Advancing the performance of scalable nanoelectrochemical transducers: Nanoimprint fabrication, 2D material integration and biosensing optimization

Abstract

The development of electronic devices for molecular detection has revolutionized the sensors technology and its application in different fields such as quality control of consumer products, pollution monitoring and medical diagnostics. Molecular sensing techniques based on electronic detection principles are advantageous by providing faster results and avoiding extensive labelling processes used in optical detection techniques. With the possibility of integrating portable readout methods, electrical sensors can be deployed for point-of-care solutions. In recent years, discovery of new frontiers in nanotechnology has critically influenced the application of electrical sensing techniques especially for biomedical applications. Development of new nanostructuring techniques and discovery of new nanomaterials with excellent electrical properties and large surface-to-volume ratio has led to the development of high-performance miniaturized biosensor platforms with sensitivities down to a few molecules. Out of many different types of electrical biosensors, microelectrode arrays (MEAs) have been one of the prominent candidates for the detection of biomolecules using impedimetric measurement techniques. MEAs have also been deployed for recording biosignalling processes from living systems such as cells using electrical cell-substrate impedance sensing (ECIS) and similar methods. The sensor performance of such platforms is closely related to the configuration of MEA devices such as geometry, number and size of the electrodes. Few examples of improving the performance of such devices include engineering the microelectrode surfaces in order to increase the surface area or to implement novel sensor principles such as molecularly imprinted polymers (MIPs) etc. However, the micron-size electrode architectures in MEAs pose fundamental limitations such as low surface-to-volume ratio for the transducers and narrower impedance spectroscopy operational ranges. In this thesis, novel methods to deal with the limitations affecting the device performance related to the size and configuration of electrodes have been worked out. In the first part of the thesis, a new nanofabrication process based on nanoimprint lithography (NIL) was established for the development of high aspect ratio metal electrodes in the nanoscale regimes using combination of nanoimprint and photolithography methods. The combined nanofabrication process was further optimized for wafer scale production of sensor chips containing nanoelectrode arrays (NEAs). Photolithography processes were used for the passivation of NEAs for liquid operations and characterized using state-of-theart structural and electronic characterization methods. Sensor chips were prepared with systematic variation in nanoelectrode configurations with parameters such as aspect-ratio and number of interdigitated electrodes. Optimized configurations exhibiting superior sensing characteristics such as an increase of dynamic range from 10 nM to 100 nM for sensing operations by comparing nano- and microelectrodes. Here, the devices were used for label-free sensing of DNA molecules. The sensing trials reveal the detection of a very small quantity of biomolecules in a small sample volume, study of faster electrochemical reactions, short response time and provide a sufficient level of sensitivity with a major increase in pattern density. In the second part of the thesis, NEAs were used for the fabrication of fieldeffect based devices using graphene as immobilization platform for receptor molecules. Chemical vapor deposited (CVD) grown graphene was transferred onto the NEAs by using an all organic polymer based transfer process yielding graphene devices with highly clean surfaces. The devices were structurally and electronically characterized using field-effect measurements in liquids followed with deployment as impedimetric biosensors for the label-free detection of the cardiac biomarker molecules myeloperoxidase and fatty-acid-binding protein in buffer solution via antigen/antibody interaction. The dynamic range of the calibration curve is covering the clinical relevant concentration of 60 ng/ml for myeloperoxidase and 19 ng/ml for fatty-acid-binding protein and the range beyond these concentrations. Furthermore, a novel biosensor platform was realized using graphene oxide as a transducer material in order to characterize cell-substrate interactions with HEK-293 cells and antibody-antigen binding events for the detection of histamine. Here, solution derived graphene oxide was used for the fabrication of centimeterlong high surface-area conductive lines. Interfacing of living cells with these graphene oxide lines and subsequent alignment of living cells along the conductive GO lines as well as detection of histamine in liquid was successfully demonstrated suggesting for potential advantages of such alternative platforms for biosensor applications. All in all, new approaches for the submicrometer structuring of metal were performed with NIL, which are capable to achieve large areas of nanostructures. The nanomaterials graphene and graphene oxide were used in a variety of labelfree biosensing schemes, where organization of those into controlled surface architectures was essential for the successful realization of the sensing effect.