Episode 66: It’s not what we’re detecting, it’s how we’re detecting it

Adam Christman, DVM, MBA: Hey everyone, welcome back to The Vet Blast Podcast. You know, we said this before on some of our other episodes about how amazing veterinary medicine is with technology. It is so innovative. Today I'm excited to learn more with our listeners too. We're going to be exploring new technology in veterinary diagnostics, and with us today is Ashley Wood, PhD, from Zomedica. How are you, my friend?

Ashley Wood, PhD: I'm doing well. Thank you so much for having me. I'm excited to be here.

Adam Christman, DVM, MBA: I'm excited, listen, I am excited to learn about this too. I've heard about it, but I wanted to hear it straight from you too.

So, to our listeners that aren't familiar with Ashley, a little bit about her. So, she joined Zomedica in 2019 to facilitate the development of [bulk acoustic wave technology] BAW technology. You're [probably] like "what is that?" We're going to chat about for use in veterinary medicine. She now leads the company's research and development activities. Ashley's expertise is in the areas of molecular biology, cell biology, imaging techniques, and biochemistry.

Prior to her current role, Ashley was part of the R&D group at Swift Biosciences where she was responsible for creating market viable products as the lead scientist in the advancement of next-generation sequencing assays. Her responsibilities included assay development, bioinformatics analysis, and transfer to manufacturing. Ashley has also served as a research assistant professor and completed a postdoctoral research fellowship in the cell and molecular biology department at Northwestern University's Feinberg School of Medicine.

She has coauthored several papers that have appeared in industry prominent journals. She graduated with honors from Duke University with a degree in biochemistry and earned a PhD in molecular biology from Johns Hopkins University.

Well, congratulations for all those accolades, my friend.

Ashley Wood, PhD: Thank you.

Adam Christman, DVM, MBA: That's fantastic. And we have to thank our friends at Zomedica for sponsoring today's podcast. And you know what let's get into it, I mean, you must be just as excited as we are at the veterinary space about all the latest and greatest in point of care services. Now I've heard about this, I heard in the pipeline a little bit about B-A-W technology. So, to our listeners, why don't you kind of peel back the curtain a little bit and tell us a little bit about what that is?

Ashley Wood, PhD: Sure. I would love to. So, BAW, or B-A-W technology actually stands for Bulk Acoustic Wave technology. And what this is—this may sound complicated but it's actually very simple as we get into it—basically, this is a microresonator technology. And it converts electrical energy to mechanical acoustic energy and when it does this, it creates a very stable and precise oscillation. We'll get into a little bit more about how we use that.

What I want you to know to begin with is the reason that we, at Zomedica, kind of focused on this technology, because these resonators are widely used in wireless technologies. So, they're in, you know, every cell phone that's out there, they're in Wi-Fi routers, they're in 5g cellular towers. So, this is a very simple, robust technology that really has widespread use. But what we've done and what's kind of different now is we're working with our partners at Qorvo Biotechnologies to adapt this BAW technology and make a biosensor. So, we're using a technology that's really well-vetted and has been used for years in wireless technologies and now we're bringing it to veterinary medicine as a biosensor, and that's what's new and innovative here. And what we're really excited to talk a little bit more about.

Adam Christman, DVM, MBA: So, this has been around [it] sounds like? So, the BAW technology—do you love by the way to our listeners how I call it my Jersey accent BAW technology?

Ashley Wood, PhD: I do. It sounds way more exciting that way, right?

Adam Christman, DVM, MBA: So, tell me a little bit about how it works in the veterinary space?

Ashley Wood, PhD: Sure. So, what we're actually talking about is a resonator. This resonator is made of a piezoelectric material, and it actually resonates or vibrates at a very specific frequency. What's really cool about the BAW technology is that it's vibrating or resonating at a very high frequency, and that's important because that's how we get to the really high sensitivity of the sensor that we're using. But, what's also interesting is, we're using a kind of traditional chemistry, so we're creating immunoassays—and for those of you who aren't really familiar with what an immunoassay is—basically this is just using an antibody to detect an analyte of interest. So, the most traditional kind of immunoassay is called a sandwich assay, you basically have one antibody that recognizes your analyte of interest. Then that first antibody is called the capture antibody, it's usually immobilized on some sort of solid surface or bead, and then it captures your analyte of interest.

So, this is whatever molecule you want to measure in a sample. It could be for us, you know, TSH, or thyroxin, or something like that. Then you have a second antibody that can come on and it sandwiches that analyze that's why it's called a sandwich assay. We get that second antibody that comes on and recognizes the same analyte. So, this is how most immunoassays work. And we're doing that same chemistry. But what we're doing is we have a different way of detecting that chemistry. So, most devices that are out there are going to use something like optical detection or they're looking at radioactivity. But what we're doing is using this BAW sensor to measure when an analyte is present in the sample. We have a resonator that's our technology, our BAW biosensor is a resonator, and we take that capture antibody, and we immobilize it on the surface of the resonator. So, we actually attach that first antibody to the sensor, and then when an analyte binds and when a second antibody binds—you can imagine if you have something that's vibrating at a specific frequency when you get weight or mass on top of that sensor, it's going to slow down. I mean, that's just logical, right? If you put something heavy on something that's vibrating, it's going to start vibrating at a slower frequency and that's what we're actually measuring—the rate of vibration.

As you get more and more analytes on the surface of the sensor, it's going to slow down, and we measure that shift in resonance frequency, and then we just convert it to an analyte concentration. So, it's a really simple process, it's just all we're doing is measuring vibration, rates of vibration, and then how they change when a sample is applied to the sensor.

Adam Christman, DVM, MBA: Give me an example then in vet med; how would that look like to us? And, you know, it sounds like it's really specific and sensitive too.

Ashley Wood, PhD: Yeah. So, we've developed a device called TRUFORMA, and we have 3 assays that are currently available, and we're developing more, but 1 of those assays is for TSH, so to look for thyroid diseases in both dogs and cats. And for that TSH assay, what I'm talking about, is a traditional sandwich assay. So, we put a TSH antibody, and we attach it to the surface of the sensor, then the sample flows over so we have microfluidics that allows that sample to flow over the sensor.

Any TSH molecules that are in that sample are going to be captured by that TSH antibody. We then release another second antibody, the detection antibody, and that flows over the surface of the sensor. And that second antibody is then going to recognize that TSH molecule as well. So, if a sample has a lot of TSH in it, it's going to slow down that resonance frequency more than a sample that has less TSH in it. And we have a standard curve that just allows us to convert that shift in resonance frequency to the concentration of TSH molecules in the sample.

Adam Christman, DVM, MBA: That's incredible and so fascinating. It really is. So, it really is about those vibrations that you're talking about. Right?

Ashley Wood, PhD: Yep. And what makes it so kind of special here is that, again, it's about the sensitivity and the robustness of the sensor. So, this is what hasn't existed kind of in previous devices that might be available. So, because that sensor can resonate at such a high frequency that allows us to capture really low concentrations of molecules and a sample, and that's something that people haven't been able to do in this kind of device previously. Also, because the sensor is so robust, small, and cost-efficient, we can put it into a really small, pretty little package, that can be a device that can go just in the clinic. It doesn't have to be in a reference lab. It's not some huge piece of equipment. It's just a very small, concise device that can go just on the benchtop in a clinic.

Adam Christman, DVM, MBA: I was going to actually say that I saw it online and I was like, "Oh my gosh," I thought when I was reading this I said, "This has got to be a huge piece of equipment." But coming into the veterinary space, I can tell you that space is a commodity and [when] I saw this I said, "Oh my gosh, this is literally like a countertop space," like it's almost even smaller than some of the centrifuges that I see out there.

Ashley Wood, PhD: It's tiny. We say it's like the size of a shoebox and I think it weighs about 7 pounds. I measured them a couple of times. But yeah, I mean, it's really small, it's really light, and you can move it around. Like if you needed to, you could move it from one place to another if things in the clinic are changing.

Adam Christman, DVM, MBA: Yes. So, is this being done on the human side at all, then?

Ashley Wood, PhD: Yeah, so our partners, I think I mentioned Qorvo Biotechnologies, so that's who we're working with to develop this technology, and they are also developing assays on a very similar device for human medicine. So, they actually have 1 assay, it's a SARS-CoV-2 Antigen Test that actually just recently received emergency use approval from the FDA. That was really exciting. We're really happy to see that because this is really showing how BAW technology is advancing in medicine across the board. But we were able to bring this to veterinary medicine first because we don't have the same regulatory constraints that we have in human medicine. So just the timeline can be faster. But it's been a really cool process to see, especially [with the], lessons learned from both sides. Veterinary medicine helps human medicine and human medicine helps veterinary medicine, and then everybody, you know, advances.

Adam Christman, DVM, MBA: Yeah, yeah, everybody advances too. You know, I’m thinking of the accuracy of something like this that you're using with the B-A-W technology, BAW technology. So, how can you be sure that BAW technology produces accurate results?

Ashley Wood, PhD: It's all about our development process. So, at Zomedica and at Qorvo Biotechnologies, we really have made an effort to make sure that we're taking all the proper steps to create really good, accurate, high-performing assays, and this starts from the very beginning. So, a lot of assays, I mean, this is just something that we all know happens in veterinary medicine, a lot of times, there's a human assay or human test that's created and optimized, and then it just gets validated for use in animals. But it really wasn't developed for use in animals. Well, Zomedica is taking a different approach.

From the very beginning, we are optimizing and developing our assays to work on the samples where we intend them to be used. Right now, we've been using dog and cat serum samples and plasma samples. And from the very beginning, whenever we do our testing, we're doing that testing on those kinds of samples, because we think it's important for our patients, you know, our animals, that we make sure these assays are optimized for use on them. Because there are differences, you know, between humans and animals, there are some differences that come about. So, if you have an assay that was, you know, made for use in humans, and then you're just using it in a cat, for example, you might not have the optimal performance, and one example of that is actually the TSH assay we were talking about earlier.

The TSH assay that's available right now, this one's a little bit different, was optimized for use in dogs. So, when you send out a TSH sample to the reference lab, you're actually getting—even if it's a feline sample—it's being tested on a canine test. Well, the problem with that is it works, and it's been validated, you know, you can measure TSH levels, but in dogs, you're really looking at high levels of TSH because you're looking for hypothyroidism and dogs where TSH levels become high. Well, in cats, cats tend to be hyperthyroid, so you're looking for very low TSH levels. Well, the canine TSH test doesn't measure low enough to really differentiate a normal healthy cat, it may just have a slightly low TSH from a hyperthyroid cat. So, that test doesn't have the sensitivity that you need to make the actual diagnosis. So, we've made sure when we were developing our TSH assay, we optimized the assay for use in canines, but also, we optimized an assay for felines, so our feline TSH assay can measure a lot lower than the canine TSH assay, and that's because that's where it matters, clinically. So that’s part of what we're doing that’s different and that makes sure not only are the results accurate, but they're also clinically useful.

But then just you're asking about accuracy. The other thing that we do is verification. We do validation on all of our assays—we're comparing the results from our tests to reference lab results, and we make sure that we're testing along the way we make sure all of our assays are functioning the way that we know that they should, and we're really comparing to what we consider a gold standard test to make sure we're giving the veterinarians an accurate result.

Adam Christman, DVM, MBA: Right, right, and, you know, I was also thinking, as a general practitioner, if I have the TRUFORMA benchtop, do I have to run an accuracy test or, you know, quality control tests every day, or how does that work from a practical standpoint?

Ashley Wood, PhD: Yeah. This is a really good question. That's one of the things about this technology that makes it kind of unique. So as opposed to some of the other detection methods that might be using optical detection, where you really have to constantly be running calibrators and making sure the instrument is performing the same on a daily basis, our instrument really does not show any sort of drift over time, and we've shown this and so we don't require that kind of constant calibration on a daily or weekly or monthly basis. The other thing that we do is all of our reagents come in a disposable cartridge. So, that cartridge contains our calibration curve and is actually factory calibrated. So, you don't have to worry about any differences from one lot to the next, which is a lot of time what you're doing when you run those kinds of calibrators. All of that is done for you by the manufacturer. So, all you have to do with your sample into the cartridge, put it in the instrument, and let it go. Yeah. So, we don't require that kind of QC over a period of time and that's just because it's a different kind of sensor, different kind of technology.

Adam Christman, DVM, MBA: You know, I want to share some interesting statistics, get a load of this. So hypothyroidism in dogs, one of the most common endocrine diseases with a prevalence rate estimated at .2% to 1.89%. That's pretty significant, and hyperthyroidism in cats is a significant cause of morbidity in older cats having an estimated prevalence of 4.5%.

Then this other statistic I always find interesting too, [this is courtesy of Qorvo.com], is Cushing's disease in dogs, another common endocrine disorder in dogs with an estimated incidence of one to two cases per 1000 dogs per year. The reason why I mentioned that to you is that I do think that we really need to start using more point of care services, you know? Because, you know, pet parents want answers yesterday or sometimes it's a matter of "Do I need to ship or refer this animal out when I have pending lab results?"

So, you know, to that point, how will the BAW technology enhance, you know, in-house diagnostic capabilities?

Ashley Wood, PhD: Yeah, and I think those statistics are exactly why we targeted these markets. You know, we think this is really a place where there's a gap right now, where veterinarians cannot do what they need to do. So we're trying to put control back in the hands of those veterinarians, so we don't want them to have to wait to get those results by sending a sample out to the lab or you know, the lab doesn't run samples over the weekend or on certain days.[If Veterinarians] have a patient that comes in on Saturday—we want them to be able to get their results on Saturday if that's what they need. By doing this, I mean, the issue has constantly been that you just can't get the same quality result in-house as you can when you send it out to the reference lab, and that's what we're trying to fix. That's why when we sat down and thought about, okay, what's missing? Why can we not provide the right result or the correct, or that most accurate or highest performance assay at the point of care? What we decided was that the problem is really the detector, it's not the chemistry, it's not the immunoassay, it's the detection method. That's why Zomedica went out and found a different detection method that we realized is actually superior to what can currently be done. And we brought this to veterinary medicine and said, “Okay, we're going to create a device that really gives veterinarians what they need at the point of care, and allows them to diagnose and provide, you know, better results to pet owners and for the patient also.”

Adam Christman, DVM, MBA: Yeah. So, what's generally speaking, the turnaround time from when I insert it into the machine and then get those results?

Ashley Wood, PhD: So right now, our assays are 20 minutes or less and we're really going to stick around that time point because I think that's something that allows the right amount of time that they need the results while the animals in the clinic. They can get it if they want to wait, maybe run it a little bit later and just get it the same day they can. But, I think that's the timing that we've established.

Adam Christman, DVM, MBA: Excellent, you know, listen, like I said, with curbside and whoever knows what the future holds in veterinary medicine. You know, it’s so helpful to have these tools and diagnostics at point of care services because me—as a dog dad myself—I want to make sure I know the answers and these are life-changing decisions that we might have to make too, so it's really important. So, I can't thank you enough for all the hard work that you're doing.

So, to our listeners that are tuning in, where can they find more information about all this, Ashley?

Ashley Wood, PhD: [Listeners] can go to our website, which is www.zomedica.com, and they should be able to find all the information they need on the assays that we have available at the moment and the instrument itself, and they can reach out we have contact information there if they want to reach out and they have additional questions, we would always be happy to talk to them.

Adam Christman, DVM, MBA: Excellent. Ashley Wood and our friends at Zomedica, thank you so much for joining us today.

Ashley Wood, PhD: Thank you so much for having me. This has been a lot of fun. We love your podcast. So thanks for everything you're doing.

Adam Christman, DVM, MBA: Thank you. This is why it's called The Vet Blast Podcast! And to our listeners thank you so much for tuning in. Thank you for all your hard work please stay safe out there and continue to stay pawesome. Take care everyone.

Transcribed by https://otter.ai