Douglas D. Frey


Contact Information

Technology Research Center (TRC), Room 252B

Frey Lab Website


Ph.D. Chemical Engineering – University of California, Berkeley, 1984
M.S. Chemical Engineering – University of California, Berkeley, 1980
B.S. Chemical Engineering – Stanford University, 1978

Research Interests

The primary goals of our research are to

  • investigate the thermodynamic, transport, and biophysical principles that underlie separation processes for biological macromolecules and related types of materials.
  • exploit this improved understanding in order to develop novel methods for both analytical-scale and process-scale separations.

Activities in specific research areas are given in more detail below.


One area of work has involved investigations of the technique of chromatofocusing. In one particular project, computational methods are being developed to optimize the conditions so that stable mobile-phase composition gradients can be formed without using the polyampholyte buffers and proprietary weak-base column packings normally used for chromatofocusing. Such systems greatly expand the range of applications possible for the technique, including to peptide separations, to high-speed, high-resolution, and high-sensitivity analytical separations performed using capillary columns, and to various process-scale systems, such as those using expanded beds. In a related project we are developing a novel hybrid chromatography method that incorporates aspects of both chromatofocusing and displacement chromatography and that eliminates the need for a traditional displacer component for accomplishing displacement chromatography.

Methods for Analyzing Complex Protein Mixtures.

Novel versions of 2D chromatography are being interfaced to various types of detectors to develop improved liquid chromatography methods for the analysis of complex protein mixtures. In one project, high-resolution chromatofocusing performed using a micropellicular (nonporous particle) column packing is being interfaced to either ESI-MS or MALDI-TOF-MS to produce a technique that can replace standard two-dimensional polyacrylamide gel electrophoresis (2DE) for the routine characterization of protein molecular weight and isoelectric point. In another project we are investigating novel chromatographic approaches for performing native LC-MS of intact proteins.

Sorting of Carbon Nanotubes.

Chromatographic methods are being developed for the efficient, large-scale sorting of metallic and semiconducting carbon nanotubes. This is being accomplished by the differential functionalization of the chiral forms of carbon nanotubes followed by the chromatographic separation of these chiral forms.

Computational and Mathematical Studies of Separation Processes for Biomolecules.

Numerical and analytical mathematical methods are being applied to chromatography and related types of separation processes for biomolecules to gain a better fundamental understanding of these processes. In one study, mathematical theories of dispersion in porous media are being used to gain a better fundamental understanding of the factors governing chromatographic band broadening. In another study, machine learning methods are being developed for system identification and process optimization and design. In addition, multiscale modeling as well as statistical mechanical perturbation theory are being employed to study the phenomenon of charge regulation when proteins adsorb onto a charged surface.

Selected Publications

P. Rezaei, L.D. Pfefferle, D.D. Frey, “Metal-Semiconductor Sorting of Large-Diameter Single-Wall Carbon Nanotubes by pH-Dependent Binding to a Hydrophobic Interaction Adsorbent” Carbon, 175, 112-123, 2021 [abstract]

R. Adiga, A.U. Andar, S. Borhani, D. Bergenson, S. Deldari, D.D. Frey, X. Ge, Y. Liu, G. Rao, …, L. Wong, “Manufacturing Biological Medicines on Demand: Safety and Efficacy of GCSF in a Mouse Model of Total Body Irradiation” Biotechnol. Prog., 36(3), e2970, 2020 [abstract]

A.U. Andar, S. Deldari, E. Gutierrez, D. Bergenson, M. Al-Adhami, C. Gurramkonda, L . Telosa, Y. Kostov, D. D. Frey, G. Rao, “Low Cost Customizable Microscale Toolkit for Rapid Screening and Purification of Therapeutic Proteins” Biotechnol. Bioengin., 116, 870-881, 2019. [abstract]

Y. Liu, S. Deldari, H. Guo, C.R. Narahari, R.C. Bates, R. Swanson, S. Ghose, Z.J. Li, D.D. Frey “Evaluation of Chromatofocusing as a Capture Method for Monoclonal Antibody Products” J. Chromatogr. A, 1568, 108-122, 2018. [abstract]

B.C. Bundy, J.P. Hunt, M.C. Jewett, J.R. Swartz, D.W. Wood, D.D. Frey, G. Rao “Cell-Free Biomanufacturing” Current Opinion in Chemical Engineering, 22, 177-183, 2018.

R. Adiga, M. Al-Adhami, A. Andar, S. Borhani, S. Brown, D. Bergenson, M. A. Cooper, S. Deldari, D. D. Frey, X. Ge, H. Guo, C. Gurramkonda, P. Jensen, Y. Kostov, W. LaCourse, Y. Liu, A. Moriera, …, G. Rao, J. Wilhide, D. Wood, A. Zuber “Point-of-Care Production of Therapeutic Proteins of Good-Manufacturing-Practice Quality” Nature Biomedical Engineering, 2, 675-686, 2018.

S. Johnson, K. A. Brorson, D. D. Frey, A K. Dhar, D. A. Cetlin “Characterization of Non-Infectious Virus-Like Particles for Viral Clearance Applications,” Applied Biochem. Biotechnol., 183, 318-331, 2017.

N. D. S. Pinto, S. D. Uplekar, A. R. Moreira, G. Rao, D. D. Frey, “Immunoglobulin G Elution in Protein A Chromatography Employing the Method of Chromatofocusing for Reducing the Co-Elution of Impurities,” Biotechnol. Bioeng., 114, 154-162, 2017.

N. D. S. Pinto, D. D. Frey, “Displacement Chromatography of Proteins Using a Retained pH Front in a Hydrophobic Charge Induction Chromatography Column,” J. Chromatogr. A, 1387, 53-59, 2015.

H. Guo, X. Li, D. D. Frey, “Development of Chromatofocusing Techniques Using Mixed-Mode Column Packings for Protein Separations,” J. Chromatogr. A, 1323, 57-65, 2014.

X. Kang, J. P. Kutzko, M. L. Hayes, D. D. Frey, “Monoclonal Antibody Heterogeneity Analysis and Deamidation Monitoring with High-Performance Cation-Exchange Chromatofocusing Using Simple, Two Component Buffer Systems,” J. Chromatogr. A, 1283, 89-97, 2013.