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Topic: CombiFlash costs and benefits  (Read 543 times)

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Offline Babcock_Hall

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CombiFlash costs and benefits
« on: February 13, 2021, 01:31:45 PM »
My present project requires that I make a greater number of organic molecules than I have made for previous projects.  One thing I have just started to consider is whether or not I should budget money for a CombiFlash in a future grant proposal.  What kinds of things can such an apparatus do that could not be done previously?  What other advantages does it have.  It would be cheaper to buy used, but is there a clear downside?
« Last Edit: February 13, 2021, 01:45:31 PM by Babcock_Hall »

Offline rolnor

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Re: CombiFlash costs and benefits
« Reply #1 on: February 13, 2021, 02:47:08 PM »
Seems like a fun apparatus. The price will vary a lot if you choose UV or MS monitoring? I think a normal manual flash setup is very fast, for me typical 30 min to pack, load and elute. To analyze fractions is around 20min. so I could not motivate bying this type of machine. I guess it is expensive?

Offline kriggy

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Re: CombiFlash costs and benefits
« Reply #2 on: February 15, 2021, 08:51:16 AM »
My boss would say that were hired for our brains not to run columns. We have two of those instruments but Im working on a scale too small for it but I have a colleague who uses it a lot for 200+mg reactions. I belive it can save a lot of time for repetitive tasks like running columns on intermediates which are required for you to carry on. Also, because of the higher pressure you get AFAIK better separation and can use C18 silica which is s#*$ to work with using normal columns.
 You can then run columns or HPLC on your final products, analyze data thinking about next steps whatever. It all depends how much do you value your time

Offline Guitarmaniac86

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Re: CombiFlash costs and benefits
« Reply #3 on: February 15, 2021, 11:52:04 AM »
I only have experience with Biotage Isolera's.

Biotage columns are expensive but very, very good. You can get knock-off brands like SiliCycle, that do a good job, but I find the biotage cartridges give better separation.

Benefits of automated chromatography:

-Fast, a 10g pre-packed column can purify your reaction mixture in under 10 minutes. A big 330 g column, depending on purity desired can take a few hours (I have done one in 30 minutes). Automated chromatography is a MASSIVE time saver.
-Gradient can be modified on the fly or pre-set before hitting "go"
-Can use UV to only collect at certain wavelengths
-Can draw a TLC on the system and it will calculate a gradient for you
-Tolerates a lot of different solvents
-Can swap the system between normal and reverse phase if you need to

Downsides:

-Cost. Pre-packed columns aren't cheap. They can be re-used a couple of times before they degrade, but you need to wash with THF, and flush with heptane or hexane and cap it to keep it wet and stable. Probably get 2 or 3 uses out of one column. Not really a good thing to do (purity issues)
-Expensive to repair when it does break down and you can lose time
-You get so used to it you become lazy and refuse to do hand columns!
-Not really scalable. A 330 g column can be easily overloaded if you want to purify more than 5 g of material. You can combine columns. Once I had to purify 50 g of material so I daisy chained three 330 columns together and put the flow rate right down (avoid overpressure). 750 g columns and 1.5 kg columns are ridiculously expensive.
-Space: you need a whole fumehood to keep it in and if space is limited, well, you are down a fumehood
-Upkeep and maintenance can be expensive. Service contracts aren't cheap.
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Offline rolnor

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Re: CombiFlash costs and benefits
« Reply #4 on: February 16, 2021, 05:54:13 AM »
If you can not re-use columns it reduces the usefulness a lot. I guess a RP-column can re-used more compared to straight-phase?

Offline phth

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Re: CombiFlash costs and benefits
« Reply #5 on: February 20, 2021, 03:16:42 PM »
If you can not re-use columns it reduces the usefulness a lot. I guess a RP-column can re-used more compared to straight-phase?
Yes but the column is cheaper than paying a professional an extra day. with auto column you can do easy two reactions a day, and more depending on the speed.

Offline rolnor

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Re: CombiFlash costs and benefits
« Reply #6 on: February 21, 2021, 01:38:15 PM »
I am not negativ but realistic, you need to include cost of service etc. how much is a column, 50, 100, 300usd? Depends on size offcourse.

Offline clarkstill

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Re: CombiFlash costs and benefits
« Reply #7 on: February 23, 2021, 04:10:22 PM »
I was able to pick up two combiflash rf200s as a job lot from an auction site for about £3.5k. Both work fine (one needed a new bulb but otherwise fully functional). I use silicycle columns which are pretty cheap and dirty but do the trick for easy separations. I wouldn't generally use it for precious material, but they are certainly a time saver for a decent chunk of separations. You normally have to TLC fractions too to check if they are cleanly separated, so really the time saving is in the fact you can walk away and do something else while fractions are collecting. Even if the detector goes bang, you can still use it as an automated fraction collector and just TLC like you would normally, which is handy enough.

The technology isnt complicated - a few pumps, valves and a UV/vis bulb and detector. In terms of servicing you can do a decent amount of it yourself.

On balance, I'd say worth going for if you can cost it into a grant without losing money elsewhere. Otherwise, worth trying to pick one up second hand. I wouldn't pay full price out of my slush money.

Offline Babcock_Hall

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Re: CombiFlash costs and benefits
« Reply #8 on: February 23, 2021, 04:24:06 PM »
I wouldn't generally use it for precious material, but they are certainly a time saver for a decent chunk of separations. You normally have to TLC fractions too to check if they are cleanly separated, so really the time saving is in the fact you can walk away and do something else while fractions are collecting. Even if the detector goes bang, you can still use it as an automated fraction collector and just TLC like you would normally, which is handy enough.
Thank you.  What would make you reluctant to use them for precious material?

Offline clarkstill

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Re: CombiFlash costs and benefits
« Reply #9 on: February 24, 2021, 01:42:34 AM »
I wouldn't generally use it for precious material, but they are certainly a time saver for a decent chunk of separations. You normally have to TLC fractions too to check if they are cleanly separated, so really the time saving is in the fact you can walk away and do something else while fractions are collecting. Even if the detector goes bang, you can still use it as an automated fraction collector and just TLC like you would normally, which is handy enough.
Thank you.  What would make you reluctant to use them for precious material?

Just a general and probably unjustified paranoia. I suppose with a manual solvent nothing is ever “out of sight” but I always fear there will be some sort of internal leak or fault that sends the product to waste. I came up with manual columns, so I guess I’m still a little bit more comfortable with them, but I think this is probably my issue rather than anything wrong with the combiflash.

Offline Guitarmaniac86

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Re: CombiFlash costs and benefits
« Reply #10 on: February 24, 2021, 12:17:34 PM »
I wouldn't generally use it for precious material, but they are certainly a time saver for a decent chunk of separations. You normally have to TLC fractions too to check if they are cleanly separated, so really the time saving is in the fact you can walk away and do something else while fractions are collecting. Even if the detector goes bang, you can still use it as an automated fraction collector and just TLC like you would normally, which is handy enough.
Thank you.  What would make you reluctant to use them for precious material?

Just a general and probably unjustified paranoia. I suppose with a manual solvent nothing is ever “out of sight” but I always fear there will be some sort of internal leak or fault that sends the product to waste. I came up with manual columns, so I guess I’m still a little bit more comfortable with them, but I think this is probably my issue rather than anything wrong with the combiflash.

I'd say justified paranoia. I only made this mistake once but a client wanted 5 g of 99.5% pure product. I put it on the biotage and set the wavelength... And it went to waste because I put the wrong collection wavelength in. Luckily, I put a new clean waste bottle down so all I had to do was vac off the 5 L of solvent that got sent there!
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Offline BobfromNC

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Re: CombiFlash costs and benefits
« Reply #11 on: March 10, 2021, 10:45:59 AM »
If you are making a lot of similar compounds in a series, and you have UV activity, it is pretty easy to set up a method that will let you inject a compound and run a column in a few minutes with full automation, collecting only the UV peaks.   In many cases, (other than free labor from graduate students) this will allow you to make and purify 2 to 3 times more compounds a day if the chemistry is simple.   I have made and purified 10 compounds a day when I have small, simple reactions to run in parallel.   

If you are doing large scale, preparative work, or have no UV activity, they are less useful, unless you either spend a lot and get ELSD or MS detector, which adds a lot of cost and complexity.   Great for big pharms, harder to justify in universities.     But I think they can make most chemists more productive, especially if they know how to use them well.   

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