Electrophoresis 2012, 33, 1311–1321 1311 Chris S. Ivanoff Timothy L. Hottel Franklin Garcia-Godoy College of Dentistry,The University of Tennessee Health Science Center, Memphis, TN, USA Received September 23, 2011 Revised January 9, 2012 Accepted January 11, 2012 Research Article Dielectrophoresis: A model to transport drugs directly into teeth The article describes an innovative delivery system based on the principles of dielec- trophoresis to transport drugs directly into site-specific intraoral targets. The hypothesis that a drug can be driven into tooth enamel during the application of an applied electrical potential difference was tested by the authors in in vitro studies comparing dielectrophore- sis to diffusion to transport carbamide peroxide and fluoride. The studies showed that these agents can be transported directly into teeth using an alternating current (AC) electric field more effectively than diffusion. It was found that a 20-min bleaching treatment on human teeth with dielectrophoresis increased carbamide peroxide absorption by 104% and, on average, improved the change in shade guide unit 14 times from 0.6 SGU to 9 SGU. After applying a 1.23% acidulated phosphate fluoride gel to bovine incisors for 20 min by dielectrophoresis or diffusion, analysis with wavelength dispersive spectrometry deter- mined that dielectrophoresis doubled fluoride uptake in the superficial layers compared to diffusion, and drove the fluoride significantly deeper into enamel with an uptake 600% higher than diffusion at 50 m depth. Finally, dielectrophoresis promises to be a viable model that can potentially be used clinically to deliver other targeted drugs of variable molecular weight and structure. Keywords: Dielectrophoresis / Diffusion / Drug transport DOI 10.1002/elps.201100505 1 Introduction An innovative technology that could potentially transport drugs “directly” into teeth using an alternating current (AC) electric field is being evaluated. This electrochemical delivery approach utilizes the principles of dielectrophoresis (DEP) and is not iontophoresis (IP). The advantages of delivering antibiotics, anesthetics, and antiinflammatory drugs directly to site-specific intraoral targets would be a breakthrough in dentistry that would potentially eliminate systemic side ef- fects and risks commonly associated with oral drug delivery. It also implies the additional benefit of efficient and targeted drug delivery that is pain-free. 1.1 Dielectrophoresis The general principles of DEP were first outlined by Pohl in 1951 [1–3]. Much like electrophoresis (EP), DEP describes Correspondence: Dr. Chris S. Ivanoff, Department of Bioscience Research, College of Dentistry, University of Tennessee Health Science Center, 875 Union Avenue, Memphis, TN 38163, USA E-mail: civanoff@uthsc.edu Fax: (901) 448-2744 Abbreviations: CP, carbamide peroxide; DEA, dielectric anal- ysis; DEP, dielectrophoresis; EP, electrophoresis; HP, hydro- gen peroxide; IDE, interdigitated (array) electrode; IP, ion- tophoresis; LOC, lab-on-a chip; PCB, printed circuit board; SGU, shade guide units the movement of particles under the influence of applied electric fields. DEP is the electrokinetic motion of dielectri- cally polarized particles in a nonuniform electrical field due to the unbalanced force of the electrical field on the particle’s induced dipole moment. The phenomenon of DEP occurs both in AC and direct current (DC) electric fields and can be applied both to charged and neutral particles. In the case of DEP, the development of nonuniform elec- tric fields will cause a net force on any polarizable object, charged, or neutral. However, the strength of the force de- pends strongly on the medium and particles’ electrical prop- erties, on the particles’ shape and size, as well as on the frequency of the applied electric field. DEP exploits the dif- ferences in particle dielectric properties to allow their ma- nipulation and characterization. Particles can be trapped or moved between regions of high or low electric fields due to the polarization effects in nonuniform electric fields. By vary- ing the applied electric field frequency, as well as the type of current (DC or AC), the magnitude and direction of the di- electrophoretic force on the particles can be controlled, thus providing the means for their manipulation, separation, or orientation [4]. DEP techniques have been used to manipulate cells, to concentrate a single cell type from a heterogeneous mixture, or alternatively, separate different cell types [5]. Washizu and Kurosawa showed it was possible to use DEP to manipu- late and stretch DNA molecules [6]. There are reports of the Colour Online: See the article online to view Figs. 1 to 5 in colour. C  2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.electrophoresis-journal.com