Corinne  Lengsfeld, Ph.D. AssociateProfessor (Mechanical Engineering) Department of Engineering, University of Denver 2390 S. York Street, Denver, Colorado 80208-2102 ph: (303)871-4843         FAX: (303)871-4450       e-mail:clengsfe@du.edu

Figure 1. Degradation of genomic DNA as a function of turbulent length scale. Degradation is initiated when length scales equal molecular length   Figure 2.  Microscope images of liposomes encapsulated using electrostatic co-extrusion. Figure 3. Model pulmonary delivery deposition system Figure 4. Photo of the insole gait sensor system.

Research interests: Dr. Lengsfeld’s Biofluids Laboratory is fundamentally interested in the forces that hydrodynamic flows impart on particles and material surfaces. This many included developing forces to oppose particle deposition in mechanical ventilators, correlating  the probability of fragmentation with turbulent length scale,  manufacturing of non-viral vectors via directed self assembly techniques, simulating the contribution of fluid flow in joint mechanics, and even developing remote sensor systems to monitor drug interactions in the aging population. Our goal is to lower the costs associated with manufacturing and delivering therapeutics while maintaining or increasing efficacy. Shear Induced Degradation of DNA Therapeutic DNA and siRNA offer the potential to cure many genetic diseases. In contrast to traditional small-molecule drugs, biopharmaceuticals possess secondary structure that maybe damaged during one of many bioprocessing steps.   Our research has determined that hydrodynamic degradation pathways dominate plasmid, cosmid and genomic DNA fragmentation during aerosolization and pipe flow. This loss of molecular structure can be attributed to turbulent length scales at or below the molecules length as well as localized cavitation events. Based on these findings we have set forth a series of guidelines for chosing aerosolization devices for the pulmonary delivery of genetic theraputics as well as bioprocessing guidelines to limit the contamination of genomic DNA during bioprocessing. Finally this project designed several mitigation techniques for classical atomizers and put forth a new safe and effective aerosolization technique for consideration.  We gratefully acknowledge the financial support for this work from two NSF collaborative grants (BES-0214015 and BES-0239940) and recognize the collaboration of the University of Colorado School of Pharmacy. In addition, some equipment donations were obtained from Bohlin and ADA Technology. Improved Synthetic Vectors by Electrostatic Co-Extrusion: The evolution of gene therapy has been hindered by the development of safe and effective delivery vectors. Electrostatic co-extrusion (a platform technology currently under patent by our lab) to manufacture non-viral vectors. This manufacturing process from provides control over particle size and size distribution from micron to the nano scale. The technique provides 100% encapsulation efficiency and enables the use of neutral lipids. We are currently investigating the limitations of molecular stability as a function of electric potential gradient and charge density. We gratefully acknowledge the financial support for this work from two NSF collaborative grants (BES-0433810 and BES-0433811) and recognize the collaboration of the University of Colorado School of Pharmacy. Improved pulmonary drug delivery to patients on mechanical ventilators: Pulmonary drug delivery to patients on mechanical ventilators currently resides around 5% of the intended dose. Applying humidity to an airflow before it enters a jet nebulizer increases Salbutamol deposition in the lung. This addition of humidity is a relatively simple, yet effective way to improve drug delivery. This finding becomes especially relevant when noting that mechanically ventilated patients generally must have some kind of humidity applied to their ventilator system. Conventional methods of applying humidity (i.e. through the corrugated tubing prior to a nebulization tee) decrease Salbutamol deposition in the deep lung due to particle growth by condensation, but applying humidity to the airflow entering the nebulizer appears to increase drug deposition in the lung. Despite the increases seen in the Salbutamol deposition in the deep lung, the corresponding increases in the amount of drug exhaled in this process is the next obvious place for improvement with this technique.  This work was funded by a PROF grant from the University of Denver and equipment donations are gratefully acknowledged from Pulmonetic Systems Inc., Michigan Instruments and Ocean Optics. Wearable sensor technologies: We have developed an sensor system that fits with the insole of a shoe and communicates gait data wirelessly to a base station. The system is currently under evaluation as a tool to detect variations in gait. We gratefully acknowledge the financial support for this work from the US Department of Health and Human Services and the University of Denver Partners in Scholarship program. Further we recognize the collaborative efforts of the University of Colorado Center on Aging. Developing a fluidic system to evaluate environment pressures on gene mutations Largely through widespread sanitation and use of antibiotics, bacterial infectious diseases have exerted a greatly decreased influence on the health and lifespan of the developed world’s population. In contrast, these diseases have continuously impacted the developing world’s population. With the increasing emergence of new antibiotic-resistant strains and the weaponization of normally rare bacterial strains, the threat of pandemic disease and its fall-out on the developed world has re-emerged.  Recognition of this threat has engendered efforts to address prevention and cure of these diseases, as well as the study of the complex interaction between the host, pathogen, and environmental factors that impact the progression and severity of the disease.  By exploiting the advances in fluidics and materials engineering, we propose to create a system to rapidly and simultaneously interrogate the myriad of culture conditions necessary for successful cultivation of target organisms. We gratefully acknowledge the financial support for this work from the Keck Foundation in collaboration with the National Academies of Science and Engineering.

Education:
Postdoc Chemical Engineering, University of Colorado at Boulder (July 1997 to August 1999)
 Ph.D.  Mechanical Engineering, University of California at Irvine (June 1997)
 M.S.   Mechanical Engineering, University of California at Irvine (December 1993)
 B.S.    Mechanical Engineering, University of California at Irvine (June 1992)

Professional Experience:
Associate Professor, Department of Engineering, University of Denver (2005- present)
Assistant Professor, Department of Engineering, University of Denver (1999- 2005)
Visiting Researcher, Process Measurements Division, NIST, Maryland (Summer 1995)

Joint Appointments:
Graduate Faculty Appointment, Department of Pharmaceutical Sciences, University of Colorado Health Science Center [2000 to present]
Graduate School Faculty Appointment, Department of Chemical Engineering, University of Colorado Boulder [1999 to 2004]

Professional Activities:
Editorial Board Member, Atomization and Spray

Board Member at-large, Institute of Liquid Atomization and Sprays
co-Chair, ILASS Technical Committee on Physics of Atomization
Executive Board Member, Colorado Alliance for Bioengineering
Past Chief Judge, ASME Human Powered Vehicle Competition

Publications (previously published under CS Connon):

1. Yi YB, and  Lengsfeld CS. Mechanical modeling of Carbonic Anhydrase motion in simple channels, Journal of Applied Physics, 2006, 100, 014701

2. Lentz, Y., Worden, L., Anchordoquy, T. and Lengsfeld, C.S., DNA acts as a nucleation site for transient cavitation in the ultrasonic nebulizer. Journal of Pharmaceutical Science, 95 (3): 607-619 MAR 2006

3. Jarmer DJ, Lengsfeld CS, Randolph TW. Scale-up criteria for an injector with a confined mixing chamber during precipitation with a compressed-fluid antisolvent. Journal of Supercritical Fluids 37 (2): 242-253 APR 2006

4. Jarmer, D.J., Lengsfeld, C.S., Randolph, T.W. Supercritical fluid crystallization of griseofulvin crystal habit modification with a selective growth inhibitor. Journal of Pharmaceutical Sciences 94 (12): 2688-2702 DEC 2005

5. Lentz, Y., Worden, L., Anchordoquy, T. and Lengsfeld, C.S. , Effect of jet nebulization on DNA: Identifying dominant degradation mechanism and mitigation methods, Journal of Aerosol Science, 2005,  36:973-990

6. Jarmer, D.J., Lengsfeld, C.S., Randolph, T.W. Nucleation and growth rates of poly(l-lactic acid) microparticles during precipitation with a compressed-fluid antisolvent, Langmuir, 2004, 20: 7254-7264.

7. Lengsfeld, C.S., Edelstein, G., Black, J. , Root, M., Stevens, K., and Whitt, M. Engineering Concepts And Communications: A first-year course sequence, Journal of Engineering Education, 2004, 93(1):79-85

8. DeLyser, R.R, Edelstein, G., Lengsfeld, C.S., Rosa, A.J., Rullkoetter, P., Whitman, R., Summers-Thompson, S., and Whitt, M., Effective Student Learning at the University of Denver, Journal of Engineering Education, 2003, 92(3):269-273

9. Biggs D.L., Lengsfeld, C.S., Ng, K.Y., Hybertson, B.M., Manning, M.C., and Randolph, T.W.  In vitro and in vivo evaluation of the effects of PLA microparticle crystallinity on cellular response, Journal of Controlled Release, 2003, 92:147-161

10. Jarmer, D.J., Lengsfeld, C.S., Randolph, T.W. A jet-swirl nozzle design for manipulating the particle size and size distribution of poly(L-lactic acid) at the nano and micro scale in the supercritical fluid antisolvent process, Journal of Supercritical Fluids, 2003, 27:317-336

11. Lengsfeld, C.S., Petira, D., Manning, M.C., and Randolph, T.W. Fundamental study of hydrophobic ion-pairing: pharmaceutical complex chemical nature and kinetic behavior, Pharmaceutical Research, 2002, 19(10):1572-1576

12. Lengsfeld, C.S., Delplanque, J.-P., and Dunn-Rankin, D. Breakup transitions within dense sprays.  Atomization and Sprays, 2002, 12(4):501-511

13. Lengsfeld, C.S., Manning, M.C., and Randolph, T.W.  Encapsulating DNA within biodegradable polymeric microparticles.  Current Pharmaceutical Biotechnology (invited review), 2002, 3:227-235

14. Lengsfeld, C.S. and Anchordoquy, T.  Shear-induced degradation of plasmid DNA, Journal of Pharmaceutical Science (invited review), 2002, 91(7):1581-1589

15. Zhou, H., Lengsfeld, C.S., Claffey, J.D., Ruth, J.A., Hybertson, B., Randolph, T.W., Ng, K.Y., and Manning, M.C. Hydrophobic ion pairing of isoniazid using a prodrug approach. Journal of Pharmaceutical Science, 2002, 91(6)1502-1511

16. Lengsfeld, C.S., Delplanque, J.P., Barocas, V.H., and Randolph, T.W.  Mechanism governing microparticle morphology during precipitation by a compressed antisolvent: atomization vs. nucleation and growth.  Journal of Physical Chemistry B, 2000, 104(12):2725-2735

17. Connon, C.S., Falk, R.F., and Randolph, T.W.  Role of crystallinity in retention of polymer particle morphology in the presence of compressed carbon dioxide. Macromolecules, 1999, 32(6), 1890-1896

18. Connon, C.S., Dimalanta, R., Choi, C., and Dunn-Rankin, D. LIF measurements of fuel vapor in an acetone droplet stream.  Combustion Science and Technology, 1997, 129(1-6), 197-216

19. Connon, C.S. and Dunn-Rankin, D. Droplet stream dynamics at high ambient pressure. Atomization and Sprays, 1996, 6, 485-497

20. Connon, C.S. and Dunn-Rankin, D. Flow behavior near an infinite droplet stream. Experiments in Fluids, 1996, 21, 80-86


Patents:

21. Lengsfeld, C.S., Falk, R.F., and Randolph, T.W.  “Microparticles of lactide-co-glycolide copolymers and methods of making and using the same.” (issued 11/20/01) US Patent #6,319,521

22. Randolph, T.W., Anseth, K., Owens, J., and Lengsfeld, C.S.  “Preparation and use of photopolymerized microparticles.”  Patent # 6,403,672 (issued 6/11/02)

23. Randolph, T.W., Anseth, K., Owens, J., and Lengsfeld, C.S.  “Preperation and use of photopolymerized microparticles.”  Patent # 6,864,301 (issued 3/8/05)


Conference Presentations:
More than 50 conference papers and presentations.