Published in IET Nanobiotechnology Received on 16th December 2009 Revised on 16th March 2010 doi: 10.1049/iet-nbt.2009.0018 ISSN 1751-8741 Integrated circuit-based instrumentation for microchip capillary electrophoresis M. Behnam 1 G.V. Kaigala 1 M. Khorasani 1 S. Martel 2 D.G. Elliott 1 C.J. Backhouse 1 1 Department of Electrical and Computer Engineering, University of Alberta, 2nd Floor, ECERF, Edmonton, Alberta T6G 2V4, Canada 2 DALSA Semiconductor, Bromont, Que ´bec, Canada E-mail: chrisb@ualberta.ca Abstract: Although electrophoresis with laser-induced fluorescence (LIF) detection has tremendous potential in lab on chip-based point-of-care disease diagnostics, the wider use of microchip electrophoresis has been limited by the size and cost of the instrumentation. To address this challenge, the authors designed an integrated circuit (IC, i.e. a microelectronic chip, with total silicon area of ,0.25 cm 2 , less than 5 mm × 5 mm, and power consumption of 28 mW), which, with a minimal additional infrastructure, can perform microchip electrophoresis with LIF detection. The present work enables extremely compact and inexpensive portable systems consisting of one or more complementary metal-oxide-semiconductor (CMOS) chips and several other low-cost components. There are, to the authors’ knowledge, no other reports of a CMOS-based LIF capillary electrophoresis instrument (i.e. high voltage generation, switching, control and interface circuit combined with LIF detection). This instrument is powered and controlled using a universal serial bus (USB) interface to a laptop computer. The authors demonstrate this IC in various configurations and can readily analyse the DNA produced by a standard medical diagnostic protocol (end-labelled polymerase chain reaction (PCR) product) with a limit of detection of ≏1 ng/ml (≏1 ng of total DNA). The authors believe that this approach may ultimately enable lab-on-a-chip-based electrophoretic instruments that cost on the order of several dollars. 1 Introduction In order for lab-on-a-chip (LOC) technologies to be more widely adopted in applications such as point-of-care (POC) disease diagnostics, inexpensive and portable instruments are essential [1]. One key microfluidic/LOC technology is electrophoresis, the basis of analysis/detection for a large number of molecular biology protocols for disease diagnostics (e.g. [2]). Although there have been significant advances in LOC technologies, the limiting factor in employing these technologies in a POC setting is the need for considerable support/operating infrastructure. Hence, there is a pressing need for LOC instruments that can perform molecular biology protocols and yet be inexpensive and compact. Although LOC systems have demonstrated extensive functionality (e.g. representative demonstrations by Easely [3], Blazej [4] and Hupert [5]), LOC systems largely rely on substantial external infrastructure [e.g. high voltage (HV) power supplies and switches, detection systems, valves/pumps and thermal cyclers]. In essence, microfluidic devices are often demonstrated in what might be called ‘chip-in-a-lab’ approaches (i.e. requiring significant support infrastructure) rather than ‘lab on a chip’ approaches. Although the ‘chip-in-a-lab’ approach is an effective way to develop and demonstrate new microfluidic technologies, and is suitable for use in centralised laboratories, it is unsuitable for POC applications. We focus on one widely used LOC technique, capillary electrophoresis (CE). Laser-induced fluorescence (LIF) is one of the most commonly used detection methods in CE, because of high sensitivity and an abundance of well- characterised protocols that have been developed in the life sciences [6]. In this paper, we present an integration of most subsystems needed to perform electrophoresis, onto IET Nanobiotechnol., 2010, Vol. 4, Iss. 3, pp. 91–101 91 doi: 10.1049/iet-nbt.2009.0018 & The Institution of Engineering and Technology 2010 www.ietdl.org