Discover > Big Ideas at µScale > Episode 06
Podcast Episode
55 min video
Full transcript
How does hydrostatic pressure play a role in epithelial cell differentiation?
Hydrostatic pressure plays an important role in shaping how cells differentiate and how organoids develop, yet accurately reproducing these forces in laboratory models remains a challenge. This conversation explores Chen Li’s research into pressure-controlled epithelial differentiation, including experiments showing that lung epithelium thickens in proportion to applied pressure. It covers custom air-liquid interface systems, microgel force sensors, and 3D-printed PDMS molds for studying pressure in gut organoids, alongside the development of microfluidic devices that provide access to both the inside and outside of organoids. The discussion also explores open-source laboratory innovation through LabGiant and its mission to make research tools more accessible.
Guests
Chen Li
McGill University
Hosts
Hemdeep Patel and Robin Boshoven
View guest's academic bio
Chen Li
PhD Candidate, CEO and Co-founder of LabGiant
McGill University
PhD student in bioengineering at McGill University’s Cellular Microenvironment Design Lab, researching how hydrostatic pressure influences epithelial cell differentiation and organoid development. Uses custom 3D-printed devices, microfluidics, and microgel force sensors to investigate physiological pressure in lung epithelium and gut organoids.
Publications
ACS Applied Bio Materials, 2025
Biotechnology Journal, 2024
Scientific Reports, 2024
Institution
McGill University
Episode
Season 01 Episode 06
Publish Date
15 September 2025
Listen on
Discover > Big Ideas at µScale > Episode 06
Podcast Episode
55 min video • Full transcript
How does hydrostatic pressure play a role in epithelial cell differentiation?
Hydrostatic pressure plays an important role in shaping how cells differentiate and how organoids develop, yet accurately reproducing these forces in laboratory models remains a challenge. This conversation explores Chen Li’s research into pressure-controlled epithelial differentiation, including experiments showing that lung epithelium thickens in proportion to applied pressure. It covers custom air-liquid interface systems, microgel force sensors, and 3D-printed PDMS molds for studying pressure in gut organoids, alongside the development of microfluidic devices that provide access to both the inside and outside of organoids. The discussion also explores open-source laboratory innovation through LabGiant and its mission to make research tools more accessible.
Hosts
Hemdeep Patel
Robin Boshoven
Guests
Chen Li
View guest's academic bio
Chen Li
PhD Candidate, CEO and Co-founder of LabGiant
McGill University
PhD student in bioengineering at McGill University’s Cellular Microenvironment Design Lab, researching how hydrostatic pressure influences epithelial cell differentiation and organoid development. Uses custom 3D-printed devices, microfluidics, and microgel force sensors to investigate physiological pressure in lung epithelium and gut organoids.
Institution
McGill University
Episode
Season 01 Episode 06
Publish Date
15 September 2025
Listen on
Cell Differentiation
Hydrostatic Pressure
Organoids
Why might hydrostatic pressure drive differentiation in air-liquid interface culture?
A lab colleague cultured lung epithelial cells on a gel that was still exposed to air, technically an air-liquid interface, but could not get them to differentiate. That led the PI to hypothesize that the small pressure difference inherent in a Transwell setup plays a role. In standard Transwell culture this pressure is only a couple of millimeters, unregulated, and varies by technician depending on how much media is added below the membrane.
How was a Transwell-based device built to apply controlled hydrostatic pressure to epithelial cells?
Instead of designing a microfluidic device, Chen built a prototype around commercial Transwell inserts. A raised media reservoir was connected by tubing to the bottom compartment to increase pressure on the cells. Assembly had to avoid materials like superglue that could affect the cell culture. A later version simplified this to a vertical tube in the bottom compartment, held with 3D-printed parts, which used less media and was easier to make.
How did lung epithelium and gut organoid monolayers respond to increased hydrostatic pressure?
In lung epithelium, stratification (thickening) correlated directly with the applied pressure, but ciliated cells formed less than under standard ALI culture. This suggested pressure is one contributing factor that could give better control over ALI differentiation, not the only driver. Gut organoid monolayers under pressure looked clearly different from controls and formed vacuoles, but this did not resemble ALI differentiation. RNA-seq analysis was still underway, and the team may refocus on lung cells.
How can forces inside 3D organoids be measured with soft hydrogel microsensors?
The team first considered microbubble sensors whose vibration under ultrasound changes with the surrounding pressure, but dropped them because detecting tiny luminal changes required characterization methods they didn’t have. Instead, they used the lab’s super-soft hydrogel sensors, which deform under force. When organoids were broken apart and regrown alongside the sensors, the sensors often ended up inside them, helped by a coating the organoids favored. Luminal pressure measurement remains difficult because organoids often stay dense without forming a lumen.
Why did 3D-printed molds replace SU-8 for fabricating lumen-accessible organoid devices?
The team is trying to replicate a published device that gives access to both the lumen and the outside of an organoid, so that a pressure gradient can be applied across the membrane. That device needs fine micropillars to hold a collagen hydrogel. Only two of six SU-8 molds worked, iterating was difficult, and mask alignment was painful. The lab bought a high-resolution 3D printer to make PDMS molds that are easier to iterate, although very tall molds make the PDMS hard to peel off.
What 3D printing limitations still affect microfluidic and cell culture device development?
Chen named biocompatible clear resins as the biggest need. He also noted that resin printers lack the easy pause-and-insert ability of FDM printers, which makes it hard to embed parts such as a cell culture membrane mid-print. Directly printed one-piece devices already allow features such as built-in liquid columns. The lab’s goal is to share device files and protocols so any biology lab can print the devices itself.
"When you culture epithelial cells under an air–liquid interface… they start differentiating into realistic phenotypes, like the same cells you have in your lungs. My work is to explore what actually makes this process work, especially the role of hydrostatic pressure, and how it affects cell differentiation."
Chen Li, McGill University
Hosted by Hemdeep Patel and Robin Boshoven. Summary written by the CADworks3D editorial team. Big Ideas at Microscale is produced by CADworks3D. The researchers used CADworks3D equipment in the work discussed and were not compensated for this interview.
On this page
How was a Transwell-based device built to apply controlled hydrostatic pressure to epithelial cells?
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Equipment referenced in this episode
ProFluidics 285D
Master Mold for PDMS
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Full Transcript
Transcribed automatically and edited for clarity. Technical terms and researcher names verified with the guests. Spotted an error? Let us know.
Part 1
Hemdeep: Welcome to Big Ideas in Microscale. The podcast where we explore groundbreaking research happening at the micro scale 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 as we dive into big ideas at Microscale.
Hemdeep: Hello and welcome again to Big Ideas at Microscale. My name is Hemdeep. I am joined by my co-host Robin. And today we’ve got an amazing guest lined up. I think is the one thing that I have always enjoyed least over the last five years, has been able to talk to those that are not PIs or running the main research, but really speaking to whether master students or PhD candidates. Because they’re sort of that, that go between the actual project, the technical part of the project, the actual procedure. Like they sort of bring together everything together in one cohesive piece. And then they end up pushing that project through. And so today we’ve got Chen from McGill University. Hi there, Chen. ⁓ So why don’t you give us some quick background to exactly what you do at McGill, the team you’re working with and things of that sort.
Chen: Happy to be here. So I’m a third year PhD student now with my PI Christopher Morais. Essentially we do tissue engineering, but we are still considering like ⁓ cells a bit as a black box, but we look at everything that goes around the cells. And that’s why our, name of our lab is cellular microenvironment design lab. What we do in general, what I do at least is fabricate some sort of device and I put cells in and see how they react to the ⁓ think we want to subject them under. So we’re a bunch of engineers trying to ⁓ do a lot of bio stuff at the end of the day.
Robin: What kind of cells does the lab work with? Does different lab members have kind of different specialties, different cells that they are looking at?
Chen: Yeah, we work with all kinds of ⁓ cells out there. Like I personally already work with episterna cells, but also work with organoids, just ⁓ all types of cells. Other people, lot of cancer cells, also other kinds of organoids. We’re not limited by the type of cells really.
Robin: And what kind of got you into tissue engineering in the first place?
Chen: So yeah, saw my background as an undergrad was chemical engineering. And I always had the interest for the bio side. Because to me, bio was something that was still at the beginning, know, on science, kind of like compared to like physics, chemistry, where it feels like a bit done. But I know it’s not, but at least I felt like bio is very much at the beginning. So I was interested in bio as a chemical engineer. couple lab, know, in, McGill that does teach engineering, like bio-related stuff. Chris was my teacher for one of my class, two of my class. I really liked his teaching and his style. I think that that has a big part in it too. That’s why I his lab and the, teaching engineering. Yeah.
Hemdeep: I noticed, I think over the weekend I was talking to my son who’s just starting to apply to universities and I think there’s a huge difference between the time that I went through the university system and what’s available now. I think that the options that are available during undergraduate program is so amazing in terms of the type of programs that you can take. You can try so much in terms of subject matter. Can you give us an idea of what kind of subject matter you had taken in your undergraduate that sort of helped you drive towards this project that you’re on right now?
Chen: Yeah. So it’s true. do think like, you know, chemical engineering is a, it’s a very old, ⁓ old, old program, but I do think that McGill does very well at integrating a lot of like the newer courses, like biotechnology and things like that. think like the traditional chemical engineer, as like a process engineer wouldn’t have had, you know, have like bio process engineering and we cover like a very broad spectrum, I would say. Also some of the more advanced. class out there is also offered as an elective to undergrad. So if you’re interested, you could really choose that, right? Like plasma engineering, like polymer science, all that thing. So really, think Meagher is doing a good job at offering more modern chemical engineering course than just the traditional process engineering.
Robin: So then what courses did you your professor Chris Morris at?
Chen: He taught fluid mechanics, which was a tough class. I managed to get an A after going to his office because it was an error. But we had to argue a bit. I managed to get an A in DM. That was good. He also taught a class called instrumentation and measurement, which I actually TA’d for many years after I took the class. And in that class, you really tried to. build some device, try to use all your knowledge that you acquired throughout your commencement degree and build a device to try to answer a real life question, right? Which is very like how that class was framed. Yeah, that’s the two classes that he taught.
Robin: It’s very bold of you to argue with your professor.
Chen: you gotta do what you gotta do to get that A in
Robin: Of course, of course. I bet he probably appreciated it considering that you’re in his lab now, right?
Chen: Yes. Yeah, and he told me that I was like the only student he remembered to have argued for a grade. was like really
Hemdeep: There many kids who argue for the grades. think they seem to always rise to the top and they usually are all standouts whenever they start doing any post-grad work and everything like that. It’s a really good personality trait to have. You stand out and you also carve out your own path. You get noticed very, very quickly. Yes, you get noticed for being a bit of a pain in the ass, but it’s still valuable. It means that you’re willing to push convention and you definitely stand out as a result.
Robin: Speaking of Pinn and the S, I remember I was like doing a little bit digging, you know, into your profile. Sorry about that. And I was on the Morazz lab and I looked at like the people section and there’s this very interesting paragraph and it’s like, occasionally you break equipment soon after you use it. There’s no hard proof. This is what Ashley said. Occasionally equipment breaks down suspiciously soon after it is used by Chen. There’s no hard evidence that proves he is responsible.
Chen: That’s all hard poof. Interesting about that was like, was actually my grad supervisor. So I started in this lab as an undergrad, as like a summer undergrad student. And back then my grad supervisor, like I showed him my paragraph and he was like, wait, let me make some adjustments. So he actually rolled that part because I do think back then, like, ⁓ I’m a bit bold in call. use the instrument, you know, I’m not that careful. I just like, I just kind of use it. don’t, I don’t really care. And then maybe I think maybe it’s me. I don’t know, but the, Yeah, it did happen pretty often back then when it was on the
Robin: Can I ask what instrument you were using?
Chen: I don’t know, it’s so many years now. Sometimes like new instrument that we have and we have to kind of try to figure out. Like I remember we got a plastic injection molding machine back then. I was not careful with it to not break out. I just fully testing it, like trying to get the thing done.
Hemdeep: guess a product manufacturer should all be reaching out to you and just giving it to these brand new equipment so that you can fully test the capabilities and the absolute limits for beta test everything.
Robin: data testing.
Chen: Yeah. If that role exists.
Robin: So now, guess, go ahead. Now you go ahead.
Hemdeep: No, can go ahead there, Robin. You go ahead.
Robin: I was just gonna get to the meat and potatoes and start actually talking about your research. Let’s first talk about epithelial cells. You mentioned it just earlier. That’s the type of cells that you specifically work with. How about you tell us a little bit about that, what they are, kind of like its purpose in the body, I guess.
Chen: Yeah, sure. So epithelial cells are basically cells that covers the inner outer lining of your body. So, know, like your skin, your lungs, your stomach, they’re all covered by epithelial cells is the most common cells in your body. I wouldn’t be able to tell you like in like a bio-wise, like exactly like other things that’s a bit of a common theme in our lab. Like when it’s past a certain point about the bio, we don’t know anymore. We’re going to ask a biologist to explain it. But for our purpose, it’s enough of understanding, where you kind of just know how they behave, how we differentiate them, things like that.
Hemdeep: Epithelial cells are in the category of adhesion cells. So in terms of within the range of all sorts of adhesion cells, do you guys work with a whole range of adhesion cells and how do you exploit the actual ⁓ key thing that you’re looking for as well?
Chen: So we don’t really categorize the cells by like, those are adhesion cells. We have other projects that look at adhesion property of those cells. And for example, one of my colleagues is injecting some kind of sensor to expand and see how much expand inside of a cell aggregate. And that would kind of give an indication of the cell adhesion in the cell aggregate. But we don’t see it as like a related. really a thing with that between APTL cells also being an adhesion cell.
Hemdeep: So what is the specific functionality of the epithelial cell that you’re trying to sort of examine with the projects that you guys have right now?
Chen: Okay. So the probably I’m trying to examine is how they differentiate. So I’ll go, I can go a bit more about the, project. basically when you culture epithelial cells, especially like the, let’s say the long epithelial cells under air-liquid interface, which is a culturing the cells so that the one side has access to liquid and the other side gets exposed to air. They start differentiating right into this realistic phenotype like into like the same. Cells that you have in your lungs. And that’s how we make those individual model to then test, do drug testing, do testing on those cells. My work is really to kind of explore that, like all the intricate property that factors that goes into it and what actually makes this air liquid interface work. Because right now, when you think about it, it is like a weird way that we are cultured cells to make individual models. like a culture and this because we, we don’t really know why that works fundamentally, right? There’s a lot of things that goes in it. And I’m like exploring a small part of it, which is the hydrostatic pressure, like a pressure that is getting pushed under that membrane, like which is inherent when you create an air-leak interface. And I’m looking at how that affects the differentiation in that process.
Robin: And I think for the air-liquid interface, there’s a specific setup that you’re using, think, with Transwell inserts and everything like that, right?
Chen: Yeah, originally when the idea was first proposed, it always goes like that where my PI will have an idea and just how can we build a device to test that. So was like, how do we put the pressure on those epicellular cells? Originally, because we do a lot of microfluidics, we thought of doing something microfluidic-wise, have a PMS device and somehow add that pressure on the cells somehow. But then I just thought, how about we build a prototype first that takes the existing commercial trans wall and just try to build a device around that to induce the pressure. And that took a while to kind of get together and work. And we kind of just stuck with that and never got back to the microfluidic version of it. I think we’ll try to stick with that before we figure out the biology behind it, before we try to optimize some kind of a microfluidic device for it.
Robin: There’s like a very interesting image or schematic where it shows kind of like how the device works. When we first did our Zoom interview, that’s where you kind of like presented that with me to me. And that really helped me kind of get a better idea of how it works. We’ll include a link to the schematics in the show notes below. So if you’re curious to see how the device works, be sure to check that out.
Hemdeep: That brings us to the end of this week’s episode of Big Ideas at Microscale. A huge thank you to Chen Li for sharing his fascinating research into tissue engineering, specifically on the epithelial cells.
Robin: Join us next week as we continue our conversation with Chen and dive even deeper into his work. Thanks for tuning in to Big Ideas of Microscale. If you enjoyed the episode, make sure to follow us and stay up to date. You can listen on Apple Podcasts and Spotify or watch the full video on YouTube. You can also follow us for more updates and behind the scenes content on LinkedIn, Instagram, Blue Sky and X. We’re Cadworx3D across the board. That’s spelled C-A-D. 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. Thank you for tuning in. And as always, stay curious, keep exploring, and never stop asking the big questions that are shaping this world. Whether you’re in the lab or on the go, or just curious about the future of technology, join us as we continue to dive into big ideas at Microscale.
Part 2
Hemdeep: Welcome to Big Ideas in Microscale, the podcast where we explore groundbreaking research happening at the microscale where micro innovations makes a big impact. We’re excited to showcase the incredible work being done by our users from around the world who are pushing the boundaries of microfluidics, lab on a chip, organ on a chip, and beyond. Through these conversations, we hope to learn from their experiences, uncover their insight, and bring their big ideas to wider audience. So whether in a lab, on the go, or just curious about the future of microtechnology, join us as we dive into big ideas at Microscale.
Hemdeep: Welcome back to Big Ideas at Microscale. I’m Hemdeep, your host and co-founder of Creative CADworks, CADworks3D, and Resinworks3D.
Robin: And I’m Robin, co-host and technical writer on the marketing team.
Hemdeep: Today we’re continuing our fascinating conversation with Chen Li, a third year PhD student at McGill Cellular Microenvironment Design Lab. Last week we explored Chen’s journey into tissue engineering and how his team uses air-liquid interface systems to study epithelial cells. There we discussed hydrostatic pressure and its surprising role in cell differentiation.
Robin: If you missed that episode, go check it out first as it the stage for today. This week, we’re diving into Chen’s pressure-inducing culture device, prototypes with 3D printing, tubing, and some clever lab hacks. We’ll hear how it evolved into a compact system and the challenges of applying it to gut organoids.
Hemdeep: From 2D models to 3D organoids, lung cells to gut tissue, this episode is all about iteration, learning from failure, and expanding the limits of tissue engineering. For the full experience, vital to check out the visual aids linked to the show notes. Whenever you hear this sound, that means that there’s a visual to go along with it, and a timestamp to match the episode.
Robin: With that, let’s jump right back into big ideas at Microscale. Because you had a media reservoir, so how did the entire setup actually come together? Like how did you build that up?
Chen: It’s just putting things together that we already have in the lab pretty much. So we have a, if I want a media reservoir and kind of raise it and the easier ways to connect media reservoir through a tubing to the compartment in which you want to induce the pressure. So it’s really much just gathering things around in the lab and then find a way to put it together without affecting cell culture. So you have to be a bit. I think I’ve been in advance there, like that you can put super glue anywhere directly because then that would affect the cells. So you have to find other way to piece it together. That’s a pretty rough prototype. We actually move away from that schematic, like that prototype. made some like a easier to make version where I just plant a vertical tube inside the bottom compartment. So then I can just, with help of some 3D printed parts and then that allow me to use less media too and easier to make.
Robin: So it was actually the hydro, talking about that model, you tested as well how the cells differentiated or if they did with like a gel soaked media and it didn’t work, right? From what I remember.
Chen: Yeah, that was actually not for me directly, but from another colleague in our lab who also did a lot of work on this lungs differentiation work. wasn’t really like ⁓ her main project, but she, tried to culture those cells on a gel and then still have it exposed to air, which is technically still air in the face, but she just couldn’t make it work. No, she couldn’t get it to differentiate anyway. And that’s what gave my PhD idea.
Robin: Colleague, yeah
Chen: that maybe it is that tiny pressure difference that when you put in a trans wall that kind of did something for the differentiation. ⁓
Hemdeep: What kind of difference in pressure are you looking at that causes these type of differentiations?
Chen: Yeah, so in the normal transport, it’s really only a couple millimeters of pressure. And it’s not regulated at all. It’s very technician-specific. Some people might add a bunch of media in the bottom compartment. Some people add just enough so they barely touch the cells. But usually, it’s only a couple millimeters of pressure. Versus in my device, I really increase that to maximize that effect.
Robin: And when you applied the pressure, the hydrostatic pressure, was the only differential marker the thickening of the epithelium or were there kind of other indicators that the differentiation was working?
Chen: We first started with lungs. Lungs was the signet of the epithelial, which we called the pseudo stratification of the epithelial. It was very obvious. It had the direct correlation with the amount of pressure I was applying. So we were super happy about that. But one thing that we didn’t get as well as the allognative phase, which is another marker, is the formation of those ciliated cells. So basically, some cilias on top of the epithelial cells, which you do have in your lungs, right, like a bit of those cilias. And those, we didn’t get it as much as the air-liquid interface. That’s what made us think that instead of us thinking this pressure thing as the only thing that matters in that differentiation, it might be just one contributing factor. And by controlling pressure, we might be able to have a better control of that air-liquid interface differentiation than if we didn’t know about this. this variable. then later, we switched. We thought, oh, if it works on lung, maybe also what works on the intestine. So we hired a collaborator from Belgium who came here for around a year. And she was the expert at gut organoid. So she helped me culture gut organoid into a motor layer on the transform. And we also applied pressure on it. And that’s We can clearly see like a morphological difference under pressure. Like the cells looks totally different than the control and also air liquid interface. So we’ve been trying to figure out what’s happening to those ⁓ gut cells for a while. That unfortunately, I think it’s not going that well. Like something’s happening, but it’s not really the air liquid interface differentiation. We’re still trying to determine like what’s happening with those gut membrane. Basically we see those vacuoles forming into inside the. inside the membrane and we’re still not sure what that is. We have the RNA-seq results, we’re still doing the analysis to try to identify what that vacuole is. But I do think at this point, might switch back to continue working on the lungs since it was working so well on the lungs.
Hemdeep: When you did start developing this one for the gut, did you just take the protocols that you had set up for the lungs and just move it across or was there any changes that you had to do to the protocol to adjust for the environment of these cells?
Chen: Yeah, like organoid cells, organoids, they’re very difficult to culture. So before it was that collaborator that was culturing them for me. So I kind of took it a bit for granted. So I thought it would be kind of similar, right? But it’s a lot of small things that you have to take into account. For organoid, you have to maybe coat the membrane a bit differently. You have to add this and that as different. All those small things. But until I started doing it myself, because then she left after a year. So I took the protocol and started. And that’s when I realized how much more difficult it is to culture those gut organoid compared to just epithelial cells. That was definitely taking too much for granted to work that she did for us.
Robin: So I think I read that the air and liquid interface technique, is it considered more of a 2D model just because the cell growth is like on a flat surface, right?
Chen: Yeah, exactly. We basically break that 3D organ noise into single cells and then we see it on the membrane to make it a monolayer.
Robin: So then you were testing as well the effects of pressure in like a 3D model.
Chen: but that’s something I’m currently working on. We’re trying to see what kind of pressure the organoid is under in a 3D model. We know that they’re embedded in a major gel, which is a hydrogel that they need to get nutrient to grow. And as they’re growing, they’re also pushing against that major gel. So there’s some type of pressure there. And also, we know there’s a luminal pressure that’s forming at the same time. So we’re trying to ⁓ have a closer look into what type of pressure those 3D organ noise is going under when they’re growing.
Robin: So what’s kind of the importance of this difference between 2D models and 3D models? Is there something like 2D models is missing where it’s necessary now to start looking at 3D?
Chen: Yeah, this is a very generic question in the field. So 3D models has been getting popularity in the recent years. There’s a bunch of reasons why this is more accurate in terms of model than 2D. The easiest answer would be just like, we are 3D creature. There’s a lot of cell interaction, cells, and property that’s not recapitulated well in the 2D models.
Robin: Okay, so it’s just to get as close as possible to like, like the actual physiology of a human body. Okay, that makes sense.
Chen: Exactly, yeah.
Hemdeep: So I guess a 2D model is really just only focusing on that membrane interface. But there are obviously missing parts ⁓ as you scale up to a 3D model that you need to worry about.
Chen: Yeah, that’s not to say that 2D models are not as useful. 2D model is still very useful in terms of sometimes we have to isolate variable. This 3D model is so complex. There’s so much thing going on in there. Sometimes you still need to go back, break it down into a 2D model to really see fundamentally, control the variable and see what’s changing at that level. So yeah, it’s not to say that 3D model is better than 2D. Exactly.
Robin: So what were the difference and challenges when it came to testing 3D modeling? I guess it’s just the complexity, or was there anything more specific that your lab really struggled with there?
Chen: I learned that culture in those 3D organoids is really much an art. like, it took me a while, like even following the protocol, there’s a lot of intricate stuff that is also very technician specific. And sometimes you just have to be able to tell that here it’s a, yeah, this thing’s not going well because of this. And none of this, you can’t really find a lot of stuff in the literature, right? Because it’s so new and a lot of people has published a lot of things about it. It’s not general knowledge. It’s pretty much of like, I would consider like an art right now. Like as long as I just, you just like, yeah, I see this what’s happening. maybe you should add a little bit of that growth factor, right? Which I can tell you why we have to do that. But there’s a lot of things that that makes it a lot harder than just normal epithelial cells or primary cells that you can pretty much just have to follow the protocol and then you just works every time, right? Organ noise very often, you just, some batch just doesn’t work or some patient derived. organoids, this patient just doesn’t work right. I think there’s one patient that works very well for us and we’re all super glad for that patients to write the organoids. It works way better than the other ones. Yeah. Those kinds of small things that makes it a lot harder to culture.
Robin: Were you able to identify what was it about this ⁓ specific patient that is helped, like, you know, working well, or is that like, it just is what it is.
Chen: Yeah, that’s me at least that’s I’m okay with that answer. Like this patient cells just seems to grow a monolayer like better than the other patients. I really don’t know. Yeah.
Robin: Okay, so what kind of luminal pressure did you actually identify in the 3D organoid and how did you measure that pressure?
Chen: Right. So originally we had this ambitious idea based on one of the paper to somehow incorporate those micro bubble sensors that change the depending on the surrounding pressure. came to realize that would be very hard to do on those micro bubble sensor. also like just to be able to characterize the tiny change inside the lumen. So we’ve been trying to look kind of have a simpler approach, which is just adding our existing microjet sensor. in our lab, we have this super soft hydrogel that we can make it very small, integrated with cell culture. And they’ll deform under any kind of forces. And then we can kind of measure the forces around in that area. So yeah, and also being trying to just stick with that sensor, just trying to get it inside the organoid, it around the organoid, see the pressure. against the major gel and see, get it inside to look at the forces that those organoids are experiencing on the inside. And the thing about luminal pressure is like it’s a liquid pressure, but those lumens don’t even happen most of the time. Often the organoid is still just dense. So yeah, there’s a lot of things that we need to kind of work on and solve before getting that luminal pressure. Can you just
Hemdeep: describe a luminal pressure in terms of how would you traditionally, how would it be traditionally measured and what is it that you, like how did you ⁓ initially propose to test it in these organoids before you decided that it might not be a strategy that was well worth doing?
Chen: So traditionally, I think one of the methods would be to have this, ⁓ it’s like a very small kind of like a needle sensor that you can just, have to poke through the organoid to get a pressure reading. Okay. We were not thinking of doing that. It’s a bit outside of my expertise, but we thought that those, ⁓ micro bubbles, which, ⁓ under ultrasonic wave, they would vibrate a bit differently. depending on the pressure around them at those micro bubbles. That’s when we saw might be feasible to do it like this, but then to be able to see that change, I think that would require some ⁓ characterization method that we didn’t think that we would have.
Robin: Because you use a different type of sensor as well, like the very soft one. I believe those called EMSG’s, but I’m not really sure exactly what that stands for. Is that something you’re still using, even though you got rid of the micropulps?
Chen: Yeah, no, that’s the sensor basically that we pivot to because it is a pretty famous sensor around our lab. It was done by ⁓ a senior PhD student who graduated already. And that sensor actually got very popular. And a lot of people in our lab is using it just to get an idea of when you want to have an idea of some kind of forces in your culture. It’s very easy to make. And you can just add some in your culture. And they’ll kind of be everywhere. And when you get lucky, then you’ll find one exactly at the spot that you want it to be. And you can get the force measurement at that spot.
Hemdeep: And how does that one work? Some sort of foreign substance that you put in there or a gas or another material that allows you to measure it?
Chen: Yeah, it’s basically a hydro job that it was tuned to be super soft. yeah. It’s too much. Yeah. don’t, I don’t remember the exact, uh, you know, like the whole, uh, the whole softness measure about it. I kind of just use it now.
Hemdeep: really? Okay.
Robin: And how you kind of ⁓ incorporate the sensors onto the organoid? Because I know it’s surrounded by a major gel, right? So like, what is the process of actually getting that sensor on there?
Chen: Originally, I thought of getting the sensor inside the organoids. I would have to try to make the organoids with the sensors.
Robin: to grow the organoid around the sense.
Chen: Yeah, yeah, somehow just to repack it together. But then I, uh, that’s, cause I think I showed a schematic of like a, it’s one of my undergrad project where I was thinking just like having a funnel where I can centrifuge all the cells together with whatever you want to add. But then it was all, didn’t need to do that. Like, uh, it really didn’t want to get in at all at first, but I figured I, as I split those organoids, so basically splitting it’s, uh, no, I break the organoids apart and then regrow them into a organoid. As I split those organoid with the sensors, very often they end up being inside of the organoids. And that’s because I also code the sensor with something that my organoids like, right? So that’s something that people have to take into account depending on the cell culture that they’re using.
Robin: So I know there’s still so much more to unpack, but that brings us to the end of this week’s episode of Big Ideas at Microscale. Don’t forget to check out the episode notes linked in the show description for all the supporting materials and resources we mentioned here today.
Hemdeep: A huge thank you to Chen for guiding us through how mechanical forces like hydrostatic pressure are being mapped and applied in organoid models.
Robin: We explored how hydrogel sensors are giving researchers a clearer view into the internal forces shaping tissue development and how 3D printed setups are making it easier to fine-tune pressure in ways that better reflect real physiological conditions.
Hemdeep: Be sure to join us next week as we wrap up this three-part series. We’ll dive into how Chen is leveraging 3D printing to develop the next generation of microfluidic devices and how that work helped spark LabGiant, a platform he co-founded that’s reimagining how research labs connect, collaborate, and share tools. You won’t want to miss it.
Robin: Thanks for tuning in to Big Ideas of Microscale. If you enjoyed the episode, make sure to follow us and stay up to date. You can listen on Apple Podcasts and Spotify, or watch the full video on YouTube. You can also follow us for more updates and behind the scenes content on LinkedIn, Instagram, Blue Sky, and X. We’re Cadworx3D across the board. That’s spelled C-A-D-W-O-R-K-S-3D. For show notes, paper references, and bonus resources on today’s topic, visit our website, catworks3d.com. That’s spelled C-A-D-W-O-R-K-S 3D.com. Thank you for tuning in. And as always, stay curious, keep exploring, and never stop asking the big questions that are shaping this world. Whether you’re in the lab or on the go, or just curious about the future of technology, Join us as we continue to dive into big ideas at Microscale.
Part 3
Hemdeep: Welcome to Big Ideas in Microscale, the podcast where we explore groundbreaking research happening at the microscale where micro innovations makes a big impact. We’re excited to showcase the incredible work being done by our users from around the world who are pushing the boundaries of microfluidics, lab on a chip, organ on a chip, and beyond. Through these conversations, we hope to learn from their experiences, uncover their insight, and bring their big ideas to wider audience. So whether in a lab, on the go, or just curious about the future of microtechnology, join us as we dive into big ideas at Microscale.
Hemdeep: Welcome back to Big Ideas at Microscale. I’m Hemdeep, your host and co-founder of Creative CADworks, CADworks3D, and Resinworks3D.
Robin: I’m Robin, co-host and technical writer on the marketing team. Over the last two episodes, we’ve been in conversation with Chen Li, a PhD student from McGill University’s Cellular Microenvironment Design Lab, following his work in bioengineering and organoid research. In part one, we explored Chen’s early research into hydrostatic pressure and epithelial cell differentiation. And we also got a behind the scenes look at the quirks of his academic lab life. including his knack for suspiciously breaking equipment.
Hemdeep: Then in part two, we took a deeper dive into how his team used custom hydrogel-based pressure sensors to build and test more realistic 3D models of tissues.
Robin: If you missed those episodes, we definitely recommend going back and giving them a listen first as they set the stage for today’s conversation in a big way. In this final part, we shift focus from experimentation to innovation. Chen shares how they repurposed a microfluidic model originally intended for placenta research to enable better access to organoids and allow for realistic pressure gradients.
Hemdeep: We’ll also get into how 3D printing has revolutionized their prototyping process and how Chen’s entrepreneurial spirit led them to co-found LabGiant, a platform designed to help labs share equipment, designs, and expertise, much like open source software communities. This episode is more than just organized. It’s about building the future of research, democratizing lab access, and rethinking how collaboration gets done.
Robin: For the full experience, check out the visual aids linked in the show notes. Whenever you hear this sound, that means there’s a visual to follow along with and a timestamp to match the episode. So, let’s get back into big ideas at Microscale.
Hemdeep: So there is, think, ⁓ a fairly famous paper discussing the controlling pressure differentials in 3D organoids written by Nikolov. How did that paper ⁓ inspire the project and the device that you’re creating right now?
Chen: Yeah. So that paper is really, I think when we saw it was, we were able to get access to the lumen side of organoid and the outside of the organoid. Before that organoid would just be a comp of cells and which have a lumen and it’s just enclosed and it’s not accessible. Like when you think about a real organ, real organ are always accessible to the lumen. That’s how they have to function. So with that kind of model, in which you can have access to both sides. Then I think that would allow us to do a lot of studies that would be more accurate and relevant to the real world. I first started working out for another PhD student that already graduated. His idea was to make placenta models within those device. Unfortunately, we never got it to work well before he graduated because it’s actually very hard to laser. shape a pattern inside a Hydro gel. It took us a while to kind of get something to close, but not enough for that patient to use it for a person in the model. But then we saw like, oh, like we could use it for my project because now we have access to both sides. Then it will be very easy to regulate, try to find a way to induce a pressure that would have an effect on one side or the other. Because before that, if you just put organoid under pressure, it will kind of just equalize on both sides. We wouldn’t have like a gradient of pressure across the membrane and that’s what we really need for my project.
Robin: So for the Placenta project, that was just your regular clump of cells. Is that right? And then now you have your unique shape that you kind of developed.
Chen: for placenta project was we didn’t get the anywhere except for putting some cells inside the whatever the shape that we carved. we didn’t really grow anything like an organoid. But right now the plan is like to see if you could replicate that paper, which is actually a lot harder than we thought to do. We thought it was, which is always like that when you try to replicate a paper and then see if you can find a way to induce that pressure. somehow very easy with a liquid column, for example, on one side or the other.
Robin: So I’d advise then that you’re trying to replicate. Are you fabricating in the exact same way or do you have your own methodology for that?
Chen: Yeah, actually that’s where the 3D printing comes in ⁓ handy, right? Like before to get anything to fabricate something of that resolution, especially there’s some micro pillars involved that holds the hydrogel, the collagen together. For those kind of features, you really need SU-8 to create the mode to get anything at that resolution. That’s why actually we decided to buy the Prophiletics 3D printer. It’s because it was so that we can make a very high resolution PDMS device. That’s the approach that we pivoted to to make those device from now on, which I’m super glad because those SU-8 mode that we had, only two of them worked out of six. The productivity was very low, right? Like every time I could only get two device to work out the six mode that I have. And if there’s something you want to iterate, you can do it that easily on SU-8. Use the studio printing, crank out another mode. if you have a feature that you want to test, it’s very easy to iterate.
Robin: specific device, like what was the time difference between the SU-8 mold versus like the 3D printed mold?
Chen: I was fortunate enough to not having to make those S8 modes. It was from the PhD student that graduated. But I know that he spent a long time with a lot of alignment process. He had to build his own device to align the mask. It’s a huge pain.
Hemdeep: Did you find when you started using 3D printing that you can now deploy different strategies of orientating certain model features or exploring other features in the Zed or anything like that on your side?
Chen: Yeah, actually, for example, some device, not for a PDMS device, because PDMS, I think we have just a high limit before it becomes too hard to peel off and make. But some existing, just like a one-piece device, then yeah, definitely. can all think that before you have to add, let’s say, for my liquid column, you have to of piece something else, like a tube or something to it. And now I can just print it directly in that direction. But in terms of a microfluidic device, we’re still limited by the mold that we’re making. If it gets too tall, then the PMS piece doesn’t come out as well.
Robin: So for the columns, you said you also 3D printed that?
Chen: No, that’s actually for another device, one of the side projects that the RPIs are making us do. And we use a lot of 3D printing for that device. It’s basically we’re trying to integrate a membrane on which we can culture the device. So maybe I could use it for my project. I don’t know, maybe. We’re trying to integrate a membrane inside a microfluidic device that’s directly printed using 3D printer. Yeah, for that to induce the flow, we’re thinking to just use a liquid column. And it’s super useful that we can just print it directly. instead of having to add another liquid column.
Robin: Is there a reason why you chose to 3D print it? It’s just like out of convenience?
Chen: Yeah, I don’t think there’s other ways to make that device at this point. So it’s convenient. Our hope is to eventually put a 3D printed device in all the biology lab so that every time we make something new, we can just send them the file and the protocol, and they could just get the device, print it out themselves. So we try to make it as easy as possible to make, like no surprise. party and the component and things like that. So ideally it would be a one piece. They just click print and they can get the device that we developed for them to use.
Robin: Essentials Syncs, we’ve talked to a couple of other researchers, and they all have that same vision where you can share devices amongst each other. Because now it’s digital file, right? And as long as you have a 3D printer that is able to print that out, it’s very now easy to share that knowledge and build that community around it.
Hemdeep: Have you noticed, is there any sort of limitations that you still find with 3D printing that you wish could be areas of improvement? I know that there’s ⁓ always a need for new materials. That I think has become one of the biggest things people are always asking about. But what is it that you would like to see improvements in 3D printing?
Chen: The biggest one is definitely the need for new material. Like for our field would be have those resin that’s biocompatible. That would be very useful. Yeah. There’s a lot of, you know, think progress on that recently. I’ve seen paper getting out about those clear biocompatible resin that the lab make themselves that still seems to achieve like a high enough resolution to be useful. That’s for sure. Like the biggest one. Now that I’m thinking about it, I could see improvement maybe for like resin specifically. That’s what we’re trying to figure out as we’re making this membrane embedded device is there’s no easy way to stop and go. Like an FDM 3D printer is so easy to just stop and add or thing and keep going. But I think it’s still very hard to do on resin. I don’t know how that would be solved. But I think that’s something that’s missing compared to the flexibility of the end FDM 3D printers.
Hemdeep: That’s true.
Robin: As you kind of progress through your line of research, is there a bigger picture once you have these in vitro models done? Is there like ⁓ a sort of disease that you’re looking to kind of diagnose using like the differentiator markers or anything like that?
Chen: Like I’m a engineering background, right? I really enjoy making those device for whatever needs is out there. But I personally wouldn’t have like a bigger goal of looking at a specific disease that’s like way outside of my expertise. Yeah. I enjoy like making the device. Like, you know, when my PI tells me like, I can make a device to make this, like to test this. like, ⁓ cool. You know, I’ll try to make that happen. But when it gets too vile, that’s the thing. I don’t even have the confidence to be able to look into things like that. But a bigger picture on my side would be trying to fully characterize the effect of the hydrostatic pressure and then see if we popularize that to some kind of a new. trans wall product or something else that we develop. So that is the norm for anyone who’s trying to do those air liquid interface differentiation so that they first know about the effect of a hydrocyte pressure and second, they can also have an easy product to use to help them induce that hydrocytic pressure.
Hemdeep: I also understand that you’ve co-founded a new lab called LabGiant. Why don’t you tell us a bit about that venture of yours?
Chen: OK, so it’s not a lab. It’s an online platform. So I can go more into it. Yeah, for sure. So basically, when I started my master’s, I noticed a lot of things that was not as efficient as I would like it to be. And you know what they say, right? Like for engineer, when something doesn’t work exactly how they want, they’re trying to find a way to fix it. That’s basically, essentially, what I did. Once, I think I had to characterize a sample, and I just didn’t know how. I eventually we managed to do something, but then after a while I saw like an equipment that exactly I thought I could use in another lab. Like they weren’t even using, it’s just collecting dust. No, just like, okay, that makes no sense. Like we should know about things like this to make it more efficient for everyone. That’s when I realized that a lot of labs in academia, it’s like works in silo, right? We don’t really know the other labs equipment expertise. know, a lot of professor end up buying duplicated equipment. That’s a lot of money wasted too. So that’s why we’ve made this marketplace that’s designed for research labs where they can share all kinds of resource, whatever expertise, even digital files. They can just put it on there and it’d be super easy for other users to look at what’s around them. And even for some of the more niche tools, let’s say the HydroSight device I made, another lab might be willing to try it out. but they don’t know how to make it. I also put that on the marketplace where they could just get it from us. I’ll ship it to them for a small price. And I think that’ll be much more efficient way of collaborating than Arcturne way, is usually is that you have to read a publication. You like that publication. then like I did, I tried to recreate that publication. And I find it doesn’t work because it just lacks the detail in the methodology to fully replicate it. A more efficient way would just be directly collaborate through the work, right? Through the product, right? If one lab is really good at making it, then just sell it to other labs. And then we can just grab the work and keep going. thought that was very similar to, if you guys are familiar, why software engineering has been able to progress so quick is because they have this system on GitHub where they can just grab the code and just keep going with the code. They don’t even necessarily understand what was going on with that code. That’s why software engineering has been able to…
progress so quick, right? It’s like very efficient system at building on each other’s work. And that’s what we’re trying to build with Labgiants.
Hemdeep: I’m actually on the site right now while we’re chatting. How do you find time for this? I’m looking at this. I’m just going, this is a well laid out site. It is extremely intuitive. can see why labs, any lab would want to be on a platform like this.
Chen: Oh, thank you, thank you, it’s really great to hear this.
Hemdeep: And you’re right in terms of collaboration, it is extremely valuable, especially in the research field. There is a lot of duplication that happens. I’ve always found that if you can figure out a way of getting someone someplace faster, you’ll always find a marketplace for it. this certainly I just am just taking a quick look and I’m wow. And do you guys have access to the next next gen AI? That sounds like something that that we need to explore further. Are you going to be creating a large language model for ⁓ microfluidics or is it worth
Chen: Yeah, no, that’s the goal. So basically, as we were having all those database of equipment resource, what we realized is that even me, as an Atherios PhD student, I love those equipment. As your idea of what they do, especially when they have a very technical name, like no one knows what the thermal ICP 2000, like I don’t know what that does. But then, would know. AI would know exactly what that does. So we implement AI so that they can recommend you the equipment resource that can know like a… just depending on your needs. So basically, you really have to tell our AI about what’s your problem, what you’re trying to solve. And our AI will be able to guide you, just, you might want to use this equipment, or use that resource, or look at this expertise from that lab, and guide you around to help you find those things easier for you. We showed that to a law professor. They also felt like it was a game changer in how we would do research. Because as the large language model gets better, you’ll give everyone out there a baseline of how to do research, of how to think of a solution to a problem. That’s our goal for LabGiant.
Hemdeep: This is fantastic. I can get lost in this rabbit hole of tools and technology.
Chen: Yeah, no, that’s why we have an export page, rather a home page where you can just like, if have something new publication, something new tool that they build that they want to share, you can just scroll the export page and just say, well, maybe I like this. I want to try this and just click the link and get one from them. I think that’s our vision for LabJet.
Robin: And are you looking to get labs all over the world on board for this or is it like regional?
Chen: We’re starting with McGill, know, still refining a platform. It’s our beachhead of the market. But no, I think it absolutely makes sense to expand, build this network of a research lab around the world so that we can all collaborate, right? Like see what’s out there too. Amazing. You know, about the first question, how do I find time for this? the real answer, it sounds a bit bad, is just like not really caring about work-life balance at this point. Just like now, it’s just, yeah, they, they time PhD weekend. I work on this with my co-founders, you know, who are, who are software engineers. And then they’ve been, they know that without them, I wouldn’t be able to make this happen. Of course. Yeah. It’s just a lot of, sacrifice on time, right? Yeah. I think that’s the advantage. Like I was, I have to do this in my twenties because if not, I don’t think I have time to do this in my four.
Hemdeep: To be young again, ⁓ No, no. This has been a very informative conversation, Chen. We got a very good sense of exactly what you do at the lab, and then you’ve introduced us to this offshoot of your work life, ⁓ where you sacrifice everything for the rest of us at labgiant.ca. And we will put the links to ⁓ this ⁓ labgiant. Thank you. Any final closing remarks, Robin?
Robin: Thank you for joining us, first of all. It’s been a real pleasure talking to you and kind of getting to know your work and what it is you do, all the devices that you’ve created. I don’t know if you’ve broken your own devices or if that’s just other labs ones.
Chen: Thank you for having me.
Robin: If there’s any other links or anything else you want to share, just please do and we’ll love to do that for you.
Chen: You guys also follow us on LinkedIn, you know, like me or LabGiant. We also have a LabGiant account there. Of course.
Hemdeep: What do do for fun? And how long in a typical week would you spend? Split your time between lab work. Obviously you have to present and start developing your PhD work and everything. And then you have lab giant. Do you breathe? Do you eat at all? Do you sleep? Are those optional?
Chen: Yeah, I try. I’ve been on the Make Your Varsity Bamenton team for a while now. This was actually my last year to be on the team. I think it was time for me to retire from Bamenton. And I’m looking into some other activity I could do, not just to stay in shape. But yeah, I would say that’s the main fun I’m having outside of ⁓ all the work.
Hemdeep: All right, then that’s great. Again, thank you very much for doing this, taking some time out to chat with us. And I think when this lab giant starts picking up a large language model, we should have you come back on because I think large AI is going to be extremely important for new development.
Chen: Yeah, no, we, we, we’re thinking of training it like not only on database, but also everyone’s like expertise publication and things like that. So I think that would really help everyone to just have an easy way to find the things around them for research.
Hemdeep: Well, we’ll see you around. Take care of yourself.
Chen: Thank you. All right. Have a good day. Bye. Bye.
Robin: And with that, we’ve reached the end of our series with Chen here on Big Ideas at Microscale. Don’t forget to check out the episode notes linked in the show description for all the supporting material and resources we mentioned here today.
Hemdeep: Over the past three episodes, we’ve explored Chen’s journey from engineering fundamentals to cutting edge bioengineering, where he’s helping reshape how we model and understand complex tissue systems. We followed his work on hydrostatic pressure and epithelial cell differentiation, saw how innovative pressure sensors and 3D organoid cultures are changing the game, and finally, we dove into the tools that make it all possible, from microfluidic devices to 3D printed labware.
Robin: Chen’s work reminds us that research isn’t just about solving problems. It’s about asking better questions, building better tools, and reimagining how we collaborate. A huge thanks to Chen for sharing his story, his insights, and his vision for the future. Next time on Big Ideas at Microscale, we’ll be talking to Andrew Wallman, Anne Tong, and John Shanley from the Sparks Group of Avdee, where we look into the role of 3D printing in drug discovery. Until then, thank you for tuning in and as always, stay curious, keep exploring and never stop asking the big questions that are shaping this world. Whether you’re in the lab or on the go or just curious about the future of technology, join us as we continue to dive into big ideas at MicroScale.