Baljit Bains  00:16

Wow, Sarah, can you believe it’s 2024? already?

Sarah Srokosz  00:19

I know, I guess that’s true what they say… time flies when you’re thinking about analytical data.

Baljit Bains  00:25

Do they say that?

Sarah Srokosz  00:28

Well, either way, it’s a new year, and we’re back to dive deeper into the world of chemical and analytical data.

Baljit Bains  00:35

Hi, I’m Bally.

Sarah Srokosz  00:37

And I’m Sarah.

Baljit Bains  00:39

And we’re your hosts for today’s episode of The Analytical Wavelength. A podcast brought to you by ACD/Labs.

Sarah Srokosz  00:46

For anyone who’s new year’s resolution was to work smarter, not harder and reduce the burden of routine analysis, today’s episode is for you.

Baljit Bains  00:54

That’s right. You might remember that back in November we recapped a presentation from our Driving Efficiency with Spectris Virtual Symposium that was given by Coralie Leonard. It introduced us to ChemisTwin, the new digital reference material platform which is built using technology from our own NMR Workbook Suite.

Sarah Srokosz  01:13

Coralie is the ChemisTwin project lead over at Merck KGaA or MilliporeSigma, as it is known in the US and Canada. She joins us today on the podcast along with another member of the project, QNMR scientist Albert Farre Perez, to tell us more about their efforts to shape the future of analytical testing.

Baljit Bains  01:32

Let’s dive in shall we?

Sarah Srokosz  01:34

Hello, Coralie and Albert, thank you so much for joining us today for this episode of the podcast. We’ll jump in with our usual icebreaker question with what is your favorite chemical? So I’ll give it to Coralie first.

Coralie Leanord  01:56

Thank you, Sarah, for that fun question. So my favorite chemical would be lactose. And the reason for it is that for the time being, I was not able to eat any dairy product for a couple of years. And it was absolutely terrible for me to live without my hot chocolate in the morning and without my cheese. So I’d say at the moment, definitely the favorite chemical that I consumed daily.

Sarah Srokosz  02:23

I love that I’m a huge chocolate person as well. Um, how about you, Albert.

Albert Farre Perez  02:31

So my favorite molecule, it’s vanillin. And it’s basically was one of my first molecules to have to synthesize when I was a student in chemistry. And since then, I used to love the smell and the flavor of the vanilla. So vanillin, I think that will be my option.

Sarah Srokosz  02:49

Yeah, I remember doing labs with vanilla, and even just the vanilla and stain for TLC as an undergraduate student. And yeah, the whole lab always smelled so good on those days,

Baljit Bains  03:01

starting with the questions then so what are the problems in the chemists workflow that you set out to solve when this project originally began?

Coralie Leanord  03:11

Yes, thanks for the question. So what we initially thought, as we collected, you know, from our customers that are using our physical reference material, what were their biggest pain point. And we also look at, overall around us what was happening with the industry in terms of what was coming into the future. And we noticed a couple of things. One, we’ve noticed that some of our chemists say, well, we always have to find greener alternative, we have to think about the environment, and we have to show that the chemistry industry is evolving to be greener. And that’s one of their preoccupations that we took in mind. One other thing was that they were always under constraint to be more and more efficient; to do more and more analysis with the same material with the same people. So we want to be more in control of our quality and the quality of our products. So that requires additional analysis and means that they have to be more efficient. And finally, another pain point that they may have is finding the right reference for their analytical chemistry workflow. So whether that is a physical product that needs to be available that they need to order, go sometime through customs depending which country they’re in. So they may not have it at hand straight away, and they have to wait for it or even if it’s a reference online, how can they really trust it? So we had all those problems coming from our customers, and on another hand, what we also saw them doing is going more and more towards digitalization transformation of this industry. And we thought, could we mix these two? Could we find a really original way within our area of expertise of producing physical reference material, to use this expertise to solve some of those problems for our chemists? And that’s how we started to think about instead of sending to the customer, the powder for the reference that he needs to analyze and then can use as a reference, what he’s really interested to is the data ultimately, can we send them directly that data. So we don’t have to produce those chemical, they don’t have to transit through frontiers. And they don’t have to be disposed at the customer site to so it is obviously a greener alternative. And when you think about digital, it’s usually immediately available. So it also help with the chemists being more efficient. So that’s how the project idea was born.

Sarah Srokosz  05:39

Interesting. So you kind of coined the term digital reference material in doing this project. So what is a digital reference material? And how are they created? And then I’m sure a lot of people from there would be interested to know, are they accepted by regulatory authorities?

Coralie Leanord  06:00

Yes, and our inspiration for thinking of digital reference material was really looking at what was happening in the music industry as well. So you can see that you’re moving from these physical CDs to the platform when you log in and you can stream the song that you can you can use and we thought, could we do the same with our physical reference material to bring our entire catalog of physical reference material onto a cloud platform, where the customer can actually go, put his own measurement, and get access to the correct digital reference material. So that term we are now establishing as being a dataset, detailing the property of a compound that you’ll find into a online platform called ChemisTwin, where you have you know, spectral information about this compound together with information like their CAS number, and other data, how they’re used, etc. Now, on how they are created, I will let Albert explain because he’s actually leading the production of our digital reference material, what I can tell you is we took all our knowledge of producer a physical reference material and we try to transfer that into producing high quality digital data, digital reference material. So Albert, if you want to detail the production, that would be great.

Albert Farre Perez  07:29

Definitely, thank you Coralie. So, the production of the DRM is basically really similar to the ones that we have used for the physical material. So, those involve always a production step, inspection, and reviewing. So, initially, the analyst acquires a spectrum of the specified material, and then we have collaborated with ACD/Labs to use the functionality of the NMR Workbook Suite for our production steps. So, first, a preliminary qualitative assessment of the raw data is conducted to ensure its quality. So, for example, we need to check that there is a correct solvent, there is no impurities, there’s a good solubility of the compound and there is also absence of a big overlap with the solvent or characteristic, solvent impurities. Then, subsequently, there is a post-processing of the spectra and an auto-assignment of the protons to the structure, and those are performed in the NMR [Workbook] Suite and then they are followed by the production step. So an inspection and a review are conducted before the DRM product is released. So this Six Eyes principle ensures the high quality of the data and the DRM are released under the ISO 9001 scope. And Coralie, I’m gonna let you answer if they’re accepted by the regulatory authorities.

Coralie Leanord  08:53

Exactly and this is a very good point on the regulatory. So, as of yet, the digital reference material is a very new concept in the industry. In the sense that the way we are doing it. So I would say it’s not immediately accepted by regulatory authorities as it is when you use a certified reference material or equivalent. We are working with our accreditation body, we are working with some metrology institutes, as well authorities to actually build a framework where these can be more automatically recognized by regulatories. The few agencies that we also were able to contact and discuss about this concept with could also foresee that it can be discussed, it can be potentially accepted but it would need to be demonstrated by the lab, why this is suitable for for their purpose. So it’s a yes and no answer. I think it’s again, one area where it will be left to us to demonstrate how it is suitable and why it is suitable prior to having this automated acceptance of such material.

Baljit Bains  10:11

Thank you, Coralie. That’s really interesting. I particularly like the analogy between streaming music and then kind of finding your digital reference material online. That is kind of cool. What’s the current scope that’s covered by ChemisTwin? And how do you think, or expect that to change kind of going into like, medium term?

Coralie Leanord  10:32

Yeah, so we had to start somewhere, because we quickly realized this is a really big task ahead that we are taking. And we do think that it’s the future of analytical chemistry to have such digital reference material available to customers, but it takes time. So we’ve decided to look at applications more oriented towards smaller molecules within the NMR space, more routine type of testing. Also, the reason why we choose this routine is again, what we wanted is our customer to win more efficiency. So we’re looking at repeat analysis, where you don’t necessarily need to have a highly trained NMR specialist because this is more like a quality check that you really have the same compound as you should have from that synthesis. And we’re not talking about elucidation of molecules. So routine testing, and the database at the moment we focused more on smaller molecules suitable for the pharma industry, but also the academia. And Albert will describe a little bit of more in detail the features that are available to you already in ChemisTwin.

Albert Farre Perez  11:43

So as you specified like ChemisTwin can perform qualitative and quantitative analysis in fairly pure samples. So inside of the qualitative analysis, the customer have two options. So it can do the purification workflow, which basically confirms the identity of a target compound in the sample, or can compare like an spectrum against the whole library and get the list of potential hits of the compounds that the sample could contain. So ChemisTwin also offers like the possibility to perform the content determination of a sample by two different workflows, a targeted workflow and a non targeted workflow, but I’m not going to go really into detail for that. So we envision to develop the quality of targeted analysis for samples containing mixtures by the end of the year. So that’s one of the medium term also. And as well, as we are currently producing DRMs, like, over time, we are also expecting that our algorithm, like prediction algorithm is going to improve over the time and also get better and better results.

Sarah Srokosz  12:47

Wow, that’s, it seems you know, ambitious from from the outside looking in. But I think it’s really great that soon, you’re gonna be able to do the qualitative analysis of mixtures. Being someone who is primarily concerned with NMR here at ACD/Labs, the burning question for me is why did you choose to start with NMR?

Albert Farre Perez  13:10

So that’s a really good question Sarah. And we chose NMR because as a starting technique, because we believe this analytical technique will develop in the future and has a very interesting characteristics for the industry. So, this technique has evolved as a very versatile and expensive analytical tool widely employed for a diverse range of applications. And as Coralie mentioned, sustainability is one of our two main goals, main driven reason why we are also developing this application. So NMR is quite sustainable technique as we need doesn’t need much solvent and he can is not a non destructive technique. Also the measurements are highly reproducible, so then you can have quite consistent and reliable results while using different instruments. And this is crucial for obtaining accurate and precise data especially in quality control or research settings. Also NMR is applied in a wide range of sample types, including organic compounds, inorganic compounds, small molecules, and complex mixtures. So, it can provide insights into the arrangement of the atoms, functional groups and connectivity, making it a powerful tool for a structural elucidation and characterization. And nevertheless, NMR is not only for qualitative purposes, but also quantitative. So that means that it can, it allows also for the determination of the concentration of different compounds in sample, making it a value for both qualitative and quantitative analysis. So that’s why other reasons we chosen NMR as the first technique to go.

Baljit Bains  14:59

You kind of touched on a couple of points that lead to my next question. So typically, most labs won’t just have one instrument. So how does ChemisTwin work? And how does it account for differences between sample conditions and variations between instruments?

Albert Farre Perez  15:15

That’s a really good point. So, as I mentioned before, like ChemisTwin and is powered by a customized NMR Workbook Suite from ACD/Labs. So it’s utilizing a trainiong algorithm that we developed while also creating our DRM as mentioned before. So then the customer can upload the spectra and the metadata of the spectrum is extracted. Then, when a candidate of DRM is selected for comparison with the sample, the solvent and the frequency are considered in  the prediction of the DRM for direct comparison with the sample. So all these steps have been automated to make ChemisTwin very easy to use. And most people that tried to perform this first full analysis was done in less than 15 minutes after registering for the first time.

Sarah Srokosz  16:05

Wow, okay, so can you take us through what that workflow looks like in ChemisTwin? So you said it takes, you know, less than 15 minutes? So what tedious steps is ChemisTwin eliminating for the chemist and speeding up?

Coralie Leanord  16:28

Yes, thank you. And I can try to take you through. And I would say maybe one of the best example is to think about the quantitative workflow. So a customer would do a measurement in the lab of their sample. And that doesn’t change whether you using ChemisTwin or not, you receive your sample, you do your dilution into your solvent, do your measurement on the NMR instrument. Where it starts changing is that normally if you want to do quantification, and in certain cases also for the identification, you need a reference measurement, and you need a standard for that. So you need to take a physical reference material, you need to weigh that physical reference material. For quantification that weighing needs to be precise, because you know how much compound, you need to know how much compound you’ve put into the tube, then you measure your sample and the reference at the same time. When you’re using ChemisTwin and you don’t need any more to measure your reference, the reference is already existing into the ChemisTwin portal, so you only measure your sample. And already that weighing process, some of our scientists internally and some of our NMR customers told us this is already a very tedious step for them to do.

Once you’ve have your raw data measurement, NMR scientists would normally open that measurement and start to look at the quality of their data, starting to look at the peak position, and starting to do the interpretation by themselves, if this is what it should look like. In the case of ChemisTwin, you don’t even need to open that measurement with the software, you directly download the raw data into the ChemisTwin portal. So you’re logging into ChemisTwin and upload the data there. The file will be read by ChemisTwin, we will display the important information for the analysis and we will show you the spectra. But you don’t really need to go into the spectra by yourself. What you need to do is then to select the digital reference material that you want it compared with, if you want to have a digital reference material that you pre-select otherwise ChemisTwin will work it out, and then you select for example, quantitative workflow. And you click on run the analysis. You may have for quantitative, you may want to enter some data like the weight of your sample and the weight of your solvent, depending on what you want as an output, but that’s it. Your measurement name, the probe ID, all the information is taken directly from the file and saved into the platform. so you don’t need to enter all of that manually.

Then the software will automatically compare your sample data with our reference data. Once that comparison is done, you’ll receive a result in the format of a report, a standardized report that we give you, where it summarizes the input data that you’ve put in, the information that we used from that data and collected, the information you inputted, and the result of the comparison. Is this the correct compound or not? And then it will also give you the quantity of that compound in the sample. And this is in a matter of a few minutes. So there is very little step for you in ChemisTwin that you need to do. That report is standardized, will always be the same, and then you can electronically sign this report and send it for a second approver, for example, if you need anyone else in the NMR lab to review, to follow the Four Eyes principle, for example, this is what we have to do at Merck, when we are doing an analysis, we need to have the analysis confirmed by another analyst. And that can be all done within the portal. So at the end, you have your analysis report, with a comparison, with the confirmation that you have the correct compound, with the quantity of your compound, and it’s all saved in a digital format.

Baljit Bains  20:31

That’s pretty impressive, especially the fact that the analysis only takes a few minutes. When you compare that sort of to doing it manually, how long would you say or what the differences are between manual with ChemisTwin?

Coralie Leanord  20:44

Yeah, I think that is a very interesting question. And it’s hard to answer to this question with precision, because it varies a lot on the manual, the manual side, how long it takes, it depends on how well trained the NMR scientist is, and it depends on the complexity of the compound. But what we’ve noticed it’s reducing at least by half, or even a third, the time that our analyst internally at Merck will take to do it manually versus using ChemisTwin.

Sarah Srokosz  21:15

Great, and besides this benefit, and further time, are there any other benefits to using ChemisTwin over doing the interpretation manually?

Coralie Leanord  21:30

Yes, I think that so beside the fact that you have this digital reference material immediately available that you can trust that it’s been produced, as we described. One other benefit that I see is towards that there’s two benefits here. This one is the harmonization, it means your sample will always be analyzed and looked at with the same process, from the same way, and also compared to a single digital reference material. So it doesn’t matter for a large company, for example, it doesn’t matter which lab you’re in or which country, you can use the same digital reference material to compare similar samples. So for me, it really brings also the standardization of the interpretation of NMR data versus the manual way that is happening today. And the second, the second aspect, where I think that it’s interesting, and this is more on the longer term, at Merck, we say we believe NMR is really a technology of the future. But one thing that we see is at the moment, refraining people from from using NMR is the cost of the instrument. But this will go down over time, like it did with LCMS in the past, but also the finding an NMR scientist, a well trained NMR scientist is very hard. So today, interpreting the results, do require to have these highly trained NMR scientists and this is a limitation to making this technology more mainstream. So by providing a solution for these routine analysis that do not require heavy NMR knowledge, this is also what we think is another benefit of using ChemisTwin. To use it as a first instance of conformation with an automated tool that requires a small amount of training.

Baljit Bains  23:19

That’s fantastic. Thank you, Coralie. I guess the question that’s kind of been bugging me this whole time is like how many of these DRMs are actually available now?

Albert Farre Perez  23:30

So that’s a really good question. So currently, we have just under 2000 DRMs is available in the portal. And we are constantly releasing new DRMs every week into the portal. These have been created from as we already mentioned, the like release physical materials, which ensure the traceability back to the starting material. Additionally, there are 57,000 theoretical, DRMs also accessible in the portal. And those theoretical DRMs have been generated using our training algorithm. And customers can utilize them as initial reference for conducting analysis until we have an existing DRM. Customers also have the option to request specific DRMs through the portal and these requests are being prioritized in the production process.

Sarah Srokosz  24:17

Great. And with that, I think it’s a good spot to end off maybe I’ll actually put you guys kind of on the spot here quickly. And if I’m not mistaken, people can go and try ChemisTwin now is that correct?

Coralie Leanord  24:35

Yeah, that’s what exactly what I was about to say that what I want to say is that we are at the beginning of this journey with the digital reference material overall, you know, within analytical chemistry. We do think that we are pioneers in something that will lead the future of analytical chemistry, but we’ve made a tremendous amount of work last year to release that ChemisTwin platform for NMR, we do think that there is already you know, a good amount of digital reference material for you to play with and with the theoretical spectra as well. So we are offering the platform free of charge for a trial. And we really want to get people using it, giving us the feedback, and as we are continuously developing the features that are also available on this platform. So you can go on www.sigmaaldrich.com. If you search for ChemisTwin, you’ll find here a way to register and and then you can register and use it for free.

Sarah Srokosz  25:38

Fantastic, yeah, we can also include that link in the show notes for everyone. So with that, I think we can just say thank you so much for joining us today. It was really informative. And I look forward to seeing where ChemisTwin keeps going. Thank you both so much.

Coralie Leanord  25:59

Thank you. And thank you ACD/Labs for this beautiful partnership.

Baljit Bains  26:05

And there you have it, a fascinating discussion of ChemisTwin, where ACD/Labs’ technology and MilliporeSigma’s expertise converge to empower scientists with digital tools for structure verification. A big thank you again to Coralie and Albert for sharing their insights with us.

Sarah Srokosz  26:21

If you enjoyed this episode, don’t forget to subscribe to The Analytical Wavelength on your favorite podcast platform. Stay tuned for more exciting discussions on the latest advancements in analytical and chemical data.

Baljit Bains  26:35

See you next time.

Sarah Srokosz  26:40

Analytical Wavelength is brought to you by ACD/Labs, we create software to help scientists make the most of their analytical data by predicting molecular properties and by organizing and analyzing their experimental results. To learn more, please visit us at www.acdlabs.com