Mettler-Toledo International Inc. (MTD) Earnings Call Transcript & Summary

Hello, everyone, and thank you for joining this webinar. My name is Jonathan Trinh, and I am an account manager at Rainin. I worked with many companies on their pipette needs, tip needs, calibrations and now asset management and verifications. We are also joined today by Dr. Murray Anderson, Vice President of Marketing and Product Development at Rainin. He's been here quite a bit longer than myself and is very knowledgeable on both Mettler-Toledo and Rainin products. Today, we will be identifying pipetting risks and will be introducing and educating you all on this new product that we've released since the pandemic began, which helps reduce liquid handling risks in the lab. So a quick -- a few quick words before we get started. The session is being recorded and your local Rainin representative can present this information to you as well at your convenience. Please make sure your microphone is on mute and your webcam is deactivated. This webinar should only take about 25 minutes. Also, if you have any burning questions or comments, I would remind you to please submit them in the chat, and we'll address them at the end of the presentation. So let's move on to looking more closely at strategies for reducing pipetting errors. So our agenda today starts with a discussion about pipetting error propagation. We will be joined by Murray to discuss this using serial dilutions as an example. We'll then talk about verifying and checking the performance of your pipettes, how this is currently being performed in lab settings and what solutions might be out there now. Here at Rainin, our main objective is helping life science researchers achieve consistent results. We understand that pipetting is a crucial part of many life science workflows, and we want those experiments to be as consistent and as accurate as possible. Here are 2 examples that exemplify the importance of pipetting for science workflows. The first example is a typical next-gen sequencing protocol. This protocol contains 6 separate workflows with a total of 39 unique pipetting steps. Across the entire protocol, the pipetting volumes range from 1 microliter up to 640 microliters. The second example is the Illumina mRNA sequencing kit. This protocol contains 24 unique pipetting steps in 1 workflow, and the pipetting volumes range from 5 to 200 microliters. As you see, there are a lot of pipetting steps and multiple volumes, and so there is plenty of room for error to be introduced in the pipetting portion of these workflows. Experimental error can propagate from many different sources, some of these are listed here. Incorrect calculations can be made when preparing an experiment, samples or reagents could be prepared incorrectly or could be unstable. Instruments, such as your pipettes can also introduce error if used incorrectly. Even your pipetting technique can add to error propagation. This means that as the protocols become more complex, there is, of course, an increased risk. Serial dilutions are a great example of a common experimental protocol that is prone to error propagation. Here, to further discuss error propagation in serial dilutions is Dr. Murray Anderson. [Audio Gap]

Jonathan?

Yes.

We're having trouble hearing Dr. Anderson.

What's happening?

We're having trouble hearing Dr. Anderson. We're simply not hearing Dr. Anderson. Do we have the audio shared?

Let me -- I'll have to stop sharing and share again. Sorry about that.

It's okay.

Deeply important factor...

So do you need me to start from the top?

Yes. If you could go back to where he begins, yes.

Many of you will be familiar with the need for serial dilution as part of an experiment.

That's good.

For example, in preparing standard curves of IC50, EC50 and LD50 experiments in cell-based assays in microbiology. In many experiments and protocols, a serial dilution is an essential part of data generation. Plus, it's the cornerstone of quantitative analysis. The fundamental component of serial dilution is the stepwise dilution of a substance in solution. Many of you will be very aware of the multiple errors that can be encountered when preparing a serial dilution and maybe there are some you're not aware of. The process should start with the initial calculations to the dilution and the understanding of dilution factor. Traditionally, we are encouraged to use low-dilution factors such as 2 or 10 as opposed to 50 or 100 or 1,000. There is also the mixture you're working with. Might there be any precipitation in stability that can affect the calculated concentration. Are the 2 solutions truly homogenous or not? Does the dilution rate that you're preparing fit with the optimal detection range of the instrument you're using? The matrix effect might be candid in some biological samples that can mask the real concentration of the [indiscernible] interest. Even the choice of analysis may have an impact on the final result. Linear or nonlinear regression analysis can lead to under or overestimating the presence of an analyte. Finally, thought must also be given to the tool commonly used to generate this serial dilution. The pipette system, which includes not only the pipetting tip, but also you, the user, an equally important factor in producing the right results from quantitative analysis. Let's take a deeper look at this pipetting system and how it can affect the final results. To begin, a quick reminder about some of the terms you might encounter when by pipetting. Pipetting accuracy is a measure of the ability of a user and working with a pipette system to provide a dispensed amount of liquid at or near the volume indicated on the volume setting. There are 2 types of there affecting the quality of dispensing. Pipetting accuracy is quantified using the term uncertainty. The first error is systematic error, which expresses how close to the expected volume is the dispensed volume. Examples of a systematic error include using a noncalibrated pipette or using nonstandard tips. Systematic errors can be qualitatively described as trueness. Random error is the repeatability of a dispensed volume and as the name implies, is not the same for every dispensed volume. Examples of random errors include temperature fluctuations and pipetting techniques. Random errors can be described qualitatively as precision. How does systematic error and random error affect overall pipetting accuracy? Remember, accuracy is the combination of systematic and random error. And so let's take a look at this diagram again. If we improve our precision, it means we are decreasing or lowering random errors. And similarly, lowering systematic errors means we're improving the trueness in our dispensed volumes. So pipetting accuracy is directly impacted by one or both types of systematic and random errors. So pipetting accuracy is a combination of several factors such as your individual pipetting technique, something you may think is identical every time, but it may not be as consistent as you think. It can also include factors associated with the pipette, the sample, the environment and several other components. Remember, pipetting accuracy is the sum of random and systematic error. So for our serial dilution example, let's start by looking at a dilution series by the systematic and random error, the overall accuracy is plus or minus 3%. For most single-step pipetting applications, we're concerned about the overall pipetting accuracy and how we can improve it. But when we prepare a serial dilution, it's no longer a single-step procedure. And depending on how many steps in the serial dilution process, the accuracy of pipetting is likely to decrease as the errors increase per each pipetting step. In this first example, we're starting with a 10 millivolt solution that we're going to dilute 9x and have calculated that the last step, our solution will be 20 micromoles of target sample. However, with a pipetting accuracy of plus or minus 3%, by the time we get to that last step, the concentration may be anywhere between 22.2 and 17.8 micromoles. This next slide repeats the same experiment, but with a plus or minus 5% accuracy. And here, you see the end result, where instead of the 20 micromoles the range can be anything between 23.68 and 16.32 micromoles. Finally, this slide goes to the extreme in showing an accuracy of plus or minus 10%, resulting in a range for the last dilution of anywhere between 27.34 and 12.66. Really, an extreme range compared with the 20 micromoles we were looking for in the beginning. Can any of these errors be reduced or eliminated? Traditionally, pipette manufacturers will recommend routine service and calibration of the pipette, choosing the right tip and maintaining a good technique. Some of these things may be easy, but some are not quite as simple. How can you check your pipetting system regularly and simply, but without taking too much time out of your busy day, you're verifying to yourself that your full system, which includes you, is ready for that critical serial dilution experiment. So let me pass you on to my colleague to provide some insights to possible solutions for you.

Well, thank you, Murray. We lost you for a second, you were on mute. So let's review some interesting data we collected from our service centers across the U.S. in 2020. We looked at all pipettes that arrived for calibration at our 4 service centers, which include pipettes of all brands. Of all those pipettes, 5.8% failed to meet either their manufacturer or ISO 8655 specification upon arrival. This means that almost 6% of all incoming pipettes were out of spec, and these were pipettes that were receiving regular calibration services, so they were maintained -- were being maintained. Imagine if these pipettes were not regularly maintained, the out-of-spec rate would be even higher. To put this in perspective, let's say there's a lab with 4 researchers each with a set of 5 pipettes for a total of 20 pipettes in the lab. At a 5.8% failure rate, at least one of those 20 pipettes is likely to be operating out of spec. That could be any of those pipettes, maybe even the 20 microliter pipette that is used every day. The problem is you won't know which pipette is out of spec until you send them all in for calibration. And by then, it may be too late since you've already run important experiments. So good science is all about controls. Well-run experiments have controls for all known variables. Experimental controls build your confidence to know that your results are real when running the appropriate controls. So how does one control for pipetting, you might ask yourself. One of the best ways to control for any pipette variation is to test -- routinely test your pipettes. This verification or quick checking is ideal when you're using pipettes that are shared or come from someone or some place that you're not familiar with. Quick checking is also ideal when pipettes are damaged or dropped or you just don't know where it's been. I mean think about it, how many times do you drop a pipette and you send out for calibration again, when maybe that pipette is actually okay? Quick checking is also ideal for when your pipettes come back from calibration service to make sure they are accurate in your environment. I also like to quick check. I also think quick checking is ideal for verifying your pipetting technique as well. So there's a little problem with how quick checking is performed now. You can use an analytical balance. But there's the caveat, you have to locate the balance, and it's usually a shared instrument, so you have to book a time on it. Once you have it, you have to prep it with evaporation trap, pipette multiple times. I believe it's about 10 readings. You have to record each weighing and then perform a series of calculations for each weighing until that accuracy of the pipette has been determined. It's definitely not so quick. But now there is an easier way, you can perform a quick check with a new SmartCheck. The SmartCheck is a super small bench-top device about the size of a tip rack dedicated to performing quick pipette by verifications. It automatically performs all calculations and delivers a simple pass-fail response with only 4 dispensers. It takes less than a minute to check a pipette. There are 7 different volume options that can be checked, and it works with all brands of pipettes. You can even check the individual channels on your multichannels. SmartCheck connects to Rainin's new PipetteX software to deliver even more advanced data processing features such as a 3% to 10% times range adjustment. It keeps a record of all SmartCheck verifications and can also collect quantitative verification data if desired. Let's take a brief look at how the SmartCheck works. [Presentation]

So here, they're using a 200 microliter single-channel pipette. If it's a Rainin pipette, you're going to want to make sure you will mark it. Adjust the micrometer to the desired test volume, in this case, to the normal nominal volume of 200 microliters and then lock it in. On the left, you can see 7 different volumes that can be read on the top of the SmartCheck. When ready, aspirate DI water, slide it open to drop shield and dispense into the SmartCheck vessel, then close the drop shield. SmartCheck identifies the verification volume and the LED light stays solid, while the unit weighs the dispensed volume. When the LED light starts flashing, SmartCheck is ready for the next dispense. This process is repeated 4 times. On our fourth dispense, it's complete and the volume is weighed, the SmartCheck averages the 4 readings and calculate the accuracy and presents a pass-fail with a solid green light, and that's all it takes. If it's red light, we recommend to try to pipette again. And if it's still a red light the second time, maybe ask a lab mate to give it a try. If it turns green for your lab mate, there could be something a little off with your technique. If it is red when your lab mate tries, then it might be time to send it in for calibration. All right. Let's see a quick comparison of quick checking with a balance and SmartCheck. [Presentation]

All righty. So now we can see that SmartCheck is a powerful tool for any lab. I'd now like to show you how we've made it even more powerful with our new PipetteX software. PipetteX connects to SmartCheck and provides a powerful database that stores all relevant information of your pipettes. When connected to SmartCheck, it records each verification and stores that data with the pipette. PipetteX also manages pipette calibration schedules, users, locations, test plans and test methods. It's flexible enough to either run on a single laptop in one lab or scale up to manage an entire collection of pipettes at a large research institute from a central server. If your pipettes are calibrated by Rainin, your certificates are electronically transferred from the service center directly to your PipetteX with the certificate being linked to each individual pipette. Finally, PipetteX is fully upgradable to 21 CFR Part 11 compliance for regulated labs. All righty, let's wrap up with a quick summary. Errors can originate from both pipettes themselves as well as pipetting technique. And this error can be propagated especially during multistep experiments. Performing quick checks on your pipettes before you begin experiments can help reduce error propagation. SmartCheck is the super easy, super fast method of performing quick checks. PipetteX software and SmartCheck are also powerful tools for today's research labs. We have had requests after these webinars for additional training, whether it be on pipetting techniques, pipetting ergonomics, calibrations, a list that goes on. Well, there is good news. These trainings are all free with Rainin. So for more information on that and a demonstration of SmartCheck and PipetteX, please reach out to your local rep in your area. They have demo units and will be happy to try into helping your labs even more. Thank you very much for your time and we will now be happy to answer your question. for regulated labs -- all right. Let's wrap up with a quick summary. Errors can originate from both pipes themselves as well as Packeting technique, and this error can be propagated especially during multistep experiments. Performing Quick check on your puppets before you begin experiments can help reduce error propagation. SmartCheck is the super easy, super fast method of performing Quick checks. Piped software and SmartCheck are also powerful tools for today's research labs. We have had requests after these webinars for additional training, whether it be on pipetting techniques, hyping ergonomics, calibrations, unless that goes on. Well, there is good news. These trainings are all free with Rainin. So for more information on that and a demonstration of SmartCheck and PipetteX, please reach out to your local rep in your area. They have demo units and will be happy to drive into helping your labs even more. Thank you very much for your time, and we will now be happy to answer your questions. So before we start with the Q&A, I would like to introduce you all to our product managers, Gustavo and [ Holly ]. Gustavo, who is our resident expert on serial dilutions and Holly, who is our go to on anything SmartCheck. [Audio Gap]

Jonathan, we do have Questions. Someone wanted to know if SmartCheck can be used without PipetteX?