Hemdeep (00:00)

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.

Welcome back to Big Ideas at Microscale. My name is Hemdeep Patel. I am the co-founder of Creative Cadworks, Cadworks3D, and Resinworks 3D. I have my co-host, Robin.

Robin (01:24)
Yes, hello, I'm Robin. Like you said, I'm the co-host and the technical writer on the marketing team.

Hemdeep (01:31)
And today we are very excited to have Majid Wakarian. Is that how you say it? keep, I think we practiced this only a few minutes ago. I still am going Yes, from UTS Australia. And he has been one of our strongest supporters ever since they, set up the company. He was this person that reached out to us in 2018.

Majid (01:42)
Majid Warkiani, that's okay.

Hemdeep (01:57)
And at that time, I remember the conversation we had because of the time difference him in Australia, us in Toronto, Canada. I woke up and stayed awake and think until midnight, one o'clock in the morning, and it was afternoon for him. And I remember having a full conversation about what he was doing and the challenges he was having when it came to 3D printing and his research and what we were doing on our side. And I think from that point on, I have had this chance of watching his research develop. through drip, drip, drip and articles coming out, just being amazed at exactly what he's been up to. And I really am excited that we get a chance to take his information and his knowledge and his research and try to show it up to a much wider audience. So welcome, Majeed.

Majid (02:45)
Fantastic. Thank you very much Hamdi. It's a great pleasure to be here to chat with you and Robin today. So I'm excited as well. So looking forward to our chat.

Robin (02:54)
know, how about you go ahead and tell us a bit about your professional background, whether it's academic or if you've worked more on the commercial side or you know, just give us your background.

Majid (03:07)
Sure. Hello everyone again. So my name is Majeed. I'm a professor of biotechnology at the University of Technology Sydney. I did my PhD in Singapore, beautiful Singapore, and I did my postdoc in Boston at MIT with a group of talented scientists who have been working for decades to develop the cool application, would say, for microfluidics. So since the start of my PhD, microfluidic field has been growing very rapidly. Of course, of the back of the advancement that we have seen around macro nanofabrication stuff in semiconductor industry. And what fascinated me since my PhD time was how cool this type of gadgets can be in mimicking the environment of the human body, where we could play with the cells, with the bodily fluids such as blood. cool stuff such as cell separation, which is the major point of my research activity here at UTS. As Hemdeep said, I've been one of the advocate of macro fabrication through additive manufacturing. So this has been an exciting field, which I believe Creative Cat work played a key role toward it because the time that 3D printing become popular, would say 15 years ago, 20 years ago, there was no dedicated machine for macro fluidics. struggled a lot with the early versions of these devices to build miniaturized chips in which it could be fully functional in the lab. So we had a lot of issues. But I was glad in 2017 and 18 I come across this nice gadget that they put together and especially all the works they did through the resin enhancement to make it works. And as he said, and we will discuss more as we have built a lot of cool stuff and not just me, a lot of scientists on the back of the works we have done. mimicked and utilized this technology to build a lot of cool sciences in which many of them are either translated to the market as a commercial products or on their way toward commercialization.

Hemdeep (05:06)
I didn't know that you were at MIT or you did your post-grad in Singapore. So that in itself gives you a really interesting, you know, gap sort of pathway to where you are right now. What is it that you were seeing at that time in terms of 3D printing? And obviously there has been an evolution, but by the time you needed some sort of tool, what were the changes? What were the applications that you started seeing that were replacing clean room and things like that?

Majid (05:32)
Exactly. Exactly. Exactly. So when I finished my master program in Iran, of course, I got to see someone who came from Virginia Tech to give a seminar. And the first time that I saw a miniaturized device, I would say it was a gas sensor, which was built on the silicon wafer for chromatography. I was so fascinated because the pictures that always remembered from that time, 2007 or eight was. how small micro channels they managed to make, which was much smaller than the human hair. And he was put an SEM photo of how channel is so cool in comparison to a sickness of a human hair. And after the chat with the gentleman, and I said, look, this is fantastic. I'm finishing off my master. I want to go somewhere to do man's microfabrication. This is nanotechnology. Things are so cool. And of course he recommended me a couple of colleges in US, in Canada. And all of a sudden, He mentioned Singapore. said, look, mean, do you know, are you aware that Singapore has fantastic colleges, NTU and US? They are in global ranking and they are so good in this field, macro nanofabrication, because the first CD by Sony was produced actually in Singapore. was Singapore was a hub of so many macro nanofabrication stuff, including of course, the birth of CD as we know. said, okay, I will look into it. I started to explore and I saw that, oh, what a beautiful colleges they have. I found some friends who went there earlier than me and fantastic scholarship they offer compared to the North American scholarship, which was much more prestigious, more generous. So I applied and I get admission in a matter of months. I ended up being in Singapore. So Singapore, as you might know, is a little island. It has a couple of university, but two of them are in top 10, top 20 global ranking national university of Singapore and NTU. And they have contributed particularly to the of micro- and nanofabrication a lot, including additive manufacturing. They have been, of course, one of the early advocates of additive manufacturing for years. There are a lot of researchers who working there. In my previous college, NTU, there is a dedicated additive manufacturing center now, which do a lot of fundamental research. Since that time, of course, I've been there. I start to get exposed to this type of machinery. So I'm very, very bulky machines at that time was either sinter powder type devices or filaments. You could not do really macro scale stuff with them. was macro scale in my opinion, but it was cool to see how things are evolving. And at that time in my PhD, course, I spent half of my life in clinical, which was so miserable. because each time that you wanted to make something smaller changes, you needed to put the guns, go through all the procedures, do all those stuff. You can imagine how much of a failure I had with SU-8 and lithography, and so many things that I wanted to do and it was not working in our favor. And of course, one of the point of discussion for us always was this way, can we do these things differently? I mean, in that time I was working in... in dimensions ranging from 100 to 150 micron for majority of the works that I do. So what I did, the trick was I started to look for some CNC, macro machining peoples, right? Who were doing mold manufacturing for injection molding. And I ended up building some molds with CNC rather than going do the lithography on the SUA at that time to do the casting on PDMS. And I was telling him that they should be a solution. 3D printing should come in between because why I should spend $1,000, $2,000, a few weeks for somebody to just do the macro milling on the back of aluminum or steel for me to build a pattern in which for majority of, as you might imagine, a macro structure, was not possible even to do the milling. But yeah, Singapore and ASR had very good macro machining facility. I mean, of course, all these fancy five axis, 10 axis CNC cuts for industrial works. which I had the privilege to play around. So again, from early days, I would have seen companies like Toyota, like Sony, they come for small projects to Singapore, in which I was part of those group discussion. They come with a piece of, for example, metals that they want to put in the next generation Toyota Camry, right? Well, it was hard to manufacture. For manufacturing advice, Singapore was always a hub, especially for... a small scale projects where resolution and quality was so important.

Hemdeep (10:08)
Amazing. And then I think obviously you went to MIT. I remember when we first chatted, I think you were using predominantly jetted materials. Correct. You wanted a mold material and you were using a jetted platform. And I think we found a solution for you. You do all of this and where is that launch off point come in where you're now fully immersed in 3D printing and microfabrication and you're now starting to develop ideas of where you're going to take your research step.

Majid (10:38)
100%. So look, whenever you graduate and you finish your postdoc, one of the recommendations your supervisor gives to you when you want to become independent is this, I mean, don't do the older stuff, go start something new. That's how you want to differentiate your career pathway. And one of the things that since I left U.S., I always wanted to do how I can contribute to emerging field in which people could benefit out of that and we could do something new.

Hemdeep (10:52)
Yeah.

Majid (11:08)
and I would say 3D macro printing, I was one of the early people who was trying to promote it in my presentation, 3D macro printing was on my bucket list. When I came to Australia, I first joined University of New South Wales, which is another good college year in Sydney. And I ended up being in a school of mechanical engineering. And in my package, I remember they gave me a few hundred thousand dollars and I spent most of it buying 3D printers. So because I told to the head of the schools, I want to set up additive manufacturing for you here. So she was nice and complimented with extra cash. I ended up buying the Project printer, if you remember, and a couple of these machines, which I ended up not using much. this new generation of SLA, miniaturized SLA desktop machine that was emerged at that time. So I remember I was looking for an open source type printer in which I was able to play myself with it, right? So I spent a lot of time, honestly, on buying and playing with the 3D printers. And that excited a lot of people. I remember that initiated a big program through Carbon 5-Ear additive manufacturing staff. And that was the time that the company of carbon becomes so popular. If you remember Adidas wide amount, right? There was one of the early people's investments, Simon. I know him pretty well. So from the back in US and then he moved to Stanford eventually. That was an example I was giving. said, look, mean, even if a simple idea of deoxygenation and things can become a multimillion dollar business. And I have those things in my shoes. And now probably I've seen all these Adidas shoes. the new generation of these firmware's, are all 3D printed and it's the back of those research. So I was one of the early people bought those shoes and I said, look, this is a 3D printed shoe. And we were having fun. we did, as I said, we did a lot of cool things. I can tell you a lot. For example, back in UNSW, there was a guy who was working on these coronary arteries and stuff. And he had a heart issue of essentially... building models around that because he wanted to do this particle image cytometry and see these things. So I helped him to do a lot of those vasculature build directly. So there was a guy who was like David Sinton in, David was in Toronto or was in UBC? I'm sure David Sinton is one of the famous in Canada. He works on several things, but one of the things was this oil and gas extraction stuff. which is very popular in Canada. In Australia, it probably is the same. There is a lot of mineral research happening here, especially coals. We built a lot of models of how, for example, gas and water propagate of those things with 3D printing that time. So I had a couple of PhD people working to model those things. So that time, I remember we used to do a lot of XEM, TEM, and we wanted to replicate the same pattern. on the back of a CAD file and vectors to could really print it and see how these things can be visualized in the lab to build new models of the mass transport and everything, essentially. We did those stuff as well. And then I slowly diverged these things, of course, toward more biological use where the story of these neogenics, the biomimetic sperm sorting come off. The Neogenics story, which we will chat more today, is very, very fun, but it's always started like this. I moved to UTS. I was still setting up my lab and everything. And there was this brave undergraduate called Steven, who is the CEO of the company, came and he told me, I'm finishing up my honor program. I want to cool projects. And I give him a cool project. So he built this 3D helical macro mixers. We made one of the first group who built this 3D macro mixers. directly printed, which was probably one of the early publications with your machine, where we show that if you want to do particle conjugations in a sort of spending hours and hours, you can do rapid mixing in these devices. And that device published multiple times by different groups, but it was a cool thing. He liked it. And he said that now I want to do a PhD. Let's find something exciting. And I had some notes. I remember that reproductive biology is the field I want to contribute. Again, something new that not many people are playing around. We started to look into problems in reproductive biology and we decided to work on the male factor, which was ignored for ages, compelled to the female factor. As you might know, in mentality of humans, people or couples with reproductive problem, they think that always the issue is female. This is something that has been around in communities and it's not just Canada, Australia, India, it's global problem. is around a decade or less that we realize that no, this is a 50-50 problem. It is not a female issue, this is. Because of that wrong mentality, any research has been done over the past 40 years has been revolving toward women. So when you look at these two fields, you see a lot of cool texts and devices and advancements and drugs and medication for female side of the story. Well, they totally forget the male because they were thinking that male don't have issues. or they don't contribute, but it is proven to be 50-50 problem. And that's where we spawned the sweet spot Hamdi five years ago where, okay, it's time to contribute. That's how all these things started.

Hemdeep (16:38)
fantastic.

Robin (16:39)
And so what did research for, like, I you do sperm, right? You're working on the sperm. What did that look like before 3D printing? Was there kind of other fabrication methods in place that you messed around with before you eventually went to 3D printing? Or yeah, how did that look?

Majid (16:59)
100%. That's right. So what we need was this. Of course, when you want to start something new, you do literature review, right? The first task I gave to Steve was that, go find the state of the art for me of how peoples play with the sperm in the lab, in andrology lab, how they, ⁓ it comes out of human body, of course, how they process the sperm. And then in early days, we realized that, my God, this is, they are still using this 30, 40 years old technology where they either put the things into centrifuge and try to use centrifugation to get rid of bad things and good things, which is proven nowadays to damage the sperm. I mean, this is something that human used to do for 40 years, but now there's a lot of data shows that centrifugation caused DNA damage, which is not visible to eyes. You cannot see it, but it can be inside those sperm that they process. And andrologists cannot see it. They can pick up a damaged sperm. And that's why the IVF success rate has been stagnating. With all these cool technologies that we have, still the success rate of IVF is around 30, 35%. What does that mean is that statistically, if they do every step right, you take your medication, husband take it, everything be perfect, still you have one out of third chance to become a parent. That means that you need to do another expensive cycles, another expensive cycles. You know that the cycles of IVF each time cost around 10 to $15,000 on average globally. It's very expensive. And then of course, Everybody, of course, when you talk in community, they're looking for problems, how these problems arise. And these are little things that you will find out. Dudes, you have been processing and handling the sperm wrongly for decades. Time to change, right? That was the question. What is the state of the art? Two technologies, centrifugation or another approach called swim up, which is a simple tilting approach. They let the sperm swim in a density gradient manner. Again, if you look at the literature over the past 10 years, try to looking at how mother of nature, how human body do the sperm selection, right? When you are looking at that, so I'm going to give you some beautiful graphs that exactly explain what is distinct, so you can definitely use it. But essentially from the point that a sperm is ejaculated and deposited in a female reproductive tract system until the time that it reached the egg, there is multi-stage of filtration and selection is happening in the body. Okay. Okay. That's something that has been preserved in all mammals. We just wrote a review articles for Nature Review Urology comparing the behavior of a sperm and the way that a sperm track across different mammals, right? Different animals. And that's how human do. So essentially, human deposit millions of sperm. eventually one or two or few of them reach the end of the track. What is happening? And people's out of curiosity, of course, have tried to explore this selection. is mechanism, we call it chemotaxis, sperm response to the chemical gradient that is happening along the way. There is a temperature differences that the sperm responds to the temperature differences. There is a lot of microglidance inside the human body. in which a sperm sense them and use them as a passage to navigate through, which we mimic with 3D printing here. I will explain more. There's a lot of these pH differences, right? The environment in entrance is so acidic that try to kill majority of them. In fact, a lot of them die because they are invaders essentially to the female system, right? They got attacked by immune systems, by the... harsh macro environment, but of course those who are brave and strong can survive and navigate through. So we know that, biologically we know that, but how you want to really mimic that egg outside the body, inside the macrofilodic cartridge. That's the whole question and the stuff that we have been trying to do. If human body can do such a fantastic selection that led just the top champions with high DNA integrity, good quality, rich to eventually fertilize the egg, how you want to build the market for the decks that can do the same almost, right? That was the million dollar questions that we wanted to answer off this back of this research.

Robin (21:27)
And with centrifugation, was that able to mimic that environment anyway or no? It was just.

Majid (21:34)
Does human body centrifuge anything? Does a human body?

Robin (21:38)
Well, I can turn around really quick.

Majid (21:44)
So we always have an animation. We have an animation, and Steven uses it in his presentation. If you put an astronaut in 1020G, you have seen their heads. How does it look like in the airplane, right? It's exactly like that. You do this to sperm, and you expect that off the back of that machine go do the job. So.

Hemdeep (22:03)
Yeah. So in terms of the available technology that you had at this time, so you identified a problem, you did research, you found that there was a big disparity between outcomes and what the expectations are and what the reality is. At that time, are you looking and saying, okay, where is the technology to sort of find new solutions? Did you look back at traditional methods of Microfab ⁓ in order to find solutions or did you really just pivot right away to 3D printing and going in that direction.

Majid (22:39)
Of course, mean, the first instance we wanted to see which of these mechanisms that I told you, this multi-selection mechanism is easy to mimic it, we can replicate it. There is a story in micro fluid community, you probably hear this called Christmas Tree Chemical Gradient, which Albert Foch was one of the pioneers, he's in your neighbor ⁓ in Seattle. He's one of the advocates of 3D printing anyway, himself. So we wanted to see, this is how we can build a chemical gradient. We wanted to make a temperature gradient, of course, needed to be more fluidics with a way to essentially control the temperature in different zones. You wanted to build these macrostructures that I said, it was very hard because it's a 3D complex networks that goes in different directions. And we find some SEM photos in literatures of those macrostructures. And instantly I realized that there is no way You could use traditional macro fabrication of planar doing MEMS or SUA to make these things. Of course, 3D printing was definitely first choice. And since because we were playing with 3D printing for other macro fluidics, we quickly come up with an idea, okay, how we can realize this. Because sometimes you say, want to 3D print this, but in order to build the structures, how even you want to build it. And we know 3D printing. itself inherently have some issue, which direction you want to print these things, how this print's gonna come off, shall I do direct printing, shall I do the, again, molding and casting with PDMS because I want to visualize all those little questions. But eventually, so we decided to mimic part of this scenario, as I said, especially the mechanism called thigmotaxis, which is this boundary behavior of the sperms, of these pre-democro structures. And we started to build the early models with the CAT, of course, SOLIDWORKS. We got some photos and we tried to replicate the copy of those photos with, of course, the software that we had. And we eventually built the early prototype of the device. Of course, again, question is how this closely mimic what is happening in human body. We needed to go through a lot of iteration. And for me, time is always the most important factors. And I would say that... One of the beautiful things about this machine is that it saves a lot of time for us and money. Traditional microfabrication on the basis that even I was able to make it, it would have taken weeks and months. We could have not have such a progress if there was no 3D printer, for sure.

Hemdeep (25:13)
And I guess in this case, you were also able to run in parallel a number of different variations at one go. you were obviously shortening your iteration time, but then you were able to run in parallel multiple projects at the same time.

Majid (25:28)
Yeah, exactly. I mean, different channel designs, of course, and different conditions that you run. So because you won't have hundreds of hundreds of these devices nicely be parallelized and interconnected to visualize, compare. Now, for example, we have another project, we call it the sperm race. So essentially using the identical structures, but we put the bull sperm, human sperm, and horse. and you're racing them together, which one goes faster. This is something that preserved and surprisingly we realized that certain animals, have better teetmo taxes behavior. And that's why the rate of pregnancy in mother of nature in those animals is higher. And we want to see how we can use that learning to transfer to the human that we could help human, right? you can do just with 3D printing because again, I think my student team, we draw it, we go to the lab, we make it, and in a matter of weeks we have some data to analyze together. This is so important. This loop of ideation to testing to change the idea and everything is so important in the field of microfluidics. And as I said, the 3D printing has been the workhorse in my lab. 24-7 has been running and running and printing for us to make these things happen.

Robin (26:47)
How about with biocompatibility? Cause you're dealing with sperm cells. Did you have any issues with, you know, keeping them alive, keeping them viable or, and did you have to like do any surface treatments or other protocols in order to kind of increase the rate of survival?

Majid (27:05)
That's a good question. For the cases that where we do the replication, we use just the 3D printing as a mold and we use the PDMS. PDMS has a very good bio-connect ability. In terms of the resins, we did a systematic study of the resident time of the sperm, the media, the interactions that media and the sperm has with the resin itself post-curing. We didn't see much of adverse effect, honestly. Even not my group, there's several publications who have studied this. We know that if the biological resident time of the cells that you're playing in the channels is not long, is a matter of five, 10, 20 minutes, you are not gonna see any effect anyway.

Robin (27:47)
Okay, so that was the case for you. It was very short amount of time.

Majid (27:50)
If you want to incubate it for days and months to do the cell culture or organ on a chip, that's something that we need to explore. And then the opportunity that arise here, I mean, we had discussion, of course, handy with TGA and you probably know that there is another company in Australia called Fertilize. So Fertilize is another company in Adelaide who is trying to build another, of course, microfluidics. So essentially is a device that hold the egg and guide the needles to inject the sperm. You know the embryologists at this stage, in the lab they are using two joysticks. With one joysticks they hold the egg, with another joystick go pick up the sperm and inject it, right? These guys came and integrate these things to minimize the error and damage because the amount of pressure you apply and everything can cause problems. They essentially build some noise. They are using three photon 3D printing somehow. of opinion machines, right? Just to let you know. And I don't just because of the resolution they want or the way that they built the devices. But the idea is that they build a gadget where you hold the egg and the needles is guided through those narrow micro channels in which they make the errors almost impossible for embryologists. It enhanced facilitation of a sperm to egg injection. It's called fertilize. I mean, you can look them up later. So it's another good again testimony where additive manufacturing can help beside our technology, number one. But the issue here they have is that, okay, it is a hard time to convince TGA FDA of these materials, right? All these materials can be directly utilized in clinics. And I know with Opinion, they did a lot of research. coatings and then building a resin that is almost similar to the polycarbonate something like that. But one of the issues of course we had from early days on, Hamdi, was that there is no way that we could take this 3D, fully 3D printed device to the TGN. I said that look I want to take to this clinic. The idea of injection molding has one always there. The reason that I'm saying is that that limits what we can create eventually because always I have in back of my mind, okay if this work Can the company do injection molding of the back of this for me or not? That's another layer of transition. Because 3D printing is fantastic, building your idea, making it works. Now you wanna scale up, build millions of these chips. It is hard to scale it up with 3D printing. I know some companies try, but it's still hard. How I'm gonna do that? Now that the transition is happening, there is limitation in traditional injection molding in terms of what they can do and what they cannot do. And that has been the course of learning Hemdeep. I've traveled to China 10 times, to Singapore five times, to Korea six times, to Japan a couple of times, to just discuss with manufacturers, yeah, this is my 3D printed, this is my PDMS, this is my device. I want it on a polycarbonate. Can you make it? Can you bond these things together for me? Can you do this? Can you do that? That's, it's fun. You love to hear those things.

Hemdeep (30:57)
You know, you give someone the opportunity to use 3D printing to develop their ideas. The only problem that you always have is that if they're looking to commercialization, there's always this bottleneck that happens. Technology is not there.

Majid (31:11)
I would call it opportunity. would call it opportunity. The next opportunity is this that some AI and design iteration where imagine that your software down the road has an AI component that has a lot of knowledge about injection molding, cross and causal limitation, in which it can feed your design in 3D printing to make it compatible with traditional injection molding, right? That's something that is missing. That's a start of opportunity in my opinion. Somebody built An open source, I don't know, software for all 3D printers that guides you through the design iteration in which it be mass manufacturability be guaranteed at the end if your 3D printing works. That's something that I believe is the cap.

Robin (31:56)
I know your lab does a lot of work. Like one of your biggest goals is to get more commercialized devices. Right. And I know you worked with a couple of industry partners. So do they also kind of play a role in helping you kind of, know, whether it's developing this AI platform or. you know, and have you kind of, is that what you do? You use injection molding when you're, if you're making devices for them or are you still doing 3D printing there?

Majid (32:27)
For small skills, would say limited use applications, 3D printing is perfect. mean, we build the models, we give them, they use it. In fact, we have built some gadgets. For example, there is a company who is working with the subsidiaries of French company. They are the only place in the world that they are making these lyophilized bacteria counts. It's a reference pills that they're using in food microbiology. And the way that they do it, essentially, they can put traditional flow cytometry to essentially count a known number of bacteria, put it in a droplet, freeze dry it, and they sell those droplet. Let's say I want ⁓ a pill with 10 lactobacillus, a pill with 20 lactobacillus, a pill with 50 lactobacillus. So it's a reference lab to build these pills globally and sell it for microbiological testing. So one of the issues they had was, of course, these nozzles. to put it onto these flow cytometry machines they have. So we did a nice design for them with 3D printing with your machine. We sold them actually. And because it's not a high throughput, they have like 20 machine. It was not needed to have an injection molding anyway. 20 piece of nozzles, we make them. Each time that is stopped working, we make another one for them. And we make money out of that, right? So it's a consultancy works. They have a problem. They didn't know that 3D printing can do this. I can do it. I have 10 of example like this. was another company, they want a just connection between two bioreactors. It was bioreactor A, bioreactor B. They wanted something in between happen. They look at all the solution in bioprocessing. There was no way to do it. So we just build a gadget for them as an intermediator. It's bulky, big like this, but it's fully 3D printed off the back of these big machines that we have. Ton of examples, Robin, I can give you where. industry had a need, they didn't know how to make it. And we make it and they didn't need to scale up because they need ⁓ limited quantities of that solution they needed to get it done, right? And that's what we do and that's what I feel is a promising application of 3D printing technology for sure.

Hemdeep (34:41)
So I have a, I'm going to rewind it just a bit. I was curious when you said that you had to mimic an entire biological process, right? The sperm has to move through a variety of environments, a variety of conditions. Are those conditions created in a microfluidic chip? Is it a design factor, meaning you are able to design certain features in place? Are you creating fields where it's a heat gradients? You didn't mention something, but you can create obviously chemical gradients that mimic PhD ranges and stuff like that. How is it that you guys sort of, and how long does it take to take a biological system and then transpose it onto a 2D plane effectively?

Majid (35:27)
First of all, there is a couple of angles to this scenario of mimicking. One is, of these multiple mechanisms, which one play a major role in selection? All of them play a role, which one contribute more? We realized that early on that the thigmotaxis, the scenario of passing this macro environment of tortoise structures, a big selection mechanism compared to the thermotaxis and thigmotaxis, right? So that was the first learning. The second learning was that, yes, thermotaxis is great. It gives results. Can I mimic it in the lab? Can embryologists use it? The pros and cons of the value of making it, is it commercially viable to be a solution in the lab or not? That's another thing. Scientifically, you can mimic stuff, But whether this is translatable or embryologists willing to spend, for example, 40 minutes for a couple of the sperms to go from point A to point B based on the temperature gradient. That's the limitation that we have here. So of these five or six mechanism that we discussed, we decided on the one that is much more effective, play a major role and is buildable and is fast enough that embryologists would love to use this compared to the traditional approach that they use. That was the critical questions that you should always ask yourself is that this elegant solution that I'm gonna make it, if people are to pay for it or not. People are willing to use it or not, or they still. So you build this fantastic Lamborghini, but the door is on the roof. Are people's willing to use the roof to get into the Lamborghini or they still want the traditional doors? This is the things that we learned in a hard way that no matter how enthusiastic you are about what you do, clinical adaptation is totally different leagues. You need to make the technology that is working, of course. It is adding new novel teams and is dummy proof. I will give you a lot of funny examples of days that simple injection of sample into the device got screwed by embryologists just because they didn't want it to follow your protocol as easy as that. And that caused that from iteration number one, version one, we are now version 12. We have built the device that is dummy proof HEMDIB now that they cannot even screw it. We try to make those simplification. along the way, because this is how things should be built. So we should write a book together on that. But yeah, so we play with those things and we realize that yes, this mechanism of the macro navigation through these trenches is very, very effective and it works very well in our favor. And 3D printing is the only solution. That was that aha moment that we like it. But again, We translation in terms of injection molding aside, the difficulty that we had, need to sacrifice certain things to make it manufacturable. And then how I can put, for example, two of these things together, how I can build two type of, for example. Now we have a device that just you saw it, it's a two stage. It does the TIGMO taxa selection, but there is a layer of hyaluronic acid at the end, which enhanced the sperm binding because the sperms like to bind with their heads. in certain proteins. This is what is happening in the body too. They, when they reach at the end of the track, they bind to the surface and epithelial layer or the surface of the egg. Even if they reach, they bind with their head and the doors get open and they get penetrate inside. We mimic that scenario of the chip, the binding scenario. So it's a two-stage filtration device, essentially. Can I do the gradient of the flow? So we can do that. We can essentially have a reversing. perfusion in the device where a sperm swim on the other side. So this is something that we call it reho taxes in biology, reho taxes. Can we do the reho taxes inside? Yes. We try thermotaxis, chemo taxes while we can mimic it. It is very hard to translate. It is very hard to get FDA approval of the back of that because putting chemicals, it add another layer of complexity in terms of regulations and everything. Okay. And of course, we are doing some long-term biological follow-up of if you do multi-stage or two-stage, how much does translate reality into the healthy embryo generation, right? If I pick up a sperm from this stage or that stage, do I see statistically too much difference in terms of life, pregnancy, embryo development or not? Those are other things that we try to build evidence around that through the clinical investigation. But short answer to a question, yes, you can make those stage mimicked in the macrophagocytes not perfectly doable. Whether they are compatible to be on the back of each other like a series, yes and no. Whether the speed is good enough or the yield, the amount of sperm you produce is good enough to convince embryologists to adopt it. That's totally different questions, right? That's where we can chat more.

Hemdeep (40:34)
Yeah. I think it comes down to the fact that it's going to be a commercial venture. It all has to make sense commercially. And if it doesn't, then it's not really worth spending the time at that point. So now where is your research in IVF? Where's the stage? know that, ⁓ you know, casually we've spoken about it, but why don't you share that part of your story now?

Majid (40:48)
Exactly. The research that we did around sperm or andrology side, it become an essential in a startup. It's called Neogenics Biosciences, which is born in Sydney by my former PhD student, Steven, who has been in touch, of course, with you, and another PhD student called Dale, who is an embryologist, come on the projects as a part-time. But eventually everything got so excited and AI got involved that he left his full-time job in IVF lab and become a CSO of the company now. So the company is, the size is like five or six people now. They raised some capital, but the idea is to bring these solutions that we're discussing into the market. At this stage, companies offering two solution. One of them is the hardware, which is the microfluidics for selection. Another one is a software. which is an AI platforms that enables a sperm search and identification in surgical samples. The reason that we built that software is that a subset of men's, there is no sperm in their ejaculation. Essentially, there is no sperm to want to put into the device to swim. So the solution for them, we call them azoospermia patient. The solution for those type of patient most of the time is surgical interventions in which they need to go donate part of their testes ⁓ in surgery, that tissue come to the lab, they open up the tissue, they might be lucky to find one or two sperm of the background of millions of ⁓ epithelial cells, red blood cells, white blood cells and everything. It's a very tedious procedure, very invasive, but that's the only way you can have a biological children, right? What we learned in the clinics is that, for this subset of men's, which is around 10 % of the patients, the way that they do it is, again, so old. They get the tissue, they bring it off the seizure, somebody sits on the microscope, spend hours and hours and hours to find maybe one or two. And because this is very, very labor intensive, it's huge amount of errors is always happening. There has been cases that embryologists said, I didn't find anything, go. That means that you cannot be father. as catastrophic as that. And when you look at the dish, there was some sperm there. He didn't find it. Errors happening catastrophically, right? So just to give you a normal time, so it typically takes six to 10 hours for one sample to be processed. Very expensive, very dangerous, and sometimes repeated biopsies needed because they said, we didn't find anything. The guy's in the theater still, cut more, right? You don't wanna even imagine it, right? So we saw that this is

Hemdeep (43:51)
feeling it right now and I'm just so uncomfortable with the entire conversation.

Robin (43:56)
Really, I feel fine.

Majid (43:59)
Yeah, you should see the movies. But what we did is, of course, we worked with couple of computer scientists. We built an AI. We built an AI, we trained it with, of course, a lot of images. Those are all published. can send you the articles to have a look. And this AI has been the corner store of lot of success for Neogenics. It has been on the BBC, CNN, everywhere. We got a lot of good coverage of this new innovation, which came out in 2024, first time. We didn't know that there is that much of need and that much of surgical intervention happening globally. Essentially too many surgeries like this is happening at global scales. And that's what I told you at the beginning. We have a major focus in the GCC region because apparently the issue is much more problematic here. So we are selling the software as easy as that. The clinics can buy the hardware. Clinics can buy this AI enabled software. where they can essentially use the AI to shrink that six to 10 hours to just 30 minute, 20 minute. And the success rate is 10 fold probably or more higher in terms of giving you the chance to find the sperm, right? So it's very beautiful. I can send you some videos to look, but essentially it's a co-pilot type software. It sits on the camera. It gives an extra strength to the embryologists to search, find more sperm at a much shorter amount of

Robin (45:21)
And is this AI able to trigger maybe like a system or a platform that can separate the sperm from the rest of the cells? Or we're not there yet.

Majid (45:33)
no, the AIS has some features so it can find a sperm, it can annotate for you the location because it's a very messy sample you could have imagined in the background of a lot of debris you want to find the little things. It can down the road score because it can rank which one has a good quality, viability and motility and everything. And of course, if you want to feed that information to a robotic arms to... tell the location where is it to go pick up because they use macro manipulation to pick up single sperms, it can guide the justices as well.

Hemdeep (46:06)
So now this is your current project and you said you had two startups, was it? So which one's the second startup that you have?

Majid (46:13)
The second startup is another one called Smart MCs. We call this Smart Macro Carriers. So it's another company that is on the business of hydrogels and macro droplet formation for bioprocessing. The main product of the company is Macro Carriers. Of course, they use a lot of 3D printing and their workhorse still is 3D printed nozzle. So they have a very high throughput stacked version of these devices. that use pressurized shampoos to produce billions of these droplets, right? Those droplets are becoming eventually through some chemical interventions, macro carriers, which are digestible, which are xenon free, there is no animal component. And that's what you need for production of virus, monoclonal antibodies, for adherence cell culture in bioreactors. So they are selling on a good scale, these macro carriers, but they have gelmol, humanicide, Multiple type of, I would say polymers also, they are producing for microfluidics and tissue engineering application. That's the second company.

Hemdeep (47:20)
And so this was built again in your lab on the backs of 3D printing. now what do you have coming down the pipeline? Doesn't sound like you're someone who actually sits still very long. Once it's done and done, you get people in place to move your idea along and you jump onto another new idea.

Majid (47:38)
I tried that, so this too, it took 12 years of my life. This is not as easy as you said, Hamdi. No, it isn't. And of course, a lot of failures. So we had two startups that we had to close down because of technical problems and people problems. It is not really easy to build a startup. You have done this yourself. You can imagine how hard it to survive and become a company who can... who can sell and be cashflow positive eventually. This is a journey. For me, the joy has been as an academic is to see my research is not just a simple publication. My research is something that there is interest around it. And there are some brave students who are willing to take all these hard works done to eventually bring that product out. And still we are halfway through, of course, for most of these startups. But my dream is to see this device that we discussed today is on the shelf of all the IVF clinics or 10 % of IVF clinics globally. The software is great. So we almost installed the software in 20 clinics now. I'm hoping this be 2000 clinics next year this time. That's what we love to see. People's are actually using, but again, reaching to that levels, it takes a lot of energy and time. So I train a lot of PhDs over 50 PhD students. Not all of them are. willing to take this risk as well, right? Many people just finish and they want to find a job and go away. So finding people who can take the risk and willing to sacrifice to essentially take the ideas to a commercial stage, that's another level. And that's one of my jobs, to find such a candidate, right? To train them, to work with them, to mentally make them ready to have a better risk appetite for such activities. So the question, what is on the horizon? We have couple of projects that is going on. One is for exosomes. You probably heard about them. are new frontiers in biology and nanoscale stuff coming off the cells. We have a couple of gadgets working with them in terms of enrichment of them and purification. If you remember, I was working on liquid biopsy and CTC, circulating tumor cells for many years, advising a company in China now who are using 3D printing. to build new generation of microfluidics for cell sorting. And that has been very, very useful. So unfortunately, due to these geopolitical issues, I guess they couldn't get off hand of your machines, but they are using Boston microfabrication. You know that they in Shenzhen. How they give them a machine. So I had the privilege to again play with different machines. So that's great. These are all happening with 3D printing. So again, honestly, if I could find my way to use of 3D printing to get something done fast, it's definitely that's going to be the case. And I'm hoping in Dubai, I could do the same. So I'm going to really put forward these proposals for new research that they will have to do. There's a lot of neurosurgery type activity happening there. These organ and achieve models that again, we're trying to, still making and a lot of research happening in that space. I believe there is ample opportunities where I want to really bang on this learning that we have to shorten this time from ideation to commercial products, much shorter, hopefully. So that's what I would love to do. And that's what I feel that you guys should be proud and do it down the road. How Mark Ruffalo digs, of course, is a podcast, but I believe some books, some commentary in nature by medical engineering. We can write together that how Markov-Faludi enables this idea testing in clinics, products, it can shorten that. And I believe additive manufacturing contributed a lot to this film.

Hemdeep (51:17)
No, I would agree. think that those teams that are starting to use microfibre creation for 3D printing, I think they're seeing it firsthand that they're shorting the iterations. I guess I'm thoroughly impressed by your conversation right now is I never had a better insight into your business acumen. And question I would have is that how did you learn that part of just this? You know, developing ideas is great. Like I speak to a lot of researchers and they have fantastic ideas. The ideas sit on shelves. They sit inside a refrigerator. They sit inside a computer. It rarely comes out. And then when it does, it's required that you have to go through the rigors of taking an idea and then sort of pulling it apart and then re putting it back together into a business. And where is it that you learn that part?

Majid (52:12)
Well, nobody teaches you this stuff, Hamdi. It's a hard way of learning, honestly. I would love to teach people down the road in some subjects that I'm hoping to design as a part of new curriculum down the road. But this is honestly a gap in our educational system. No matter it's in North America or Australia or in Asia, this is something that we never teach to students how to be resilient and how to be essentially curious enough to know what's happening around yourself in terms of technology and availability of those technologies and how you can essentially use the power of those technologies to build something useful. That's what I don't like about our academic environment, that there is not much of that, there is not much of these things. But for me, the lucky side is that since my Singapore time, I was always in some groups that was part of the mission of that group, right? My PhD supervisor was a very curious guy who was always getting industry grant and who was always doing projects that was had always deadline and you needed to deliver. It was not just sake of academic type research. I learned a lot through that one. So we were a group of 10 people. We built a very big machine that time for ultra-large scales, water filtration, bacteria separation. And my PhD was about building these miniaturized isoperiodic membrane and filters to utilize that using microfabrication. And back in U.S. and activities that we did, again, was the idea was to how to commercialize it, how to build a microfluidics for liquid biopsy and early cancer diagnostic. And that become a startup. I learned a lot that time. I was not involved. just see how they come and license our technology, take it out, build a machine around it, how much money is spent. I saw, I had some good observation, I would say so. And then I started to play myself. So I built my own startup. It didn't work out. We shut it down after one year. The second one, again, arguments, no money. Third one, until you crack the code to find the right people. It's a puzzle that elements should come together that eventually become like that. Even I remember I had a very good chat with MIT IP filing department. So I remember I saw one of their seniors that time in Boston and he told me something interesting. said that of every hundred patents we file at MIT, 99 % of them become nothing. We just make money off the back of that 1%. But if that 1 % becomes something, it becomes Dropbox, it becomes that gigantic multinational pharmaceutical that JSK buy it out, it becomes a subsidiary of Roche, that's on that. That's the mentality that they have even in such an institution that a lot of good research is happening. They don't expect that all the research in the years that they protect even through expensive patent filing becomes something. But the reward is so high of this risky investment that you do. It is like that. That's what I feel that some academics should learn that it's a risky procedure. There's one or two percent that you could make it eventually, but if you make it, the story is to be very, very sweet.

Hemdeep (55:37)
You're good with that, Yeah, go ahead, of course.

Robin (55:40)
I have a question actually. Because you said a lot of great positive things about 3D printing, which we love, but there has to be some limitations, you know? So I guess my question is, where does 3D printing need to go to kind of reach the next stage in your opinion?

Majid (56:02)
I believe, as I mentioned in part of that, AI intervention in the software that operate these machines should definitely get in. Either it helped to optimize the design process. You have limited chance of failure during the printing. Hamdi can comment. When you do 3D printing, there's a lot of times you're printing fail for very, very simple mistakes that you do in terms of designing orientation. layer sickness, macro structures and everything. So if you could really minimize, and of course, because of that, you'll waste a lot of materials. So one of the big issues that I have in my lab is that a lot of failed print that could have not happened because of the mistake of the user, sometimes machine, sometimes not clean the surface of the tray properly, the filtration of the oils, the layer of the film. There are so many things, right? So I feel that we can do much better in terms of harmonizing how these things communicate. And that's where I would see there is a good opportunity. You probably saw the news, Hamdi. There is two ladies off the back of Google last week. They raised few hundred million dollar on a valuation of five billion to use AI to optimize chip manufacturing, the processors on the back of the computers. when the AI is getting to that, where you want to put this elements of component is everywhere. AR is not just a chat GPT to help you write a script or anything. It can help a lot. I feel this could be a nice task. It could be on the startups, how we can really build a software that make the 3D printing dummy proof, like what I said, make the failure less, which is in our favor. And second, another layer of that where it could give you hints that, yeah, this is my design. It tells you, can print it. 10 different ways or ask yourself some questions, give you some nice readouts where you choose, you still get the same biological effect you want, but it tells you if you go this way, that is always easier way to do injection molding at the end. That's where I see improvement can happen to idea, minimizing the errors in the printing and everything. And this one, more materials, this is what I believe these guys are good at it. More chemistry, biochemistry research is still needed. in terms of the materials by compatibility question that you asked, how we can really educate FDA of these materials, because there is limited communication between companies and materials get developed and those that ended up being an FDA approved type products, right? We need to bridge that gap because it's an unknown factors and they are asking us to do a lot of stupid experimentation and third party validation of this and that. If a company come and do that and say that, look, for this resin, I've done everything. It's clear, you just come and use it. You're opening up a big opportunity for yourself because there is a lot of, as I said, research doing that. Even for the case of gamete, I didn't know that. For the case of egg and sperm, they don't accept simply testing on a cancer cell line or a stem cell. Gametes are totally different the way that they look at it and assess your data. So that's another thing. When you start to file and pay for this expensive assessment, you learn, I wish, Hemdeep was told me in 2018 I could have done that. And many more. as you said, you touched, I believe there is a lot of rooms for improvement and we're going to see much more innovation. could see people's and innovative companies like Boston Microfabrication. These guys are pushing the boundaries, solving issues that exist 2018, 2017. Now they doesn't exist, which is great. But I believe there is much more to be done. And dedicated centers, dedicated research lab, dedicated government, government investment should come. That hype of 3D additive manufacturing is gone. You remember Hemdeep, 2015, you write something about that, you get big checks. But because it didn't deliver, a lot of VCs got called. But I believe now that we reaching a plat, we passed that high plateau and everything. When more examples like Neogene's and many more is coming out, people build trust that 3D printing can really deliver. And we need more examples like

Hemdeep (1:00:27)
No, I would agree. think right now we're at the phase of 3D printing where a lot of established players are really firmly establishing the rigors of 3D printing and the iterative cycle, I think, has been proven beyond anyone's need. Now they don't need to ask what are the benefits. It's pretty much there for them to see.

Majid (1:00:49)
Exactly.

Robin (1:00:50)
think it's just letting them piece together what the actual, the range of applications are. For example, the industry partners we work with, they probably didn't even realize 3D printing was their solution. So I feel like, well, that's purpose of this podcast, partially, is to kind of get to a wider audience, like really what 3D printing can do. It could do so much more than what we initially thought of back in 2018, back in 2015.

Hemdeep (1:01:18)
And it would be researchers, they take these ideas and whatever was sitting on a shelf or in their computer that they have not formalized. Now all of a sudden there might be an opportunity where the 3D printing sort of allows them to iterate far more quicker and get potentially commercial ideas go out there. You actually jumped on, I think it was I think 2019 or something like that. You actually helped us validate master mold. for PDMS, you know, that the first material that we made for the master mall. Can you tell me, are you using PDMS devices as your platform now, or are you doing a monolithic devices like what materials are you using right now?

Majid (1:02:02)
No, are using still, I remember that brown color polymers we got at that times and we play a lot. We are using both direct printed devices where we show that, of course, build them in an open way channels and then bind it to, we double-sided add to another layer of PMMA to have closed looped microfluidics. That looks beautiful. Majority of the time, as I said, we use the 3D printing as a master mold. to build a replica of these things. You would be surprised that I even use 3D printing to do nickel casting to build injectable of that. I didn't told you that, right? So we use your replica to build injection molding mold of the nickel. So we essentially bypass the CNC cutting of a stainless steel because we wanted to do some coarse injection molding. And one idea is to use 3D printed molds to do traditional electroplating like that. So they can use as that. So I did that with a company in Melbourne. Most of the cases I said, we use of course, PDMS replica. The reason that we use PDMS replica is that I always want to give that element of visualization to the peoples. People believe what they see is very clear. Where does sperm go? How does it bind and everything. And for majority of academic application, That's the reason we are using the PDMS of course, to visualize the records to things. But yeah, so we, as I said, we can use directly the resins, we can use the PDMS. We know how to make mold of that to could go down the road, inject mold these things into the polycarbonate or PMMA.

Hemdeep (1:03:42)
I think that possibly it means that we've come to an end to this. Could this be even true? I think Mary Frances is gonna have a great time editing this one. This one, I think the amount of sort of, I was all over the place because so many ideas were coming into my mind as we were talking. So good luck to Mary Frances as she tries to edit this and put it all together. So, let me then end this off by thanking Majid. You woke up early on a Saturday morning to be with us. That was very nice of you for doing that. As I had expected, it always is very interesting to talk to you. I think the amount of work that you've put into the startups that you've started and the failures, obviously, that every business person has. are interesting because they sort of identify the person that you are and then the success that you have. I wish you all the success in the upcoming year in Dubai. I'm sure that we'll connect that time. And thank you very much.

Majid (1:04:51)
My pleasure. Thanks for having me guys. Enjoy the rest of your days, I guess, Friday afternoon, right? Yeah. Hopefully you will get to see some beautiful rain rather than snow now and a nice cup of tea with your family. So looking forward to chat with you more or see you in upcoming conferences, Hamdi. Great. Nice chatting with you. Thanks, Manjeet. Bye-bye. All right. Bye-bye. Bye. Bye-bye.

Hemdeep (1:05:11)
I hope so too. All right. Thank you guys. Thank you.

Robin (1:05:16)
so much. 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 Cadwork3D 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.

Hemdeep (1:06:02)
Thank you for tuning in and as always stay curious, keep exploring and never stop asking the big questions that are shaping our world. Whether you're in the lab, on the go or just curious about the future of technology, join us as we continue to dive into big ideas at Microscale.