PAPER www.rsc.org/loc | Lab on a Chip An integrated CMOS high voltage supply for lab-on-a-chip systems M. Behnam, G. V. Kaigala, M. Khorasani, P. Marshall, C. J. Backhouse* and D. G. Elliott Received 12th March 2008, Accepted 3rd June 2008 First published as an Advance Article on the web 21st July 2008 DOI: 10.1039/b804275f Electrophoresis is a mainstay of lab-on-a-chip (LOC) implementations of molecular biology procedures and is the basis of many medical diagnostics. High voltage (HV) power supplies are necessary in electrophoresis instruments and are a significant part of the overall system cost. This cost of instrumentation is a significant impediment to making LOC technologies more widely available. We believe one approach to overcoming this problem is to use microelectronic technology (complementary metal-oxide semiconductor, CMOS) to generate and control the HV. We present a CMOS-based chip (3 mm × 2.9 mm) that generates high voltages (hundreds of volts), switches HV outputs, and is powered by a 5 V input supply (total power of 28 mW) while being controlled using a standard computer serial interface. Microchip electrophoresis with laser induced fluorescence (LIF) detection is implemented using this HV CMOS chip. With the other advancements made in the LOC community (e.g. micro-fluidic and optical devices), these CMOS chips may ultimately enable ‘true’ LOC solutions where essentially all the microfluidics, photonics and electronics are on a single chip. Introduction Despite progress in lab on a chip (LOC) systems, the cost effectiveness, ease of manufacturability and portability of the external instrumentation remains largely unaddressed. 1 Mi- crofluidic chips have been demonstrated in a wide range of medical diagnostic applications, from genetic profiling and diagnosis 2 to disease monitoring, 3 but this has been done in conjunction with expensive and large instruments. To realize a truly portable LOC system it is necessary to replace this external infrastructure while simultaneously reducing cost, size and power consumption. Capillary electrophoresis (CE), a key LOC technology, has important medical applications but typically requires high voltage (HV) power supplies, optics, and interface circuits that limit portability and hinder the develop- ment of a LOC-based point-of-care tool. Several advancements in the integration and cost-effectiveness of optical detection on microfluidic chips 4,5 have been made and many photonic components have been ported to microelectronic chips, 6 yet so far, little has been achieved in miniaturizing HV components. Much of the infrastructure needed for CE is for the high voltage sub-system, consisting of high voltage generation and control, switching and interfacing. We recently demonstrated 4 a $1000 genetic analysis tool that implements CE and is an advancement in portability and cost-effectiveness. In that system, the HV subsystem accounts for almost 50% of the system cost and most of its size. In a more general context, HV components are central to the operation of many micro-electro-mechanical system (MEMS) devices in addition to CE systems, yet there are no demonstrations of truly miniaturized HV sub-systems. Department of Electrical and Computer Engineering, University of Edmonton, AB, T6G 2V4, Canada; Fax: 1 780 492-1811; Tel: 1 780 492-5357. E-mail: christopher.backhouse@ualberta.ca In terms of electrophoresis, there are presently several bench- top electrophoresis platforms such as the ABI PRISM 3100 (Applied Biosystems, Foster City, CA, USA), Agilent 2100 Bioanalyzer (Agilent Technologies, Santa Clara, CA, USA), and the Microfluidic Tool Kit (lTK, Micralyne Inc., Edmonton, AB, Canada). These systems are based on relatively large external high-voltage power supplies (and relays) requiring complex control/interface hardware and software, thus are not suitable as portable systems. In recent reports relating to HV sub- systems for CE, 7–10 the required HV is generated using either one or multiple off-the-shelf DC–DC converters (e.g. a widely used commercial component made by EMCO, Sutter Creek, CA), and switching is performed either by manual switches or electro-mechanical relays assembled on printed circuit boards (PCBs). Often, to also ensure electrical isolation, multiple circuit boards are used, one for the HV components, and the other for the control circuitry—this further increases size. Additionally, the interface and communication with these components adds to complexity and cost. Recent developments involving HV sub-systems include: Jackson et al. 7 incorporated a DC–DC converter into a CE system with electrochemical detection. In another demonstration, Kappes et al., 10 presented a battery- powered CE system that could generate up to 30 kV with amperometric, potentiometric and conductiometric detection. Similarly, Garcia et al. 9 built a battery operated 3-channel HV supply (with 3 DC–DC converters). Erickson et al. 11 introduced a single HV module that generates up to 700 V, but provides only a single channel (i.e. a single DC–DC converter) with manual switching. In a related demonstration, to achieve HV precisely, Collins et al. 12 presented a resistor divider network to vary the generated voltages, based on the use of a DC–DC converter. One of the first demonstrations of a portable CE system was by Sandia laboratories, 8 in work that miniaturized the entire CE system (with DC–DC supplies and relays) and is 1524 | Lab Chip, 2008, 8, 1524–1529 This journal is © The Royal Society of Chemistry 2008