Making patient impact with ions: A conversation on the value of mass spectrometry

(audience applauding) [Victoria Zhang] All right. Let's sit, okay. So thank you for joining us this afternoon. My name is Alex Chin. I'm a scientific partner with Medical Scientific Affairs with Roche Diagnostics US. Today I'm honored to be joined by Dr. Victoria Zhang from the University of Rochester, who's currently a professor of the Department of Pathology and Laboratory Medicine, Vice-Chair of Enterprise Strategy and Director of the Clinical Mass Spectrometry and Toxicology Laboratory, along with Clinical Chemistry at the University of Rochester Medical Center. Also, thank you for joining us, Dr. Zhang. Right. Thanks for having me. It's a great pleasure to be here.

Yeah, so today we're talking about something that's very passionate with laboratory professionals, right? So the role of mass spectrometry in patient outcomes. But particularly, we could maybe go over the first slide. Basically, what is mass spectrometry?

Yeah, well, that's a very good question to start the panel here. Mass spectrometry, when I think about that, I really think of this as a platform. So there's several parts. So I will start, as the slides shows, I'll start for mass spec, since we call that mass spec, right? So what is the mass spec? So mass spec for one is short for mass spectrometry. So don't have to say the whole word. Just say mass spec. It's fine. And there are different kinds of mass spec. When we see mass spec, it's not just one thing, it's actually a group of various instruments, but they all commonly have three parts. One is the mass analyzer, which is to get the compound ionized. And then we have the mass analyzers, the ionizers and then mass analyzers to analyze the mass-to-charge ratios and the detector. So detectors typically, they're not much to talk about, but a lot of differences with how we get the compound ionized, the ionizer, and analyzed. So here we're showing you here as most people see it as a triple quad, right, so.

[Alex Chin] Okay. Sorry, we have a technical difficulty here. So we'll have the slide up in a few seconds. 

[Victoria Zhang] Oh, that's not, okay, not projecting there. (laughs) Sorry. So we'll be there. 

All right, I try to get more graphic when I talk. All right, so. (laughs) So when we think about the mass analyzers, right? Triple quad is one thing that we hear a lot. Time-of-flight is another one with analyzer. The goal is the same, to analyze the mass over charge ratio, right? So before that, mass spec is one unique feature, that is, it can only analyze compound that is being ionized. That's why the title also say the impact with the ions. So to get them ionized, we have the ionizers. So electrospray ionization, that's what people normally see. MALDI is another one. Those are the soft ionization methods. There are several others. I think MALDI and ESI are the most commonly used. So those are mass spectrometry portion of that. 

But for mass spec to work and function, we also need a part before that, that is chromatography. That's when people see LC, mass spec. That could be liquid chromatography. Or we can use a GC, that is gas chromatography, right? For GC mass spec. So the chromatography, their function is to separate the compounds. Let's just think about the body fluids, right? We have a lot of things in blood, so we gonna have a lot of them to, you know, to form mass spec to be most effective, We have to separate them. So you don't wanna, you know, to shoot everything inside. So chromatography can help with that. But even before that, what we call the sample preparation, right? I frequently get phone calls from the clinicians, say, "Hey, I have this compound in serum, can you measure that for me?" Some of them I'm like, "Well, it's not that straightforward." She's like, "Well, you can just shoot in your mass spec and do it." (chuckles) I'm like, "Well, before that we normally do, you know, preparation, we have to figure out the chromatography or the parameters." So most people just think, hey, I got something I can just inject. 

Well, it's not that easy. So that's part of the, you know, what we do at the profession, right? That's why we are kind of the platform for the mass spec to be able to work in the lab, right, it doesn't require a lot of expertise and functions for it to kind of fulfill its needs and requirements. So that's why we have here to show sample preparation and then go to the chromatography and then mass spec portion of that. And afterwards, there's still a lot of work that needs to be done. That's for instance, peak integration, how do we know the system is working, QC, right, calibration if we wanted to do quantifications. So anyway, I can even speak a lot more, but at least overall this is the overall workflow that we have. Use mass spec as a platform.

Okay, thank you for that elaborate description. So yeah, essentially like we see on the slide like four different discrete steps, but you could probably break it down even further. But you really alluded to the challenges associated with a manual type of process as much as we could probably get even semi nominated in many modern labs. But those are the real challenges that you face. What part of this do you think would be the most challenging for mass spec?

Yeah, that's a good question. As a multi-stepped manual and labor intensive process, (laughs) I would say, you know what began with the end in mind, which is for mass spec to be happy, we have to really start from a sample preparation. I always say the sample preparation is the most challenging part. If your sample preparation is done well, the rest becomes easy. But at least in me, when I work with my lab and talk to people, I feel like the simple preparation needs to be well done. And frankly, that part is also the one that takes the most manual labor process, yeah.

[Alex Chin] Okay. Thank you for that. Sure.

So we talked about mass spec, and another powerful method that we have in the clinical laboratory is automated immunoassays. And so obviously these two potentially, there are both powerful tools that we have in the toolkit for laboratorians. But maybe go over what are the disadvantages, or advantages or disadvantages of mass spec in automated immunoassays?

Yeah, yeah, yeah, great question. Those two compare constantly, right? Do I use mass spec? Do I use immunoassay? And why do I use them? I will say, just like, you know, the Swiss Army, right? The knives, you wanted to have a different kind of tool in your toolbox. I think that's the same way I think about mass spec and immunoassays. They are really complimentary to each other, right? So for immunoassay, a lot of them in the core labs, we already know, you may have the analyzers just behind us. That's very easy to use. You can have random access and very high throughput. You put the samples there, you walk away, right? And there's a lot of support also from the vendors. And now you guys did a phenomenal job in helping with the customers. Even getting, you know, FDA approved assays. The majority of them I think are FDA approved assays on the analyzers. So I think that provides a lot of confidence and ease of use for the customers. It's like over the shelf and you can do it. So, but on the other hand, for the immunoassay, there are some things that cannot be done or cannot be easily done, or it doesn't have enough volume or need for a vendor like you guys to work on it, right? You have to have ROI for your own, you know, the assays. So there is a gap between the patient's needs versus what the immunoassay could provide, right? 

On the other hand, some of the immunoassay we know is antibody based. With the antibody, even though it has monoclonal antibodies, there's still some interference that is involved with the assay. So there's another challenge that we have with immunoassay. So I'll say, as I talk about the limitations with the immunoassay, that's off the flip side, provided the opportunities for mass spectrometry, right? So number one, with mass spec, with specificity, it's very specific. Immunoassay might be kind of a group of compounds. Drug abuse is a good example, right? We also, the class of a compound, right? Opiates, you don't see, you know, I get to identify more often or different compounds. It's the class. So in a way it's very efficient, but on the other hand, you miss the opportunity to identify individual compounds. So mass spec provided that. And also to some level, the sensitivity, which is you can measure very low levels of compounds, much better with mass spectrometry. 

So those are, you know, another very good example of that. Another one I think I wanted to see is the multiplexing. You know, with the mass spec, we know the MRMs, which is multiple reaction monitoring, which is a very important feature for the quadrupoles, so we cannot just measure one, two. 

Many assays have 10, least for my own lab, like 20. I mean, we can do, technically speaking, if you allow your chromatography long enough, you could go like hundreds of compounds within one significant wrong. So that's a very powerful technique there for us to use. 

Yeah, so very good. Thank you. So essentially if you take these two methods and, you know, employ 'em together into a clinical laboratory, you do have a really, you know, almost a perfect marriage, if I tell you. - [Victoria Zhang] I hear you, yes. I agree. For patient care.

[Victoria Zhang] Yep. So essentially we're talking about the specificity, right, of mass spectrometry, and can you tell us a little bit of your experience at the University of Rochester and how it has been employed for patient care and patient outcomes?

Yes, yes, absolutely. We have a very big core lab being in Upstate New York. We're essentially the, I would like to think we're the largest academic medical center at Western New York. We also have seven affiliate hospitals. Part of my function as the vice-chair is to integrate all the clinical services together. So we see hospitals from 12 beds to over 900 beds, kinda anywhere in between. So mass spec actually provided a great value for our system. Being in the system, that means people, hospitals sent samples to us. This is a picture that we have on the, I think this side. I did not take a picture before we moved in. So you can still see this is real life. We have the, you know, other things on the bench. We have the samples there. 

But this is actually our new facility. The hospital realized the value that we have to healthcare, which had to have a brand new offsite facility for us. So those provide a lot of great value to the system. I can just give some examples. For instance, like immunosuppressant drugs, right? That's one of the common drugs that people use. We actually, I see that's probably one of the, I call the fast turnaround time assays. We have the same day turnaround time mass spec that's provided, like we do hundreds of testing every day. The other one, well, vitamin D. I think everybody already knows that we do that as well. Drug abuse, we have that two other confirmation and we also have a large panel for screening. Some endocrinology testing as well. We do have a whole strain like a, we have a reasonable size of test manual on mass spec. So all of them, I think, provide a great value for our patients.

So another one I do wanted to mention, as you see the picture here, when I designed the lab, this also got the opportunity... You don't get many chance to design your own lab (chuckles) in your career. But this is one of the opportunity I had. So when you think of a mass spec, it's not just an instrument. You cannot just wheel that in and it's gonna work, right? It takes a lot of infrastructure. For instance, it needed nitrogen, right? And you takes a lot of power. When we think about the power, like, well, 110, so what about during the design? That's going to the... One of the architect talk to us, "Hey, we wanted to review. How many mess spec do you have?" I'm like, "Okay, I have a dozen." Like, "Okay, I have like a dozen plugs for you." I'm like, "Okay, so tell me where they are." I'm like, "Oh, here, here, here." I said, "Okay, this sounds really good. What's the voltage of that?" "They're like a 110." I'm like, "Okay, let's need to change that to 220." And then on the other hand, I'm like, "Well, I think there are two or three plugs for each mass spec." 

But it did not stop there. "Why do you do the HPLC too?" You know, I'm like, "Oh, we can count that, you know, with one plug, one power supply." I'm like, "Hmm, why don't you take a tour to the lab?" (chuckles) I counted, I turned out, so there's like 12 or 15 plugs for one HPLC. The person literally stood there like, "I think I need to go back and talk about the budget." (chuckles) They did not plan on that. This is just an example to see there's a lot of things we need to think about in mass spec. But also one thing I ask them is, you can see here we don't have nitrogen tanks. I'm like, okay, I don't care where you put it. I want the nitrogen tank outside of the lab. As of today, I refuse to ask where the nitrogen tank is. So a lot of things we, I mean, there's many, many things need to be considered for mass spec. So on the other hand, I think all of these are worth it. 

You know, given the stage we have with technology and the value that it provides for healthcare. You know, we tolerate this in a way, right? I would love to have something better, but this is what we have. We have to work around it. But all of this, I wanted to give people the right image of mass spec. It's not like it can do a lot of things, but on the other hand, it takes a lot of expertise. 

And I find what's striking about this image here is that you have a whole lab of mass spectrometry, right? And so the space requirement, the infrastructure. And second, you're also talking about turnaround time, right? So operational efficiency. So the reason why you have so many mass spectrometers is because you have a downtime or what happens, right? So can you speak to a little bit of that and what

Yes, yes, downtime is challenging. I would love to have backup for all the assays. We cannot afford it. (laughing) I can tell you, we cannot afford it. We do strategic backups like assays. And some of them we have to back up probably on different instruments, split them up. You know, we have to be creative. But on the other hand, like for Roche, I mean, we have Roche too, everything redundant is not a problem because it's availability is there and the functions there, and it's really, it's just you can relatively easier and cost effectively purchase them to fulfill that need, right? But for us, we need to, we do have some, we strategically place them. Obviously to have full backup, we're not there yet. 

So, yeah. Great. So it kind of leads into the role of mass spectrometry in clinical practice guidelines. So we have some images here or just screenshots of various guidelines. It's probably not exhaustive, but you see there's various areas or disease areas where mass spectrometry is employed. What are your thoughts on what we can do to get, or can we do more for patient care and work with clinicians regarding mass spectrometry? 

Yeah, yeah, that's an outstanding question. I will say we spend money for a purpose, right? It's only how can we justify the purpose? Patient care is the purpose. I always say, you know, half a million dollar instrument is not the issue. It's only the issue if I cannot see the benefit, you know, first of all, money wise and the patient service perspective, right? Even something like, hey, I spent $10 million, I can make 20 million. 

Well, that's pretty cheap, (chuckles) right? It's not the absolute amount. It is how much value we can bring to the system. I think mass spec is that expensive toy, but it can bring a lot of value. I think those give great examples from direct patient impact. By the end of the day, right, can we provide sufficient services and cost effective options for the patient so that they can get what they need under a reasonable cost, right? So, you know, when I see this, I kudos to the group that have done a lot of things guiding the group to choose mass spec as a choice. I have to say there's, I would say there's a lot more possible applications of mass spec than what we see now. People probably even use endocrinology as an example, right? Should you use testosterone or even free testosterone or testosterone for women? Should that be on mass spec? Should that be on an immunoassay? 

Well, you can do that on immunoassay, but it's just not accurate, right? So those are things the providers have to be educated on. I mean, we constantly do this. I go around with the endocrinologist group. We constantly have, I mean, every time, every year they have residents, they invite me. I specifically talk to their residents about mass spec so that they can order the right test. But that's not true everywhere, right? But I think there's still a lot of value. And those papers and guidelines really give people the opportunity to understand the value of mass spec. But as I see those lists, for instance, microbiology has been used, mass spec, right? I think there's some, probably some guidelines or to be their evolving group as well. 

I mean, protein-targeted mass spec starts to show, you know, more instead of small molecules, we start to do proteins and large molecules. I think there's room for us to further, you know, work on expanding the function of mass spec too. - Okay, and so basically it seems like a collaboration of clinicians and in the laboratory for a really, even though it costs a lot, but really the patient value and the benefits downstream is kind of really driving that, you know, the collaboration and also bringing in mass spectrometer, even though it's an expensive piece of technology.

Absolutely. - Okay. - Absolutely. Yeah. - Thank you. So in closing, what makes you excited about mass spectrometry? What does it do? I mean, we see in this slide here that, you know, there's different, I guess, cohorts where immunoassay and mass spec could be brought to the table. What makes you excited about mass spectrometry? - So many things. (laughs) When I think of mass spec, I'm excited. There are a lot of things we can think about for mass spec. Number one, right? As I mentioned, I don't think mass spec is going to take over the world. I mean, as people know, I started the mass spec and separating science division when at the time people say, "Hey, I goal to go on mass spec to take over the world." I'm like, "That's a great idea, but I don't think that's good for patients," right? If anything comes cheaper, why would we use something more expensive, right? So the idea is that we use the right tool for the right purposes. 

So when I think about this, I really think that mass spectrometry and immunoassay are complementary. So we just have different tools for the right purpose and the right assay that we are going to use. You're starting with a collab. I like the graphic that you put together. You know, when we think about the patients, that's the center, right? What the patient needs and what kind of assay and what platform can fulfill the patient needs? I think that's the fundamental question we have to ask, right? So a lot of the immunoassay comes to the first answer. But on the other hand, I think mass spectrometry is going to come into play, for one, is that even with the current platform, we need to think more like, are we using the right platform? I really think mass spec can be utilized more as a whole for our society. And secondly is how do we mass spec even more accessible to the community? That's something I've been working on for the last few years, is educating people, what can we do with the mass spec, right? 

Another is so that people can easily set that up and for what they do. Some they don't even have that in house or become too expensive to send out. Something becomes cost prohibitive. I mean, we all learned what that means when your bottom line is red, right, during COVID. That's pretty scary. So that becomes a challenge. But on the other hand, I think if we could make mass spectrometry more streamlined, more automated, I'm going to put the word there, more automated because I really wanted to see the automation of mass spec. I've been reading and talking about many things. I think that is going to be a game changer. Get people accessible. And just sitting right next to an immunoassay becomes a choice for the patient's needs rather than becoming a choice of can we afford it, so.

Yeah, that's a perfect, I think end to this presentation, really the accessibility, right? And I think that really resonates with labs that have little mass spec or maybe no mass spec experience, but even to those that have mass spec experience and also I guess expanded to other areas of our clinical laboratory. 

 \[Victoria Zhang\] Yeah. Yeah. - Okay. I'm very excited about it. - Yeah. (Victoria laughs) So thank you. I think we'll just end this session. But any questions from the audience? - \[Moderator\] If you have a question for Alex and Victoria, we'll bring a microphone around to you. Feel free to just raise your hand. Thank you. - Well, if not, can I just add one more thing? - Sure, yeah. - All right. (laughs) I think another thought I have is, you know, when we think about the future, right? So the current workflow, I use drug abuse as an example, because many people do it. That's kind of one of the largest assays that we have. The current workflow is we use immunoassay as a screening. And then for the positives, we use mass spec as a confirmation. There's many considerations to this. So just think about if mass spec is as easily accessible as immunoassay, as cost effective as immunoassay, why do we need the first step? Right, wouldn't that be nice? 

(chuckles) - Yeah. - Right. So we can take that out of the, a lot of, you know, save some time for the patients, save some money for the patients. You get directly there to the right testing. So I think that's, you know, great. And another is, I use testosterone again, as an example. What happens is many times they run an immunoassay and the provider realizes, you know, oops, we got the wrong assay. Most of the time they don't have that easily accessible, right? 

The same way as here, if we have mass spec easily accessible and just right there as cost effective as immunoassay, and basically the cost is going to be out of the picture and people just go, "Hey, we have immunoassay, we have women, right? And we should automatically reflect that to mass spec because that is the right assay for this test." So rather than we think about, okay, how much is it that cost, (chuckles) right? So that's why I am also thinking about putting mass spec right next to the immunoassay analyzers. There is going to be so many potentials we are going to have for our own laboratory and also for patients.

 - Yeah, good point. I think regarding the quality management process and how much it costs for automating immunoassay, but the security of mind to have that whole, you know, start to finish being all kind of taken care of, instead of going piecemeal, let's say for a manual process to take care of that quality management process, it could be quite daunting and a lot labor intensive, right? - [Victoria Zhang] Yes, absolutely. Yes. - Any other questions? Okay, well, I think we'll close today's session. - [Moderator] Yes. Thank you, Alex and Victoria. Let's give them one more round of applause. (audience applauding) Thank you very much for this meaningful conversation. (audience applauding)