High Resolution Read-out Circuit for DNA Label-Free Detection System

Daniela De Venuto
Politecnico di Bari, Italy


Abstract

Surface based methods for the detection of biological molecules such as DNAs and proteins have revolutionized the biological detection. However, only limited use has been made of the electrical properties of biologically modified interfaces as a basis for biological sensing. The wealth of available DNA sequence data makes it possible to identify many diseases as well as biological threats such as the presence of an infectious agent in the environment. Improving the sensitivity, selectivity, speed, simplicity and reducing the cost of such assays are important goals that will significantly affect the administration of health care at locations ranging from the patientís bedside to the battlefield. Alterations in gene expression have profound effects on biological functions. These variations in gene expression are at the core of altered physiologic and pathologic processes. DNA array technologies provide the most effective means of identifying gene expression and genetic variations. DNA is prepared from a wide variety of samples such as tissue, bacteria, saliva, etc. For genotyping analysis, the sample is genomic DNA. For expression analysis, the sample is cDNA, DNA copies of RNA. The DNA samples are tagged with a radioactive or fluorescent label and applied to the array. Single stranded DNA will bind to a complementary strand of DNA. At positions on the array where the immobilized DNA recognizes a complementary DNA in the sample, binding or hybridization occurs. The labeled sample DNA marks the exact positions on the array where binding occurs, allowing automatic detection. The output consists of series of hybridization events, indicating the presence or the relative abundance of specific DNA sequences that are present in the sample. Conventional arrays often rely on the detection of fluorescence from a molecular fluorophore. Electronic detection of hybridization is expected to require less complicated instrumentation and feature similar detection limits compared to the traditional optical methods. Recently a sequence specific DNA biosensor based on capacitance monitoring of the hybridization event has been developed. The approach is based on the detection of capacitance changes produced by the DNA hybridization events onto the sensing interface. This approach is particularly suitable for the realization of a complete, single-chip solution through the integration of the sensing element with the micro-fluidic and electronic parts that complete the system. The hybridization of targets increases the quantity of biological material that insulate the gold electrode from the electrolyte solution, hence the thickness of the capacitance dielectric. Furthermore, it changes also the relative dielectric constant of the insulating layer. Variation of the sensor capacitance in the order of 30-50% are expected as result of DNA hybridization. However the sensing system capability depends on the appropriate choice of electronics readout. For the sensors geometry considered in our experiments, the sensor capacitance values can range between 20nF down to 100pF, depending on the electrodes area, solution concentration and biological material quantity. Since it was realized a single board to measure different kinds of sensors, the electronics has been implemented such to follow the capacitive swing saving the needed linearity and reaching the desired resolution (>10bit). Moreover the readout system has been design to offer the possibility to perform an absolute capacitive measurement and also to compare the value of the changed capacitance of the sensor with the starting one to have a fast detection of the amount of the capacitive shift and then of hybridization occurrence. In this paper, the focus is on the readout system for the novel sensor. The designed electronic system is able to detect the absolute value of the capacitance of the sensor with a resolution better than 1% and also the capacitance shift with a resolution better then 0.01%. The electronic systems described here is suitable for integration allowing a complete single-chip solution together with the micro-fabricated sensor.