Marking 100 years since Rudolf Höber’s discovery of the insulating envelope surrounding cells and of the beta-dispersion exhibited by tissue

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Journal of Electrical Bioimpedance 3 (2012): 74-79, doi:10.5617/jeb.401.Between 1910 and 1913 Rudolf Höber presented proof that the interiors of red blood cells and muscle cells contain conducting electrolytes, and that each conducting core is contained within an insulating membrane. He did this by demonstrating, in a series of remarkable electrical experiments, that the conductivity of compacted cell samples at low frequencies (~150 Hz) was about ten-times less than the value obtained at ~5 MHz. On perforation of the membrane, the low-frequency conductivity increased to a value approaching that exhibited at MHz frequencies. Apart from representing a major milestone in the development of cell biology and electrophysiology, Höber’s work was the first description of what we now call the dielectric b-dispersion exhibited by cell suspensions and fresh tissue

Impedimetric measurement of DNA–DNA hybridisation using microelectrodes with different radii for detection of methicillin resistant Staphylococcus aureus (MRSA)

Due to their electroanalytical advantages, microelectrodes are a very attractive technology for sensing and monitoring applications. One highly important application is measurement of DNA hybridisation to detect a wide range of clinically important phenomena, including single nucleotide polymorphisms (SNPs), mutations and drug resistance genes. The use of electrochemical impedance spectroscopy (EIS) for measurement of DNA hybridisation is well established for large electrodes but as yet remains relatively unexplored for microelectrodes due to difficulties associated with electrode functionalisation and impedimetric response interpretation. To shed light on this, microelectrodes were initially fabricated using photolithography and characterised electrochemically to ensure their responses matched established theory. Electrodes with different radii (50, 25, 15 and 5 µm) were then functionalised with a mixed film of 6-mercapto-1-hexanol and a thiolated single stranded ssDNA capture probe for a specific gene from the antibiotic resistant bacterium MRSA. The complementary oligonucleotide target from the mecA MRSA gene was hybridised with the surface tethered ssDNA probe. The EIS response was evaluated as a function of electrode radius and it was found that charge-transfer (RCT) was more significantly affected by hybridisation of the mecA gene than the non-linear resistance (RNL) which is associated with the steady state current. The discrimination of mecA hybridisation improved as electrode radius reduced with the RCT component of the response becoming increasingly dominant for smaller radii. It was possible to utilise these findings to produce a real time measurement of oligonucleotide binding where changes in RCT were evident one minute after nanomolar target addition. These data provide a systematic account of the effect of microelectrode radius on the measurement of hybridisation, providing insight into critical aspects of sensor design and implementation for the measurement of clinically important DNA sequences. The findings open up the possibility of developing rapid, sensitive DNA based measurements using microelectrodes

Test structure and measurement system for characterising the electrochemical performance of nanoelectrode structures

This paper presents a complete test structure and characterisation system for the evaluation of nanoelectrode technology. It integrates microfabricated nanoelectrodes for electrochemical measurements, 3D printing and surface tensionconfined microfluidics. This system exploits the inherent analytical advantages of nanoelectrodes that enables their operation with small volume samples, which has potential applications for onwafer measurements

Test Structures for the Characterisation of Conductive Carbon Produced from Photoresist

Conductive carbon films are highly attractive for use as electrodes in electrochemistry and biosensing applications. Patterned photoresist films can be transformed into carbon electrodes using standard photolithographic techniques followed by pyrolysation of the photoresist in a furnace under a reducing atmosphere. Previous studies have been made of the electrical properties of blanket carbon films created using this method of fabrication. However, there is a need to investigate pattern dependent effects, particularly the extent to which the dimensions of the patterned films shrink during the high temperature processing. This study applies microfabricated test structures to the process characterisation of conductive carbon produced from standard positive photoresists

Wafer Level Characterisation of Microelectrodes for Electrochemical Sensing Applications

This work presents a system for the in-line wafer-level characterisation of electrochemical sensors. Typically, such sensors are first diced and packaged before being electro-chemically tested. By integrating their characterisation into the manufacturing process, the production of electrochemical sensors becomes more efficient and less expensive as they can be parametrically tested midway through the fabrication process, without the need to package them. This enables malfunctioning or failed devices to be identified before dicing and reduces costs as only functional devices are packaged (in many cases this can be more expensive than the sensor fabrication). This study describes wafer-level characterisation of a simple electrochemical sensor design using a photoresist hydrophobic corralling film for the electrolyte and a probe station for contacting to individual dies

Optimisation and characterisation of durable microelectrodes for electroanalysis in molten salt

This work presents microfabricated microelectrodes, capable of quantitative analysis in molten salt (MS). MSs are an electrolytic medium of growing interest, especially in the area of nuclear reprocessing. However, designing sensors for a MS-based nuclear reprocessing system is a challenge, owing to the usually corrosive nature and high operating temperatures (typically 450 - 500◦C) of MS. Microelectrodes are well placed as sensors, with numerous advantages over macro-scale electrodes. As a consequence, there have been previous attempts to utilise microelectrodes inMS. However, these have not been successful and all have suffered disadvantages inherent in traditional microelectrode manufacturing. The microelectrodes presented in this work were produced using standard microfabrication techniques and characterised in MS. An analysis of failure mechanisms guided a systematic study of material combinations. This resulted in a sensor, which is capable of delivering quantifiable electrochemistry in MS. However, the lifetime and yield of the sensor were determined to only be 46% and 1.4 hours respectively. Further investigation of the microelectrode failure mechanisms guided several layout changes to the microelectrode design. By reducing critical area, where defects or pinholes could form, these resulted in improvements in performance. This increased the yield to 65%, while the average lifetime increased up to 45 hours. Test structures were designed to investigate the causes of the continued microelectrode failures and identified shorting between the electrode metal and silicon substrate. This suggests the existence of defects in the underlying insulator are the cause of the 35% of microelectrodes which never functioned. Separate test structures suggested the lifetimes of the microelectrodes could also be improved by removing the need for a metal adhesion layer. Tantalum has been suggested as a replacement electrode metal and a proof of concept study demonstrated the feasibility of employing thin film tantalum as an electrode metal in LKE. Using this technology as a platform, several proof-of-concept microelectrode designs are also presented: liquid microelectrodes, microelectrode arrays, and a nanoelectrode. These are targeted at specific sensing applications, and provide an expanded spectrum of measurements in MS

Dataset for paper 'Advances in electroanalysis, sensing and monitoring in molten salts'

Microelectrodes have a number of advantages over macroelectrodes for quantitative electroanalysis and monitoring, including reduced iR drop, high signal to noise and reduced sensitivity to convection. Their use in molten salts has been generally precluded by the combined materials challenges of stresses associated with thermal cycling and physical and corrosive chemical degradation at the relatively high temperatures involved. We have shown that microfabrication, employing high precision photolithographic patterning in combination with the controlled deposition of materials, can be used to successfully address these challenges. The resulting molten salt compatible microelectrodes (MSMs) enable prolonged quantitative microelectrode measurements in molten salts (MSs). This paper reports the fabrication of novel MSM disc electrodes, chosen because they have an established ambient analytical response. It includes a detailed set of electrochemical characterisation studies which demonstrate both their enhanced capability over macroelectrodes and over commercial glass pulled microelectrodes, and their ability to extract quantitative electroanalytical information from MS systems. MSM measurements are then used to demonstrate their potential for shedding new light on the fundamental properties of, and processes in, MSs, such as mass transport, charge transfer reaction rates and the selective plating/stripping and alloying reactions of liquid Bi and other metals; this is will underpin the development of enhanced MS industrial processes, including pyrochemical spent nuclear fuel reprocessing.University of Edinburgh, School of Chemistry. (2016). Dataset for paper 'Advances in electroanalysis, sensing and monitoring in molten salts', [dataset]. http://dx.doi.org/10.7488/ds/1338