A HYBRID BACTERIA AND MICROPARTICLE DETECTIONPLATFORM ON A CMOS CHIP: DESIGN, SIMULATION ANDTESTING CONSIDERATIONS
, Jaouad El-Fouladi
, Sylvain Marte1
and Yvon Savaria
NanoRobotics Laboratory, Department of Computer and Software Engineering,
Department of Electric Engineering,École Polytechnique de Montréal, Campus of the University of Montréal,Montréal, QC, CANAD
Abstract- This paper presents a hybrid bacteria and microparticles detection platform based on a CMOS technology.Vertical face to face microelectrode arrays are implemented ontoCMOS chips by connecting the metal and via layers together. ACMOS post-processing procedure based on Deep Reactive Ion Etching (DRIE) is used to release the microelectrodes and to construct microchannels in between. With medium flow of the fluid, Bacteria and microparticles are allowed to pass through the microchannels, where impedance variations are measured using a microelectrode pair on the wall, and then detected byelectronic circuits embedded on the same chip. This microelectronic/microfluidic hybrid system targets screeningindividual bacterium or microparticle with high throughput and accuracy. The system architecture is presented first, followed by the detailed model, design, simulation and parameters of the prototype. The CMOS post-processing, specific packaging and testing procedures are also introduced in this paper. Finiteelement analysis method (FEM) and circuit simulations confirm that a single microparticle, 5
m in diameter, can be detected by the proposed microsystem. Based on preliminary etching results, pairs of released electrodes 10
H), also contribute to validate the feasibility of the CMOS post- processing procedure.
Detecting bacteria or microparticles is becoming moreand more important in the field of biology, pharmaceuticalindustry, bio-medicine and anti-bio-terrorism. In food- orair-borne disease control, early detection of singlebacterium rather than later detection of largerconcentrations is critical for disease control. The currentmost widely adopted technology for this type of task,named flow cytometry , is based on fluorescent reactionswhen the targeted particles pass through the detecting area.Due to the required light source and the complexity of itsdetector, fluorescent based flow cytometry with paralleldetection is very difficult to achieve. Furthermore, thetargeted particles or cells have to be prepared, generally bycoating them with a fluorescent label before detection. Itlimits the application of this technology, and it alsoincreases the overall detection time. Thus the throughput islow and the screening speed is relatively slow.Another conventional bacteria detection technology isbased on electrochemical sensors [2~5], also referred to asamperometric or impedimetric sensors. These sensorsdetect changes in the electrical characteristics of themedium containing the bacterial cells. Although theelectrochemical sensors offer advantages such as highsensitivity, low cost and ease of integration onto aMEMS/NEMS device, long detection times (usually a 12hours to 7 days process) are expected due to the long pre-amplification period if the initial concentration of bacteria isvery low. Meanwhile, most bacteria and particles are notmotile, and the diffusion rate of the bacteria and particles isvery slow; especially under low Reynolds number laminarconditions. It takes a long migration time for target bacteriaapproaching the detection or sensing area where theelectrodes are implemented. The required signal processingis another challenge for impedimetric sensors. Due to thevery small impedance signal, very precise and complexsignal processing circuits are needed.With the recent development of MEMS and microfluidictechnology, especially bioMEMS or Lab-on-Chip,combined with conventional microelectronic technology,traditional biosensors can be integrated onto CMOS chips.Although most of these systems need some post-processingprocedure or special package, their integration with aCMOS chip not only significantly reduces the fabricationcost and alleviates the requirements of signal processing,but also greatly increases the sensitivity, throughput,robustness, and reliability of this kind of system. Amongthe benefits expected from the miniaturization of CMOSbased biosensors: we can cite a reduction in the requiredbio-reagent and samples volume. Another benefit is that fastdetection and analysis can be performed. Moreover, highdensity of biosensors with multiple functions can beimplemented onto a same substrate, which may greatlyincrease the screening speed. Indeed, on-chipmicroelectronic circuits make parallel signal processing andproduction of real-time analysis reports possible. In the lastdecade, different kinds of CMOS based biosensors havebeen presented for bacteria detection, bio-analysis andneuron activity monitoring [6-8]. For most of thesebiosensors, the top metal layer or metal deposited with post-processing is used to construct coplanar electrodes arraysfor electrical impedance spectroscopy. Highly integratedmicroelectrode arrays and on-chip detection have also beenreported. However, confined by the size of themicroelectrode and the planar orientation, the sensitivity of these devices is not sufficient to detect bacteria with verylow concentration. Meanwhile, the microelectrodes in thesebiosensors have to be coated with some noble andbiocompatible material such as Gold and Platinum, whichnot only increases cost, but also requires complicatedmicrofabrication procedures.In this paper, we present a CMOS basedmicrofluidic/microelectronic system for faster single
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