Multiplex Fluorescence Immunohistochemistry using the Ultivue InSituPlex Platform on the Leica Biosystems BOND RX

Hello everyone and welcome to today's live broadcast, “Multiplex Fluorescence Immunohistochemistry Using the Ultivue InSituPlex Platform on the Leica Biosystems BOND RX,” presented by Traci deGeer, Global Product and Innovation Manager BOND RX, Leica Biosystems and Alex Klimowicz, Principal Scientist, Boehringer Ingelheim Pharmaceuticals. I'm Alexis Krauss of Labroots, and I'll be your moderator for today's event. Today's educational web seminar is brought to you by Labroots and sponsored by Leica Biosystems. For more information on our sponsor, please visit leicabiosystems.com. 

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This presentation is educational and thus offers continuing education credits. Please click on the Continuing Education Credits tab located at the top right of the presentation window and follow the process to obtain your credits. I'd like to now introduce our presenters, Traci deGeer and Alex Klimowicz. For complete biographies on our speakers, please visit the Biography tab at the top of your screen. Traci, you may now begin your presentation.

Thank you so much Alexis. I'm an open innovation manager for the research platform here at Leica and one of the things that I do in my position is bring companies like Ultivue to Leica to form partnerships so that we can bring innovation to the researchers that we work with. One way that we do that is through the BOND RX system, which is our research platform. My presentation today is going to walk you through a little bit about the BOND RX platform and how that works with open innovation to allow researchers like Alex to bring things onto their system that are brand new. Let's get started and I'll show you a little bit about the system and how it works with our open innovation partners like Ultivue. 

The Freedom to Discover

One of the principal things about the platform that we bring to our customers is it gives them the opportunity to explore new ideas, accelerate test programs, and then, if you're talking to people like Ultivue or some of our other open innovation partners, they look at it to commercialize discoveries. That's something that the open software that we're going to talk about in just a little bit allows them to do with the system. 

Explore Your Ideas

Now let's start with, explore your ideas, and when you're talking about a piece of automation, what do you mean when you, say, “explore your ideas?” 

Tests Automated on BOND RX

One of the things that you can do is if you talk about a system that you can bring your third-party assay onto, and if you think about it, you see lots of little things in the check boxes. You see in many fluorescents, you see circulating tumor cells. You see TSA, which is tyramine, we're going to talk about that in a little bit. You see TUNEL. You see multiplexing. All of those different things. All of those things can be done on the same platform. 

Do you see that unique little box up in the corner that says “your test here?” Well, when we go to talk to an open innovation partner, this is somebody that's got something new and novel that not many labs are running right now in the research world. We go and actively look for those people and what we want them to do is to push the instrument to their limits and try to get their assay automated on the system and their assay becomes the next “your test here.” In this case it happened to be Ultivue that has the “your test here” button. And that's what we've done with them and you're going to see some other partners that we've done that through the years with and there's a whole pipeline of those partners that play on the system.

Things that we put on ourselves are things like the Novocastra antibodies. We've put Kreatech probes on there and we have our own detection chemistries that we run on the system that are the exact same between the clinical instrument and the research instrument. What we're trying to do is find new ways to bring things onto the clinical system through exercising what we can do on the research platform. 

Technology Introduction Timeline

There's a long history of doing things like that. If you look back to when the very first BOND RX was released in 2011, over the last seven years or so, we formed many partnerships and we've gone through many iterations of software, each time making the system a little bit more flexible. 

Open Possibilities

That opens all kinds of possibilities if you happen to be a researcher. It allows you to do things like break apart probes. It allows you to do all kinds of fluorescent multiplexing. It allows you to do IHC. People have tried all kinds of things on the system. 

Endless Customization Options

You get an endless amount of options that you can play with. That's one of the things that makes my job easy. I can walk into a laboratory and talk to a pharmaceutical company or a biotech company that's got this great idea, and ask them, “have you thought about automating it?” We can kind of play around to see if there's some way that we can make that happen. 

Pre-Staining Preparation Customization

You can do all sorts of freestanding customization. You can play with heat. You can play with, deparaffinization. All of those are things that Ultivue had to look at as they were putting together their new assay. Each company goes through things a little differently, and each one works to get a protocol that they can put on the system and make work. Some of them start with assays that are manual. Some of them start from the ground up and build an assay. 

Pre-Staining Antigen Retrieval Customization

Sometimes it's antigen retrieval that makes all the difference. Sometimes it's being able to change incubation times and temperatures. Sometimes it's the way that you wash your slides and each one of those things contributes to how well an assay will work on an instrument. 

Staining Customization

Sometimes it's bringing able to put a third-party marker onto the system, or sometimes it's not being able to run a detection chemistry that you want to run that makes a difference. Now one of the things we lean on a lot with our open innovation partners is they don't start out running a detection kit that we create. If you look at someone like Ultivue, what they do is they take open containers and they actually pour their reagents in it and they put them on the system. Things don't come in a container that we make. That's what each of our open innovation partners does. As a researcher, Alex has the same ability to do something that one of our open innovation partners does.

If he decided he wanted to run a detection color tomorrow but we as a company don't make, he could go anywhere and buy that detection color and he could give that a whirl if he wanted to. That's openness in a system that researchers like to play with. I come out of a research lab and being a researcher, I like to tinker. The ability to tinker on the system is something that makes most researchers happy. You want to be able to put what you want on the system when you want. A lot of times it's about being able to do that more than a lot of things to get your assay to work. 

There were a lot of things that when we started working with Ultivue had to be customized. Some of their reagents didn't like water. You must customize to that. One of the things at the very end of their procedure was that it couldn't sit in water. There's customization that went into their procedure and that's what happens with our open innovation partners. They helped us create our new software that came out and that's one of the things that's so wonderful about working with researchers is they come through and they help us become better. 

Accelerate Your Test Program

The “Accelerate Your Testing Program” is something that we value a lot when it comes to our customers and our researchers and our partners. 

Speed

A lot of times, speed is not something that's as important in research as it is in the clinic, but it does help us get better. A lot of times with the antibodies in the clinical laboratory, you can get those done in about 2 ½ hours. One of the things that the instrument does well is each of the drawers run independently. If we're running something like Ultivue, we can run that on one tray and run something completely different on another tray. That lets the instrument function in like two or three separate instruments. 

Efficiency

It also makes things very efficient. Now the new instrument that just came out has a way of relieving some of the strain on the laboratory by adding some visual management, which is something we didn't have on its predecessor. It has both bottles that flash colors. If you have an instrument that has a bottle fluid that's low, first it will change colors in white, and then if it really gets irritated at you, it will turn the bottle red and then it expects to get some attention for that red bottle. 

The instrument is small now. There is a bench top version of it, but the top-of-the-line instrument is a floor model. Given the size of some of the other instruments on the market, it tends to be a little bit smaller. The footprint is not extremely huge. 

One of the newest things that came on the instrument was a change in the software GUI. Now again a GUI which is a front screen that you look at and it was redone to give a little bit more visual management. You can see your bulk bottles on the front screen. You can see all the reagents that you have loaded over on the right hand side and you can see each individual drawer and what you have on it. That helps you keep track of things on the instrument a little bit better. You also get better auditing controls, which is really nice and it makes it easier to set your runs up.

These were the bulk bottles that we were talking about. This is the visual management. If you've got a bottle that is decommissioned, it looks gray. If you've got one that's in a natural state, it looks just a little bit backlit. If you've got one that needs attention, it'll have a white light behind it, and if you have one that's really in trouble and it gets very aggravated with you, it turns red. 
The bottles can have fluid added to them on the fly. You don't have to stock your instrument to do anything to the bulk bottles, you can just remove them and add fluid to them. Or unscrew the lid and add the fluid to them. That can help keep the instrument running without you having to stop and adjust anything. 

Consistency

One of our hallmarks of the instruments that has worked so well for the researchers over the years, and one of the things that our open innovation partners have found to be a key to success has been the covertiles. These let us do some unique things. One of the partners I work with works with circulating tumor cells. The thing that they have found that helps them the most is the way the covertiles work, because it preserves those very rare cells in place on the slides. You get excellent retention of the cells. It holds everything in place and keeps things from moving around. It also provides a place for the antibodies to incubate. It keeps the cells from drying out, so it's kind of a hallmark of the technology. 

They went back and redid the way that part of their cell spreader works to suit the covertile that was on the instrument rather than asking us to make a change to the instrumentation. It's an interesting way that these things sometimes work together.

Access to New Tests From a Range of Partners 

One of the things that's interesting about the instrument is the way it functions and the way that we've been able to form partnerships based off the technology that we bring to the table so that we can go out and seek other companies that have good technology to bring to researchers. Ultivue is the one that we're talking about today, because they have such wonderful technology, but we have a history of forming partnerships with great companies. One of the companies that we have a partnership is PerkinElmer, who does multiplexing. We have a partnership with a little company called RareCyte, which is a circulating tumor cell company and they are fully automated on the system as well. The company that we're also very excited about today is Ultivue. 

Ultivue has their UltiMapper reagents and they can do their five plex on the system as well in a fully automated fashion. This is one that we were very excited to be able to bring to our researchers and they've been a wonderful company to work with as well. We also have a partnership with a little company called Clearbridge Diagnostics. Clear Bridge is a company from Singapore and they are a circulating tumor cell company. 

Our longest lived partnership is with Advanced Cell Diagnostics out of California and this was our first company that went all the way through our open innovation program and they started out on the BOND RX just like all of the other companies that you just saw. Now they have partnerships based on the research side and on the clinical side with us, so they're on more than one instrument platform with us. That's how these companies go from the open innovation on the research and the openness of the system all the way through to the ability to commercialize on the clinical side. It's a wonderful path for companies and a great collaboration for us as a company, which is why we're so excited to have Ultivue as part of that family of companies. 

The Ideal Balance

It's a wonderful way for us to be able to take the freedom and flexibility that the BOND RX offers and the consistent results that we're able to offer to our partners in conjunction with their wonderful reagents to be able to bring something very special to the researchers today. 

It creates a unique pathway; a pathway from open innovation, being able to offer something unique to the researchers, and hopefully a path forward to bring something very special to the clinic at some point in time. That lets us provide a commercial path for some of our wonderful partners and hopefully provide something unique to our customers and our researchers and hopefully to their clinical patients in the future. Now, Alex, I'm going to hand it over to you and let you tell them a little bit more about our special partner Ultivue.

Thanks, Traci. Let me first just speak to my disclaimers. Leica Biosystems did not sponsor the studies that I'm about to talk to you about. And the opinions expressed in these presentations are my opinions as a scientist, having experience with the equipment and the reagents that are being presented and are not considered an official endorsement by Boehringer Ingelheim of any of these products or services described.