[RASMB] Viscometer technology

[Stephen Harding]

John: interest in protein intrinsic viscosity is that it is a far more sensitive function of conformation in solution compared with the sedimentation coefficient. In addition,  interest in absolute viscosity is important in for example monoclonal antibody based formulations – high viscosity is a problem in terms of administration.
For conformation work, problem in the past has been that of sample heterogeneity – sedimentation velocity could resolve away aggregates etc, viscometry couldn’t – not until the advent of the differential pressure viscometers (measuring relative viscosity by pressure tranducers rather than photosensors) – which could be linked onto SEC columns and concentration detectors.  These instruments (Wyatt Viscostar or the Malvern Viscotek) are so sensitive that they can measure relative viscosity at concentrations low enough so that a concentration extrapolation of the reduced viscosity to zero concentration c=0 are not necessary (there are other tricks as well!).
There have been difficulties largely arising from corrosion of the transducers after being exposed to salt ions in aqueous solution but they seem to have got round that now by appropriate coating  - indeed its nice instrumentation.
David – yes the rolling ball viscometer (Anton Paar) although its been good for looking at polysaccharide solutions – the ability to vary the angle of flow changes the shear rate so you can monitor for non-Newtonian behaviour as with Cone and Plate (but much lower volumes) is really useful….. but bad for protein solution work. That was the view 5 years ago at the great BITC meeting in Galveston – and is still the same.  The Anton-Paar team were really helpful when we approached them about silanization and this improved things but not really enough.  For polysaccharides yes, proteins no.
For intrinsic viscosity measurement on proteins we would probably still go for the standard Ostwald U-tube capillary (1st choice) or if polydispersity is suspected the Viscostar (2nd choice).  For polysaccharide/ glycoconjugate work, the Viscostar would be 1st choice.
The new Malvern Viscosizer is based on a different principle altogether.  Malvern for some time have been trying to see if dynamic light scattering on particles of known size can be used as a measure of the viscosity of a medium from the relation of the diffusion coefficient with viscosity, and the Taylor dispersion based instrument I guess is a development from that so it would be interesting to see how it goes.  The problems of protein adhesion sounds ominously familiar!   It looks to me anyway as if its intended for absolute viscosity measurement rather than being accurate enough for intrinsic viscosity.
All best,
Steve
________________________
Steve Harding DSc (Oxon), RFOO (Norway)
Professor of Applied Biochemistry,
University of Nottingham,
School of Biosciences,
Sutton Bonington LE12 5RD, England
(44) (0) 78110 90635
www.nottingham.ac.uk/Biosciences/People/steve.harding<http://www.nottingham.ac.uk/Biosciences/People/steve.harding>
National Centre for Macromolecular Hydrodynamics (NCMH):
www.nottingham.ac.uk/ncmh<http://www.nottingham.ac.uk/ncmh>

Genetic Survey of North West England:
www.nottingham.ac.uk/-sczsteve/survey.htm<http://www.nottingham.ac.uk/-sczsteve/survey.htm>
(BBSRC Watson-Crick Anniversary Award)
________________________


From: RASMB [mailto:rasmb-bounces at list.rasmb.org] On Behalf Of John Sumida
Sent: 03 June 2015 17:32
To: 'David Hayes'; 'RASMB'
Subject: Re: [RASMB] Viscometer technology

Dear David,

Your post piqued my curiosity.  Please forgive my ignorance on the topic, but why is protein viscosity something one would be interested in?  And for those who make these types of measurements, what is the variability in protein viscosity?

Thank you all for your comments and responses, now and in the past.  This bulletin board has been a great learning tool.

Best regards,
John Sumida
University of Washington

From: RASMB [mailto:rasmb-bounces at list.rasmb.org] On Behalf Of David Hayes
Sent: Wednesday, June 03, 2015 5:23 AM
To: RASMB
Subject: [RASMB] Viscometer technology

Hi all (especially hoping Steve Harding is active),

I recently saw the Malvern viscosizer.  It is a capillary viscometer and taylor dispersion instrument.  (Taylor dispersion looks at the diffusion pattern of a small plug of sample in a capillary).  Because of the small volumes used, it could be useful for screening early limited supply proteins for viscosity problems.

Are there any general thoughts on the technology?

I remember Steve Harding telling us at BITC that you never use rolling ball viscometers on proteins:  the proteins stick to the ball.
Recently we found out here that the regular Anton Paar cone and plate rheometers sometimes need PS-80 in protein samples or the air water interface around the outside edge can predominate the viscosity measurements.

I did ask whether most samples just stick to the capillary and disappear or run anomalously, but the answer was they had a super coating so most things won’t stick.  This coating makes the capillary impossible to clean (so you buy more capillaries from Malvern).  And that the taylor dispersion fitting will tell you if and approximately how much the sample interacts with the capillary walls.

Kind Regards,

David Hayes





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