Biosensors and Bioelectronics 20 (2004) 606–619 Electronic manipulation of DNA, proteins, and nanoparticles for potential circuit assembly Lifeng Zheng a , James P. Brody b , Peter J. Burke a,b,∗ a Electrical Engineering and Computer Science, University of California, Irvine, CA 92697-2625, USA b Biomedical Engineering, University of California, Irvine, CA 92697-2625, USA Received 29 October 2003; received in revised form 8 March 2004; accepted 8 March 2004 Available online 24 May 2004 Abstract Using gold electrodes lithographically fabricated onto microscope cover slips, DNA and proteins are interrogated both optically (through flu- orescence) and electronically (through conductance measurements). Dielectrophoresis is used to position the DNA and proteins at well-defined positions on a chip. Quadrupole electrode geometries are investigated with gaps ranging from 3 to 100 m; field strengths are typically 10 6 V/m. Twenty nanometer latex beads are also manipulated. The electrical resistance of the electronically manipulated DNA and proteins is mea- sured to be larger than 40 M under the experimental conditions used. The technique of simultaneously measuring resistance while using dielectrophoresis to trap nanoscale objects should find broad applicability. © 2004 Elsevier B.V. All rights reserved. Keywords: Dielectrophoresis; DNA; Proteins; Nanoparticles 1. Introduction 1.1. Motivation The development of lithographic fabrication techniques has lead to astounding advances in integrated circuits, but at the same time the limits of lithography prevent nanometer scale electronic devices from being economically manufac- tured. This has led to proposals for alternative nanoman- ufacturing technologies based on “bottom-up” chemical self-assembly techniques. Two key challenges in the manufacturing of sub- lithographic size electronic devices (i.e. molecular elec- tronics (Heath and Ratner, 2003)) are (1) chemical (i.e. bottom-up) control of the electronic properties of the circuit elements, and (2) electrical connection to the macroscopic world. One approach to the challenge of chemical control is de-novo design of unique chemistry for electronics ap- plications (Tour, 2000; Luo et al., 2002). An alternative approach is to build on 4 billion years of evolution and ∗ Corresponding author. Tel.: +1-949-824-9326; fax: +1-949-824-3782. E-mail address: pburke@uci.edu (P.J. Burke). use or mimic existing biochemistry, using DNA as a tem- plate for chemically programmed assembly of molecular scale devices. Recently several groups have made important progress in using DNA as a template for the construction of higher order structures (Braun et al., 1998; Winfree et al., 1998; Mirkin et al., 1996; Alivisatos et al., 1996). Because of the attractiveness of the second approach we have de- cided to concentrate on the electronic manipulation and interrogation of DNA and proteins in this work. The second challenge of making an electrical connection to the macroscopic world to date has mostly been achieved passively. Much work to date on single molecule devices involves passive diffusion of molecules to small, albeit lithographically fabricated electrodes followed by passive covalent bonding to the electrode (Chen and Reed, 2002). It would be a distinct advantage if this assembly process could be actively, electronically controlled. 1.2. Dielectrophoresis Dielectrophoresis (hereafter DEP) is an electronic analog of optical tweezers using audio frequency, rf, and microwave electric fields generated from microfabricated electrodes on a chip. An ac electric field induces a dipole moment which, 0956-5663/$ – see front matter © 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.bios.2004.03.029