This paper proposes a simple approach to optimize the operating frequency band of a lab-on-a-chip based on bio-impedance cytometry for a single cell. It mainly concerns applications in low-conductivity media. Bio-impedance allows for the characterization of low cell concentration or single cells by providing an electrical signature. Thus, it may be necessary to perform impedance measurements up to several tens of megahertz in order to extract the internal cell signature. In the case of single cells, characterization is performed in a very small volume down to 1 pL. At the same time, measured impedances increase from tens of kilo-ohms for physiological liquids up to several mega-ohms for low conductivity media. This is, for example, the case for water analysis. At frequencies above hundreds of kilohertz, parasitic effects, such as coupling capacitances, can prevail over the impedance of the sample and completely short-circuit measurements. To optimize the sensor under these conditions, a complete model of a cytometry device was developed, including parasitic coupling capacitances of the sensor to take into account all the impedances. It appears that it is possible to increase the pass band by optimizing track geometries and placement without changing the sensing area. This assumption was obtained by measuring and comparing electrical properties of yeast cells in a low-conductivity medium (tap water). Decreased coupling capacitance by a factor higher than 10 was obtained compared with a previous non-optimized sensor, which allowed for the impedance measurement of all electrical properties of cells as small as yeast cells in a low-conductivity medium.
The limit of detection of a biological sensor is an important parameter because, when it is optimized, it allows the detection of a reduced number of biological cells and the reduction of the detection time. This parameter can be improved upon with a reduction in electrode size, but the rate of detection is similarly reduced as well. To avoid this problem, we propose a sensor matrix composed of 20 × 20 µm² coplanar square electrodes with a standard clean room manufacturing process. However, it was observed that the exposition of electrode connection tracks to the solution reduces the normalized impedance variation. In this pursuit, we propose in this paper an analysis of electrode connection tracks on the normalized impedance variation and cutoff frequencies to biological cell measurements by impedance spectroscopy. The experimental results were obtained using the E4990A Keysight impedance analyser (Keysight Technologies, Santa Rosa, CA, USA) with a frequency band ranging from 100 Hz to 12 MHz, thus allowing for good measurement accuracy. Therefore, it was found that, for the measurements between the electrodes with 9 µm of connection tracks in contact with the solution, the normalized impedance variation was from 3.7% to 4.2% for different measurements, while, for the electrodes with 40 µm of connection tracks in contact with the solution, the normalized impedance variation was from 1.8% to 2.1% for different measurements.
New technologies, such as biosensors and lab-on-a-chip, are reducing time consumption and costs for the detection and characterization of biological cells. One challenge is to detect and characterize cells and bacteria one by one or at a very low concentration. In this case, measurements have very low variations that can be difficult to detect. In this article, the use of an insulation layer on the connection tracks of a biosensor with coplanar electrodes is proposed to improve a biosensor previously developed. The impedance spectroscopy technique was used to analyze the influence of the insulation layer on the cutoff frequencies and on the normalized impedance variation. This solution does not induce changes in the cutoff frequencies, though it permits improving the normalized impedance variations, compared to the same biosensor without the insulation layer.
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