Using OMNISEC to examine PLGA composition

Between talking to customers and working in the Applications Lab, I hear about all sorts of GPC/SEC sample types.  However, there is one sample type that continues to receive regular interest: PLGA.  This material, poly(lactic-co-glycolic acid), is popular for several reasons.  It is a green polymer, generated from renewable sources, it is biodegradable and generally biocompatible, and it possesses decent mechanical strength.  And most importantly, its composition, or the ratio of lactic acid to glycolic acid (PLA to PGA) affects these properties, providing researchers a handle to tune these materials for specific functions.

How can OMNISEC help?

Controlling the ratio of PLA to PGA during the polymerization process is one thing, but it would be helpful to analyze the polymer product for confirmation.  This is where OMNISEC can help!  As a versatile, multi-detector GPC/SEC instrument, OMNISEC allows you to observe differences in molecular structure.  And as I’ll show later in the post, those differences can be as slight as the ratio of PLA to PGA in a series of PLGA samples.

I’ll present a series of PLGA samples with known PLA:PGA ratios to demonstrate how OMNISEC can differentiate between them.  Then, we’ll examine a sample with an unknown PLA:PGA ratio and attempt to characterize it based on the data of the known samples.  


The following is a multi-detector chromatogram of a sample with a 50:50 ratio of PLA to PGA, what I’ll describe as 50:50 PLGA.  This type of material has a relatively low dn/dc value in THF, less than 0.050, but the sensitivity of OMNISEC’s refractive index and light scattering detectors (the ones affected by dn/dc value) is more than enough to overcome that challenge.

Fig 1. PLGA chromatogram

A second purpose for presenting the above chromatogram, and the ones that follow, is to show that the differences between PLGA samples of different composition are not necessarily visible in the chromatograms.  I know you’re thinking, “wait, but you said OMNISEC could tell them apart!”  I did, and we’ll get to that in just a minute.

Below are the overlays of a single detector’s response to the four PLGA samples of different PLA:PGA ratios.  The detectors utilized in the figure below are refractive index (RI), right angle light scattering (RALS), low angle light scattering (LALS), and intrinsic viscometer (IV). The samples are PLA (11 kDa; red & purple), PLGA 75:25 ( 65 kDa; orange & light green), PLGA 65:35 (35 kDa; blue & gold), and PLGA 50:50 (45 kDa; green & black).  These are presented as further proof that the only difference immediately observable between the samples is the retention volume and molecular size.

Fig 2. PLGA standard overlays

Mark-Houwink plots

Fortunately, the data available from OMNISEC isn’t limited to the chromatograms.  There are a number of calculated results available in the OMNISEC software, one of which is the Mark-Houwink plot which displays the intrinsic viscosity as a function of molecular weight, both on log scales.  As discussed in my last post on analyzing branched samples, the Mark-Houwink plot is an excellent way to compare the molecular structures of different samples.  And it is the exact tool we need to study the composition of these PLGA samples.

Fig 3. PLGA standard M-H plot overlays

The Mark-Houwink plot above displays the same four samples whose chromatograms are overlaid above.  But this time, the differences in molecular structure are apparent!  The Mark-Houwink plot of the pure PLA sample sits above the others (and to the left because of its lower molecular weight), indicating that for a given molecular weight (a vertical slice of the plot), the intrinsic viscosity of PLA is greater than any PLGA mixture.  And more importantly, the trend continues, so that as the PGA content increases, the samples exist lower on the Mark-Houwink plot. 

Analysis of a PLGA with unknown composition

If we use the results of these known samples as a sort of calibration, then we can run a PLGA sample of unknown composition and observe where its Mark-Houwink plot sits relative to the known samples.  The placement of the unknown will tell us about its composition.

Fig 4. unknown PLGA M-H plot

As you can see from the plot above, the unknown sample (dark grey & forest green) overlaid nicely with the PLGA 50:50 sample, suggesting that the unknown’s composition is an even mix of PLA and PGA.  This analysis is in addition to the general molecular characterization data available, such as molecular weight, intrinsic viscosity, hydrodynamic radius, and concentration.  That’s a lot of valuable information from one instrument!

Final thoughts

I hope the example described in this post helps you understand the types of structural analysis your OMNISEC system can assist with, whether you’re working with PLGA or a different type of samples.  If you have any questions, please don’t hesitate to contact us or email me directly at

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