Perhaps no other word in the world of analytical instrumentation suggests both opportunity and uncertainty in such nebulous terms.  From a scientist this can be translated as meaning “we’d love to have this capability,” or “this doesn’t do what we need it to do.”  For an instrument manufacturer it can provide a window into the next generation of instrumentation, and present a challenge in how to realize the user’s desires.  Nowhere is this more true than in the rapidly-developing field of large molecule biotherapeutics.

One traditional method for the screening of biotherapeutic formulations has been that of dynamic light scattering (DLS), an area of core expertise for Malvern Instruments.  But what happens when characterizing particle size distributions doesn’t provide enough detail?  For example, when it is unclear how a protein is unfolding, or whether the unfolding mechanism is reversible.  Such information can be critical when deciding on the correct formulation for a consumer product.

Protein AggregationEnter Malvern Instruments and the Bioscience Development Initiative (BDI)*.  The scientists of the BDI team have come up with a hybrid technique for providing you more.  In this case, more consists of measuring protein structural information while maintaining the ability to monitor particle size through a combination of Raman spectroscopy and DLS (DLS-Raman).  The novel technique of DLS-Raman allows the user to monitor changes in the secondary (backbone) and tertiary (side chain) structure of a protein under various conditions, and to correlate these structural variations with changes in particle size.  All this at the small volumes demanded by pre-formulation studies.

Would you like to watch the evolution of secondary structural changes in a sample as a function of stress (e.g., temperature, denaturant, etc), while monitoring the size distribution for the onset of aggregation?  Perform experiments under formulated conditions without dilution or additional sample preparation (i.e., over 100 mg/ml with included excipients)? Observe the solvent environment around tyrosine/tryptophan residues, or watch the disulfide bond reducing directly from the spectra?

Similar experiments (and more) will be covered by our academic colleague Professor John Carpenter (University of Colorado – Denver) on March 18th when he discusses his latest research:

Prof. Carpenter will offer a thorough description of the DLS-Raman technique, as well as provide in-depth descriptions, through example, of how much more DLS-Raman can provide.  More detail.  More understanding.  More control.

* Malvern Instruments’ Bioscience Development Initiative is based in Columbia, MD and consists of a team of scientists and engineers dedicated to bringing the next generations of relevant analytical technologies to the bioscience sector.