I am Anjli Venkateswaran, and it is my pleasure to introduce Tia Coleman, who will be joining me on today’s podcast. Tia is the assistant director of clinical pathology at Biomere’s site in Worcester, Massachusetts. Tia received her bachelor’s degree at the University of Massachusetts Amherst and has over a decade of experience as a medical laboratory scientist. Biomere is a preclinical CRO with locations in Worcester, Richmond, California, and has multiple sites in China. The company’s portfolio includes comprehensive discovery, DMPK, non-GLP, and GLP toxicology services. You can learn more at www.biomere.com. So with that, let’s get into today’s topic on clinical pathology testing and the development of panels to support in vivo studies. Tia, thank you so much for joining me today. I’m very excited about our discussion.
Anjili: Let’s get right into this. The analysis of blood and biofluid samples to identify changes in specific markers, such as analytes and proteins, are very commonly used in the clinic as well as in preclinical studies. So let’s start with what’s going on at Biomere and what you guys are doing to support in vivo studies.
Tia: So here at Biomere, we have a clinical pathology department with both hematology and clinical chemistry analyzers. We have two hematology analyzers, and the newest of those is the Sysmex XN-1000 Analyzer, which has a very high throughput and very specific platelet markers for more precise analysis. And then we have a Beckman Coulter DXC 700 AU clinical chemistry analyzer, which also has a very high throughput and allows us to perform analysis on very small serum or plasma quantities.
Anjili: Let’s dig a little deeper. You mentioned hematology as well as clinical chemistry. Maybe we’ll start with the clinical chemistry part of it. Beckman has a lot of different analyzers. You mentioned the AU, which I think the DXC is the newer system, and the AU is a little bit older but more suitable for smaller labs. Tell us more about why Biomere invested in the DXC and how many samples your lab is analyzing on a weekly or daily basis.
Tia: In the past, we had a different analyzer, something called an Alfa Wassermann Vet AXCEL. And that analyzer required such a large volume of serum that it was not feasible for us to do very much, especially for any animal model besides a non-human primate. So unless we could provide several hundred microliters of sample for that analyzer, we were not able to get very many analytes analyzed. So we invested in the Beckman Coulter DXC 700 AU, and we shopped around for a few different options. But that analyzer was able to give us the most precise small-volume sample. For example, one of the first studies we ran on that analyzer, when we got it up and running, we only needed 20 microliters of serum, and we were able to get two results off of that, which is exactly what the client wanted. We were able to use a mouse model on that study and also provide interim testing as opposed to just one big bulk testing at the end of the study upon necropsy.
Anjili: This, I think, segues perfectly into something I wanted to talk a little bit more about: typical study design, because I think a lot of these analyses essentially support in vivo studies. Can you tell us a little bit more about the typical study design that generates the samples for your lab to analyze?
Tia: Sure. And to answer, I think I missed one point in your last question, too. The other challenge with that previous analyzer is that it was super slow. So, this analyzer, again, to address the throughput, can sample hundreds of specimens in a matter of hours as opposed to one or two every 30 minutes on the previous analyzer. We would load up that old analyzer and walk away for the day sometimes, whereas this analyzer, I think I ran 80 specimens on Tuesday in about an hour and a half, so very much. And that’s fast. And that becomes a big deal because if you have a lot of studies going on, you don’t want a backlog.
The one other thing that I do want to add about that analyzer is that it is an open-channel analyzer. So, we have the ability to bring on and validate analytes that may not be provided by Beckman Coulter, which is something we’ve done recently at the request of a client who was looking for something very specific. We were able to do research, and we actually found the same exact reagent that was used in a previous study that the client was addressing for the same test article or a similar goal for their test article. We found that same exact reagent, we were able to validate it, bring it on board for them, and give them the test results they were looking for.
Anjili: That’s amazing. I mean, that to me just lends that kind of customization, because I’m sure you have a lot of regular studies that can be addressed with the available analysts, but there are always going to be studies with custom needs, or it would be really great if you could add “X” or “I don’t want A and B; I want to add this.” So that’s amazing. Is this customization process very difficult to do on the Beckman Coulter analyzer?
Tia: It’s not difficult. It takes planning, of course, and to be honest, the more we do it, the more familiar we get with the process. I’ve done it three times now myself, and I’ve observed them doing it for us. In the past, they used to come in and do all of the validation, but when it’s a special analyte, such as a non-Beckman Coulter thing, then that’s something that we would be responsible for validating. And we’ve gotten pretty good and quick at it. I love it. As long as we can plan ahead, we’re able to perform the work, validate it, make sure that it is feasible for the study and the animal model, and then go from there for study testing.
I think that’s a huge benefit because it’s good to have these markers, and some are more informative than others. So if a client program or a specific drug is attached to a very unique biomarker, then it’s very important. I think this customization is really interesting.
Anjili: What does the raw data from the analyzer look like, and what kind of post-experiment data analysis is required to deliver a meaningful report to clients?
Tia: So that all varies on what the client is looking for. We will usually provide the client with the raw data. We perform a peer review of the work before we put it into a data summary that we provide in an Excel format file. And then from there, if the client is also interested in statistics, we provide an average and a standard deviation, usually for each of the groups. And then if there are additional customizations to statistics that they’re interested in, we can always discuss that prior to the study starting or even upon some interesting changes or findings mid-study. We can always make those adjustments per client request. We’re extremely flexible here, which is something that when you and I have spoken in the past, I’ve mentioned. When you’re in a GLP environment sometimes, you are kind of confined to the rigidity of an SOP or a protocol, whereas here at Biomere, we have some flexibility for non-GLP studies where we can make decisions and changes on the fly, of course, provided the client and study director perform amendments, etc. But we are much more flexible and able to go with the flow on most of our studies.
Anjili: And we’ll go into that a little bit more because I have some questions for you on client behavior and the evolution of a study. So, we’ll definitely come back to that point.
I’m going to ask, I mean, again, when I was looking at the different clinical chemistry panels that are out there, and I’m sure all of us have been to the doctor, had blood work done, and looked at lipids or whatever, metabolic panels, what have you, CBCs. So tell me a little bit more about the panels that you guys typically run. Are they similar to what we see in the clinical setting with patients? Or are they very different?
Tia: They’re exactly the same. So, the analyzers that we have—the two primary analyzers are the Sysmex XN-1000 for hematology, and then again the Beckman Coulter DXC 700 AU—are the same analyzers that they use over at UMass Memorial Health Center. These are two of the premier analyzers that are top-competitive in the market for analysis in the clinical setting for human beings. Some of our medical technologists, in fact, we chose them and interviewed and brought them on board because of their experience with these analyzers. And that experience is hard to find in the field unless you’re looking for a med tech, and often those med techs come from the hospitals.
Anjili: So, this is truly a translational concept, right? I mean, I think drug discovery is littered with a lot of challenges where studies, you know, from the animal model often have a tough time translating to the human stage. So the fact that the same kind of instruments and the same kind of readouts and the same kinds of panels are being used in preclinical and then also in the clinic is a huge benefit, and it really, you know, lends credibility to the data. I wanted to also ask you about sample collection and processing. So, you know, you’ve mentioned, like, peripheral blood, and I’m guessing that you also work with other biofluids, like urine or synovial fluid or something like that. What are the main sources of your samples and how are they processed?
Tia: We do work with a variety of biofluids. Plasma, serum, urine, cerebrospinal fluid, and recently we’ve actually been bringing on synovial fluid. That’s a new sample type for us to test, and that’s been in a non-human primate study. And so that has, that’s been a little difficult. But we have, we’ve gotten a lot of good experience with that, and it’s been going well. We do still work with whole blood, and so often with mouse and rat models, we will get whole blood and run both hematology and clinical chemistry on those. And it’s very important to use a small volume, of course, because, you know, the total volume of blood in a mouse is very, very small. But with the DXC 700 and the XN-1000, we’re able to run both of those analytes on small specimens. But you are right that we do work with a large variety of different sample types. And the processing, we have a variety of different processing instruments that we use here in the lab as well.
Anjili: And I wanted to just also maybe kind of… my last question to you is, what do you see for the future? So, what are some new things that you’re looking forward to? Or what are some new offerings, service offerings in the clinical chemistry space that you guys are looking forward to?
Tia: Well, we’ve actually just received an LC/MS, a liquid chromatography-mass spectrometry instrument, and we’re looking to develop our protein biomarker, and also we want to get into the space of looking at small metabolites and things like that. That’s on our short list for bringing on more assays.
Anjili: That’s super exciting. I mean, LC/MS is just a workhorse instrument and a lot of different, you know, preclinical spaces. So that’s super exciting. So, Tia, thank you so much for joining me today. I really appreciate your time. To everyone out there, I hope you enjoyed this conversation with Tia Coleman. If you’d like to learn more, please visit biomere.com. Thank you so much, Tia.
Tia: Thank you, Anjli. Thank you for having me. I had a great time, and I hope you all enjoyed the conversation.
