Monolithic columns never taking off

[DJ]

Why is it these columns never seemed to take off?

[Andy Alpert]

1) They're a great way to do mediocre chromatography fast.
2) They have reputations as solvent hogs, especially if you're running a mass spec.
3) Any monolith with phase density high enough that one can start doing some decent chromatography exhibits backpressure pretty close to that of a regular packed column.

[tom jupille]

Andy's points are valid, but I'm not as pessimistic about them as he is.

From what I've seen of the present commercially available monoliths, they give efficiencies (plate counts) about like those of 3 - 5 micron packed columns, but with the back pressure of 10-15 micron columns. So yes, you can up the flow rate and get very fast separations, with so-so efficiency. Or, you could couple columns to increase the length and get back some of the plates and still run at reasonable pressures.

The "solvent hog" is a direct consequence of high-flow rate for fast separations. That problem is mitigated by using capillary monoliths, but they require specialized low-dead-volume instrumentation that's not yet "mainstream".

The low phase ratio is a consequence of having a lot of macro-pore volume (lots of room for solvent to flow through, which is what gives the nice low pressure). While this does affect the loading capacity quite a bit, I really don't see it as that serious a problem; it basically means you use weaker mobile phases to get equivalent retention. By the way, I've heard presentations by Tanaka (the "inventor" of the silica-based monoliths) where he described his ongoing work to get the phase ratio up, which involves shrinking the macro pores and does increase the back pressure. I came to the same conclusion as Andy: if you extrapolate from the performance of a 5 micron with the pressure of a 15 micron, what you come to is the performance of a 2 micron with the pressure of a 2 micron.

I think there are a couple of other (perhaps simpler) reasons for the slow acceptance:

1. HPLC is something over 40 years old, and as such is a mature market. There's a large installed base and a corresponding "if it ain't broke, don't fix it" mind set. My take is that a new technology has to offer at least a 10-fold advantage over an established technology in order to be "disruptive" and take over the market abruptly. That can mean twice as fast and one-fifth price, but it has to work out to a factor of 10. One can argue the pros and cons of the monoliths, but they aren't 10 times better than existing packed columns.

2. The monolith technology is patented, by Tanaka for the silica-based materials (I believe licensed to Merck Darmstadt) and by Frank Svec for the polymeric materials (I think licensed to LC Packings -- which was swallowed by Dionex -- which was swallowed by Thermo). Until they go off-patent and other companies get into the act, I think development and acceptance will be slow. There's a precedent in the history of glass capillary GC columns, which languished in the US until they went off-patent. W

[Peter Skelton]

To some extent I've found that UPLC has made them redundant. I've used and developed methods on both, and the key advantage of the monolith was the short analysis time. However, this was only achieved by ramping the flow rate to 3ml/min, and the problem was much more elegantly solved in the end by using an ion pairing method running at a more normal 1ml/min.

Compare that to UPLC flow rates of 0.2-0.5ml/min and the difference is even starker, and if you want to hook up to a mass spec or ELSD 3ml/min is asking for trouble. Also if you're doing a lot of analysis or you have a hot corporate responsibility/green chemistry person, you might find that either the running cost becomes much higher than expected or you come under some extreme pressure to redevelop a more environmentally friendly method. I've yet to find a monolithic column method that won't transfer to a normal column, so you probably don't have an argument that using the monolith is the only way to achieve your separation.

Also the reduction in stationary phase area makes loading trickier, and generally reduces the mass you can load overall. This isn't necessarily a problem if you have a highly sensitive detector or a strong response from your compound, but if you don't then it can make detection tricky.

As Tom says, because of patent issues there are very few monolithic columns even available to buy, which makes them a longer shot for method development than going with a column from someone who makes a much wider variety of columns.

[unmgvar]

the monolith columns from Merck (onyx from phenomenex is a merck column packed for them) has one major draw back
in order to work you need to go to 2 ml/min with a 4.6 column
it is so because of the van-deemter they have. in order to work at column potential.
so you end up using a lot more solvent- because of the injector dead time that never changes. not very green
so it is best to use a 3mm ID column, then the flow rate is 0.8ml/min. at that ID you can still work on a HPLC
also at 0.8ml/min you do not need to adjust the UV speed.
you get better gradient mixing.

another problem of the columns is that the max lenght is 100mm and in order to move a method from a 250mm 5u colummn you need many times to couple a 100mm and a 50 column together. many do not like the idea. so you do not get to make alot of impurity methods on them. the advantage is that you generally need to change only the 50mm column and not both of them

but the column has one very big advantage, it cloggs a lot less than particle columns.

[Victor]

As pointed out above, the 3mm ID monolith which should reduce the solvent consumption considerably,(less than half the solvent required) but I don't know how its performance compares to the 4.6 mm monolith in terms of efficiency. I know Merck spent a long time working out how to do it.

There is also a second generation monolith out from Merck. It seems this column has better performance, but again I don't know if there is a second generation 3 mm monolith.

I have seen research papers that refer to new monoliths produced by GL Sciences and by Kyoto monotech. Again, they are supposed to show improvements over the first generation Merck monolith, but not sure if they are commercially available yet.....

[Csaba]

If there was a monolithic column, 15 cm long with 2 mm iD, then it would be a great succsess!