Reliable and Low Cost Medical and Environmental Detection System for DNA and Bacteria, Based on Capacitive Electrical Sensors

Luis Moreno-Hagelsieb, Yannick Nizet, Xiaohui Tang, Jean-Pierre Raskin, Jean-Luc Gala, Laurent Francis, Denis Flandre, Devices Integrated and Electronic Circiuts (DICE), Université catholique de Louvain, Belgium
Corresponding author: [email protected]

Simple, low cost and low consumption devices are required in medical applications. In Dr. Luis Moreno-Hagelsieb's laboratory, aluminum oxide interdigitated capacitors have been developed and successfully tested on DNA hybridization test as well as on bacteria, all of them showing comparable results to the state of the art using existing standard biological protocols procedures that open new opportunities for medical and environmental applications.

Our technology demonstrates high-performance CMOS integrated circuits; easy integration of special devices, sensors and MEMS; operation in harsh conditions (micro power, high-temperature, remote RF link, etc.); very low power consumption; and broad applications in biomedical and environmental sectors. Integration into a small easy to use measuring and monitoring equipment has been also successfully demonstrated. Furthermore, our devices deliver excellent performance compared to the state of the art.

In our laboratory, high-performance DNA sensors have been developed, i.e. interdigitated capacitors sensors using micromachining technologies, which can be used in health monitoring, biological and environmental detections.

Figure 1. CMOS technology Interdigitated Capacitor Design Structure.

For biological sensing, interdigitated capacitive transducers have been built on CMOS chips using Al electrodes protected by a thin (50-100 nm) highly-reliable anodized alumina layer. Excellent performance has been demonstrated for DNA hybridization detection (down to 30 pM target concentrations) and applied on the transcription factor TP53 showing a successful discrimination of the wild-type form of codon 175 (175WT) versus mutated form (175GA).

Figure 2. ID Capacitor on DIL packaging placed into the Capacitance and Monitoring Measuring Equipment.

As well known, bacterial contamination is a common cause of several sicknesses. Staphylococcus aureus is the causative agent of a wide variety of infections in humans including diseases of the skin and soft tissues and continues to be a prominent agent of nosocomial infections. We show here that when coated with an appropriate anti- Staphylococcus aureus monoclonal antibody (MoAb), this device also permits to specifically detect this bacteria. The binding of bacteria to the microsensors induce a significant capacitance and conductance shift that is proportional to the amount of immobilized bacteria, thus enabling a possible quantitative analysis.

Figure 3. Global conductance and capacitance changes for the ID Capacitor for bacteria detection with MoAb only, with control samples and with S. aureus with concentrations of 1x109, 2x108, 4x107 CFU/ml, respectively
Figure 4. TP53 DNA Hybridization discrimination test using our interdigitated capacitors system.

Completing our system, a datalogger capable of measuring and monitoring capacitance changes was developed with the help of our partners at JDT to allow a fast readout in real time of our device, thus, the variation can be registered before and after the biological test or even during the whole process.

Finally, our technology allows MOS devices and multiple sensors to be integrated on the same chips (as demonstrated with our breathing monitoring system with temperature and humidity sensing in parallel), which opens the door to many new emerging applications with higher performance even in harsh environments (i.e. temperature between -20 to 300°C, high humidity, …) at lower cost, lower power consumption and higher integration into a wireless system.

Our design is now at the stage of the creation of a Spin-Off that will be based on this device as well as more MEMS and SOI sensors and circuits. This application is promising taking into account the large amount of test being done, more than 9,000 millions done in 2007 in Europe (300 millions in Belgium). The expected initial production is estimated in 100,000 sensors.

Partnership needed: industry and research organization, partners for the sensors production (including packaging), kits fabricator to integrate our device for a fast electrical measurement, distributors especially for our UV sensors, industry with needs in electronic miniaturized low-power, wireless or high-temperature sensors for process control, monitoring, data acquisition and investor for the start-up of the company.

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