Micro/Nano Patterened Integrated Electrochemical Sensors for Implantable Applications Muhammad Mujeeb-U-Rahman*, Mehmet Sencan**, Dvin Adalian***, Axel Scherer**** * California Institute of Technology, Pasadena, CA USA,mrahman@caltech.edu ** California Institute of Technology, Pasadena, CA USA,msencan@caltech.edu *** California Institute of Technology, Pasadena, CA USA, dvin@caltech.edu **** California Institute of Technology, Pasadena, CA USA, etcher@caltech.edu ABSTRACT Electrochemical sensors are important candidates for autonomous integrated sensing applications. Such sensors can provide accurate and long-term measurements of multiple analyte for applications in complex environments e.g. in body fluids. As such sensors are made smaller and need to be fully integrated, special approaches need to be taken in order to achieve functional sensitivity, stability, and longevity. Here, we provide details of CMOS compatible, integrated design and fabrication of these sensors on very small scales using micro/nano scale fabrication and surface modification techniques. We also present in situ functionalization and novel interface design techniques. We also provide a comparison between integrated reference electrodes fabricated using CMOS compatible fabrication techniques. Finally, we show examples of sensing Glucose and DNA concentration in biological samples. Keywords: electrochemical sensors, integrated, fabrication, CMOS compatible, functionalization 1 INTRODUCTION Implantable electrochemical sensors have attracted considerable interest lately as they are easily integratable with signal processing circuitry required for many sensing applications for completely wireless implants [1]. These sensors can provide selective and sensitive results in complex environments, in vivo environment being a very relevant example. Devices utilizing electrochemical sensors have been shown to work for long term implanted applications and have shown the promise of such technology [2]. Furthermore, use of Complementary Metal Oxide Field Effect Transistors (CMOS) technologies has the advantage of providing ample processing capabilities with minimal area and power requirements using materials that are easily adaptable towards long-term biological applications. Hence, an electrochemical sensor on CMOS system is very promising towards realizing the ultimate goal of chronic implants for biomedical applications. So far in this field most sensors are quite large and pose numerous challenges for widespread use in different applications. In most cases the sensors are designed on separate dies and are then integrated with signal processing circuitry using bonding/assembly techniques to realize fully functional devices. This leads to difficulty in miniaturization, increase in cost, and decrease in overall system performance. Hence, these devices tend to be larger and pose significant challenges towards implantation and long-term use. It has been proposed that smaller devices can have significant advantages for large scale application of this technology making it even more practical. In this work, we present our results towards a fully integrated electrochemical sensor on standard substrates, including CMOS substrates, utilizing micro/nano fabrication to miniaturize the sensor. The small size is advantageous in reducing the bio-fouling problems associated with such implants since it leads to reduced disturbance in the body, foreign body reaction, implantation damage, and inflammation [2]. 2 SENSOR DESIGN Design constraints include the total die area sensors take, biocompatibility and non-toxicity, and operation time ranging from few weeks to few months. The sensors are designed for small sub-mm sized implants. The total area is restricted to a 500μm by 500μm square implant chip. Later on these square CMOS dies can be shaped to other more favorable shapes for implants e.g. circular dies. The sensor can be fabricated on the top metal layer having the circuit underneath utilize all but the top metal layer. Since the integrated system has its own power harvesting subsystem, power distribution is done using lower metal layers without any significant problems. Alternatively, sensors can be fabricated on the bottom of substrate after it is thinned down and passivated. We have used both design approaches and both have their own advantages and limitations. After setting up the design constraints, three electrode based electrochemical sensors are designed to fit within the die area and are made using biocomaptible materials. The geometrical design starts with some guidelines from literature [3]. For example, counter electrode (CE) should be much larger than working electrode (WE), and reference electrode (RE) should be as close to the WE as possible. This can be done using various geometries. We found no rigorous work comparing these geometries. For large scale (macro) devices, this is not very significant, although still relevant, since adequate performance can be achieved using many different types of geometries. However for small scale devices it is very important to study all the factors that NSTI-Nanotech 2013, www.nsti.org, ISBN 978-1-4822-0584-8 Vol. 2, 2013 134