Label-free Electrochemical Impedance Detection of Ovarian Cancer Markers CA-125 and CEA
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Label-free Electrochemical Impedance Detection of Ovarian Cancer Markers CA-125 and CEA Allison M. Whited1, Kanwar V. Singh1, Raj Solanki1, and David R. Evans2 1 Department of Physics, Portland State University, Portland, OR 97207-0751, U.S.A. 2 Sharp Laboratories of America, 5750 NW Pacific Rim Blvd, Camas, Washington 98607, U.S.A. ABSTRACT CA-125 and carcinoembryonic antigen (CEA) are two biomarkers present in blood that can indicate the presence of ovarian cancer. They can also be used, both in conjunction with each other and independently, to determine the effectiveness of the treatment being meted for the disease. A label-free multiplexed interdigitated electrode array (IDEA) immunosensor was developed to detect both CA-125 and CEA in buffer solution at levels typically seen in patients with ovarian cancer . Electrochemical impedance spectroscopy was used to measure the increase in impedance when a binding event occurred between the target antigen and its specific antibody that was anchored to the surface of an interdigitated electrode array. CA-125 was detected in concentrations as low as 10units/mL and as high as 80units/mL. CEA was detected in concentrations as low as 1pg/mL and as high as 10µg/mL. INTRODUCTION Biosensors and impedance spectroscopy The recent surge in the development of biosensors has been driven by evidence that the early detection of an illness or disease can save lives. Conventional bioassays are expensive and time consuming and require a trained professional and specialized equipment to analyze them. Label-free biosensors offer numerous benefits including low cost of production, the ability to make continuous measurements in point of care situations, portability, and ease of use [1-3]. Biosensors can be used to detect a variety of proteins, including enzymes [4-6], antigens or antibodies [7-10], and DNA fragments [11-13]. They may use a variety of techniques including voltammetry [14,15], amperometry [16], and impedance spectroscopy [17] to sense an electrochemical signal that is then translated by a signal processor to give a reading. Most follow a procedure of functionalizing the physiochemical transducer of the biosensor and anchoring to it an active biolayer composed of a suitable probe molecule [18]. Impedance spectroscopy is a simple, straightforward method of measuring changes that occur at the interface of the transducer and the biological layer that is responsible for recognizing the target analyte [19-21]. A small sinusoidal voltage is applied to the electrochemical cell over a spectrum of frequencies, typically ranging from less than 100 Hz up to the kHz range, and the responding current is measured. This current reading yields information about the resistive and capacitive components of the device. These in turn can be modeled with the Randles equivalent circuit [22-25]. When a biolayer is attached to the transducer, the impedance of the system is increased. Binding events that occur at the biolayer layer between the anchored probe molecule and the target molecu
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