email from my….

Speaker 2: 23:34

You can upload it as well, if you can't, I can upload it as well, because we can upload PDFs for everybody, all the speakers, if you have stuff. So we're going to have to move on, mainly because of time concerns. However, hemdeep, you can actually write your answer in the Q&A box. Just type answers for these people. So sorry guys, we have to move on because we have only 90 minutes here. All right, so we're going to move on to our next speaker. Thank you so much, hemdeep. Excellent presentation, I really learned a lot. Our next speaker Thank you so much, hamdi. Excellent presentation, I really learned a lot. Our next speaker is Paul Marshall, ceo and, I guess, founder or co-founder of RapidFlex. Hi, paul.

Speaker 2: 24:14

Hi Jenny From across the pond right. Are you still in the UK?

Speaker 4: 24:19

Yeah, we are based in Newcastle, northeast England. Now, if I can share my presentation, let's try that. Does that come up okay?

Speaker 2: 24:35

Yep.

Speaker 4: 24:36

Fantastic. Right, let me find the other window, which is there. It's not. It's this one. Bear with me, I'm on a different screen.

Speaker 4: 24:45

So, yeah, I'm Paul Marshall, I'm CEO and one of the founders of Rapid Fluidics, based here in Newcastle, northeast England. Unlike Cadworks, we are a user of 3D printers, so we provide rapid prototypes of microfluidics using a range of 3D printing systems, including Cadworks, and what I'm going to do is explain the services that we offer, what we're trying to do and how we do it. So let's go through. So, yeah, we provide microfluidic prototypes. The basis of the company came from my experience in a diagnostics company developing a point of care molecular diagnostic system using disposable microfluidic cartridge which, at volume, is going to be injection molded, but for prototyping it was expensive, it was time consuming, it was poor quality, what we're trying to do. So we worked with the local university here in Newcastle to come up with a process for 3D printing microfluidic channels suitable for PCR amplification. Once that all was completed, I saw the opportunity to take that service to a wider audience, offering next-day delivery, effectively, of bespoke microfluidic components. We also work with our customers on the design side of things. We're not just a prototyping shop. We have a team of very skilled engineers here who can work on anything from the you know the microfluidic side of things, the mechanical design for manufacture up to the full systems, electronics and software as well, and then, obviously, when it comes to the scale up, when you're taking your device from prototype through to mass manufacturing, you know there is a limit as to where you can go to in terms of quantities with additive manufacturing. So that's where we'll bring in partners. So we know a range of injection molding companies, for example, around the world, and we'll make those connections. We can bring in the design for mass manufacturing at an early stage, at the prototyping stage, or we can partner up and share the experience. So our main capability as Hemdeep just demonstrated there is the ability to create fully enclosed microfluidic devices.

Speaker 4: 26:59

Now we started off very much on the more traditional, the more traditional two and a half D side of things, creating flat, linear microfluidic systems. We've expanded from that into the more three-dimensional side of things as well to really show the benefits of 3D printing. So that's got us into manifolds, anatomical geometry, things like that. We're now moving into alternative manufacturing as well. We're looking at thermoplastic forming, so pressure forming and hot embossing. I'll show a few examples of those later on in the presentation, partially as a stepping stone towards the injection molding so you can transfer materials to thermoplastics, and also as a more suitable batch production side of things so we can turn around higher quantities in a quicker time than you can with 3D printing. And then also the embedded electronics. This is something that's quite neat that's come about over the last year or so. Adapting the process of print pause print to actually embed different components into the 3D printed part Materials is always an interesting one. Yeah, absolutely love that little reveal. You just did hem deep. That was wicked um.

Speaker 4: 28:10

With 3d printing in resins, um, it's not thermoplastics. There's limitations. You can't weld it, for instance. It's a thermoset. Most of it is methylacrylate based resins, um, but we have got a range, we've got access to an angel we all start with. You know the basic modeling resins that you can buy on amazon for 20 quid a bottle. Um, and that works for something. You can actually, if you correctly wash and cure these, these materials, correctly they're moderately by putting these out through micro fluid channels in standard resins.

Speaker 4: 28:38

You don't have to go for the biocompatible materials, but you know they'll glow like crazy on the uv. They're not totally biocompatible. There's definitely limitations there. So we've got a range. We can go from the the cheap resins up to the more expensive materials. We can go opaque, we can go to transparent um high temperature resistances, for even the basic materials will cope with um pcr type temperatures but we can go up to 170 or so with the materials we've got in stock at the moment.

Speaker 4: 29:03

Um. We've been doing some pretty cool stuff with flexible materials. Recently We've been working closely with Applied Molecules over there in Boston with some of their new materials and we've got some really nice silicon-based materials we've been developing with them. At the moment, as I say, biocompatible, which is a bit of a misnomer when it comes to this particular application for microfluidics, especially less so for medical devices, the biocompatible certification is related to human contact, so wearables, implants and so on not necessarily biocompatible at a cellular level, but it probably is and we can work with, you know, with third parties to verify that the materials are suitable for particular applications.

Speaker 4: 29:43

And then, obviously, we mentioned integrated electronics. In the same way, we can integrate flexible membrane, we can integrate optical components. Again, it's even this printable or print technique that we sometimes use. There we go.

Speaker 1: 29:59

Capabilities.

Speaker 4: 30:00

So this is a little out of date and not totally accurate, if I'm totally honest with you, but it's the question everyone always asks how small can you go? It depends on the material, it depends on the printer. As I say, we have a range of printers. We have the CADworks, we have a couple of the Sega printers. We've got the commercially available printers, as Henry phrased it, then the SLA LED printers which allow us to go to large format printing as well. The DLPs, ultimately, are more accurate.

Speaker 4: 30:28

You can get feature sizes down to maybe two pixel sizes With the LED machines. You're looking four or five pixels to get the decent definition. And it varies on the materials. The low viscosity materials you can get better definition. The biocompatible materials tend to be higher viscosity, so it's harder to get that size. The footprint footprint that we've mentioned there, the 51 by 29, that's a bit of a limiting factor. That's our seagull max 27 um which has this footprint of 51 by 29. That will go smaller. So, as we say there, you know we can create with a non-biocompatible material. We can create a channel 100 microns feature size at 70 microns we can actually go smaller. We've created channels 50 by 50 microns, fully enclosed. So 50 by 50 microns square section channel using the ASEGA MAX27. If it's an open channel, so if we're not enclosing it, we've managed to create channels 50 by 10 microns, so 10 microns deep, 50 microns wide. Again, moving to the biocompassable materials, you have 200 or 300 microns minimum and that's really the more comfortable side. So we can go down to 50, but it's a hell of a challenge and it depends on the complexity of the geometry. We prefer to be slightly larger, but then we can go really quite large. We've recently done some manifolds, created some manifolds that were three millimeters, with an array of channels that were in the region of one millimeter. So much more on the millifluidic side of things. But as an alternative to TNT machining and bonding, it showed the opportunities for our particular customer who needed these large manifolds. We were able to do them in a matter of days, whereas the lead time on the machine passed for six or eight weeks, so much quicker than when we can do that.

Speaker 4: 32:15

One of the really cool things with 3D printing is you can integrate other geometry. So if you want external fluid connections, so lower locks, mini lowers you can integrate stainless steel, tubing, barbs, threads. We can go down to M1.6, rather not Again, m3 is a nice size, m2.5 maybe yeah, m1.6 we have done. But the more standard M6 or quarter 28 fertilizers absolutely fine can integrate that channel tube directly into the part without any more minimal secondary post-processing. We have what we call the modular microfluidic system. This is a system that's on our workshop, which has nothing to do with 3D printing really, other than the fact that we do 3D print the components that form it, and it's an over-centre locking clamp system to create a breadboard style system for developing an instrument. The intention is to start adding components heaters, coolers, magnet actuators and so on, light sources and the like, so you can build up an instrument. That's work in progress, but it that allows us to connect to a flat and open port progress, but it allows us to connect to a flat and open port.

Speaker 4: 33:33

And then we get on to manifolds. This is this isn't is quite an interesting application of microfluidics came from an existing customer who asked us if we could make a valve manifold. We'd never even thought of it before but we were able to, they say, with the other to machine and bond a manifold. You're often looking six weeks or so lead time. We were able to make these parts in a day or two and that's opened up some huge opportunities for us within the fluid handling lab automation sector. We've been doing a lot of work with a variety of valve companies.

Speaker 4: 34:03

The top picture there you can see see is an optimized model where we've basically taken all the excess material out of the manifold. We were presented with a design which was to be originally three layers of acrylic to be machined, drilled, bonded together, and, as I say, that'd be six weeks or so, we were able to print that in 11 hours. I think it was to print that. But then we took the whole design, optimised it, so we took out all the excess material, made the most of 3D printing, got rid of all the right angle corners for the fluid tracks to improve fluid flow, improve the manufacturability, and we got that print time down from 11 hours to two and a half hours. And typically the quantities that manifolds like this are required in is a few hundred, is a few thousand. So actually the batch production of 3d printing works really really well here.

Speaker 4: 34:52

So when we looked at the costing of that, you know we could 3d print the equivalent for pretty much the same price as a machined part but massively quicker, optimized it. We reduced the cost. So with the material we got down, um, we got 70% of the material out of there. We knocked 80% of the cost up to that, so over a quantity of 200 of those. It works out a saving of £36,000 to 3D print them rather than machining, which blew me away when we worked that out, and again a lot of interest in that from the market there. So yeah, minimize volumes, reduce weight, save on shipping costs. There's absolute winners. It's a fantastic opportunity that we're pushing. All right, is that video going to run? Let's see. All right, struggling to play the video, never mind, it's obviously too large.

Speaker 4: 35:45

So, embedded electronics, this is an interesting one. So the basis of our original concept when we set the company up five years ago and the PhD that predated that was using this process, called print-pause-print, which is fairly common knowledge and only certain printers allow you to do this where you print effectively, the open channels, take the part out of the printer, you take it out, you then use a secondary material, a sacrificial material, to fill the channel so you can put it back in, print the lid directly on, and that's how you get your fully sealed micro-threaded and the knowledge of how to use that material. That's our specialty. That's what we can do really really well. We know what material it is, we know how to apply it, we know how to remove it. We don't always use it, though. As printers have got better, it's less applicable. It certainly doesn't work with circular cross-sections and complex geometry, but that pausing process allows us to do other things. So, as I say, we can put glass components in there, we can put flexible membranes in, we membranes in, we can put electronics in.

Speaker 4: 36:42

Knowing that electronics are really useful for, especially for electro-biosensing, electrochemical biosensing, we thought, well, let's try and put a PCB in that. And because we've got some larger format printers, we thought let's put it into a well plate. So if this video played and I think it's on our website it demonstrates a very customized well plate. So the left-hand side, there is wells of a 96 well size. We've got 16 and 32 well sizes in there as well. We've got micro channeled between the wells. The pcb is wired up to a control system that detects fluid. It's got fluid detection. It's got heaters. It's got thermistors as well to monitor the temperature. You've got light sources and you've got an open one in there as well. So we're're trying to promote. You don't have to be restricted to the layout of a well plate, but you can still use a well plate reader to run your particular experiments. Obviously, as we are embedding the electronics in that, we can have the fluid directly in contact with the electronics or we can insulate it and embed it slightly within the resin itself. So let's say you've got electrical insulation and then we get onto my favorite stuff the anatomical models. These things are amazing.

Speaker 4: 37:56

This came out if those of you who follow me on LinkedIn you'll see I posted about this recently because quite a lot recently. It came originally from creating a leaf model. That came from the idea of can we avoid using straight lines? Can we take a sketch, turn it into a 3D STL and 3D print that? And we started off with taking an X-ray of a leaf to generate the microfluidic channels of the leaf venation. That got the attention of people involved in vascular systems and that opened up further opportunities. So the model at the top there is actually a prostate. It's taken directly from an X-ray. We've converted the X-ray to monochrome image, black and white image. We've converted the X-ray to monochrome image, black and white image and then converted that into a three-dimensional circular sectioned STL file that we 3D printed, the one at the bottom.

Speaker 4: 38:42

It's called, if I can get the Latin right, metamorablus. It's a vasculature network, I think, in the brain, which is for research, r&d purposes, of research chemicals going in through the vasculature and at the moment you can only use on a live brain, which means using lab animals. So in the move to reduce lab animal testing, by 3D printing these shapes which come directly from the CT scan, we can create vasculature networks for research. The channels that go across the middle, if you imagine that sort of H-shaped the channels task as your networks for research. The channels they go across the middle. If you imagine that sort of H shaped, the map channels that go across the central bar. They're 250 microns in diameter, fully circular and all over the place.

Speaker 4: 39:21

These things are brilliant, absolutely love them. We've all. We've done kidneys, we've done livers, we work in the heart model at the moment and it really shows what you can do with 3d, 3d printing that you simply cannot make any other way. So what's next? Is that video going to play? Rouch, the video's not playing. If it played, there's a reading. Oh no, it's trying to.

Speaker 2: 39:45

I think it's going to work. Yeah, the video's going to work.

Speaker 4: 39:51

Yeah, there we go. Yeah, we're live. So that's a time lapse of making key chains, which you may ask. Why do we make key chains For a swag to give away at trade shows? But it demonstrates the batch production capability. So we made these chains there. They're not the size of a bullet. Perhaps You've got a spiral microfluidic channel going there.

Speaker 4: 40:09

Obviously we've got the logo embossed into it and we make those 150 at a time. You've got three rows of 50, so 5 by 10, I think it is components all in one go. It's, I don't know, an eight-hour print or something that's. One printer can make 150 parts in eight hours. Two printers can make 300 parts. You can make 600 parts in a day. You can really see the benefit.

Speaker 4: 40:30

If you design for additive manufacturing, batch production, larger scale production starts to become very, very feasible, and that's what I'm keen to promote, as 3D printing has a lot of advantages. It's very early days really in the manufacturing side and I think it's additive manufacturing. The world over, every sector is looking at how to scale up and it's slowly becoming much more normal. The example at the bottom is pressure formed thermoplastic. I haven't got a photo of the hot embossed parts, but we've been 3D printing tools to do hot embossing so we can turn around the tool in a matter of hours and then hot emboss it so you can then translate into thermoplastic. So if you need to use COC, cop, polystyrene, whatever the idea is, we can actually do a genuine rapid prototype in COC or polystyrene and so on and get that out within a day or two.

Speaker 4: 41:19

Yes, the tool isn't gonna last very long. You might only get 10 parts from it. You might only get two, depends on the complexity, but you can do it. That's the key thing here and I think there we go. That is the last slide.

Speaker 4: 41:32

Hopefully this one plays. Please play, Yay there we go.

Speaker 1: 41:39

So that's the leaf that I mentioned.

Speaker 4: 41:40

It's just super cool. I love that one. As I say, we're based in North East England, New Caledonia. There's a growing biotech sector here, but we work with customers all across the UK, across Europe, across North America, a coupled in Australia as well. We're slowly getting over there as well. We make small parts. It's very easy to ship them globally. Tariffs or no, it's not a massive problem and hopefully that's kind of covered everything we do.

Speaker 2: 42:08

So there we go. Thank you, paul. Your presentation always wowed the audience with the incredible visuals and videos. So people who have questions please put them in the Q&A box, because I can't keep track and I cannot handle explosion of questions, 10 at a time, the last minute of the session. So my question is how do you work with typically work with customer uh, who wants to let's say, a large customer who wants to mass produce something? How do you walk them through your design process to your manufacturing process?

Speaker 4: 42:42

yes, the application depends what they're trying to get out of it if if somebody comes along to me.

Speaker 4: 42:47

So say, hypothetically not totally hypothetically scientific startups spins out of university. They've got a novel assay, a novel biosensor. They're trying to turn it into a platform. They they want to work with us to do the rapid prototyping, but their five-year plan involves transitioning to to injection molding. Depending on where they're located in the world, we'll basically hook up with a local injection molding company who's got the specialist skills and we'll get them involved at a really early stage so we can consider the design for manufacturing. So you know exactly what's needed to actually, you know, to get them involved, we'll go through the process. We'll help them on the on the iterations of design.

Speaker 4: 43:26

If they don't have any engineering support, if they are genuine, just a small scientific company, we'll help them on the design side. If it's getting more complex, we've got a team of microfluidic experts we can bring in when we need to. We'll help them on the manufacturing side of things. We'll help them on the instrumentation side and then, when it involves scaling up, as I say, we'll start that conversation at the very early stage so that we know what we need to do, and this is why we're moving into the thermoplastic forming as well. So, as I say we've got that stepping stone so we can actually transition, because ultimately the resins that you're 3d printing in do behave differently, um to the thermoplastic. So we understand them and we know what what the limitations are. We can do everything possible to modify contact angle with, with coatings for instance, to make them the correct hydrophobicity to represent what they're going to need in the future. But there is that transition and we can kind of cover that, depending on what they need to do.

Speaker 2: 44:21

Okay, we have a question from the audience that says how to integrate microvalve into these 3D printed microphotics.

Speaker 4: 44:30

That's a really good question and something we enjoy doing. So the easiest way is simply putting a flexible membrane over the top. Um, so again, with the print print print technique you can change material. So you, you, you print the bulk of the part, change the material and then print a flexible material to create a flat membrane that can be externally actuated either by an external pneumatic system or mechanical actuator. So that's the simplest way of doing that.

Speaker 4: 44:55

We've been looking at ways of integrating that more into the part, if we can the other way is obviously you can actually use an external, you know flange mounted valve, micro valve and the likes of stygo or spc or anyone great.

Speaker 2: 45:10

I have another question from actually several questions from luano. He says how did you overcome the clocking issue? Are the channels fully enclosed or do you use a welded hemi layers? Hemilayers, sorry, Hemilayers.

Speaker 4: 45:27

I don't know how do we ensure that?

Speaker 2: 45:32

Yeah.

Speaker 4: 45:33

I'm going to say that this is our secret sauce. This is our knowledge of how we ensure that these channels are completely clear. I'd like to say it's magic. It isn't. I've just got some very clever people.

Speaker 2: 45:45

Yeah, no proprietary information. It's fine.

Speaker 4: 45:47

Don't tell us secrets, you can tell us you know, a lot of it comes down to experience. We've been doing this for five years, so we know how to well, the team knows how to drive the printers to use the correct print settings for the correct materials, so we can actually ensure that these process correctly well, at least we know it's achievable by human, yeah, okay.

Speaker 2: 46:10

So, uh, let's see what is acceptance rate in fabrication for your works I don't know, what that means yeah no, no yeah

Speaker 2: 46:22

sometimes yeah, sometimes I was like is this like a scientific term that I don't know, because it's very possible. Okay, it sounds like somebody from uk is asking a question. Lots of love from there. It says a few stack questions here. Okay, for embedded electronics, are they being fully embedded into the resin print? Does this, yeah, okay, or is this voided being created? And so the answer is yes, all right. All right, let's see. Are you working with injection molder on the scale up? I think you just said it theoretically.

Speaker 4: 46:58

Oh, I see, yeah, yeah, yeah. I see that question Theoretically going after their work. We're not going after that work. We're never going to. For the people who want a million parts, it's just not, it's not within our ballpark. I have no intention of doing that. I want to work with the injection molding companies and we can do the, the, the one off, the two off, the 10 off, the iterations. We can do the hundreds off, maybe the thousands off for the batch, batch productions, for the data generation.

Speaker 4: 47:22

But when it gets to actually making a commercial product, the target costs that people want their disposable cartridges to come to, we can never match that price with 3d printing. You know, in theory and I have priced up making a million parts a year for a job and it wasn't insane, it wasn't as cheap as 3d printing, but actually it basically meant buying a whole room full of 3d printers, employing a team of people to operate them. But when you broke it down into the unit cost per part, it wasn't stupid. It was an order of magnitude or two higher than you can get with 3d printing. So it's never going to go anywhere. So that's, that's how we work and that's why I get on well with the injection molding companies well, if I've learned anything from doing these webinars is never say never so oh, yeah, absolutely yeah, all right, cool, we have quite a few questions still, like I, I said, you know, the earlier you submit your question, earlier you can get in line.

Speaker 2: 48:17

But we are running out of time and I want to move on. Paul, excellent presentation again. I think I need to rewatch this to really fully grasp everybody's content. So we're going to move on and then we're going to come back to you later for a panel discussion. Okay, yeah, awesome. Okay, our next speaker is professor Christopher Marais, who is a professor at McGill universities or lots of Canadians today. Let's see, let's see, let's see. Okay, there we go. Now we're in business.

Speaker 1: 48:57

If you can share your screen.

Speaker 2: 48:59

that would be great, I can there we go. Is that?

Speaker 5: 49:03

working. Yep, it's working now. All right, wonderful, okay. Thank you, jenny, for the invitation and thank you everyone for being here.

Speaker 5: 49:11

I think I present a slightly different viewpoint on this. I am a very, very end user, right? So we certainly don't make the 3D printers. We don't work with other people to design, you know, different usages of that printer. We instead use the 3D printer directly in my research lab to solve a number of different problems. So my work is in microscale tissue engineering. I'm currently at McGill University in the departments of chemical and biomedical engineering.

Speaker 5: 49:38

My work is in building tiny versions of tissues so that we can understand how they function, and I'm particularly excited and interested in the mechanics of those tissues and how mechanical forces change disease function. Here's a sort of big picture overview of what my lab does. We build organs on a chip, so these are again tiny versions of tissues that can be fluidically connected to each other. We look at various disease processes and we look at various developmental processes, our general workflow. The thing that has emerged over years in the lab is we build a microscale version of that tissue. We use the fact that we have constructed it from the ground up to manipulate some feature of the microenvironment. This could be mechanics, this could be oxygen availability, this could be nutrient availability, this could be a number of different parameters that are external to the cell but still play a really important role in getting that cell to function in a realistic way. Because we've built the tissue ourselves, because we've manipulated various parameters ourselves, it allows us to ask questions and probe the tissue in ways that are quite unusual, right Like quite impossible to do in an animal model or in a human being. This leads to some pretty unusual insights.

Speaker 5: 50:52

My group works with microfluidics and fabrication. My PhD was spent largely in a human being. This leads to some pretty unusual insights. My group works with microfluidics and fabrication. My PhD was spent largely in a clean room building these kinds of devices where we can precisely control fluidic flow. We also spend a lot of time designing our own biomaterials and we use them for various organoid applications. So organoids are stem cell-derived culture systems which can really capture a lot of the complexity of in vivo tissues. We merge those ideas microfluidics and fabrication with biomaterials and organoids through computational models to really get a biophysical understanding of what is happening inside of those tissues. And then we often have to deal with custom imaging problems as well. So we build our own microscopes and custom design our microscopes so that we can image all of these together to get the kind of data that we want.

Speaker 5: 51:40

I have lots of different interests, but we've applied this sort of workflow to a number of different biological systems. We have active projects in the pancreas, in the lung, in breast cancer, understanding the placenta, understanding brain development and very recently in the gut and also now in spinal cord. So my interests are really quite broad in the biology side. But I think that 3D printing is emerging as one of these tools that can really facilitate this cycle, this ability to rapidly probe and understand biological systems, this ability to rapidly probe and understand biological systems. For today I'm going to ignore all of the cool stuff that we do in a biological system, but I'm going to talk a little bit about our microfluidics and fabrication and then how we integrate that with biomaterials and organoids. I'm anticipating that if you have questions about it, I'd be happy to take them. Questions about it? I'd be happy to take them.

Speaker 5: 52:38

So here's how we traditionally did this. I learned how to do this in a clean room, so this was 15 years ago. Training in the clean room took about three weeks to a month. This is the fabrication process, which you've already seen slides off, so I'll skip it. We'd end up with our devices, and every time we wanted to change one of these devices, it was roughly two to three weeks once you got good at it. So after four years in my PhD, I got good at this. I was able to produce a new style of device every two weeks For someone who's brand new. This whole process takes a lot longer. There's a lot of skill that's involved in making this happen, but you can anticipate a two to three week turnaround time and any changes in the device that you wanted to make.

Speaker 5: 53:16

When I was doing my postdoc at the University of Michigan, I was first exposed to this idea of 3D printing, so this was back in 2012. Scott Hollister and Glenn Green they produced a really remarkable workflow which just got me extraordinarily excited about this field. What they did was they were working with patients, in this case a baby who had a tracheal problem, and the trachea would collapse frequently. This is a life-threatening illness, of course, and Scott Hollister and his team came up with a strategy to build a bioresorbable tracheal stent. It would fit in, hold the airway open and then slowly get absorbed into the tissue. This was incredibly exciting. I had nothing to do with this work, right, but I was in the building at the time. So this is the Carl Gerstacker building on the University of Michigan campus, and the feeling that you got was just so exciting that this was a possibility. Right, this is something that you could do, and for me, this was touted as the first time that 3D printing had saved a life.

Speaker 5: 54:17

I got very, very enthusiastic about it and, just like with all technologies that have come through my lab, I went through various cycles of believing and disbelieving in this technology. So this is the Gartner hype cycle. I'm sure you're all aware of it. For me, this is my personal view of 3D printing over the last little while. For me, this finding being in the building at the time that Dr Hollister was doing this work, that was the technology trigger.

Speaker 5: 54:42

Everyone got really, really excited about it, and then we started to hit this trough of disillusionment. I feel as though we're currently in this stage where we're slowly figuring out what this is good for and what we can use it for, and then, ideally, we'd eventually get to plateaus of productivity afterwards. So when we first saw this happening, we said, okay, what else can we use 3D printing for? We tried a number of different things and we got disillusioned fairly quickly. So I tried to encapsulate those difficulties as best as I could.

Speaker 5: 55:16

First is there are limited by definition. If you 3D print something, you have to limit your materials right. The material has to be compatible with the whole process of 3D printing, and that limits the number of the things that you can use. This is particularly important for biological applications. You've heard a lot about the biological compatibility of resins that are coming out Hemdeep. I'm super excited to try the new CytoClear resin. 90% is way better than we've seen before, but for many of the applications in my lab, 90% is just not enough. When you start with a stem cell and you grow it up to an organoid, the cell might survive, but it just doesn't behave the way that it's supposed to or that we expect it to. So cytocompatibility is really a touchy subject for many people and we found it to be particularly painful when trying to work with the limited range of materials that are available for 3D printing.

Speaker 5: 56:12

I'll also say that the resolutions that we've got from 3D printing. I'll also say that the resolutions that we've got from 3D printing. They don't compare to the tools I've already used, so I've learned how to. I grew up in the clean room. I know how to make devices that go down to five microns one micron resolution. The 3D printed approaches that are generally available to us don't really compare to that kind of resolution. So for me, I had to make a big switch in terms of the design practices that I use to try and avoid these sort of situations where I need really high resolution prints.

Speaker 5: 56:46

I think another key issue is that there's limited availability of the infrastructure but, more importantly, limited availability of maintenance capabilities and skills to keep these machines going. Right now, this feels like a problem that is getting more and more tractable, right Like where the instruments are becoming cheaper and cheaper. More and more expertise is becoming available, but we're also interested in making devices in really resource-limited regions of the world, and if you want to make devices where they need to be, you need an entire infrastructure of people to have that happen, and so this was one of those big concerns for us. But honestly, with the rate of technology development and the rate that things are changing, I'm hoping that this will be a thing of the past soon.

Speaker 5: 57:34

So what do we do with the 3D printer in the lab? Well, we have the filament printers. I won't talk about the details of this, of course, but I'll say some things about what this is useful for. It's easy to swap out resins. Biopla, we found, is one of the most biocompatible materials that we can get and it doesn't mess with our cells at all. Printing with PETG is great. From building solid devices, we can print flexible devices.

Speaker 5: 57:56

Resolutions here go down to about one millimeter in XY, 0.3 millimeters in the Z direction. Here's an example of the kinds of things we do. We rapidly turn around mechanical devices. This is an example of a system that we built that will allow us to rapidly produce droplets, microfluidic droplets, from one of these pores. The 3D printed parts allow us to really improve the uniformity of droplets that come out of it. There's a ton of sample holders, sample forms, cases and supports All of the stuff that is needed for a lab to run but which we don't often spend a lot of time thinking about how much time and effort it takes us to put together, and my students have loved the ability to rapidly iterate on these devices and produce things very, very quickly.

Speaker 5: 58:48

Now, of course, there's downsides to those filament printing. They're not really good for microfluidics. Resin printing would be. We've had a range of resin printers in the lab. High-resolution printing can go down to less than 100 microns in X and Y, 20 microns in Z, but, as has already been discussed, photopolymerization chemistries really change your capabilities, especially with really advanced biological systems. What was really cool to us, though, when we first started in this, this was our first printer back in 2016.

Speaker 5: 59:23

When we first started in this, we realized that the 3D printers allow us to build designs that you cannot manufacture in the conventional cleanroom, and we wanted to try and capitalize on that to come up with applications where we could use this capacity to build genuinely weird structures that are not machinable any other way in in the lab. So there's a few way, different ways. This is gone. This is one application. We work with the company here in montreal, nanofacile. They are making a really interesting system to produce lipid nanoparticles that contain different system to produce lipid nanoparticles that contain different cargoes. The lipid nanoparticle production system is now a 3D-printed toroidal micromixer, so we print this directly into a resin, much like CytoClear that Cadillacs was mentioning, and we can use these to produce lipid nanoparticles with really really good consistency and really good reliability in the device, right? So simple application, but we were able to tune these parameters on demand, with you know, with roughly two hours worth of turnaround time, which is really quite amazing.

Speaker 5: 1:00:27

We then set ourselves to try to understand how do we use these tools to work with more advanced and complex biology, and here's an example of something that we did. We 3D printed spheres using a resin mold. So this is on CadWorks' black resin system. You can print these large devices. This looks like. Imagine a golf ball sitting on the lawn in front of you, right, that's what these devices look like.

Speaker 5: 1:00:54

This device in itself has not got great biocompatibility, particularly for stem cell applications. What we did instead was to replica mold this device into a polyacrylamide gel. Polyacrylamide is extraordinarily good at being protein resistant and also being compatible with most biological processes. This is a hydrogel now, and because of the shape of the hydrogel that we get from making these overhanging structures, single cells can enter the little vessels, enter the little chambers there, they can aggregate together and form spheroids or, more recently, organoids, and because of the size of them, they can't come out again. Because they can't come out again.

Speaker 5: 1:01:32

This allows us to monitor in real time, on an organoid by organoid basis, each one of these tissues. We can treat them directly on the chip, which means that we can wash out the liquid and replace the liquid with the treatment agent. We can label them, we can analyze them all while sitting on the chip and if you want to take them out, you simply flip the chip over and, because it's a flexible material, you centrifuge them and all of the organoids pop out the bottom. So this is what that 3D printed mold looks like. Here's this closeup view of the 3D printed part. This would not have been possible even five years ago, but you really get very clean resolutions on the surfaces and you're able to produce these really fine scale, high resolution parts with excellent surface finishes.

Speaker 5: 1:02:17

This allows us to make these highly uniform devices. Each one of these little units is a pancreatic organoid that we're taking from stem cells to islets. The idea here is we're making pancreatic islets eventually for replacement therapies. It was really interesting using this device because the organoids all maintained exactly the same size over 27 days of culture in the devices. In conventional models, where you've got a stirred tank, bioreactor or something like that, these organoids all fuse together and they create weird structures that are difficult to model and difficult to work with. So there's big advantages in combining 3D printed tools with bioengineered and biocompatible materials in these ways right, and that's been a common theme in the lab. We're going to continue pursuing that for many different applications.

Speaker 5: 1:03:06

I'd like to talk a little bit, though. I've talked, about replacing the material, using the material as a mold and then replacing the material for the stuff that comes in contact with the biology. I think that there's some possibilities to use the materials directly with biology, even with the more advanced kind of stuff that we do. So the reason we wanted to go to 3D printed devices directly for organs on a chip is because whenever collaborators come to us to talk to us about things that they want to do, they're excited now, right, or they're excited yesterday when they read the paper that gave them this idea. Chances are pretty good that a month from now they're going to be less excited and less enthusiastic, right, and then people have trouble funneling resources towards new projects.

Speaker 5: 1:03:49

The other issue that came up is that my students can't always keep up with the demand, right. Some of these experiments take three months to do. We make a device for them and then it goes away for three months and then three months later we hear back. My students have graduated and moved on to something else. Right Like it's very, very difficult for them to keep up with the demand that happens for these longer-term developmental projects. I'll also say that fine-resolution device fabrication it's still finicky, still takes some skill, it doesn't transfer easily between students and you'll always need these iterations.

Speaker 5: 1:04:19

So we've been spending a lot of time over the last year or so wondering how do we design devices so that they're as fast and as cheap as possible to make, so that my collaborators can turn this around in their lab. Recently, 3d printers have started coming out at $500 price points. At this price point I can afford to put one in my collaborators lab. They can press the button and we can work on the design components of it. This allows us to collaborate with people who are not just in Montreal but all across the country and all across the world as needed, and there's now a lab in New Zealand that's using some of our devices with this system. I won't show you the 3D printing process, of course you all know that, but the concept is that we can press the button and have these devices turn up.

Speaker 5: 1:05:05

However, the difficulties still exist. Right Like materials, compatibility is a problem. 3d live bioprinting is still a challenge that I don't know how to resolve really well for advanced biology. And then there's resolution limitations. So I'll point out two things that have come up recently. David Yonko, a colleague here at McGill, recently published this paper where they looked at using, where they came up with a new kind of ink, and the new kind of ink can be used in the really inexpensive printers. You don't get the resolutions that you get with some of our more advanced printers, especially like the ones you've seen today, but you do get good enough resolution for some of these organ-on-a-chip applications. And his group came up with an ink. When I saw the biocompatibility data for that ink, that's when I got really excited and started using these for our more advanced biological models. It's custom formulated, so we do have to make this from scratch in the lab. We're taking that ink and then we're combining it with some clever integration strategies that I think will reduce the resolution limitations. So maybe we don't need better and better 3D printers to go to finer and finer resolutions. Perhaps we can get away by integrating them with other components.

Speaker 5: 1:06:13

You've already seen some of the world-to-chip interfaces. I completely agree with Paul. This is surprisingly game-changing for us. Every time a microfluidic device fails, it's because of this world-to-chip interface. And the ability to put in completely monolithic world-to-chip interface structures, such as lure locks, really hugely improves the reproducibility and robustness of our devices, particularly when we put them in other people's labs.

Speaker 5: 1:06:39

We've also taken to integrating nanoporous membranes into the devices. So here's an example where you have a nanoporous membrane that is fitted into this space, while the rest of the device is 3D printed. This allows us to flow in solutions, and those solutions are maintained stably underneath the nanoporous membrane. They can flow into the channels and move through the fine networks later on. The last thing this allows us to do the idea of integrating different parts is we can integrate bioengineered parts into these devices. So here's an example of our bioengineered spheroid making system. We flip that over and stick it into the device, and then we can take a plug and seal the whole device off, so that you now have a well-engineered system that can be compatible with the tiny pore sizes that are available via the metaporous membrane. That can be built in a couple of hours in someone else's lab. So that is very exciting for us. Here's a super simple demonstration where we just try and solve a very simple problem that has big applications and big ramifications for others.

Speaker 5: 1:07:47

Culturing cells under flow and not high shear stresses, but just replacement of fluid, is something that is really promising in terms of many organoid development platforms. Here's a fully 3D printed device where we just fill up the tank and allow the tank to drain very slowly through a high resistance channel and our cells are cultured in that region there. We could print it this way, but this is slow and expensive. We've also figured out ways to integrate our devices with existing biological standard equipment that's in the lab. This is the 50-mil Falcon tube that my students cut up and screwed into the 3D-printed device and that works without leaks or anything. It's quite amazing.

Speaker 5: 1:08:26

In these devices we've shown we can get flow rates that are less than half a microliter per minute. That's maintained over a very long time. So again, these capabilities. They don't come easily in microfluidics but we're able to produce them with a 3D printed part. I'll stop there. This is my lab group who really does all of the work. They're a fun group of people to work with and they're quite willing to mess with both biology and engineering and it takes a special kind of student to do that. So I appreciate them very, very much and our funding sources, and that if you have any questions, I'd be happy to take them.

Speaker 2: 1:08:57

Okay, Thank you so much, Professor. Let me see if there are some questions for you. Yes, there is. Julie is asking are there coding innovations that can assist in integration of the various materials in the printing flow that you're working with?

Speaker 5: 1:09:15

That's a great question. I can imagine several ideas where you know as a product is being printed, a monitoring system looks at it and adjusts the exposure time or adjusts the flow rate or adjusts the removal of a liquid in response to that right. I think that means doing more than just coding. I think that's a hardware and software integration that will allow for real-time monitoring of this process. The process. It's getting way, way better than it used to be. Right Like. It's gotten to the point where my students brand new, they show up in my lab two days later they're producing printed parts. Right Like. That is pretty wonderful, but it's still finicky in the sense that if we have an off day in Montreal and the humidity is really high, that changes the outcome of the device. So I can certainly see applications that would put a process flow control loop directly into these systems, but I don't know if that's just a software solution.

Speaker 2: 1:10:16

In other words, how can AI help your work? Just want to bring some keywords. I mean, have you guys tried? I mean, when I do a really quick news search for the last week, you know, whatever that comes out, it's always there's like at least 20% of them would have machine learning and AI embedded in the title. So just curious, have you guys like try to explore some of the ways that can optimize your work? Oh for, us.

Speaker 5: 1:10:44

Yeah, I don't currently have anyone in the lab doing that kind of doing that kind of project. I can certainly see the applications, though I do a little bit of work with breast cancer diagnosis especially, and in that field there is a whole lot of interest. Just like with every AI system, you need an excellent training data set, which means that you need a lot of well-characterized, well-labeled data, and I think that's where that is going to be the next big push in all of these different areas. The AI models have proven they can work. Now we need enough data to feed them.

Speaker 2: 1:11:17

Yeah, data is the key. Okay, we have a question from Peter. How does post-processing affect biocompatibility?

Speaker 5: 1:11:26

Yeah, For example, soaking chips longer in IPA. Oh, okay, so the idea is that there are leachates that are within the photopolymerized resins, right, Right, those leachates have to come out. Generally, if you've got a photoactivated molecule or a photoinitiator, presence of that photoinitiator produces free radicals, which are great for the polymerization reaction, which are terrible for the biology, right, yeah, so removing them is a no-brainer. That has to happen. There's many different tools to do that. You can do an IPA wash for several weeks. Eventually you'll get to the point. But that sort of takes away from the objective of printing a device really fast and then having it turn around.

Speaker 5: 1:12:08

Currently we print our devices and we do five-day washes in IPA and in PBS. It's not ideal, but it is necessary to remove as much of it as we can. We remove as much as we can. We don't get it all and we know that what's left does make a difference to the biology. As you get to more and more sensitive assays, the viability stuff cells will survive an awful lot, right? The differentiation from a mesenchymal stem cell down all the way through a neural progenitor lineage to a neural cell that's much more complicated and that tends to be much more sensitive to anything that's left in the material.

Speaker 2: 1:12:49

Maybe there is an idea for automation and accelerate this washing and post-processing process.

Speaker 5: 1:12:55

Yeah, yeah, Okay cool, many of Paul's innovations being very useful even for that.

Speaker 2: 1:13:02

Thank you so much for your presentation. We're running out of time so we need to move on to our last speaker so we can have a panel discussion. Thank you so much, professor, and you can type in the answer for some of the questions, and people can continue to put questions for you, but I'm going to introduce our last but not the least speaker so that we can stay on time, jeff. So our next speaker is Jeff Schultz, the CEO and co-founder or yeah, I guess are you the CEO? I'm not really sure, actually. Or yeah, I guess are you the CEO I'm not really sure, actually Of Phase a brand new 3D printing microphotics company.

Speaker 3: 1:13:41

All right, well, thank you, jenny. Thanks for everybody for the 3D Heels for hosting today. I'll try to get to the point. Phase is an early stage startup. We're actually still in technology development, but I have a long career in additive manufacturing, 3d printing, and I want to sort of share some things that I've learned along the way in the aerospace and defense adoption of 3D printing and how we, as a collective group of people interested in microfluidics and 3D printing, should you know, think about how to move forward and show you a little bit of what we're doing at Faze.

Speaker 3: 1:14:21

So, as Jenny mentioned, I'm Jeff Schultz. I'm one of the co-founders of Faze. The other co-founder is Zeke Barlow. My background is sort of the material science behind 3D printing and also developing business around unique 3D printing and additive manufacturing technology. Fase is currently funded through NIH research contracts to develop an additive manufacturing process to 3D print, pdms. We also have funding from the North Carolina Biotechnology Center and also the state of North Carolina and we're located just north of Charlotte, north Carolina. In our current research programs we collaborate with Georgia Tech, master General, harvard Medical and Virginia Tech. On this slide I'll take a moment to pause and sort of tell you about the genesis of where we are and why we went down the road of trying to develop our technology. Zeke and I are friends, colleagues with Rafael Davalos, who was at Virginia Tech, now at Georgia Tech, and we were discussing with him. Actually sorry.

Speaker 2: 1:15:45

Jenny is my video off.

Speaker 3: 1:15:46

I didn't mean to leave my video off.

Speaker 2: 1:15:52

No, your video is not on.

Speaker 3: 1:15:56

It says it's disabled by the host, so maybe you can turn it on. So we were discussing with Raphael, who's a longtime user of both 3D printing and microfluidics, and we were actually developing a technology that used liquid dielectrophoresis to shape photocurable resins and then we would 3D print from there. And we were discussing the technology with him and he said you know, it's a great idea. He's like I just want to be able to 3D print SILGARD 184. It's a great idea. He's like I just want to be able to 3D print Silgard 184. He's like that's the material. We know, for better or worse, it has its limitations and complications, but we understand it and we would just like to be able to print devices. As Chris said, the process of photolithography is laborious and slow and it takes many weeks. And he said you know, eventually we run out of funding. So we always end up with kind of a microfluidic device that has kind of a B minus like usability, like if we just had, you know, one or two more reps on the molds, you know we would get something good. But if I could just 3D print PDMS, you know that would be SILGARD 184 specifically, that would. That would really just, you know, make our device designs easier. So that that was the genesis of Phase and and why we, you know, sort of headed down the road of looking at how do we 3D print SILGARD 184 as it is, without any 3D print SILGARD 184 as it is, without any, you know, additions of photo initiators or photo catalysts, just print thermally curable PDMS? I want to quickly also kind of I mentioned I have you know, hopefully a perspective that is somewhat unique amongst the crowd. It is somewhat unique amongst the crowd.

Speaker 3: 1:18:00

My early career started out developing a PhD was funded by a company that's now part of 3D Systems and really understanding what the properties, both the rheologic and thermodynamic properties of a material are that actually make them 3D printable. You know this was probably before most people, a lot of people on this call, were even born. This was in the late 90s. And then I moved into metal additive manufacturing where we developed a technology where I was the first inventor on all the patents to actually print really large scale metal structures which is now being applied to printing tank holes and very large components relatively quickly out of advanced materials. And then I moved on to really developing sort of production scale additive manufacturing. I was the GM for a large Swiss industrial conglomerate's additive manufacturing business.

Speaker 3: 1:18:56

And this was production additive manufacturing. We operated one of the largest or at the time the largest called Service Bureau sort of a production of metal additive manufacturing parts and then sort of moved on to left that and really wanted to get back into technology. Development identified microfluidics as a place where 3D printing should absolutely be the norm but just wasn't being adopted. Is why isn't, as people who are trying to develop additive manufacturing, 3d printing for microfluidics is? You know why isn't additive manufacturing being adopted at the rate that we think it should? And you know how do we enable 3D printing in the microfluidics world? And I like to think about this sort of from an equation standpoint where you know the adoption risks have to be much, much less than the rewards. And you know a lot of this comes from my history with, you know, going through the adoption side bioimplants for orthopedics as an end user, you know there's introducing a new material, you know there's always unexpected interactions. So that's, you know, a significant risk when you're thinking about a large research program or assay development where you know the end user often sees the microfluidic device as the packaging and they don't want to risk their project on packaging, even though I think most of the people on the call appreciate that microfluidics can be a lot more than just the packaging. There's also a new manufacturing process, especially on the more biologically heavy end users not familiar with CAD or operating 3D printers, much more familiar with pipettes and syringes and microscopes. Often going to 3D printing introduces a completely new design. There's also the associated capital costs, although you know, we have seen a dramatic reduction in the cost of printers, you know. And then there's also, you know, the learning curve risk for every user. And then on the reward side, which I think is what we as a community sort of need to sell more and empower is, you know. Sell more and empower is you know. I think we've seen it here today with a lot of the, you know, chip to world interface things that we can do that are inherently hard when you're doing soft lithography. So how do we not just make a microfluidic chip that is has better performance, but how do we also make it much more usable in the lab? By putting lure lock interfaces on or integrating the tube connectors, putting in valves, and those things can actually lead to overall lower system cost and improved usability if you think about the time a grad student might spend in the lab trying to make those devices and then like developing chips that do ultimately lead to improved protocols and assays. You know, if you're in a research environment or even a small biotech, you know, and if you're trying to introduce a product, you know this. You know an advanced design can potentially lead towards you know a market-leading position in your assay and ultimately lead to customer growth in new design applications. So I want to walk through a couple of sort of historical things where I think that it can inform us about the adoption of 3D printing and microfluidics that come from the aerospace, defense and biotech side. So prior to 2015,.

Speaker 3: 1:23:03

Fuel nozzles for sort of jet aero engines were basically this is a conventional aero engine fuel nozzle it was about 20 parts, 20 welds. Because you have so many parts and so many welds, you have a high potential for failure. Assembly costs were high. And then GE introduced this LEAP fuel nozzle, which is one part 25% lighter, improved durability. Lighter improved durability, the ability to add more complicated flow channels ended up in overall improved performance and this really was what launched a good part of the 3D print things and put them in safety applications that require real safety critical qualifications and the things that I think we should take away from this as thinking about microfluidics. This was like an extremely high reward situation where it basically allowed GE to make fuel nozzles that were better, cheaper, faster, stronger.

Speaker 3: 1:24:19

The other thing that I think is really interesting about this is the material they used for these fuel nozzles was because here again we have a new design, a new manufacturing process. They leveraged a cobalt chrome alloy that was actually a relatively well-known alloy. So they knew how to qualify the part, inspect the part, because they knew what the fatigue life, what the corrosion performance, what the basic mechanical properties needed to be to show that they manufactured this part correctly. You know, and I've kind of lost track, but I know there have been, you know, over 200,000 of these printed and you know most of us, I'm sure, have flown on a plane that had these in them. So when people talk about, you know, is additive manufacturing, 3d printing, a commercially viable process? You know it absolutely is. It's all about, you know, as we've heard before, designing the part for the process.

Speaker 3: 1:25:17

Another interesting application spinal implants. This is a conventional part Ti6-4. It was machined. And then, if you look at the 3D printed version, same material, ti6-4, but it has much better osseointegration. Looks much more like you would think the inside of a bone should look. Again, significantly improved performance. 3d printing allows you to change, have multiple sizes, but again, this was the same material.

Speaker 5: 1:25:46

There wasn't a material change.

Speaker 3: 1:25:47

It was just a process change and design change here. Finally, you know the area of orthodontia. You know we've had braces, you know, since we were all little kids. But you know, in the past decade we've seen dental liners, you know, conventionally called Invisalign. I think most people didn't even realize for a long time that these were actually 3D printed design. 3d printed, you know, but that's been, you know, a game changer in terms of changing the way people approach orthodontia, especially as applying orthodontia to adults. And again, this was a it wasn't a known material, but it was a known-ish material in that market because dentists have long used UV curable resins, so there was always a familiarity with it. So it wasn't exactly introducing, you know, a brand new material.

Speaker 3: 1:26:40

So what are the sort of takeaways that you know? I think we should all think about? I think one of the things it's been alluded to. But I think for 3D printing to really shine, we need to not do like-for-like substitutions. You're never going to 3D print a part that's currently injection molded or a very simple 2D microfluidic design, and be competitive. I mean you need to enhance the performance. Again, there's always prototyping scenarios where you might make some very simple microfluidics, but we need to help educate our end users about how to incorporate multiple elements. You know, maybe you have multiple mixing elements valves, membranes, all in one device and those things you know are enabled by 3d printing.

Speaker 3: 1:27:36

So, again, not like for, like you know, the you know performance improvements in the devices have to be, you know, significantly better than the switching costs when you're trying to convince someone that they don't need to use, you know, soft lithography to to make their devices um. It also opens, um, you know, new alternative approaches, like in the Invisalign example, and the risk reward really has to be highly favorable, especially for the first mover. On PDMS is that we employ industry standard materials. That you know. If there is an ISO spec, an ASME spec, an ASTM spec, it really helps bridge a gap for the users in terms of adopting a new technology. And again, don't 3D print 2D devices. If you look back, you know this is one of Whiteside's devices and it's from a you know famous paper. And you know this is one of Whiteside's devices and it's from a you know famous paper and you know who wants to connect all those tubes. But if you look, take an example, this is actually a pretty complex 3D printed manifold that Moog has used as an exemplar.

Speaker 3: 1:28:49

Really, you know you have a lot of tubing connections now and you just have to bolt up four flanges and now you have a relatively complicated manifold. So I think that's how we need to think about selling our customers on 3D printing. So now on to phase specifically the device. You see on the screen. There is a 300-layer sort of basic 3D mixer design with 2D mixing elements. You know, one of the things that you know we focus on is one Sylvard 184.

Speaker 3: 1:29:24

That's the material we always use with known biocompatibility. We actually I'll actually focus a little bit back on the slide there for some key aspects we always print on a microscope slide so our devices fit into sort of standard workflows. The user gets a device that is 3D printed right on a microscope slide so it's ready to fit in their conventional microscopy workflows conventional microscopy workflows. One thing that we do that sort of eliminates some of the problems that are conventionally found when you bond a soft lithography PDMS part onto a microscope slide is there's often leaking at the interface. We actually print down a solid um pdms substrate right on or not print down a solid pdms base on top of the microscope slide before we start printing any channels so our devices can actually be completely removed from the device to um without leaking. Again, we have the design freedom of 3d printing. Uh, our goal is to replicate the resolution of the in vitro environment.

Speaker 3: 1:30:38

I'll talk about our size scale in a bit Rapid design iterations. That's key to what we do and our success. Typically takes us about 30 minutes to print a part and we will go do three or four design iterations a day usually and that's very important for us to getting the right microfluidic design with the right material. And again, we focus on scalable production. Our process is fast, our hardware allows us to produce things at volumes and price points where we could actually go into production and we also, using some similar techniques that we've heard about before, we integrate electrodes and membranes into our devices. I'll move quickly so we have some more time for the panel discussion. On the left you can see a normally closed vacuum actually.