Ultrasensitive Memristive Biosensors
In this Tutorial, the very best worldwide ever-reported electrochemical biosensors based on a memristive effect and aptamers or antibodies are presented. These novel sensing devices are developed to propose a completely new approach in the co-design of Bio/Nano/CMOS interfaces for cancer diagnostics. In this new approach, affinity-based techniques are presented for the detection of the prostate specific antigen (PSA) and the Vascular Endothelial Growth Factor (VEGF). The hysteretic properties of memristive silicon nanowires functionalized with proper biomolecules provide a completely new measuring method for label-free and ultrasensitive bio-detection. In order to fully understand the new approach, both model and a physical theory about conductivity on this new class of memristive devices will be presented in details. In order to develop innovative diagnostic systems based on such a new measurement methodology, a new CMOS instrumentation is required too. Therefore, this tutorial will also show and discusses novel circuit approaches for an automated and quick characterization of arrays of memristive biosensors. One new memristive parameter, collaed “Voltage Gap”, will be shown as directly proportional to the target molecules concentration. Thus, CMOS readouts acquiring such width, meanwhile sorting-out faulty devices, i.e. non-conducting nanowires in the array, are presented together with analog-to-digital conversion for the acquired voltage gap. A prototype of these circuits is shown as an example of design in 0.35μm CMOS technology will be presented as well. The integration of the CMOS readout with the nanoscale sensors and a microfluidic platform is a must for the design of robust biosensing-systems for quick data acquisition in cancer diagnostics. Therefore, the development of an improved chip-platform for cancer diagnostics based on nanofabricated Memristive Biosensors integrated, for the first time, with a microfluidic structure is also presented in this lecture by also addressing critical issues, e.g., the problems related to long connections between the Memristive Biosensors and the CMOS frontend. Finally, validation with tumor extracts from oncological patients will be shown to demonstrate the applicability and potential impact in society of such new powerful class of biosensors.
Sandro Carrara is an IEEE Fellow for his outstanding record of accomplishments in the field of design of nanoscale biological CMOS sensors. He is also the recipient of the IEEE Sensors Council Technical Achievement Award in 2016 for his leadership in the emerging area of co-design in Bio/Nano/CMOS interfaces. He is a faculty member at the EPFL in Lausanne (Switzerland). He is former professor of optical and electrical biosensors at the Department of Electrical Engineering and Biophysics (DIBE) of the University of Genoa (Italy) and former professor of nanobiotechnology at the University of Bologna (Italy). He holds a PhD in Biochemistry & Biophysics from University of Padua (Italy), a Master degree in Physics from University of Genoa (Italy), and a diploma in Electronics from National Institute of Technology in Albenga (Italy). His scientific interests are on electrical phenomena of nano-bio-structured films, and include CMOS design of biochips based on proteins and DNA. Along his carrier, he published 7 books, one as author with Springer on Bio/CMOS interfaces and, more recently, a Handbook of Bioelectronics with Cambridge University Press. He has more than 250 scientific publications and is author of 13 patents. He is now Editor-in-Chief of the IEEE Sensors Journal, the largest journal among 180 IEEE publications; he is also founder and Editor-in-Chief of the journal BioNanoScience by Springer, and Associate Editor of IEEE Transactions on Biomedical Circuits and Systems. He is a member of the IEEE Sensors Council and his Executive Committee. He was a member of the Board of Governors (BoG) of the IEEE Circuits And Systems Society (CASS). He has been appointed as IEEE Sensors Council Distinguished Lecturer for the years 2017-2019, and CASS Distinguished Lecturer for the years 2013-2014. His work received several international recognitions: several Top-25 Hottest-Articles (2004, 2005, 2008, 2009, and two times in 2012) published in highly ranked international journals such as Biosensors and Bioelectronics, Sensors and Actuators B, IEEE Sensors journal, and Thin Solid Films; a NATO Advanced Research Award in 1996 for the original contribution to the physics of single-electron conductivity in nano-particles; five Best Paper Awards at the Conferences IEEE NGCAS in 2017 (Genoa), MOBIHEALTH in 2016 (Milan), IEEE PRIME in 2015 (Glasgow), in 2010 (Berlin), and in 2009 (Cork); three Best Poster Awards at the EMBEC Conference in 2017 (Tampere, Finland), Nanotera workshop in 2011 (Bern), and NanoEurope Symposium in 2009 (Rapperswil). He also received the Best Referees Award from the journal Biosensor and Bioelectronics in 2006. From 1997 to 2000, he was a member of an international committee at the ELETTRA Synchrotron in Trieste. From 2000 to 2003, he was scientific leader of a National Research Program (PNR) in the filed of Nanobiotechnology. He was an internationally esteemed expert of the evaluation panel of the Academy of Finland in a research program for the years 2010-2013. He has been the General Chairman of the Conference IEEE BioCAS 2014, the premier worldwide international conference in the area of circuits and systems for biomedical applications.
Imaging Systems and Effectiveness of Physiological Imaging Systems in Early Diagnostic Process
For diagnostic purposes, many medical imaging devices having different imaging capabilities have been used in clinics. For anatomical imaging, in general Computerized Tomography (CT), Magnetic Resonance Imaging (MRI) Systems, Diagnostic Ultrasound Systems, Digital X-Ray Systems are used. Computerized tomography is used for imaging densitive tissues but for soft tissues MRI systems can be used. For x-ray based imaging systems like CT and conventinal x-ray systems, the danger of ionization radiation must be taken into account.
Gama Camera, Positron Emission Tomography (PET), Termal Imaging Systems can be used for physiological imaging of the tissues. In early stage, variations in metabolic activities can be detected by means of the physiological imaging systems. In PET, glucose consumption can be monitorized for early diagnosis of malignities of tissues. But in thermal imaging systems, infrared waves representing tissue’s metabolic activity are converted to the thermal image. Medical thermal imaging systems detect changes of temperatures on human body and enables doctors to diagnose specific diseases and disorders in early stages. Medical thermography is a passive imaging system with no harmful side-effects that can diagnose effects that cannot be seen by traditional medical imaging devices.
Digital infrared thermal imaging for detection of breast cancer has undergone for several decades. Numerous medical centers have been used thermography as diagnostic purposes. Clinical thermography is a procedure that detects, records, and produces an image of a patients skin surface temperatures. Digital infrared thermal imaging does not include ionizing radiation and it does not pose harm to the patient. The breast thermography provides information on the normal and abnormal physiologic functioning of the tissues.
Dr.Irfan Karagoz received the B.S. and M.S. degrees from Boğaziçi University at İstanbul in 1983 and 1985 respectively, and the Ph.D. degree from Hacettepe University at Ankara in 1993, all in electrical and electronics engineering. He established the Gülhane Military Medical Academy Biomedical and Clinical Engineering Center in 1989. He worked as the founding chairman of this center between 1989-1999. In 2001, he started to work as Associate Professor in Gazi University Electrical and Electronics Engineering Department. In 2005, he established the Gazi University Biomedical Calibration and Research Center and since 2005 he is the founding director of this center. Currently, he continues his work in Electrical and Electronic Engineering Department in Gazi University as Professor. Dr. Karagoz’s research activities are in the field of Biomedical Instrumentation, Biomedical Calibration, Medical Technology Management, and Biomedical Signal and Image Processing. Dr. Karagoz has written three books, namely “Medical Technology Management”, “Medical Imaging Systems”, and “Biological Signals and Medical Devices” published in Turkey.