Automation is key to enabling high-throughput analysis for any analytical method, and automation of digital PCR (dPCR) is now a reality. Join us for this conversation with Dr. Clarence Lee, Senior Product Manger, about how Thermo Fisher is delivering the benefits of dPCR, along with high-throughput automation that saves time and enables diverse application areas.
Modern science, especially in the genetic and molecular biology spaces, generate vast amounts of data, and require vast amounts of data to be generated for thorough analysis. For example, finding a rare gene mutation such as BCR-ABL as a biomarker for chronic myeloid leukemia is like searching for a needle in a haystack. For a situation like this, dPCR is an ideal method, but high-throughput automation is also needed.
Dr. Clarence Lee, Senior Product Manger at Thermo Fisher Scientific, tells how the QuantStudio™ Absolute Q™ AutoRun dPCR suite helps make the benefits of digital PCR available in an easy-to-use high-throughput system. The conversation covers how automation benefits are provided by MAP16 plates, system software, and the AutoRun plate hotel and loading robot. Clarence also talks about customer applications where he sees automation like this being applied to innovate and drive science forward.
In the career corner portion, we learn about Clarence’s journey from chemist and biophysicist, to roles in industry and his current role as a product manager. He shares what he loves most about his job and what he’s most proud of over his career that has spanned several diverse roles.
Visit the Absolute Gene-ius pageto learn more about the guests, the hosts, and the Applied Biosystems QuantStudio Absolute Q Digital PCR System.
Jordan Ruggieri 00:00
I told a joke about dPCR at the lab once, but it didn't amplify well.
Christina Bouwens 00:16
Welcome to Absolute Gene-ius, a podcast series from Thermo Fisher Scientific. I'm Christina Bouwens.
Jordan Ruggieri 00:21
and I'm Jordan Ruggieri. And today we have a special episode featuring Dr. Clarence Lee, a Senior Product Manager at Thermo Fisher.
Christina Bouwens 00:28
Clarence and I will be at BioProcess International this week in Boston, presenting on workflow efficiencies using QuantStudio™ Absolute Q™ AutoRun dPCR suite. If you're not able to attend his presentation, this interview is going to be a really great opportunity to learn about his role in the lab and the use of digital PCR technology. We'll also be talking to Clarence about his role as a product manager and how his past bench experience helps him better serve his customers.
Jordan Ruggieri 00:57
Well, Clarence, thank you very much for joining today's episode of the Absolute Gene-ius. We're super thrilled to have you.
Clarence Lee, PhD 01:04
Well, thanks for having me. Super thrilled myself just to hang out with the two cool colleagues at Thermo Fisher. Proud to say that I've been part of Thermo Fisher for about 18 years now in a variety of roles. Really started off within R&D. But within those 18 years, I'm super happy to say that for the past few years, I am the Senior Product Manager for our digital PCR business. So currently very focused on our assays and applications efforts within that role.
Christina Bouwens 01:35
Yeah, and that's where we actually first got to know each other, is way back when we got started with all of the dPCR and you were actually one of the first people to start, you know, building out our application spaces and that that could be a good place to get started is talking about, you know, where we, where we really started on our applications, and, you know, where, where our first ventures were into dPCR.
Clarence Lee, PhD 01:57
That was very recent, actually. Feels recent, feels a while ago, at the same time. But I mean, Christina, yeah, you, I learned a lot from you actually. And a lot of our assay efforts have been very focused within the cell and gene therapeutic space, as well as, of course, with liquid biopsy. So built out a menu of liquid biopsy assays as an example to really take into account the circulating tumor DNA and the size of that and looking for that needle in a haystack. The mutations that we want to see which cross the cancers for treatment monitoring, or just MRD and all of that stuff, or minimal residual disease, for people not familiar with that term. And then the side of things within the cell and gene therapy spaces, we just see a lot of activities and interests in terms of using the Absolute Q and digital PCR system to quantify things without the need for a standard curve as we started building out these therapeutics. Ensuring that it's built properly, and then making sure it has great efficacy when it's being used for clinical research efforts.
Christina Bouwens 03:06
One of the spaces that we see digital PCR being used for really commonly is the cell and gene therapy space, right. We see a big boom in people looking to adopt digital PCR technology. So Clarence, can you talk about why, why we would see digital PCR being such a useful application, and why it kind of parallels qPCR so well?
Clarence Lee, PhD 03:24
It's a great question, I think, in terms of what has been developed within the cell and gene therapy space as they look to develop analytical tests, process development, ensuring that what they're building is actually potent, and at the end of the day, it's a biologic, meaning it's an extremely complicated process. Being able to map out that process and study and understand and ensuring that process, across the hundreds and thousands of steps that I'm sure it takes, is extremely valuable. A lot of the stuff that has been built out is with qPCR. But that is what's interesting with qPCR and measuring is that you need a standard curve. Everything is based off of a relative value across controls that are, let's say, well characterized or understood. But you can imagine if there's a potential discrepancy with that control, then how do you ensure that what you're measuring is true and everything's measured off of, let's say a ruler. All right, so I'm measuring off a ruler that's set at this particular dimension, from zero to 15 centimeters, but if I didn't place that ruler at the correct spot in terms of what I'm measuring, then my ruler’s shifting. So how do I measure that? Am I really sure that measurement's great? Now, the beauty of digital PCR is that you are literally measuring a molecule, and you have a, you know that there is statistically a single molecule, and you start amplifying it and measuring that, and you don't need a set of standards to be able to quantify it. It's called digital because you're measuring the signal itself and saying, “Is it there, yes or no?” and then you're just simply counting. And so that's really helps provide some confidence. I mean, ultimately, the confidence that you are calling it correctly. And as you think through that, it's a less complicated problem as well. You don't have to make sure the standards are set properly or prepared properly. You have just greater productivity and being able to really ensure that the process is sound when you're developing your cell and gene therapy efforts.
Christina Bouwens 05:51
Yeah, and that's really cool for things like rare molecules that you're looking for as you're looking for products within the cell and gene therapy process, but that can also be super helpful when you're looking for novel markers too, right? You're not having to go find and source standards for novel targets. I can see that being a really big advantage as well.
Clarence Lee, PhD 06:11
When you know what you're looking for, then, yes, it's definitely something that helps out. You don't need to waste time and real estate, let's say, to prepare a set of standards where, okay, I want to build a set of standards so I know what that needle looks like and how much it should be. And instead, I'm just going to, “Nope, going to see, I'm going to do my analysis and look for those, that biomarker that I know I'm interested in, or a potential contaminant.” In that sense you're also trying to show, “Yeah, I do literally have a needle in the haystack.” Of course, people are always concerned about the reproducibility of your results as you go from user to user. And here you’re kind of taking away one variable, a very important variable, when you think about it. Okay, how do I how does that person interpret what that standard should be and where, like, how, how I should do it, and that could be within the lab or in between labs and stuff like that. And now it's like, well, we have a method where, oh, everyone knows how, like, is there a signal or not? Yes or no? That's it. And so now there's a common agreement, and you see the value of what digital PCR can bring.
Christina Bouwens 07:35
So, kind of on that same line, thinking about, kind of removing variables, the Absolute Q does it itself, right? Like we remove a lot of the variables out of the digital PCR process just by automating so much of it through the single plate, single instrument design. And I know one of the topics we wanted to talk about today was how that translates to higher throughput needs, right. So when you really start to scale up your operation, you need to turn to robots. I'll start kind of like rounding us back in applications and Clarence, can you talk about, you know, where are some applications where you see the need, some use cases where a group or a set of, you know, users might turn to automation to really help them improve their workflow?
Clarence Lee, PhD 08:17
When you think of automation, sometimes people just think assembly line, right? Like, put it through, like building a car, or whatever the case may be. In certain aspects, that can be true. But the, ultimately, what we're trying to, what you can enable with automation is just higher productivity. How to better use your time. Do I really want my super important graduate student or somebody important within biopharma, spending your time loading an instrument? Probably not, right. I want them really applying their critical thinking skills. And so, Christina as you've noted, what's great about the Absolute Q and how it's been built out, is that I like to use the term the plate is the machine. When you think about it, the plate and the cool innovation about the plate is really what drives a lot of simplicity and ease of use that we have with the instrument. And so you can definitely have an automated setup, whether it's, “Hey, I just want to run a lot more samples overnight and then come to data so I can just start analyzing it and just keep on going.” And so we see that with particular applications from an environmental testing standpoint. Or with, you know, a core lab where you might have multiple users wanting to run things and so they just set the plates and then just run it overnight and come back to data. The other beauty of the Absolute Q as we think about the entire solution, it's not just instrument, but our assays, our consumables and ensuring that we have the capabilities where we can have automation, because you just want to kind of set it and forget it for a lack of a better term. And so we do that as well. Now, to add to that, since you're asking, well, what about like, what other applications definitely from a high throughput automation, like, if you're just running hundreds of samples, and we get that frequently when just research within infectious disease, or again, going back into the cell and gene therapy where people are developing therapies with adeno associated virus and they just are looking at a variety of samples across the process, from, let's say crude lysates to, all the way to just the initial, the final purification process. So they understand the process. And that's definitely other aspects that people are looking into.
Jordan Ruggieri 11:10
So easy a robot can do it.
Clarence Lee, PhD 11:13
I like to say so easy that Clarence can do it.
Christina Bouwens 11:19
I love that it's super approachable automation. I think because so much, I think you inadvertently are already doing so much of it automated just by using the Absolute Q as a base and then just the way that the automation can take over to just and, you know, I think you have it right, enabling better productivity. It's just, it's, it's very approachable for whatever scale that you need.
Jordan Ruggieri 11:42
Clarence, maybe taking the Absolute Q into consideration here, how do we enable automation outside of the of the plate and of the Absolute Q ? How else are we enabling automation with our product offering and in collaboration with our customers?
Clarence Lee, PhD 11:58
With Thermo Fisher, we joke, but we do literally have pretty much everything. And so we do work with a lab automation team, with experts in terms of understanding how to automate from a sample storage to actually getting out the data and analyzing it appropriately. And so if there are needs to integrate the Absolute Q within automation that we have set up like a cold storage box, whatever the case may be, we have the, we have the capabilities to do that. The other capability, of course, as I kind of highlighted before, is just the amount of service and support. So you may already have high throughput automation already enabled. You want to integrate it into solutions that you have. So, you know, we have a service and support team that can point you in the right direction, and we, we clearly have software that helps enable that. And then the other aspect is with the Absolute Q, kind of highlight this, but not really. We do have what we what is the new Thermo Fisher Absolute Q AutoRun digital PCR suite. And so as part of our efforts, with our lab automation team, we have successfully built out a unique system with a spinnaker microplate mover robot that helps scale, right. Like so now you don't need that big, huge, complete soup-to-nuts automation. We have a suite where we enable plate loading and also provide some guidance in terms of loading the plates with our liquid handle ware. You can kind of set it and forget it with this AutoRun system with the spinnaker microplate mover. We have hotels where you can just load up the plates and you just hit go with the software. And what's really nice about the software, actually, and well, the one cool part about automation is that you're just going to get a wealth of data, right. Now instead of a single plate of data, well, I'm getting hundreds of data sets now, hundreds of samples within my data set. And so the really cool and innovative part with the AutoRun and Absolute Q software now is that we're enabling the capability, for the first time in digital PCR, analyzing hundreds of samples in the single data set.
Christina Bouwens 14:28
Those tools are extremely valuable for being able to analyze big data sets. I know that that is one challenge, especially when you look at qPCR, which is just known for its really, high throughput capabilities, where you are able to just generate just massive amounts of data and digital PCR is a little bit different to look at, right? You're looking at lots of dots and thresholds and copies per microliter. So to be able to visualize all that together, and be able to threshold, to group and to analyze all of that data together, can really give a little bit of extra confidence. I know it's been really helpful in kind of showcasing that to customers and showing them what their data looks like across plates, and helping to showcase just how you know, consistent and reproducible things look.
Jordan Ruggieri 15:13
Did you know that the Quant Studio, Absolute Q dPCR system is powered by microfluidic array plate, or MAP, technology. This technology offers numerous advantages, such as consistent microchamber filling, uniform sample digitization, and efficient analysis of more than 95% of the loaded volume.
Christina Bouwens 15:32
So when you are looking for a needle in the haystack, it's pretty important that you don't throw away all of the hay first, right?
Jordan Ruggieri 15:40
Exactly. You can learn more at thermofisher.com/map16. That's M, A, P and the number 16, or visit the Absolute Gene-ius web page. The Applied Biosystems™ QuantStudio™ Absolute Q™ dPCR System is for Research Use Only. Not for use in diagnostic procedures. And now back to our conversation.
Christina Bouwens 16:02
One of the big applications that we've seen get a lot of traction, especially after the big movements with wastewater, is this environmental DNA testing. And one of the reasons why, you know, we've seen a lot of popularity is because of this buzz around inhibitor tolerance and dPCR. So I think this would be a really nice opportunity, Clarence, to get your expertise as to, you know, why we see this quote, unquote inhibitor tolerance, because we know it's not that dPCR is immune to it. So, so why do we see this with digital PCR?
Clarence Lee, PhD 16:34
Oh, so, that's a great question. So digital PCR definitely is more robust to PCR and its inhibitors. And so for people who may or may not be familiar, of course, you know as you're doing real time PCR, and you're doing an amplification of DNA or RNA, as the case may be, in a bulk volume. There might be potentially within environmental samples, and you can easily imagine wastewater, there might be a lot of things in there that would kind of stop and really make it hard to amplify DNA and RNA. And so the very cool thing about digital PCR in general, is that now you're splitting up that bulk reactions into tens of thousands of micro reactions, a lot smaller volumes. And so now the probability of an inhibitor being in the same reaction as a molecule, single molecule that you're trying to amplify is a lot less, and hence you're going to have a greater probability, and hence the robustness of being able to amplify even with inhibitors in place. So you'd definitely see people wanting to use digital PCR for just in general, environmental testing and pathogen detection. And the very interesting thing, I don't want to say cool, because we don't want to deal with a 100, once in a century pandemic ever again. The silver lining in this is that it really showcases how environmental testing and wastewater testing can have such an impact in being proactive within just public health.
Christina Bouwens 18:22
One other thing that I wanted to touch on, too just thinking about you know, better confidence and better tolerance to inhibitors is some of the features within MAP technology itself, right? We know that digital PCR, you just talked about how good it is, in that kind of like naturally diluting out inhibitors so those they have less of an impact on the final, you know, reaction kinetics. But there's a lot baked into MAP technology that helps to further reduce the impact of false positives. Can you talk a little bit about that?
Clarence Lee, PhD 18:52
The very cool thing about the MAP technology and the innovation associated with that, I already highlighted earlier, the plate is the machine, and it's really true because of the innovations put into it. You don't worry about wasted sample, because you're going to process most of, like 95% of the volume that you actually input it. Because the really cool part about the technology is actually, if you've never seen the plate, there's only an input, there's no output. Meaning that you push in things. It's a gas permeable plastic underneath, so that all of the gas bubbles, everything else is pushed out. You're maintaining your volume.
Jordan Ruggieri 19:34
Clarence, I have another question for you. Are there any considerations as you scale up from, you know, maybe you only have a handful of samples to hundreds of samples when it comes to the number of micro reactions that you want to make sure that you're utilizing?
Clarence Lee, PhD 19:48
You know, that's an interesting question, Jordan. I think to your point, if you've got a big, giant haystack looking for that one needle, then you need to look at a little bit more volume. And what's nice about a plate format is that, and actually with the Absolute Q, is that you can do what we call digital pooling. You can load your sample across multiple arrays and then analyze all of those arrays as one single sample. So if you're really looking for that one in a million event, literally, you can. So one example would be like looking for BCR-ABL, right. Like just looking for that particular biomarker, and they're looking at 0.0032%, if I'm doing the math correctly in my head. And so you can do that using the plate technology, and you don't have to, what's nice also about that, again, getting back in terms of the consistency about just the data or generating those micro reactors, you can be confident that, let's say you need 100,000 micro reactors. All right, I'm just going to load up five different sample wells to get that 100,000. I don't have to worry about, “Oh, am I only going to get 80,000? Am I only going to get 60,000?” The other thing that you kind of highlighted like, okay, maybe what if you're not doing hundreds of samples, if you're doing only four samples? The beauty of a plate technology, and actually with the Absolute Q is we've put that into consideration. You don't have to use the whole plate at a single time. The plate is set up where you can actually provide like four samples, like using what we call our MAP16 plate as an example. The MAP can analyze 16 samples at a given time. You can load up a single column of samples, and then, as long as those other columns haven't been used, the system's smart enough, because there's a barcode so that you can reuse that plate. So if you have another four samples, you can reuse that plate. You're not wasting it. Just use that plate again and just reload the next four samples.
Christina Bouwens 22:06
Yeah, there's a lot of flexibility. I like that you're kind of calling out, like, the two sides of flexibility there. There's the flexibility where you actually need more reactions per sample and you're able to like, like digitally pool your data within a single well to artificially create like, a larger well. And you've also kind of talked about earlier, where we're talking about digitally pooling studies together where you're actually able to achieve the like the sample per run throughput that you need without actually having to make a consumable selection based on you know what your desired throughput need is. So you're really selecting you know exactly what works for your experiment based on analysis post.
Jordan Ruggieri 22:48
All right. Now we get to hop into the career corner part of the podcast, and it is Jordan's Career Corner now. So trumpet sounds, French horns, any brass instrument. That's right! So Clarence, and you know, talking a little bit about your background, you mentioned you were, you know, went into NGS, and you spent time in the lab and all of that. How did you go from working in the lab to a product management position where I imagine it's more about market trends, products to develop, and even, you know, the R&D aspect is not, maybe, necessarily the lab chemistry or, you know, developing assays, but tweaking software, right, or tweaking hardware? Can you kind of kind of bridge that gap from bench work to automation and projects you know that that you're currently working on from a market standpoint?
Clarence Lee, PhD 23:49
So in terms of my background, grew up in Canada. Actually went to University of Western Ontario, but actually I'm a chemist by training. So I did my PhD in chemistry and biophysics. I pivoted to genetics and sequencing as part of my postdoc. To kind of highlight how old I am, it was because of the movie Gattaca, right. It's like this dystopian future of what people what happens when you do rapid sequencing. So that's how I got into doing a postdoc at UC-Santa Cruz to work on nanopore sequencing. And decided I want to go into the business. So I actually took quite a few different roles on the business side. So, I went from R&D to strategy and tech assessment, to actual global marketing development, commercial operations, and now within product management. So that's how I approached it. And ultimately, from a career standpoint, what really helped is a couple of things. One, just being proactive. And two, although I'm not very good at it, is just making connections and networking. I don't like social media. I'm not an influencers. I am an old person, but, but definitely, one knows,
Jordan Ruggieri 25:13
There's more to connections than social media. You we like to chat till late, sometimes for you too.
Clarence Lee, PhD 25:20
We do because, again, we all while the two of you are awesome. And like I said, a lot of the working with Thermo Fisher is awesome. There's just, we just want to serve, and we really do. It sounds very cliche, but when we say that we want to enable our customers to make the world healthier, cleaner and safer, it really is true.
Jordan Ruggieri 25:43
That's really our job is to, is to make science easier, you know, for everybody in the lab. So I echo that, 100%. Can you elaborate a little bit on the day and the life of a product manager? You know, and our audience is a lot of times in the lab. So what, what does it look like to be a product manager? And kind of, what does the day to day encompass?
Clarence Lee, PhD 26:09
Oh, well, I think what brings me the greatest joy about product management is that it every day is different. You're managing a portfolio of products, and you're trying to, your main goal, of course, is to increase revenue. You're part of a business. But to do that, you interact with people across functions. You work with marketing, commercial, operations, and manufacturing, R&D. You're working across all of these different functions. There are certain days where you are interacting more with manufacturing, because maybe there was an issue with a manufacturing process and you're trying to address that. Or you want to work with commercial and operations, because you see data that suggests, “Hey, if we focus on this particular area, we can address more customer needs and help generate revenue.” The common thing, and why I love it so much, is because, again, I get to learn something new every day from different people. Oh, the cool part, also, I forgot the one cool thing about product management, I get to talk a lot with customers. I mean, that's the best part. I find a lot of joy in just hearing what they're doing. The one thing about me getting into science, ultimately, is that I just love science in general. So just hearing about all of the different things that they do as an example. I'm going to geek out a little bit. So my PhD was on the lateral diffusion of peptide aggregates in model membrane systems. A very, very specific, narrow topic. But now, by working as a product manager and supporting a whole bunch of customers across different segments, I learn about cell and gene therapy. I Learn about liquid biopsy, non-invasive prenatal testing, food safety, and a lot of cool things that I never thought would have been possible.
Jordan Ruggieri 28:21
Sounds fun. All right. My last question, it's a two-parter. We ask everybody this. So are you ready? What is your most embarrassing lab moment? And what is a moment that you're most proud of?
Clarence Lee, PhD 28:38
Oh, all right, the most embarrassing moment. This one you'll love. I can't believe I’m going to say this on the podcast. So my most embarrassing moment was during my PhD, I was actually working with fluorescent probe and synthesizing retro benzodiazol. While I was getting it all prepped up, getting it all scooped up, I sneezed. You can see where this is going, so
Jordan Ruggieri 29:05
Don't sneeze in the lab!
Clarence Lee, PhD 29:09
This is me, like trying to tare it appropriately, measure it appropriately for my chemical reaction, and just walking around, didn't realize, I thought, I thought it wasn't bad, and whatever. And then a fellow grad student comes walking in. Laughs her entire, like howling with laughter because I had my safety goggles on, but then all this probe was all over the bottom half of my face exploded all over me. But it's a fluorescent probe. It's not coming off. So I had this probe on my face for a few days. Suffice it to say, I called in sick a couple days.
Jordan Ruggieri 29:56
Oh, that's amazing. And what about your proudest moment?
Clarence Lee, PhD 30:00
The one, I made a small dent in the scientific community. So one, my one geeky thing, I'll say non-invasive prenatal testing. So, I was actually very fortunate to work with the people that basically invented it for next generation sequencing. And so I worked on a few papers and collaborations on that. Now, non-invasive prenatal testing is a standard, right. It's definitely used for people that hit a, women that hit a particular age where they might be at higher risk. And so my one kooky, geeky, proud moment was when my wife was expecting our third child, the geeky part was because she had a higher risk, the physician and genetic counselor is like, “Oh, you should do some non-invasive prenatal testing. Testing.” And so I geeked out on that, just because, well, I played a part in that. So I have to say that was a proud moment.
Jordan Ruggieri 30:56
That's awesome. Clarence, thank you so much for joining us on this episode of the Absolute Gene-ius. We really enjoyed our conversation with you. Thank you very much.
Clarence Lee, PhD 31:05
Thank you for having me.
Christina Bouwens 31:10
That was Dr Clarence Lee, Senior Product Manager for dPCR at Thermo Fisher Scientific. We had a great time with Clarence and we can't wait to share more great science with you in the future. If you're around BPI this week, stop by booth 206, and say hi to the whole dPCR team. Until then, stay curious.
Christina Bouwens 31:26
Like I'm going to be there too. Come see me. Christina is also very cool. I'll be in the booth. Hanging out. Doing demos.