New Publications are available for Biosensors
http://dl-live.theiet.org
New Publications are available now online for this publication.
Please follow the links to view the publication.Live cell index sensing based on the reflection mode of tilted fiber tip with gold nanoparticles
http://dl-live.theiet.org/content/conferences/10.1049/cp.2010.1166
We presented a micrometer size tapered fiber tip for real-time refractive index measurement of live cell. The tip is cut with a specific tilted angle. Only the cutting surface of tip apex is coated with gold nanoparticles (GNPs) by selective bonding method. The evanescent wave at the apex will excite the localized surface plasmon resonance (LSPR) of GNPs. With enhanced scattering at the resonance wavelength, the tip reflection will experience a loss, which is analogous to attenuated total reflection (ATR). By measure the reflection beam, a wavelength dependent loss dip in the reflection spectrum or an intensity loss of a specific wavelength could be used to detect the refractive index of live cell.Beyond mobile coronary care - a telehealthcare case study
http://dl-live.theiet.org/content/conferences/10.1049/ic.2007.1693
The following topics are presented: distribution of acute coronary deaths; percentage of cardiac deaths occur in the home and circulatory arrests that are unwitnessed; future sensing of vital signs in the home; self-care, telecare, and early intervention; communication technology; wireless noninvasive vital signs platform; wireless vital signs (WVS) platform- Holter as an example product; WVS platform advantages; motion artefact reduction; WVS platfor- vital sign inputs; noninvasive patch-based vital signs monitor; patient management; WVS platform roadmap- disposable; biosensing- patient identification; home-based vital signs monitoring; atrial fibrillation; and microcardia atrial defibrillator technical assessment.A question of identity - wiring in the human
http://dl-live.theiet.org/content/conferences/10.1049/ic_20060257
This paper discusses the RFID implants for identification via a sensor network. Brain-computer implants linked in to a wireless network. Biometric identification via body sensors is also discussed. The use of a network as a means for remote and distance monitoring of humans opens up a range of potential uses. Where implanted identification is concerned this immediately offers high security access to specific areas by means of only an RFID device. If a neural implant is employed then clearly the information exchanged with a network can take on a much richer form, allowing for identification and response to an individual's needs based on the signals apparent on their nervous system. (5 pages)Direct adsorption of chemically modified biomolecules onto gold: a rapid method for biological functionalization of MEMS
http://dl-live.theiet.org/content/conferences/10.1049/ic_20060453
The present work reports a simple, rapid and versatile strategy for glycoprotein immobilization, based on the targeted functionalization of carbohydrate residues with disulphide "anchors" derivatives able to spontaneously chemisorb onto gold, with no need of surface pre-functionalization. Different glycoproteins as enzymes and antibodies were chemically modified using this "one step" bio-immobilization protocol and directly adsorbed onto gold coated interfaces. Surface plasmon resonance (SPR) and Electrochemistry techniques revealed that direct adsorption of a modified glyco-enzyme (horseradish peroxidase) onto gold led to the formation of a densely packed SAM, where each single biomolecule is several thousand times more active than a non modified one. In the case of antibodies, the specific location of the carbohydrate moieties in the constant region resulted in the formation of active and site-oriented SAMs. This bio- immobilization method was applied to the bio- functionalization of a degenerate mode MEMS sensor (MEMSens). Preliminary results obtained for the detection of protein S-100ββ (brain injury marker), indicate a promising low detection limit.Protein engineering for biosensor design
http://dl-live.theiet.org/content/conferences/10.1049/ic_20050120
The use of biological materials (molecules, cells or tissues) to impact specificity and sensitivity to sensors is well established and has had some notable successes, for example in blood glucose measurement. However the use of natural biological materials suffers from the singular disadvantage that their properties have evolved to fit their biological function rather their application to sensor technology. One approach that overcomes this disadvantage is the use of biologically inspired synthetic materials. The alternative, which I will illustrate in this presentation, is to re-engineer the biology to overcome the inherent limitations of natural materials. (21 pages)Mechano-biochemistry
http://dl-live.theiet.org/content/conferences/10.1049/ic_20050121
The emergence of microfabricated cantilever sensors, which can directly translate molecular recognition binding events into a nanomechanical response, offers a highly sensitive method to detect chemical and biological molecules. This novel nano-mechanical actuation mechanism has important advantages because it requires no sample labelling and so analytes can be detected in a single step reaction. Furthermore these miniaturised sensors are highly suitable for parallelization into integrated, portable devices and the first microarray of levers for multiple DNA detection has recently been demonstrated. The goal of our research is to explore the versatility of this new sensing mechanism, probing systems of growing complexity; from small molecule binding interactions, through to DNA, protein and cancer cell studies. Central to this work is the delicate interplay between surface chemistry and mechanics and current efforts are focused on developing a fundamental understanding of surface stress at the solid-liquid interface. Novel surface chemistries and polymer coatings are being explored in order to enhance the surface stress signal. Also different cantilever geometries, material properties, actuation and detection methods will be discussed. (13 pages)Lab-on-a-chip: from research to market, a case study on commericialising new technology
http://dl-live.theiet.org/content/conferences/10.1049/ic_20050592
A collection of slides from the author's conference presentation is given. (13 pages)Design of wireless network of sensors for continuous monitoring of vital biosignals
http://dl-live.theiet.org/content/conferences/10.1049/ic_20030151
The concept of a wireless integrated network of sensors, already applied in several sectors of our everyday life, such as security, transportation and environment monitoring, can provide an advanced monitor and control medium for healthcare services. By networking medical sensors wirelessly, we create the appropriate infrastructure for continuous and real-time monitoring of the patient without discomfort. Moreover, the utilization of existing mobile communications networks in such an application releases patient's telemonitoring services from almost any spatial constraint. In this paper we describe the architecture of a modular and ambulatory telemedicine system used for continuous monitoring of vital biosignals. We focus on the design of the wireless network of medical sensors, attached to the patient's body, with emphasis being given to the software and hardware infrastructure that supports the communication between the nodes.Closed chamber PCR-chips for DNA amplification
http://dl-live.theiet.org/content/conferences/10.1049/ic_20000184
The polymerase chain reaction (PCR) is a well described method for the selective identical replication of DNA molecules. By an enzymatic in-vitro amplification process, the concentration of a DNA species is nearly doubled in a process, stepping through three different temperatures. In this way, the DNA concentration can be multiplied more than million-fold by 20 to 30 cycles of temperature. The advantages of miniaturized PCR chips are many such as rapid temperature cycling, smaller quantities of rather expensive reagents needed, low cost fabrication and the portability, which is of great use for environmental screening as well as in the medical sector. In this paper the fabrication and packaging of miniaturized reaction chambers etched into silicon are described. Advantages of the PCR chip are the small size of the chip (6 mm×4 mm×1.5 mm) and the sealing of the chamber with a Pyrex wafer using the anodic bonding method. The transparent surface of the Pyrex makes it possible to incorporate optical readout methods. The microchambers of 1 μl volume can be easily filled with the reagents using hypodermic needles and the fabrication process is simple. For fast thermocycling and control, platinum heaters and a temperature sensor have been integrated onto the chip. This ensures increased performance due to the closeness to the reagents and reduction of power and size. Only standard micromachining processes are used for the fabrication. (5 pages)Selected Topics in Advanced Solid State and Fibre Optic Sensors
http://dl-live.theiet.org/content/books/cs/pbcs011e
<p xmlns="http://pub2web.metastore.ingenta.com/ns/">The authors provide descriptions of the operation, characteristics and applications of the sensors on which they work, together with recent advances and prospects for the future.</p>Chemical sensor analysis
http://dl-live.theiet.org/content/conferences/10.1049/ic_19970828
Chemical sensors are devices which incorporate a chemical recognition element which is in intimate contact with a transducer, the aim of which is usually to provide a digital electronic signal. Such devices are usually operated continuously, to provide a real time analysis of a specific chemical, or group of chemicals. It is also possible to use these devices to make one-shot, spot checks, or to incorporate them into instrumentation such as flow-injection analysers, or automated multi-analysers. The recognition element is the key feature of chemical sensors and may be an inorganic or organic compound or of biological origin. In the latter case, the devices are termed biosensors. The use of biological components has created considerable interest due to the often very high selectivities of these materials for their target analytes. Examples of these recognition components are discussed as well as some sensor types: ion selective electrodes, ISFETs, amperometric sensors, optical chemical sensors. (3 pages)The lab on a chip
http://dl-live.theiet.org/content/conferences/10.1049/ic_19971060
Using the example of open-tubular liquid chromatography, the authors demonstrate improved performance, cheap and simple production and miniaturisation through microengineering. Improved performance can result from efficient heat transfer (capillary electrophoresis and PCR), reduced diffusion path lengths (chromatography and coupled chemical reactions) and from the ability to produce devices with optimised geometry. Microengineering can also allow method integration, leading to the concept of an entire analytical facility on a single chip. Given the early promise, it is likely that these devices, or less complex microengineered structures which couple chemical or biochemical sensors with suitable sample processing packages, will become important tools in industrial, environmental and clinical measurement. (3 pages)Nanosensors for near patient and in vivo diagnostics and closed loop drug delivery
http://dl-live.theiet.org/content/conferences/10.1049/ic_19971063
The trend towards primary care and disease management based consolidation of major healthcare companies is leading to closer market relationships between disease therapy (often a drug) and its diagnostics. This changing market environment enables integration of drug and diagnostic to be considered, particularly at the levels of drug usage and drug delivery. At the scientific level, the need for near patient and in vivo diagnostics is usually seen as the main driver for the development of reliable and biocompatible devices to report biochemical or biological parameters in blood and other body fluids. There are two main approaches to the development of small devices to operate in the body, which reflect the overall directions of microelectronics and particularly nanotechnology. In order to combine the benefits of biorecognition with biophysical detection methods, we have been developing sub-micron sized assemblies to sense and produce amplified signals that can be resolved by biophysical detection and imaging methods. We find liposomes a particularly successful vehicle for this approach. (3 pages)Minimally invasive glucose and lactate sensors
http://dl-live.theiet.org/content/conferences/10.1049/ic_19971059
We have further developed an in vivo technique which appears to overcome most problems of existing glucose and lactate sensors: the open microflow. This exploits the small negative hydrostatic pressure of subcutaneous tissue to enable continuous flow of buffer solution around the electrode tip. This pumpless fluid flow hydrates local tissue, yet remains under physiological control as part of the balance of transcapillary fluid exchange, as determined by osmotic and hydrostatic pressure balance (Starling's forces). The functional outcome of the needle-microflow combination in the case of glucose, is rapid in vivo stabilisation, identity of blood to tissue levels, a tissue lag time of under one minute and maintained stability. (2 pages)An intelligent multi-sensing sensor-array
http://dl-live.theiet.org/content/conferences/10.1049/ic_19961383
A miniaturized multi ion-sensor (IS) array based on coated silver-stripe (CSS) technique is described. The K<sup xmlns="http://pub2web.metastore.ingenta.com/ns/">+</sup>-CSS-IS, Na<sup xmlns="http://pub2web.metastore.ingenta.com/ns/">+</sup>-CSS-IS, and Ca<sup xmlns="http://pub2web.metastore.ingenta.com/ns/">2+</sup>CSS-IS studied so far show very good coated-wire electrode properties comparable to conventional ion-selective electrodes (ISE); the main characteristics are the near-Nernstian response over clinical range, a better selectivity and short response times. A very thin (300 nm), wide (1 mm), and long (70 mm) with circular tip area of 7 mm<sup xmlns="http://pub2web.metastore.ingenta.com/ns/">2</sup> silver metallic layer deposited on a glass substrate using chemical vapor deposition. It is shown that this approach could be used for the development of a cost-effective miniaturized multi-sensor array systems for clinical application for the determination of the ion activity or concentration by zero-current potentiometry method. (4 pages)Flow and microflow - applications in biomedical sensing devices
http://dl-live.theiet.org/content/conferences/10.1049/ic_19961016
Fluid microflow using porous filters and capillaries offers a valuable means of transferring small volumes of fluid sample and reagents located within one element of a sensor complex to another, viz. the detector surface. Alternatively, fluid microflow directed over a sensor surface can provide a mobile self-cleaning barrier protecting the sensor interface. Useful advances in the application of microflow technology for biomedical sensing devices have been achieved at the University of Manchester using both these strategies. This presentation concerns the role respectively of microflow at electrochemical sensors for in-vivo needles to measure glucose and in-vitro planar sensors for immunomediated hormone analysis. (3 pages)Temperature dependence of SH-APM delay-lines on quartz: design rules for (bio)chemical sensors
http://dl-live.theiet.org/content/conferences/10.1049/cp_19960035
In this paper, we propose new results in the case of SH-APM delay-lines on quartz substrate. These modes propagate at discrete frequencies that are defined in the case of free surfaces. We describe in detail the SH-APM, its propagation characteristics and its responses to temperature variations in order to design biochemical sensors; theoretical studies of temperature dependence are examined and experimental results with various frequency modes for different plate geometries are presented. They show the frequency-temperature sensitivities.Sub-micrometre fibre optic chemical sensor
http://dl-live.theiet.org/content/conferences/10.1049/ic_19951221
The near-field interaction between an optical aperture of sub-micrometre diameter and a sample surface can be exploited to spectroscopically probe a biological medium with a resolution unattainable with traditional far-field techniques. A simple, low-cost technique is described for producing a chemical sensor which is based on the principles of near-field optics, and preliminary results obtained using this device to measure pH within individual mammalian cells is reported. (6 pages)Silicon-on-insulator integrated optical biosensors for environmental monitoring
http://dl-live.theiet.org/content/conferences/10.1049/ic_19951117
It is shown that the fabrication of a family of silicon based evanescent optical field sensors can be produced using well established silicon microelectronics processes. Such devices offer advantages of low cost and high sensitivity compared with conventional technologies. A further cost advantage arises from the generic nature of the technology. This is largely due to the active features of silicon circuits. New sensors will only require the development of appropriate receptor layers. Ink-jet printing provides the means to produce highly controlled droplets of very low volume. These can be printed at high speed and are controlled by a microprocessor. It is therefore possible to produce small receptor film regions. (6 pages)Dielectrophoretic sensors for microbiological applications
http://dl-live.theiet.org/content/conferences/10.1049/ic_19951512
Novel microbiological sensors based on the dielectrophoretic (DE) effect have been demonstrated. Co-planar electrode sensors have been shown to have excellent selectivity and collection efficiency for ozone treated and untreated Cryptosporidium parvum oocysts, demonstrating the potential of DE as a basis for rapid sensing of microbiological species of interest to public health. The principle of grid electrode sensors for high flow (i.e. on-line monitoring) applications has been demonstrated; although quantitative different DE collection efficiencies of ozone treated and untreated Cryptosporidium parvum oocysts were observed compared with the co-planar electrodes sensors. However, sufficient discrimination was retained for viable sensing. Finally, on-going and future work on fully micromachined grid electrodes is well advanced and is showing promising progress. (2 pages)Fabrication methods for integrated biosensors
http://dl-live.theiet.org/content/conferences/10.1049/ic_19951514
The use of sensors in medical and environmental applications is increasing rapidly. Biosensors make up a proportion of this market. By modifying fabrication techniques from the well established electronics industry the manufacture of cheap and reliable biosensors could be realised alongside the development of integrated biosensors. By incorporating the necessary electronics on the same substrate as the sensor, noise and cost could be reduced. All steps for the fabrication of the sensor part of an integrated glucose sensor have been developed, along with a useful technique for the deposition of polymer membranes. The set polymer must not be soluble in acetone for this technique to work. (5 pages)Optical instrumentation for respiration measurement in magnetic resonance scanners
http://dl-live.theiet.org/content/conferences/10.1049/ic_19951223
Magnetic resonance imaging (MRI) is a non-invasive technique for visualising the internal structure of the body. The method involves placing the subject in a strong static magnetic field (c. 1.5 T) and using various combinations of radiofrequency energy and pulsed magnetic field gradients, known as pulse sequences, to produce images. Most MRI pulse sequences acquire data over an extended time period in order to produce an image. Any physiological motion, e.g. movement of the heart, respiration etc., during this time period will cause artefacts and blurring. Various approaches have been employed to try and reduce this sensitivity to motion, including the synchronisation of data collection with the subjects electrocardiogram (EGG) to minimise cardiac motion and the development of fast pulse sequences to acquire the data within multiple breath-hold periods, between 10 and 20s. We have been employing both techniques together to acquire dynamic images of cardiac function. The requirement for data collection over multiple breath-holds however, is that each breath-hold must be reproducible, so that the heart is in the same position within the thorax each time. Even with highly motivated subjects it is difficult for them to breath-hold in a consistent manner. This paper outlines the adaptation and development of the Fibre Optic Respiratory Plethysmograph (FORP) to produce a MRI gating system (FORP-GS). This consists of a PC based, non-invasive respiratory sensor and a joint optical feedback system to the subject, allowing accurate monitoring of the thorax position in real time without any electro-magnetic interference. (5 pages)BIOPTICAS: optical biosensing techniques for monitoring organic pollutants in the aquatic environment
http://dl-live.theiet.org/content/conferences/10.1049/ic_19951119
The aim of the BIOPTICAS project is to develop optically-based analytical techniques for the detection and measurement of low concentrations of organic pollutants in the aquatic environment. A number of sensors and biochemical methods are being investigated, enabling the potential development of highly sensitive biosensing instruments for the measurement of pesticides and herbicides in surface, ground and drinking waters. (4 pages)Integrated optical surface plasmon resonance biosensor for pesticide analysis
http://dl-live.theiet.org/content/conferences/10.1049/ic_19951120
We report the design, fabrication and performance of gold coated waveguide surface plasmon resonance biosensors for the detection of the pesticide simazine in aqueous solution. The operation of the sensor was verified against the biotin-avidin biochemical model. The output power of the sensor showed a decrease of 32% on binding a dual layer of biotin-avidin. Calibration of the sensor against standard simazine solutions using a competitive test format was performed and the system was determined to have a detection limit of 0.22 μg/l. (6 pages)Protein–gold nanoparticles interactions and its application for alkaline phosphatase assay
http://dl-live.theiet.org/content/journals/10.1049/mnl.2012.0455
Proteins-modified gold nanoparticles (AuNPs) have been considered as attractive materials in many fields especially in biosensing. In this Letter, the authors have studied the relationship between ratios of specific amino acids and protein–AuNPs interactions. A new indicator <i xmlns="http://pub2web.metastore.ingenta.com/ns/">R</i><sub xmlns="http://pub2web.metastore.ingenta.com/ns/">w/s</sub>, calculated from the ratios of certain hydrophilic amino acids, is proposed to reveal the affinity coefficient between proteins and AuNPs. Experimental results show that the proposed <i xmlns="http://pub2web.metastore.ingenta.com/ns/">R</i><sub xmlns="http://pub2web.metastore.ingenta.com/ns/">w/s</sub> can indicate the binding status of proteins and AuNPs effectively. The authors have also introduced alkaline phosphatase, a protein with relatively low <i xmlns="http://pub2web.metastore.ingenta.com/ns/">R</i><sub xmlns="http://pub2web.metastore.ingenta.com/ns/">w/s</sub>, for detection by the colorimetric shift based on strong protein–AuNPs interactions.Direct electrochemistry and electrocatalysis of immobilised cytochrome <i xmlns="http://pub2web.metastore.ingenta.com/ns/">c</i> on electrodeposited nanoparticles for the reduction of oxygen
http://dl-live.theiet.org/content/journals/10.1049/mnl.2012.0622
Direct electrochemical response of cytochrome <i xmlns="http://pub2web.metastore.ingenta.com/ns/">c</i> (cyt <i xmlns="http://pub2web.metastore.ingenta.com/ns/">c</i>) on the modified electrode was studied by cyclic voltammetry. The results indicated that cyt <i xmlns="http://pub2web.metastore.ingenta.com/ns/">c</i> could be adsorbed on the surface of the electrodeposited cobalt oxyhydroxide nanoparticles (CoOx NPs) modified electrode. A couple of well-defined redox peaks can be observed in a phosphate buffer solution (pH 7.0), whose formal potential, <i xmlns="http://pub2web.metastore.ingenta.com/ns/">E</i>°′ (defined as the average of reductive and oxidative peaks), was −86.5 mV with respect to the reference electrode equal to 110.5 mV against normal hydrogen electrode. Cyt <i xmlns="http://pub2web.metastore.ingenta.com/ns/">c</i> adsorbed on the surface of CoOx NPs shows a remarkable electrocatalytic activity for the reduction of oxygen. Based on these, a third-generation biosensor could be developed to detect the concentration of oxygen in aqueous solution.Dynamic analysis of fixed-free single-walled carbon nanotube-based bio-sensors because of various viruses
http://dl-live.theiet.org/content/journals/10.1049/iet-nbt.2011.0057
In the present study, the vibrations of the fixed-free single-walled carbon nanotube (SWCNT) with attached bacterium/virus on the tip have been investigated. To explore the suitability of the SWCNT as a bacterium/virus detector device, first the various types of virus have been taken for the study and then the resonant frequencies of fixed-free SWCNT with attachment of those viruses have been simulated. These resonant frequencies are compared with the published analytical data, and it is shown that the finite element method (FEM) simulation results are in good agreement with the analytical data. The results showed the sensitivity and suitability of the SWCNT having different length and different masses (attached at the tip SWCNT) to identify the bacterium or virus.Sensitivity enhancement in SiGe-on-insulator nanowire biosensor fabricated by top surface passivation
http://dl-live.theiet.org/content/journals/10.1049/mnl.2012.0214
The oxidation caused by Ge condensation increases the Ge fraction in a SiGe-on-insulator (SGOI) and significantly increases the hole mobility. This effect can be exploited to improve the sensitivity of SGOI nanowires. However, previous studies have found that the sensitivity of SGOI nanowires degrades when the Ge fraction exceeds 20%, because a high Ge fraction destabilises the surface state of SiGe. In this work, a top surface passivation plasma-enhanced chemical vapour deposition SiO<sub xmlns="http://pub2web.metastore.ingenta.com/ns/">2</sub> layer deposited on a Si<sub xmlns="http://pub2web.metastore.ingenta.com/ns/">0.8</sub>Ge<sub xmlns="http://pub2web.metastore.ingenta.com/ns/">0.2</sub> nanowire improved its sensitivity by ∼1.3 times that of the nanowire sample without a top passivation layer.Lateral field excited film bulk acoustic resonator for detection of protein–ligand interactions
http://dl-live.theiet.org/content/journals/10.1049/el.2012.2156
Presented is a lateral field excited film bulk acoustic resonator for real-time sensing of protein–ligand interaction using the biotin–streptavidin system as a model. The film bulk acoustic resonator works at 2 GHz in shear mode. For biosensing, the biotin was immobilised on one face of the resonator as the probe. The resonant frequency of the biotin-immobilised device drops rapidly at first and gradually reaches equilibrium when exposed to the streptavidin solutin due to the biotin–streptavidin interaction. Consequently, the lateral field excited film bulk acoustic resonator can be used to study the kinetics of protein–ligand interaction without the use of labelling or molecular tags. The proposed device shows promising applications for disease diagnostics, prognosis, and drug discovery.Mimicking the biological olfactory system: a Portable electronic Mucosa
http://dl-live.theiet.org/content/journals/10.1049/iet-nbt.2010.0032
In this study the authors report on the development of a new type of electronic nose (e-nose) instrument, which the authors refer to as the Portable electronic Mucosa (PeM) as a continuation of previous research. It is designed to mimic the human nose by taking significant biological features and replicating them electronically. The term electronic mucosa or simply e-mucosa was used because our e-nose emulates the nasal chromatographic effect discovered in the olfactory epithelium, located within the upper turbinate. The e-mucosa generates spatio-temporal information that the authors believe could lead to improved odour discrimination. The PeM comprises three large sensor arrays each containing a total of 576 sensors, with 24 different coatings, to increase the odour selectivity. The nasal chromatographic effect provides temporal information in the human olfactory system, and is mimicked here using two-coated retentive channels. These channels are coated with polar and non-polar compounds to enhance the selectivity of the instrument. Thus, for an unknown sample, the authors have both the spatial information (as with a traditional e-nose) and the temporal information. The authors believe that this PeM may offer a way forward in developing a new range of low-cost e-noses with superior odour specificity.Adaptive, integrated sensor processing to compensate for drift and uncertainty: a stochastic ‘neural’ approach
http://dl-live.theiet.org/content/journals/10.1049/ip-nbt_20040213
An adaptive stochastic classifier based on a simple, novel neural architecture - the Continuous Restricted Boltzmann Machine (CRBM) is demonstrated. Together with sensors and signal conditioning circuits, the classifier is capable of measuring and classifying (with high accuracy) the H<sup xmlns="http://pub2web.metastore.ingenta.com/ns/">+</sup> ion concentration, in the presence of both random noise and sensor drift. Training on-line, the stochastic classifier is able to overcome significant drift of real incomplete sensor data dynamically. As analogue hardware, this signal-level sensor fusion scheme is therefore suitable for real-time analysis in a miniaturised multisensor microsystem such as a Lab-in-a-Pill (LIAP).Self-assembling of proteins and enzymes at nanoscale for biodevice applications
http://dl-live.theiet.org/content/journals/10.1049/ip-nbt_20040639
Different nanotechnological strategies have been selected to implement biomolecular devices following a bottom-up or top-down approach depending on the biomolecule and on its functionality. Biomolecules have particular functionality and self-assembling capabilities that can be exploited for the implementation of both bioelectronic devices and multipurpose engineered biosurfaces. Surface preparation with supramolecular methods and microcontact printing have been developed and optimised to realise suitable functionalised surfaces. These surfaces can be used to link metalloproteins and enzymes for the implementation of nanobioelectronic devices and planar biosensors or to bind cells in order to promote their growth along predefined tracks and grooves. Some possible applications of these biosurfaces are shown and discussed. Results are presented for the realisation of a biomolecular nanodevice working in air based on the metalloprotein azurin immobilised in the solid state, the formation and characterisation of functional glutamate Dehydrogenase monolayers for nanobiosensing applications, the results of soft lithography processes on azurin for biosensor implementation, and the development of physiological self-assembled patterns of laminin-1 for cell culture applications and hybrid devices.Microdevices for separation, accumulation, and analysis of biological micro- and nanoparticles
http://dl-live.theiet.org/content/journals/10.1049/ip-nbt_20031127
Microfabrication and performance of a novel microsystem for separation, accumulation and analysis of biological micro- and nanoparticles is reported. Versatile chip functions based on dielectrophoresis and microfluidics were integrated to isolate particles from complex sample solutions such as serum. A bead-based assay for virus detection is proposed. Separation of micro- and sub-μm beads employing dielectrophoretic deflector and bandpass structures is demonstrated. Individual antibody coated beads with hepatitis A virus bound to their surface were trapped by negative dielectrophoresis in a field cage and analysed by fluorescence microscopy.Spectral tuning of localised surface plasmon-polariton resonance in metallic nano-crescents
http://dl-live.theiet.org/content/journals/10.1049/ip-nbt_20050016
The utilisation of plasmonic effects in metallic nanostructures is gaining importance for applications in molecular sensing. Of special interest is the local field enhancement effect, which enables surface-enhanced Raman scattering and significantly boosts the sensitivity of the Raman technique. For <i xmlns="http://pub2web.metastore.ingenta.com/ns/">in vivo</i> biological research, the ability to excite the resonance of localised surface plasmon-polaritons within the biological window is often desired. A new nanostructure called the nano-crescent is introduced and exhibits strong plasmonic activities within the biological window using a novel intra-particle plasmonic coupling scheme.Selective enzymatic cleavage of gold nanoparticle-labelled DNA on a microarray
http://dl-live.theiet.org/content/journals/10.1049/ip-nbt_20045016
The use of the restriction enzyme <i xmlns="http://pub2web.metastore.ingenta.com/ns/">Eco</i>RI for the manipulation of double-stranded DNA on microarrays is introduced. Gold nanoparticles are attached to a microarray via base pairing between complementary DNA sequences on the array and on the particles. These particles could be detected by light scattering measurements following an enhancement step, in which silver islands were deposited on top of the gold particles. This deposition of silver could be completely suppressed if the particles were removed by enzymatic cleavage of their DNA linker molecules. This cleavage step critically depends on the presence of a specific enzyme recognition site.Ligand-installed PEGylated bionanosphere
http://dl-live.theiet.org/content/journals/10.1049/ip-nbt_20055021
The synthesis of poly(ethylene glycol)-b-poly(2-<i xmlns="http://pub2web.metastore.ingenta.com/ns/">N</i>,<i xmlns="http://pub2web.metastore.ingenta.com/ns/">N</i>-dimethylaminoethylmethacrylate) processing an acetal group at the PEG chain end (acetal-PEG/PAMA) is reported. The obtained acetal-PEG/PAMA block copolymer was found to reduce tetrachloroauric acid at room temperature to produce gold nanoparticles. The size of these nanoparticles was controllable in the range of 6 to 13 nm by changing the initial Au<sup xmlns="http://pub2web.metastore.ingenta.com/ns/">3+</sup>: polymer ratio. In addition to the reduction of tetrachloroauric acid, acetal-PEG/PAMA bonds on the surface of the obtained gold nanoparticles to improve their dispersion stability in an aqueous medium even at a salt concentration as high as two. Biotinyl-PEG/PAMA-anchored gold nanoparticles undergo specific aggregation in the presence of streptavidin thereby revealing their promising utility as colloidal sensing systems for use in biological systems. Biotin-PEG/PAMA can also be utilised for the preparation of a functionally PEGylated quantum dot (QD). When CdCl<sub xmlns="http://pub2web.metastore.ingenta.com/ns/">2</sub> and Na<sub xmlns="http://pub2web.metastore.ingenta.com/ns/">2</sub>S were mixed in aqueous media in the presence of the biotin-PEG/PAMA, a CdS QD with an ∼5 nm size was prepared. The polyamine segment was anchored onto the surface of the formed CdS nanoparticle, whereas the PEG segment was tethered onto the surface to form a hydrophilic palisade, thus improving the dispersion stability in aqueous media even under a high salt concentration condition. An effective fluorescent resonance energy transfer (FRET) was observed by the specific interaction of the biotin-PEG/PAMA stabilised CdS QD with TexasRed-labelled streptavidin with the physiological ionic strength of 0.15 M. The extent of the energy transfer was in proportion to the concentration of the TexasRed-streptavidin. This FRET system using the PEGylated CdS QD coupled with fluorescent-labelled protein can be utilised as a highly sensitive bioanalytical system.Planar silicon nitride waveguides for biosensing
http://dl-live.theiet.org/content/journals/10.1049/ip-nbt_20030571
The principles of attenuation of the light intensity due to multiple reflections are realised in a planar silicon oxide (SiO<sub xmlns="http://pub2web.metastore.ingenta.com/ns/">2</sub>)/silicon nitride (Si<sub xmlns="http://pub2web.metastore.ingenta.com/ns/">3</sub>N<sub xmlns="http://pub2web.metastore.ingenta.com/ns/">4</sub>) waveguiding structure for the purpose of developing optical biosensors with improved sensitivity. The analysis of the experimental data shows that the large difference in refractive indices of core and cladding layers gives rise to an increase in sensitivity by a factor of 3 over previously reported structures. Composite polyelectrolyte self-assembled thin films containing cyclo-tetra-chromotropylene as an indicator and enzymes glucose oxidase or urease were employed in the superstrate as a sensing membrane. Individual enzyme reactions as well as their inhibition by pesticides were studied by monitoring the intensity of light output from the planar waveguide. The results were compatible with those obtained by conventional ultraviolet-visible absorption spectroscopy. The instrument detection limit for Imidacloprid pesticide was found to be as low as 10 ppb in concentration.Gold-nanoparticle-assisted oligonucleotide immobilisation for improved DNA detection
http://dl-live.theiet.org/content/journals/10.1049/ip-nbt_20055019
Colloidal gold nanoparticles are investigated as a potential scaffold for the assisted immobilisation of probe oligonucleotides on silicon surfaces. A preliminary study is devoted to the examination of the immobilisation of DNA-modified gold nanoparticles as a function of time, concentration, salt and pH. The DNA-modified nanoparticles self-assembled onto solid surfaces in a three-dimensional self-assembled architecture. The functionalised surfaces are evaluated in diagnostic assays, where their potential to improve the efficiency of the hybridisation reaction is tested. The system utilising DNA-modified nanoparticles produced an enhancement in the hybridisation efficiency and the sensitivity limit by a factor 10 to 100 as compared to a conventional DNA immobilisation system on a planar surface.Infrared up-converting phosphors for bioassays
http://dl-live.theiet.org/content/journals/10.1049/ip-nbt_20045014
The development of up-converting phosphor reporter particles has added a powerful tool to modern detection technologies. Carefully constructed phosphor reporters have core-shell structures with surface functional groups suitable for standard bio-conjugations. These reporters are chemically stable, possess the unique property of infrared up-conversion, and are readily detected. In contrast to conventional fluorescent reporters, up-converting phosphor particles do not bleach and allow permanent excitation with simultaneous signal integration. A large anti-Stokes shift (up to 500 nm) separates discrete emission peaks from the infrared excitation source. Along with the unmatched contrast in biological specimens due to the absence of autofluorescence upon infrared excitation, up-converting phosphor technology (UPT) has unique properties for highly-sensitive particle-based assays. The production and characteristics of UPT reporter particles as well as their application in various bioassays is reviewed.Sensors made of RNA: tailored ribozymes for detection of small organic molecules, metals, nucleic acids and proteins
http://dl-live.theiet.org/content/journals/10.1049/ip-nbt_20050047
Nucleic acids are well suited to serve as biosensors for the fast and reliable detection of small organic molecules, such as a number of metabolites or antibiotics, specific nucleic acid sequences, peptides, proteins or metal ions. One of the main advantages of using nucleic acids as biosensors is that they can be modulated to respond allosterically to specific effectors. Thus molecular recognition is transformed directly into a catalytic process with observable results. In particular, catalytic RNA structures, such as the hammerhead and hairpin ribozymes, have been used for biosensor engineering. The review reports on the function mode of nucleic acid biosensors and introduces recent developments and applications in the field.Resonant nano-cluster devices
http://dl-live.theiet.org/content/journals/10.1049/ip-nbt_20045013
The resonance-enhanced absorption (REA) by metal clusters on a surface is an effective technique on which to base bio-optical devices. A four-layer device consisting of a metal mirror, a polymer or glass-type distance layer, a biomolecule interaction layer and a sub-monolayer of biorecognitively bound metal nano-clusters is reported. Experiments indicate a strong influence of the resonator homogeneity on the absorption maximum. Layer stability plays an important role in the overall performance of the device. Techniques and optimised lab protocols to set up biochips that use the REA process in the detection are presented. The sensors show one to three narrow reflection minima in the visible and or infra-red (IR) part of the spectrum and therefore they do not suffer from the spectral limitations associated with spherical gold colloids. Metal clusters (synthesised by thermal step reduction) as well as metal- dielectric shell clusters (synthesised by various shell deposition processes) are used to precisely shift the readout of the device to any frequency in the visible and near IR range. Disposable single-step protein chips, DNA assays as well as complex biochip arrays are established that use various DNA/RNA, antigen–antibody and protein–protein interaction systems.Biomolecule-compatible support structures for biomolecule coupling to physical measuring principle surfaces
http://dl-live.theiet.org/content/journals/10.1049/ip-nbt_20040691
As part of studies on biomolecule-compatible interfacial structures for practice-relevant biosensor and biochip developments, new film-forming aminocelluloses of the ‘P-CH<sub xmlns="http://pub2web.metastore.ingenta.com/ns/">2</sub>-NH-(X)-NH<sub xmlns="http://pub2web.metastore.ingenta.com/ns/">2</sub>’ type (P=cellulose) with spacer structures (X=special oligoamine residues) at C6 and solubilising groups (S=tosylate or carbanilate) at C2/C3 of the anhydroglucose unit (AGU) were synthesised and their film properties and covalent coupling with enzyme protein examined. Depending on the nature and degree of substitution (DS<sub xmlns="http://pub2web.metastore.ingenta.com/ns/">(S)</sub>) of the ester groups (S) at C2/C3, the new aminocellulose derivatives are soluble either in DMA and DMSO (with S=carbanilate) or in water (with S=tosylate). The aminocellulose derivatives form transparent films from their solutions. AFM investigations of the film surfaces have either shown very flat (topography <1 nm) films or tubular topographies of nanostructure size, depending on structural and environment-induced factors of influence. Especially in the case of films from water-soluble aminocelluloses with oligoamine residues at C6, inter alia, enzyme-specific pH values and different positive charge distributions can be adjusted by partial protonation of the NH<sub xmlns="http://pub2web.metastore.ingenta.com/ns/">2</sub> end groups. By means of the covalent coupling of the new aminocelluloses with glucose oxidase (GOD) it was shown that the enzyme coupling efficiency can be decisively optimised by the interplay of aminocellulose structure, coupling structure and enzyme protein.Surface-enhanced Raman spectroscopy biosensors: excitation spectroscopy for optimisation of substrates fabricated by nanosphere lithography
http://dl-live.theiet.org/content/journals/10.1049/ip-nbt_20050009
In the 28 years since its discovery, surface-enhanced Raman scattering (SERS) has progressed from model system studies of pyridine on a roughened silver electrode to state-of-the-art surface science studies and real-world sensing applications. Each year, the number of SERS publications increases as nanoscale material design techniques advance and the importance of trace analyte detection increases. To achieve the lowest limits of detection, both the relationship between surface nanostructure and laser excitation wavelength and the analyte–surface binding chemistry must be carefully optimised. This work exploits the highly tunable nature of nanoparticle optical properties to establish the optimisation conditions. Two methods are used to study the optimised conditions of the SERS substrate: plasmon-sampled and wavelength-scanned surfaced Raman excitation spectroscopy (SERES). The SERS enhancement condition is optimised when the energy of the localised surface plasmon resonance of the nanostructures lies between the energy of the excitation wavelength and the energy of the vibration band of interest. These optimised conditions enabled the development of SERS-based sensors for the detection of a <i xmlns="http://pub2web.metastore.ingenta.com/ns/">Bacillus anthracis</i> biomarker and glucose in a serum–protein matrix.Preliminary electrochemical characterisation of cytochrome P4501A2-clozapine interaction
http://dl-live.theiet.org/content/journals/10.1049/ip-nbt_20030534
Cytochromes P450 are a large superfamily of heme-thiolate enzymes involved in the metabolism of many different organic substrates such as drugs, fatty acids and toxic compounds. The aim of this work is to analyse the binding between the cytochrome P4501A2, in solution and in gel-matrix, and its substrate (clozapine), utilising voltammetric tests. The interaction measurements were carried out using two different screen printed electrodes (rhodium–graphite and graphite–riboflavin), and the results were compared. It was demonstrated that it is possible to realise a biosensor prototype to detect the presence of clozapine indirectly by chronoamperometry.Surface plasmon resonance imaging for biosensing
http://dl-live.theiet.org/content/journals/10.1049/iet-nbt.2008.0012
Surface plasmon resonance imaging (SPRI) is a useful tool for the study of surface biomolecular interactions allowing for label-free detection and elegant instrumentation. SPRI imaging system is described in this review with an emphasis on recent applications with examples of different biological interactions and high throughput analysis. Signal amplification in SPRI using nanoparticle and waveguide-based optical coupling is introduced. Finally the detection sensitivity of the SPRI system is examined in terms of other competitive methods.Nanostructuring of heme-proteins for biodevice applications
http://dl-live.theiet.org/content/journals/10.1049/iet-nbt_20060020
Proteins represent versatile building blocks for the realisation of nanostructured materials to be applied in the nanobiotechnological field. The Langmuir–Blodgett (LB) technique was utilised as a means to develop nanobiodevices based on protein molecules. Namely, engineered Cytochrome P450 thin films were fabricated and characterised. The possibility to employ LB-based protein structures to use in biosensors has been exploited. The characterisation process was performed in order to verify the best working parameters. As a first step' the protein films were studied at the air–water interface and then transferred into a solid support for further characterisation. The films were characterised by different techniques such as: UV–vis spectroscopy, nanogravimetry, atomic force microscopy and biochemical assays. The results showed that it was possible to form active cytochrome P450s nanostructures by the LB technique.Dielectrophoretic assembly of insulinoma cells and fluorescent nanosensors into three-dimensional pseudo-islet constructs
http://dl-live.theiet.org/content/journals/10.1049/iet-nbt_20070027
Dielectrophoretic forces, generated by radio-frequency voltages applied to micromachined, transparent, indium tin oxide electrodes, have been used to condense suspensions of insulinoma cells (BETA-TC-6 and INS-1) into a 10×10 array of three-dimensional cell constructs. Some of these constructs, measuring ∼150 µm in diameter, 120 µm in height and containing around 1000 cells, were of the same size and cell density as a typical islet of Langerhans. With the dielectrophoretic force maintained, these engineered cell constructs were able to withstand mechanical shock and fluid flow forces. Reproducibility of the process required knowledge of cellular dielectric properties, in terms of membrane capacitance and membrane conductance, which were obtained by electrorotation measurements. The ability to incorporate fluorescent nanosensors, as probes of cellular oxygen and pH levels, into these ‘pseudo-islets’ was also demonstrated. The footprint of the 10×10 array of cell constructs was compatible with that of a 1536 microtitre plate, and thus amenable to optical interrogation using automated plate reading equipment.Bacterial detection using a carbon nanotube gas sensor coupled with a microheater for ammonia synthesis by aerobic oxidisation of organic components
http://dl-live.theiet.org/content/journals/10.1049/iet-nbt.2008.0011
In this study, the authors propose a new bacteria detection method using a carbon nanotube (CNT) gas sensor and a microheater, which were coupled into a Bio-MEMS (microelectromechanical systems)-type device. Bacteria were heated by the microheater in air so that ammonia (NH<sub xmlns="http://pub2web.metastore.ingenta.com/ns/">3</sub>) gas can be generated by the oxidation reaction of organic components of bacteria. Thus generated NH<sub xmlns="http://pub2web.metastore.ingenta.com/ns/">3</sub> gas was detected by using the CNT gas sensor, which was fabricated by dielectrophoresis (DEP) and combined with the microheater to form a small chamber. Cyclic pulsed heating operation was employed so that the CNT response to elevated temperature did not mask NH<sub xmlns="http://pub2web.metastore.ingenta.com/ns/">3</sub> response. It was demonstrated that the proposed device could detect and quantify 10<sup xmlns="http://pub2web.metastore.ingenta.com/ns/">7</sup> bacteria cells (<i xmlns="http://pub2web.metastore.ingenta.com/ns/">Escherichia coli</i>). Possible application of DEP to trap and enrich target bacteria on the microheater was also discussed.AC electrothermal manipulation of conductive fluids and particles for lab-chip applications
http://dl-live.theiet.org/content/journals/10.1049/iet-nbt_20060022
AC electrokinetics has shown great potential for microfluidic functions such as pumping, mixing and concentrating particles. So far, electrokinetics are typically applied on fluids that are not too conductive (<0.02 S/m), which excludes most biofluidic applications. To solve this problem, this paper seeks to apply AC electrothermal (ACET) effect to manipulate conductive fluids and particles within. ACET generates temperature gradients in the fluids, and consequently induces space charges that move in electric fields and produce microflows. This paper reports two new ACET devices, a parallel plate particle trap and an asymmetric electrode micropump. Preliminary experiments were performed on fluids with conductivity at 0.224 S/m. Particle trapping and micropumping were demonstrated at low voltages, reaching ∼100 µm/s for no more than 8 Vrms at 200 kHz. The fluid velocity was found to depend on the applied voltage as <i xmlns="http://pub2web.metastore.ingenta.com/ns/">V</i><sup xmlns="http://pub2web.metastore.ingenta.com/ns/">4</sup>, and the maxima were observed to be ∼20 µm above the electrodes.Integrated circuit-based instrumentation for microchip capillary electrophoresis
http://dl-live.theiet.org/content/journals/10.1049/iet-nbt.2009.0018
Although electrophoresis with laser-induced fluorescence (LIF) detection has tremendous potential in lab on chip-based point-of-care disease diagnostics, the wider use of microchip electrophoresis has been limited by the size and cost of the instrumentation. To address this challenge, the authors designed an integrated circuit (IC, i.e. a microelectronic chip, with total silicon area of <0.25 cm<sup xmlns="http://pub2web.metastore.ingenta.com/ns/">2</sup>, less than 5 mm×5 mm, and power consumption of 28 mW), which, with a minimal additional infrastructure, can perform microchip electrophoresis with LIF detection. The present work enables extremely compact and inexpensive portable systems consisting of one or more complementary metal-oxide-semiconductor (CMOS) chips and several other low-cost components. There are, to the authors’ knowledge, no other reports of a CMOS-based LIF capillary electrophoresis instrument (i.e. high voltage generation, switching, control and interface circuit combined with LIF detection). This instrument is powered and controlled using a universal serial bus (USB) interface to a laptop computer. The authors demonstrate this IC in various configurations and can readily analyse the DNA produced by a standard medical diagnostic protocol (end-labelled polymerase chain reaction (PCR) product) with a limit of detection of ∼1 ng/µl (∼1 ng of total DNA). The authors believe that this approach may ultimately enable lab-on-a-chip-based electrophoretic instruments that cost on the order of several dollars.