Although, I work mostly with GC-MS based protocols for metabolomic analysis, some of my colleagues do use LC based systems for their metabolic profiling. The ones they use are Agilent and Waters systems which are very easy to use and can handily export the data on various platforms. I have worked with Shimadju and Perkin Elmer for similar systems and have noticed that although, these are bit expensive, they are generally worth investing for.

Combining both proteomic and metabolic data over the same machine is a bit challenging and you have to compromise beyond a certain point. So, overall, one of your profiling (proteomic or metabolic).

Have a check with either Waters or Agilent if their LC-LC/MS will be good (this system uses two columns simultaneously for both polar and non polar samples) and will likely cover more of the sample. However, if you are clear on certain things, the Waters system you mentioned does a decent job. Personally, in our labs, we try to avoid this and use a combination of MALDI-TOF for proteomics and above mentioned systems for metabolomics, This way, we have seen a good quality data without much of the problems. I hope this helps.

Thank you Avinash. I appreciate your help. 

Hi,

although the joint option is possible, I would try to have platforms/instruments separated for proteomics and metabolomics. Using a joint platform you may found problems in the short run because of contamination, unproper cleaning, solvent and buffer mixtures, and even computer capacity for data storing. As well, with two separated platforms if repair is necessary in one of them you could going on working with the other one at least and not all due work is halted.

Regarding manufacturers, I have worked with a Bruker instrument and am now working with a WATERS instrument. Both they have their own pros and cons. Possibly, software from Waters is robust and easier to use. Instruments from ABSciex have demonstrated for a long time to be robust and consistent but I am not very confident on software though I belive it has been improved. I can tell you from others that Agilent platform works satisfactorily but maintenance service is not so good though it may vary for different world areas.

Finally, I recommend you to bear in mind that maintenance and spare parts of these instruments are currently somewhat expensive.

Hope this serves you to make the better choice for your lab requirements    

Thank you Olimpio for sharing your insights and experience.

Hi

I too also agree, a joint option is possible but there are far too many compromises both in terms of robustness as they use different flows as well as the actual day to day usability of the entire platform. 

I have worked with AB and Bruker systems and they both have their pros and cons. It all depends on the user level of expertise and specific applications.

AB systems have a more simplified acquisition software, though it is sometimes too simple and lack of many essential tuning control available to users (except to engineers). Bruker systems in my experience are more sensitive and have generally quite intelligent algorithms for data collection and formula estimations (which is good for small molecules analysis) though they require users with more MS experience as it has quite a bit more parameters to control (can sometimes be good or bad, depend on how much you want to learn it).

AB systems are also quite tedious to switch between small molecule turbo ion sources and proteomics nanospray sources as they require intricate tools and if you are not careful can get a nice jolt from the high voltage. Bruker systems likewise will have some difficulty in certain older sprayers like the online-nano spray. Also, AB has traditionally been more active in protein analysis type applications while my understanding of Bruker is that they are an MS company and does not associate to any particular application.Anyhow, best of luck in your search. But most importantly try not to buy into all the marketing and focus on what you are really doing.

Malinda

Dear Malinda,

Thanks a lot for sharing your experiences and advice. I appreciate it.

Coming back to your original questions: I would definitely vote for two discrete LC systems. Proteomics nowadays usually relies on nanoflow chromatography to allow for working with minute sample amounts. The actual column chemistries are fairly standardized. Metabolomics on the other hand is usually done with regular analytical HPLC, and depending on your compound classes of interest you will need to switch to other chemistries as well. If you try to do this all on the same LC system, the downtime from this change of column setups - including solvent changes, reequilibration, cleaning of column, HPLC maintenance and the occasional breakdown - will translate 1:1 to downtime of your whole setup. With two LC systems you should always have one coupled to the MS and can perform maintenance/repairs on the other if necessary. For this it would also be a good idea to have a UV detector especially for the analytical HPLC. Switching the MS ion sources is not too much of a hassle on the modern systems - it can be tied in with the necessary cleaning/maintenance/calibration of the mass spec. I would highly recommend to not change the usage type every day anyway, but rather block-book the instrument for e.g. 2-3 weeks of proteomics use, 2-3 weeks of metabolomics or similar.

One recommendation: you should look very closely at the localized support and service that the different vendors can supply in your place, both for the MS and for the HPLC, because you will be needing it. Complex systems do need training and the occasional maintenance and repair, so ask the companies for a very detailed explanation of how they are planning to support you in all regards. It would also help if you have another, ideally more experienced lab in striking distance (i.e. who can be visited and/or contacted to exchange experience) running same or similar equipment. 

Good luck with your plans, purchasing equipment on this scale can be both scary and exciting at times!

Thank you very much Chirstof for your comprehensive feedback. I appreciate your help.

Hi,

I am from the field of proteomics, so I can't give you detailled info about metabolomics, but I have worked together with some metabolomics guys.

As mentioned by the others, proteomics and metabolomics require different LC-systems. If you want to do "high-performance" proteomics you will need a nanoUHPLC. For metabolomics, a UHPLC would be the best choice.

As a instrument for both applications, I would suggest a Thermo Q-Exactive instrument. It is one of the best instruments for proteomics and easy to use. A friend, who does metabolomics, also said he had good experiences with this instrument. But you have to keep in mind that the Q-Exactive can't perform MS3 experiments (only possible with in source fragmentation + HCD, but I guess it doesn't work properly). If you have to go for MS3 in metabolomics, you should look for another instrument.

The AbSciex triple-ToF instrument is one of the best for proteomics SRM analysis but you can do this also very nicely on a Q-Exactive instrument. If you go for ABsciex, I recommend not to buy an Eksigent LC. I had the bad luck to work with a nanoLC from Eksigent and it was always making trouble. Waters and Dionex are the better choice, at least for nanoUHPLC.

If you have money and you want to separate isobaric metabolites that co-elute, the waters synapt instrument could be interesting. It has the option to separate by ion mobility.

I think, it's best if you can talk to some guys from metabolomics and proteomics. I just can say that I would go for the new Q-Exactive instrument for proteomics. You can also ask the companies to measure some test samples for you. However, the results will also be dependent on the application scientist and the effort, they put into it. Best you tell them which LC-method and column they should use if possible. LC can have a dramatic effect on you results.

Best Stephan

You do not say what metabolic applications you have in mind?- samples can range from brain biopsies to transgenic tomatoes and they all have different analytical requirements. As some previous responders have indicated it is very unwise to mix applications on one instrument. Yes it IS possible to have a mass spectrometer that can do both- all MS systems have different analytical properties, capabilities, sensitivities and mass resolutions- what is claimed by each manufacturer is not always what you get either. The fact is that for each application and sub-set of applications there are niches for all. It is technically  possible to get a mass spectrometer that can do everything - FTICR for instance - but if you are that rich you can afford more than one machine! Likewise Orbitraps can technically fulfill both requirements but are less well suited to UPLC type separations for metabolites because the UPLC peakwidths are so tight that significant residence time in the trap (to give the high mass resolution that these machines can achieve) can compromise peak sampling- it is  a trade off.  Waters Xevos can do both functions (there is no such problem with a UPLC front end because the ToF is fast- however the mass resolution is worse- and also Synapts (which have the added advantage of ion mobility to separate on cross sectional area/Stokes radius- useful for small and large mols). Some people tend to have pet manufacturers and stick to them like glue- this is not scientific you need to design the system capability for the best overall efficiency of scientific discovery. Also chromatographic and or other front end requirements are entirely different and swapping between them is less easy than any of the manufacturers say unless you have very skilled technical staff- and you have to consider the ionisation sources as well which can vary markedly between manufacturers. Even mixing metabolic applications is undesirable (although usually necessary in most labs because of lack of equipment). My advice is do NOT mix the purposes but if you do then do not swap between applications on a very regular basis or you will have huge down time- actually if you swap more than twice a week you will have no up time! The fact is that even switching between say urine and plasma in a metabolic application takes at least a week for the whole spectrometer system to recondition itself- this is a physical process in the analytical system and can be proved directly by injecting hundreds of biofluid samples interspersed with QA mixtures and monitoring how long it takes for the QA samples to co-map using multivariate statistics. How do i know this? because we have done this exhaustively setting up the MRC-NIHR National Phenome Centre and the Imperial Clinical Phenome Centre in the UK which together have about 50 mass spectrometers in total  (although the NPC Core is centred on multiple Waters TQs and QToF systems in a parralel arrays and we are now in the process of publishing all our standardv assays and procedures) from all the major manufacturers which we run for a variety of purposes from untargetted through to biopanels and fully quantitive targetted assays for epidemiology to real-time diagnostics. We dedicate instruments to highly specific uses- e.g. there are separate positive ionisation and negative ionisation machines for each biofluid and each column type and even dedicated technical staff to each sub-assay type. We have to do that because we run up to 100K samples per year. Now this might seem a bit off the track of your question- but the point is that when you run with dedicated machines for each application you get about 95% up-time which is nearly unheard of for MS- and hence we can run thousands of samples in a row without a machine falling over. So if you are forced into getting one system to fit all purposes, then whatever system you get, you need to time manage the applications really carefully to avoid giant leaps between sample types, separation procedures, solvent systems etc because this will massively increase the efficiency of whole operation. In practice that means gathering all your samples together for a particular application and run them as a big batch (possibly over weeks or even months) before you swap over to another big batch of similar samples or applications. This of course means managing all the interested parties who want to get on the machine as well which might be as hard as the analytical chemistry itself so good luck with that!

Do not use Waters. Agilent is much more user friendly and there are step-by-step procedures for almost everything you want to know.

I agree with LLian, Agilent Q-ToF is very user friendly, Waters is very expensive. I think that the Orbitrap for Thermo is an option that you need consider.

yest, that is true, Agilent Q-TOF is much easier to use, you can consider to have more than one if you could afford it after all each instrument have its own pros and cons