Abstract SFC 2015

Understanding the Real Value of Prep SFC Technology: A Better Way to Look at System, Component, and Process Design

Jeffrey Kiplinger, Paul Lefebvre, Keith Galyan

The only important criteria for adoption of a technology are economic.  Is the cost of implementation (systems, infrastructure, personnel, training, retirement of old technology) less than the profit derived from it (efficiency gains, new products, reduced personnel/infrastructure costs)?  These explain why a new technology replaces an older one, but don’t always guide the design of an instrument system or lab.

As an example, the benefit of linking mass spectrometer detectors to preparative HPLC systems seems obvious when many crude samples of desired reaction products must be purified.  But while the coupling of the hardware was and is straightforward, the long effort to develop software that integrated the new systems into workflow was not easily anticipated or calculated.  The technology itself had limited value for several years due to the high costs of design and implementation of workflow integration.

In our lab, the cost/benefit equation is the same as in any organization using preparative SFC for purification or isolation.  However, because our revenues and expenses come from operation of chromatography instrument systems, we can monitor the impact of any change to our technology platform directly and immediately.  This unique viewpoint allows us to experiment with many modifications to instrument systems while observing their economic impact, positive or negative, large or small.

In recent years we have quantified the economic impact of common stacked injection protocols1, backpressure regulators and alternatives2, solvent modifier choices3, solvent pumping systems4, adaptations to fraction collection timing schemes, open bed fraction collection design5, batch-to-batch cross contamination and system cleanout protocols6, and an alternative fraction collection design.  The last two categories represent our most recent work, and in this presentation we demonstrate an entirely new fraction collection methodology with dramatic economic benefits.

Partial details of some modifications have been presented previously, but without the quantitative impact data.  In this presentation we focus on the economics of the choices we all make in instrument setup and batch process design.  We suggest that direct measurement of economic impact can result in better instrument design and better planning for new technology implementation in R&D workflow.


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  1. “Process and Performance Enhancements for the Thar Prep80 Benchtop SFC System”; J. P. Kiplinger, Thar SFC User Symposium at 2nd International SFC Conference, Zurich October 1 2008
  2. “At-Column Dilution in Achiral Preparative SFC: Improving Column Performance”; J. P. Kiplinger, P. M. Lefebvre; 2009 CSSC Csaba Horvath Symposium, Hartford CT April 28, 2009
  3. “Orthogonality of SFC versus HPLC for Small Molecule Library Separation”; H. N. Weller, K. Ebinger, W.Bullock, K. J. Edinger, M. A. Hermsmeier, S. L. Hoffman, D. S. Nirschl, T. Swann, J. Zhao, J. Kiplinger, P. Lefebvre; Comb. Chem. 12, 877-882 (2010)
  4. “Improving Productivity in Preparative SFC Separations” J. P. Kiplinger; 4th International SFC Symposium, New York July 18 2011
  5. “Evaluation of a New Preparative Supercritical Fluid Chromatography System for Compound Library Purification: The TharSFC SFC-MS Prep-100 System”; Ebinger, H. N. Weller, J. Kiplinger, P. Lefebvre; Published online 17 May 2010; J. Assn. Lab. Automation
  6. “Capture, Crosstalk, Carryover, and Cleanout – Toward Better Preparative SFC Fraction Collection”; Jeffrey Kiplinger, Paul Lefebvre, Keith Galyan, and Emma Gatley; Waters International SFC Users Meeting at 8th International SFC Conference; Basel Switz October 8 2014