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before prepositions: So, our column chemistry, the housing, the frits, and the whole fluidic pass in the UPLC system are manufactured with the MaxPeak surface technology to prevent non-specific interaction with the metal surface. And then here just an example on what does it do. So, we compare the conventional, this is the C18 column that's very common for doing synthetic oligo separation. So on the left, you have the conventional stainless steel column, and on the right, you have the conventional stainless steel column, and on the right, you have the Max Peak Surface, and it's under the trade name, a brand name of Acuity Premier. If you see Acuity Premier, that means the the column has Max Peak Surface Technology. So if you look at the out-of-box solution, yeah, if you do a first injection, either the stainless steel column or the premier column, you'll see the drastic difference in profile and the peak shape, and the recovery. So, you seem like you're getting a lot more oligos recovered if you use the Max-P technology. And on the stainless-steel column, you will have to do many, many injection to condition the column. And eventually you will get similar profile that's reproducible, but on the premier column, your first injection match up with the well-conditioned situation. So, we can call it like an out of box solution. And here's an example, a 21 mer oligo, synthetic oligo, that's heavily modified. If we run this sample, try to separate out the impurities from the full-length product, you can see that this is on stainless steel column. You can see the full-length products right here, and you do get some nice separation from the shorter MERS and the longer MERS. But if you repeat the same experiment, the premier technology column, and then you all of a sudden you start seeing the same full-length product, but you do start seeing a lot more impurities being well separated. impurities being well separated. That's definitely a benefit of having good recovery from the MaxPeak technology to prevent those non-specific interactions from the low-level impurities with your fluidic path. And I just wanted to highlight there's actually saw the emanation piece actually being well resolved from the Fortland's product. I will talk a little bit about the emanation piece. So, from my presentation, so we work with industry lab quite often, and we do get their feedback on what waters can do to help their analytical method development. One of the things that kind of come to us recently is that some of the labs wanted to move their single quad method into a more high resolution mass spec just because maybe when they developed a single quad method, the synthetic oligo is pretty short it's not as complicated, but as the drug modality gets longer and bigger, and more cap. And there's definitely a need to look at higher resolution mass spec that can help characterize those impurities. And yeah, so here just a highlight, a slight highlight, what low resolution mass spec performs versus high resolution mass spec performs. So, for a low-resolution mass spec performs than versus high resolution mass spec performs. So, for a low-resolution mass spec, you get nominal mass resolution, and then you will have difficulty to measure charge states for some of those species if they're pretty big. And it is good for target analysis. That's why it's pretty popular in the QC GMP environment because you can do target analysis, and the technical skill is pretty not as high say operating a single quad instrument. You can easily train somebody to do target analysis. But it requires a good chromatography separation. If you get a really nice chromatography separation to tease out the impurity that has similar mass to your full-length product, definitely the single-quad instrument is suitable for doing impurity profiling. But if you look at the high-resolution mass spec, what are the benefits, right? So, it gave you isotopically resolved ions, M over Z value, and it can measure multiple charges. So, you can do charge deconvolution without any trouble to get the molecular weight measurement. And you can do targeted and untargeted analysis because sometimes you may not know what's in your sample. So, it has, definitely you can do untargeted analysis with high-resolution instrument. And it also has fragmentation for structure elucidation. I think my previous speakers already talked about using MS-MS to do a structured confirmation for impurities. So yeah, so there's definitely a need to maybe move from a single-quant method to a high-res mass-back method. And this is actually a slide I referenced from FDA presentation. So, FDA also talked about the benefit of using high-res mass spec for increasing structure complexity. Again, you know, here's a nominal mass versus highly resolved M over Z isotope profile. You can see the monoisotopic peak. This is an example from Nucinesin, a highly modified 18-mer therapeutic synthetic oligos. And here's just an example on why you want to use high-res mesbeth. So, if you have two different impurities, one is the full-length product minus U versus minus C, your exact mass from those two impurities are just 1,000 different. And if you look at the M over Z at the four charge states, it's really, really close. So, a single quad mass spec would not be able to accurately measure the molecular weight. I must say, though, if they're co-eluting, it's also very difficult. You wanna try to resolve them and then do charge deconvolution and measure the molecular weight differences. Here's an example, I actually do see a case for the deamination I showed earlier in my previous slide. The deamination peak eludes after the full-length product, and you can see the monohisotopic mass are shifted. And this is, I think, a three-charge state. So, it's shifted by 0.3 Dalton. And that's almost like at one Dalton mass shift. And then that's coming from 5-methylcytosine converted into simidine.