Education:

B.S., Mathematics, 1975
University of Oregon-Eugene

M.S., 1979
Sc.D., 1984
Electrical Engineering and Computer Science
Massachusetts Institute of Technology

Research Interests:

Professor Siegel's research interests lie in drug delivery systems, focusing on novel methods for achieving spatiotemporal control of drug release. Three projects are underway.

In the first project, a micromachined valve is being constructed that will provide glucose-sensitive control of insulin delivery. An integral feature of this valve is a polymer microgel that binds glucose and, as a result, changes its degree of swelling. This microgel is embedded inside a silicon microchip into which microfluidic channels have been machined. The gel's glucose-sensitive swelling and deswelling is harnessed to open or close channels through which an insulin solution flows. The result of this project, which lies at the interface between drug delivery, polymer science, and microfluidics, will be an "artificial pancreas" which delivers insulin to counteract rises in blood glucose and will be used to treat Type I diabetes.

In the second project, an implantable device is being developed that delivers hormones in rhythmic pulses. Such a device will be particularly useful in the treatment of reproductive disorders that stem from the failure of the hypothalamus to secrete gonadotropin releasing hormone in its normal rhythmic pattern. The proposed device includes a hydrophobic, polyelectrolyte hydrogel that pulsates (i.e., changes its swelling state) in the presence of glucose. Rhythmic pulsations are due to mutual feedback between the transport of blood glucose through the hydrogel and the enzyme glucose oxidase, which converts glucose to acidic hydrogen ions, which in turn alters degree of swelling and hence the rate of glucose transport through the gel. Swelling pulsations enable modulation of hormone release rates.

In a third project, a microfluidic point-of-administration mixing system is being developed for nasal delivery of diazepam, a drug that is effective in the prevention and control of epileptic seizures. In this project, a combination of thermodynamics, fluid mechanics, and microfabrication is brought to bear on delivery of a poorly soluble drug that is difficult to administer nasally.

Research Group:

Information about Dr. Siegel's research group is available.

Selected Publications:

Carlson J.C.T., Jena S.S., Flenniken M., Chou T., Siegel R.A., and Wagner C.R.  Chemically Controlled Self-Assembly of Protein Nanorings.  J. Amer. Chem. Soc. (in press).

Lei M., Baldi A., Nuxoll E., Siegel R.A. and Ziaie B.  A Hydrogel-Based Implantable Micromachined Transponder for Wireless Glucose Measurement.  Diabetes Tech. Therap. 8: 112-122 (2006).

Baldi A., Lei M., Gu Y., Siegel R.A. and Ziaie B.  A Microstructured Silicon Membrane with Entrapped Hydrogels for Environmentally-Sensitive Fluid Gating.  Sensors and Actuators B 114: 9-18 (2006).

Hou H. and Siegel R.A.  Enhanced Permeation of Diazepam through Artificial Membranes from Supersaturated Solutions.  J. Pharm. Sci. 95: 896-905 (2006).

Siegel R.A.  Characterization of Relaxation to Steady State in Membranes with Binding and Reaction.  J. Membr. Sci. 251: 91-99 (2005).

Nuxoll E.E., Siegel R.A. and Cussler E.L.  Layered Reactive Barrier Films.  J. Membr. Sci. 252: 29-39 (2005).

Siegel R.A. and Ramanathan M.  Commentary: Stochastic Phenomena in Pharmacokinetic, Pharmacodynamic and Pharmacogenomic Models.  AAPS J. 7: E141-E142 (2005).

Dhanarajan A.P. and Siegel R.A.  Time-Dependent Permeabilities of Hydrophobic, pH-Sensitive Hydrogels Exposed to pH Gradients.  Macromol. Symp. 227: 105-114 (2005).

Ziaie B., Baldi A., Lei M., Gu Y. and Siegel R.A.  Hard and Soft Micromachining for BioMEMS: Review of Techniques and Examples of Applications in Microfluidics and Drug Delivery.  Adv. Drug Deliv. Revs. 56: 145-172 (2004).

Siegel R.A. and Cussler E.L.  Reactive Barrier Membranes: Some Theoretical Observations Regarding the Time Lag and Breakthrough Curves.  J. Membr. Sci. 229: 33-41 (2004).

Siegel R.A., Gu Y., Baldi A. and Ziaie B.  Novel Swelling/Shrinking Behaviors of Glucose-Binding Hydrogels and Their Potential Use in a Microfluidic Drug Delivery System.  Macromol. Symp. 207: 249-256 (2004).

Lei M., Gu Y., Baldi A., Siegel R.A. and Ziaie B.  A High Resolution Technique for Fabricating Environmentally Sensitive Hydrogel Structures. Langmuir 20: 8947-8951 (2004).

Bairamov D.F., Chalykh A.E., Feldstein M.M. and Siegel R.A.  Impact of Molecular Weight on Miscibility Between Poly(N-Vinyl Pyrrolidone) and Poly(Ethylene Glycol).  Macromol. Chem. Phys. 203: 2674-2685 (2003).

Baldi A., Gu Y., Loftness P.E. Siegel R.A. and Ziaie B.  A Hydrogel Actuated Environmentally Sensitive Microvalve for Active Flow Control.  J. Micromech. Syst. 12: 613-621 (2003).

Rosner B.I., Siegel R.A., Grosberg A. and Tranquillo R.T.  Rational Design of Contact Guiding, Neurotrophic Matrices for Peripheral Nerve Regeneration.  Ann. Biomed. Eng. 31: 1383-1401 (2003).